Category

Adipose
tissue

Autoimmunity

More info:

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Results: positive / unclear/modest / negative

nm

mW

W/cm2

J/cm2

Inflammation

Yoshimura

Brazil
(So Paulo)

2016

J Biophotonics

Photobiomodulation reduces abdominal adipose tissue

inflammatory infiltrate of diet-induced obese and hyperglycemic
mice.

Mouse

LED phototherapy

843

60

0.019

18

5.7

3.14
cm2

300

"Non-irradiated control animals display inflammatory areas almost five times

greater than the treated group (p < 0.001). This result on inflammatory infiltrate
may have caused impacts on the significant lower blood glucose level from
irradiated animals (p = 0.04), twenty-four hours after the last irradiation session."

PubMed

Multiple
sclerosis

Gonalves

Brazil
(Ararangu)

2016

Autoimmunity

Low-level laser therapy ameliorates disease progression in a

mouse model of multiple sclerosis.

Mouse

Experimental
autoimmune
encephalomyelitis

660

30

3.6
(?)

10

0.06
cm2

20

30

"Our results showed that LLLT consistently reduced the clinical score of EAE and
delayed the disease onset, and also prevented weight loss induced by
immunization.

PubMed

904

30

Link

sec

3
0.10
cm2

Furthermore, these beneficial effects of LLLT seem to be associated with the

down-regulation of NO levels in the CNS, although the treatment with LLLT failed
to inhibit lipid peroxidation and restore antioxidant defense during EAE.
Finally, histological analysis showed that LLLT blocked neuroinflammation through
a reduction of inflammatory cells in the CNS, especially lymphocytes, as well as
preventing demyelination in the spinal cord after EAE induction.
Together, our results suggest the use of LLLT as a therapeutic application during
autoimmune neuroinflammatory responses, such as MS."

Autoimmunity Multiple

Muili

sclerosis

USA
2013
(Milwaukee, WI)

PLoS One

Photobiomodulation induced by 670 nm light ameliorates MOG3555 induced EAE in female C57BL/6 mice: a role for remediation of
nitrosative stress.

Mouse

Experimental
autoimmune
encephalomyelitis

670

2100

0.028

375

180

"Cell culture experiments demonstrated that 670 nm light-mediated

photobiomodulation attenuated antigen-specific nitric oxide production by
heterogenous lymphocyte populations isolated from MOG immunized mice.

PubMed

Experiments in the EAE model demonstrated down-regulation of inducible nitric

oxide synthase (iNOS) gene expression in the spinal cords of mice with EAE over
the course of disease, compared to sham treated animals.

LED phototherapy

Animals receiving 670 nm light treatment also exhibited up-regulation of the Bcl-2
anti-apoptosis gene, an increased Bcl-2:Bax ratio, and reduced apoptosis within
the spinal cord of animals over the course of disease.
670 nm light therapy failed to ameliorate MOG-induced EAE in mice deficient in
iNOS, confirming a role for remediation of nitrosative stress in the amelioration of
MOG-induced EAE by 670 nm mediated photobiomodulation."

Autoimmunity

Multiple
sclerosis

Muili

USA
2012
(Milwaukee, WI)

PLoS One

Amelioration of experimental autoimmune encephalomyelitis in

C57BL/6 mice by photobiomodulation induced by 670 nm light.

Mouse

Experimental
autoimmune
encephalomyelitis

670

2100

0.028

375
skin

5
skin

75
cm2
array

0.432
spinal
cord

0.012
spinal
cord

2.9

0.116
cm2

1.5
/point

75

0.02
cm2

3.3

120

0.028
cm2

180

"Disease was induced with myelin oligodendrocyte glycoprotein (MOG) according

to standard laboratory protocol. Mice received 670 nm light or no light treatment
(sham) administered as suppression and treatment protocols.

PubMed

670 nm light reduced disease severity with both protocols compared to sham
treated mice.
Disease amelioration was associated with down-regulation of proinflammatory
cytokines (interferon-, tumor necrosis factor-) and up-regulation of antiinflammatory cytokines (IL-4, IL-10) in vitro and in vivo."

Bone

Bone grafts

de Oliveira
Gonalves

Brazil
(Bauru)

2016

J Photochem
Photobiol B

Effects of low-level laser therapy on autogenous bone graft

stabilized with a new heterologous fibrin sealant.

Rat

Bone

Bone
metabolism

Sayuri Suzuki

Brazil
(So Paulo)

2016

J Biophotonics

Low-level laser therapy stimulates bone metabolism and inhibits

root resorption during tooth movement in a rodent model.

Rat

Bone

Bone
metabolism

Patrocnio-Silva

Brazil
(So Carlos)

2016

Arch Endocrinol
Metab

Low-level laser therapy associated to a resistance training protocol Rat

on bone tissue in diabetic rats.

830

30

Alveolar bone

810

100

Diabetic rats

808

100

0.2586

3.57

18
(?)

33

24

Exercise+LLLT on
bone tissue

"In conclusion, low-level laser therapy stimulated bone regeneration and

accelerated the process of integration of autogenous bone grafts."

PubMed

"Taken together, our results indicate that LLLT can stimulate bone remodeling
reducing root resorption in a rat model. LLLT improves tooth movement via bone
formation and bone resorption in a rat model."

PubMed

"In conclusion, it can be suggested that the resistance exercise program

stimulated bone metabolism, culminating in increased cortical tibial area, bone
mineral content, bone mineral density and biomechanical properties. Furthermore,
the association of physical exercises and LLLT produced higher values for bone
mineral content and stiffness."

PubMed

Star: Parameters were well reported.

Bone

Bone repair

Atasoy

Turkey
(Trabzon)

2017

Braz Oral Res

The efficacy of low-level 940 nm laser therapy with different energy

intensities on bone healing.

Rat

Bone

Bone repair

Mohsenifar

Iran
(Tehran)

2016

Lasers Med Sci

Evaluation of the effects of pulsed wave LLLT on tibial diaphysis in

two rat models of experimental osteoporosis, as examined by
stereological and real-time PCR gene expression analyses.

Rat

940

5
10
20

"No significant change was observed in the number of osteocytes, osteoblasts,

osteoclasts and newly formed vessels at either time period across all laser groups.
Although LLLT with the 10 J/cm2 energy density increased fibroblast activity at the
4th week in comparison with the 5 and 20 J/cm2 groups, no significant change
was observed between the laser groups and the control group. "

PubMed

"These results indicate that low-level 940 nm laser with different energy intensities
may not have marked effects on the bone healing process in both phases of bone
formation."

Ovariectomized rats

890

1.08

0.972

1
cm2

900
/p

24

Pulsed LLLT

Bone

Bone repair

de Almeida

Brazil
(Araatuba)

2016

Arch Oral Biol

Influence of low-level laser therapy on the healing process of

autogenous bone block grafts in the jaws of systemically nicotinemodified rats: A histomorphometric study.

Rat

Autogenous bone
block graft

660

35

Bone

Bone repair

Medalha

Brazil
(So Paulo)

2016

J Photochem
Photobiol B

Low level laser therapy accelerates bone healing in spinal cord

injured rats.

Rat

Spinal cord injury

(SCI) --> Tibial bone
defect

808

30

Bone

Bone repair

Rajaei Jafarabadi Iran (Tehran)

2016

Lasers Med Sci

The effects of photobiomodulation and low-amplitude highRat

frequency vibration on bone healing process: a comparative study.

A transverse critical
size defect (CSD) to
femur

830

40

Bone

Bone repair

Medalha

Brazil
(So Paulo)

2016

J Photochem
Photobiol B

Low level laser therapy accelerates bone healing in spinal cord

injured rats.

Rat

Spinal cord injury

(SCI) --> Tibial bone
defect

808

Bone

Bone repair

Freddo

Brazil
(Porto Alegre)

2016

J Oral Maxillofac
Surg

Influence of a Magnetic Field and Laser Therapy on the Quality of

Mandibular Bone During Distraction Osteogenesis in Rabbits.

Rabbit

Bone

Bone repair

Bosco

Brazil
(Araatuba)

2016

J Photochem
Photobiol B

Effects of low-level laser therapy on bone healing of critical-size

defects treated with bovine bone graft.

Rat

Bone

Bone repair

Acar

Turkey

2016

Arch Oral Biol

Bone regeneration by low-level laser therapy and low-intensity

pulsed ultrasound therapy in the rabbit calvarium.

Bone

Bone repair

Havlucu

Turkey
(Istanbul)

2015

J Oral Implantol

Bone

Bone repair

Soares

Brazil
(Salvador,
Bahia)

2015

Braz Dent J

Brazil
(So Paulo)

2015

1.7

2.8

100

27

0.028
cm2

94

"Concurrent treatments of PW LLLT and alendronate produced the same effect on

osteoporotic bone. Since the PW LLLT has osteogenic effects, different
parameters should be investigated to verify whether an appropriate PW LLLT
protocol in combination with a proper(s) anti osteoporotic agent(s) might reverse
the detrimental effects of OP."

PubMed

"Nicotine harms bone formation in the bed-graft interface and LLLT action can
mitigate this."

PubMed

"The results of the histological and morphometric evaluation demonstrated that the
SL group showed a larger amount of newly formed bone compared to the SC
group. Moreover, a significant immunoexpression of runt-related transcription
factor 2 (RUNX2) was observed in the SL group. There was no statistical
difference in the biomechanical evaluation.

PubMed

In conclusion, the results suggest that LLLT accelerated the process of bone
repair in rats with complete SCI."
4

1.7

2.8

830

30

Rabbit

810

100

Effects of Light-Emitting Diode Photobiomodulation Therapy and

BioOss as Single and Combined Treatment in an Experimental
Model of Bone Defect Healing in Rats.

Rat

618

Repair of surgical bone defects grafted with hydroxylapatite + TCP and irradiated with =850 nm LED light.

Rat

Surgical bone defect

850

PubMed

"The results of the histological and morphometric evaluation demonstrated that the
SL group showed a larger amount of newly formed bone compared to the SC
group. Moreover, a significant immunoexpression of runt-related transcription
factor 2 (RUNX2) was observed in the SL group. There was no statistical
difference in the biomechanical evaluation. In conclusion, the results suggest that
LLLT accelerated the process of bone repair in rats with complete SCI."

PubMed

"The LLLT group exhibited a larger amount of newly formed bone and a larger
number of osteoblasts in the cell division phase, but the difference was not
statistically relevant compared with the control group."

PubMed

"LLLT can improve bone formation process in CSD filled or not with BBG in rat
calvaria, but it is not able to accelerate particles resorption of this material in the
interior of bone defect."

PubMed

LLLT enhanced new bone formation in comparison to the untreated controls.

PubMed

11

"Within the limitations of this study, LPT has positive effects on bone healing
histopathologically and histomorphometrically for the defects filled with BioOss 3
weeks after the rats' femora injury."

PubMed

"It may be concluded that the use of LED phototherapy was effective in positively
modulating the process of bone repair of bone defects in the femur of rats
submitted or not to biomaterial grafting."

PubMed

"Microscopic analysis revealed a significant decrease in inflammatory infiltration,

intense trabecular bone matrix and periosteal formation, and an increase in newly
formed bone after laser irradiation."

PubMed

660

Bone graft

100

"The biostimulation effects of PBM or LLLT and of low-amplitude high-frequency

WBV both had a positive impact on bone healing process, for critical size defects
in the presence of a stainless steel implant. But their combination, i.e., low-level
laser therapy and low-amplitude high-frequency whole body vibration (LV),
interestingly did not accelerate the fractured bone healing process."

0.42

19.44

30.85

0.07
cm2

120

0.02

150

20

1
(?)

0.5
cm2

LED phototherapy
Bone graft (HA + TCP)

Bone

Bone repair

Sella

Lasers Med Sci

Effect of low-level laser therapy on bone repair: a randomized

controlled experimental study.

Rat

808

0.02
mm2

Additional info

Comment

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More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Year

Journal

Title

Bone

Bone repair

Marques

Brazil
(Bauru)

2015

Lasers Med Sci

New LLLT protocol to speed up the bone healing processhistometric and immunohistochemical analysis in rat calvarial
bone defect.

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

sec

830

50

16
3.7

9
3

Results: positive / unclear/modest / negative

8
(?)

"The results suggest LLLT using the protocol 2 hastened the bone healing process
in the early periods after surgery."

Link

PubMed

Comment: At 45 days, there was no difference between the groups, but at 15

days, the amount of newly formed bone seemed to be a little bit higher in the laser
groups.
Comment: It seems that spot/beam size wasn't reported in this study.

Bone

Bone repair

Magri

Brazil
(So Paulo)

2015

Lasers Med Sci

Photobiomodulation and bone healing in diabetic rats: evaluation

of bone response using a tibial defect experimental model.

Rat

Diabetic rats

808

100

3.57

Tibial bone healing

0.84
1.68
3.36

30
60
120

0.028
cm2

8
16
33

6
12

"In the histological and morphometric evaluation, all laser-treated groups showed
a better histological pattern and a higher amount of newly formed bone compared
to DCG. An intense RUNX2 immunoexpression was observed in the laser-treated
groups, 15 days after the surgery.

PubMed

There was no statistical difference in the biomechanical analysis among the

groups.
In conclusion, PBM, in all fluences used, showed an osteogenic potential in bone
healing of diabetic rats"

Bone

Bone repair

Batista

Brazil
(Uberlndia)

2015

Lasers Med Sci

Low-level laser therapy on bone repair: is there any effect outside

the irradiated field?

Rat

Systemic effects?

830

Bone

Bone repair

Altan

Turkey
(Kocaeli)

2015

Lasers Med Sci

The effect of dosage on the efficiency of LLLT in new bone

formation at the expanded suture in rats.

Rat

Suture expansion

820

50
50
100

1.6
1.6
1.6

0.15
0.65
198

5
20
6300

d=
2 mm
(?)

3
13
1980

"Laser therapy presented a positive local biostimulative effect in the early stage of
bone healing, but the LLLT effect was not observed a long distance from the
evaluated area."

PubMed

"Low-level laser therapy with both 5 and 6,300 J/cm(2) doses was found to be
significantly effective, while the 20 J/cm(2) dose did not show a significant effect in
increasing new bone formation. This finding reveals that the efficiency of the
therapy is affected by the dosage."

PubMed

Note: There was increase in bone formation in the medium dose group as well, but
it was a little bit less pronounced. The bone formation increase was clearly highest
in the "low dose" group (87%) compared to medium (41%) and high (51%) dose
groups.

Bone

Bone repair

Akyol

Turkey
(Rize)

2015

Lasers Med Sci

The influence of low-level laser therapy with alendronate irrigation

on healing of bone defects in rats.

Rat

Alendronate
potentiation

808

0.01

20

"Our findings demonstrated that Aln has a more positive effect with LLLT on bone
healing in rats.

PubMed

It was concluded that combining LLLT with Aln irrigation has a beneficial effect in
bone repair. It was demonstrated experimentally that Aln irrigation during the
surgery had a significant effect to enhance bone formation, and LLLT significantly
potentiated the osseous healing effects of Aln on bone defects. This administration
method is able to minimize the dose of Aln in order to avoid both systemic and
local adverse effects as well as the local injection times during the bone healing
process."

Bone

Bone repair

Batista

Brazil
(Uberlndia)

2014

Lasers Med Sci

Effect of low-level laser therapy on repair of the bone compromised Rat

by radiotherapy.

Radiotherapy

830

50

0.04
cm2

120

"The result demonstrated a positive local biostimulative effect of LLLT in normal

bone. However, LLLT was not able to revert the bone metabolic damage due to
ionizing radiation."

PubMed

Note: The parameters in the abstract seemed to contradict the parameters given
in the full text.

Bone

Bone repair

Barbosa

Brazil
(So Paulo)

2014

Acta Ortop Bras

Laser therapy in bone repair in rats: analysis of bone optical

density.

Rat

660
830

100

Bone

Bone repair

Fazilat

Iran
(Tehran)

2014

Photomed Laser
Surg

Cellular effect of low-level laser therapy on the rate and quality of

bone formation in mandibular distraction osteogenesis.

Rabbit

810

200

0.400

1.5

1
cm2

40

4
7
11

"Based on the radiographic findings, G (830nm) showed more complete bone

regeneration, as shown in the gray shades of the images."

PubMed

d=
0.8
mm

7.5

"This study shows that a low-level GaAlAs (:810 nm; P, 200 mW) laser hastens
new bone formation only in the early stages of the consolidation period in
distraction osteogenesis, and has no significant effect in later stages."

PubMed

Comment: This paper had beautiful scanning electron microscope (SEM) pictures.

Bone

Bone repair

El-Maghraby

Egypt
(Cairo)

2013

Arch Oral Biol

Assessment of the effect of low-energy diode laser irradiation on

gamma irradiated rats' mandibles.

Rat

Gamma radiation

904

30

5.4

1
cm2

180

"Thin irregular bone trabeculae and widened marrow spaces were identified in the
control group. The lased sides of groups 1 and 2 demonstrated regular, thick and
continuous bone trabeculae."

PubMed

"Normal-sized osteocytic lacunae were seen in the lased groups, as compared to

the wide lacunar spaces noted in the control group. Histomorphometric analysis
showed a significant increase in the area of bone trabeculae, as well as the width
of compact bone, for the lased groups."
Note: A nicely written paper, with nice results and electron microscopy pictures of
bone tissue!
670

Bone

Bone repair

Mota

Brazil
(Uberlndia)

2013

Res Vet Svi

Low-power laser therapy for repairing acute and chronic-phase

bone lesions.

Rat

Bone

Bone repair

Ekizer

Turkey
(Kayseri)

2013

Lasers Med Sci

Light-emitting diode photobiomodulation: effect on bone formation

in orthopedically expanded suture in rats--early bone changes.

Rat

LED phototherapy

618

Bone

Bone repair

Omasa

Japan
(Tokyo)

2012

Photomed Laser
Surg

Low-level laser therapy enhances the stability of orthodontic miniimplants via bone formation related to BMP-2 expression in a rat
model.

Rat

Orthodontic miniimplant in tibia bone

830

30

90

273

0.02

200

54

195

d=
4.2
mm

270
(2p)

(spot)
(/p)

Bone

Bone repair

Bossini

Brazil

2012

Exp Gerontol

Low level laser therapy (830nm) improves bone repair in

osteoporotic rats: similar outcomes at two different dosages.

Rat

830

Bone

Bone repair

Kocyigit

Turkey
(Kirikkale)

2012

Photomed Laser
Surg

A comparison of the low-level laser versus low intensity pulsed

ultrasound on new bone formed through distraction osteogenesis.

Rabbit

650

Bone

Bone repair

Pires-Oliveira

Brazil
(So Paulo)

2010

Osteoporos Int

Laser 904 nm action on bone repair in rats with osteoporosis.

Rat

904

Bone

Bone repair

Nascimento

Brazil
(So Paulo)

2010

Photomed Laser
Surg

Effect of low-level laser therapy and calcitonin on bone repair in

castrated rats: a densitometric study.

Rat

830

Bone

Bone repair

Oliveira

Brazil
(So Carlos)

2010

J Mater Sci Mater

Med

Low level laser therapy does not modulate the outcomes of a

highly bioactive glass-ceramic (Biosilicate) on bone consolidation
in rats.

Rat

830

Bone

Bone repair

Medalha

Brazil
(So Paulo)

2010

Photomed Laser
Surg

Comparison of the effects of electrical field stimulation and lowlevel laser therapy on bone loss in spinal cord-injured rats.

Rat

830

Bone

Bone repair

Bashardoust
Tajali

Canada
(London)

2010

J Orthop Surg
Res

Effects of low power laser irradiation on bone healing in animals: a

meta-analysis.

Metaanalysis

100

60
120

600

0.05

10

14
(2p)
(?)

250

0.028
cm2

PubMed

"Periotest values were significantly lower (0.79- to 0.65-fold) and the volume of
newly formed bone was significantly higher (1.53-fold) in the LLLT group. LLLT
also stimulated significant BMP-2 gene expression in peri-implant bone (1.92fold)."

PubMed

LLLT treatment led to higher amount of newly formed bone and granulation tissue
compared to control.

PubMed

1
/d

"LIPUS and LLLT applied during the distraction period accelerated the DO
treatment."

PubMed

"Low-level 904-nm laser (50 mJ/cm(2)) accelerated the repair process of

osteopenic fractures, especially in the initial phase of bone regeneration."

PubMed

"The La and CaLa had significantly higher bone mineral density than the control
and Ca groups."

PubMed

"Our findings suggest that although Biosilicate exerts some osteogenic activity
during bone repair, laser therapy is not able to modulate this process."

PubMed

12

"We conclude that the mentioned treatments were able to initiate a positive bonetissue response, maybe through stimulation of osteoblasts, which was able to
determine the observed morphometric modifications. However, the evoked tissue
response could not determine either biomechanical or densitometric
modifications."

PubMed

20

0.03

"New bone formation area (p = 0.024, 1.48-fold), number of osteoblasts (p <

0.001, 1.59-fold), number of osteoclasts (p = 0.004, 1.43-fold), and number of
vessels (p = 0.007, 1.67-fold) showed higher values in the experimental group
than the control. Bone histomorphometric measurements revealed that bone
architecture in the LPT group was improved."

60
120

100

PubMed

"LLLT enhanced the stability of mini-implants placed in rat tibiae and accelerated
peri-implant bone formation by increasing the gene expression of BMP-2 in
surrounding cells."

0.028
cm2

0.025

"Laser-treated animals showed significant increases in serum alkaline

phosphatase levels and had an effect on biomechanical property, resulting in a
gradual increase in bone stiffness. Laser therapy aided the bone consolidation
process and favored the physiopathologic mechanisms involved in bone tissue
repair, and its effects were more prominent when treatment started during the
acute phase of the injury."

70
/p

"Studies indicate that low power laser irradiation can enhance biomechanical properties of bone during fracture healing in animal models. Maximum bone
tolerance was statistically improved following low level laser irradiation (average random effect size 0.726, 95% CI 0.08-1.37, p 0.028).

PubMed

While conclusions are limited by the low number of studies, there is concordance across limited evidence that laser improves the strength of bone tissue
during the healing process in animal models."

Bone

Bone repair

Pinheiro

Brazil
(Salvador,
Bahia)

2009

Lasers Med Sci

Bone repair following bone grafting hydroxyapatite guided bone

Rat
regeneration and infra-red laser photobiomodulation: a histological
study in a rodent model.

830

40

d=
0.6
mm

"When the groups irradiated with implant and membrane were compared, it was
observed that the repair of the defects submitted to LPBM was also processed
faster, starting from the 15th day. At the 30th day, the level of repair of the defects
was similar in the irradiated groups and those not irradiated. New bone formation
was seen inside the cavity, probably by the osteoconduction of the implant, and, in
the irradiated groups, this new bone formation was incremental."

PubMed

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Bone

Bone repair

Pinheiro

Brazil
(Salvador,
Bahia)

2008

Photomed Laser
Surg

Infrared laser light further improves bone healing when associated

with bone morphogenetic proteins and guided bone regeneration:
an in vivo study in a rodent model.

Rat

Bone

Bone repair

Torres

Brazil
(Salvador,
Bahia)

2008

Photomed Laser
Surg

Does the use of laser photobiomodulation, bone morphogenetic

proteins, and guided bone regeneration improve the outcome of
autologous bone grafts? An in vivo study in a rodent model.

Rat

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

sec

"The results showed histological evidence of increased deposition of collagen

fibers (at 15 and 21 d), as well as an increased amount of well-organized bone
trabeculi at the end of the experimental period (30 d) in irradiated animals
compared to non-irradiated controls."

BMPs + LLLT

PubMed

Note: This paper seems quite similar as Gerbi's paper, even though they were
published separately and they are clearly not identical... Though, some of the
photomicrographs are quite identical. Maybe they used the same animals, but
wrote two slightly diffeerent manuscripts for some reason?
790

50

10

"The results showed that in all treatment groups, new bone formation was greater
and qualitatively better than the untreated subjects. Control specimens showed a
less advanced repair after 40 d, and this was characterized by the presence of
medullary tissue, a small amount of bone trabeculi, and some cortical repair."

PubMed

"We conclude that LPBM has a positive biomodulatory effect on the healing of
bone defects, and that this effect was more evident when LPBM was performed on
the surgical bed intraoperatively, prior to the placement of the autologous bone
graft."

Bone

Bone repair

Mrquez
Martnez

Brazil
(Camaragibe)

2008

Lasers Med Sci

Effect of IR laser photobiomodulation on the repair of bone defects

grafted with organic bovine bone.

Rat

Bone grafts + LLLT

Bone

Bone repair

Gerbi

Brazil
(Recife)

2008

Photomed Laser
Surg

Infrared laser light further improves bone healing when associated

with bone morphogenic proteins: an in vivo study in a rodent
model.

Rat

BMPs + LLLT

830

40

Bone

Bone repair

Lopes

Brazil
(So Jos dos
Campos)

2007

Photomed Laser
Surg

Infrared laser photobiomodulation (lambda 830 nm) on bone tissue

around dental implants: a Raman spectroscopy and scanning
electronic microscopy study in rabbits.

Rabbit

Dental titanium
implant on the tibia

830

10

Bone

Bone repair

Pinheiro & Gerbi

Brazil
(Salvador,
Bahia)

2006

Photomed Laser
Surg

Photoengineering of bone repair processes.

Review

4
(?)

86

"There was histological evidence of improved collagen fiber deposition at early

stages of the healing; increased amount of well-organized bone trabeculae at the
end of the experimental period on irradiated animals. It is concluded that LPBM
has positive biomodulative effect on the healing process bone defects."

PubMed

"The results showed histological evidence of increased deposition of collagen

fibers (at 15 and 21 d), as well as an increased amount of well-organized bone
trabeculae at the end of the experimental period (30 d) in the irradiated animals
versus the non-irradiated controls."

PubMed

"It is concluded that infrared laser photobiomodulation does improve bone healing,
and this may be safely assessed by Raman spectroscopy or SEM."

PubMed

"The results of our studies and others indicate that bone irradiated mostly with infrared (IR) wavelengths shows increased osteoblastic proliferation,
collagen deposition, and bone neorformation when compared to nonirradiated bone. Further, the effect of laser therapy is more effective if the treatment
is carried out at early stages when high cellular proliferation occurs. Vascular responses to laser therapy were also suggested as one of the possible
mechanisms responsible for the positive clinical results observed following laser therapy."

PubMed

"It is possible that the laser therapy effect on bone regeneration depends not only on the total dose of irradiation, but also on the irradiation time and the
irradiation mode. The threshold parameter energy density and intensity are biologically independent of one another. This independence accounts for the
success and the failure of laser therapy achieved at low-energy density levels."
685
830

35
50

Rat

830

40

Molecular structure of the bony tissue after experimental trauma to

the mandibular region followed by laser therapy.

Rat

633

35

Effect of low level laser therapy on the repair of bone defects

grafted with inorganic bovine bone.

Rat

830

40

Bone

Bone repair

Blaya

Brazil
(Santa Maria)

2006

J Contemp Dent
Pract

Histologic study of the effect of laser therapy on bone repair.

Bone

Bone repair

Gerbi

Brazil
(Salvador,
Bahia)

2005

Photomed Laser
Surg

Assessment of bone repair associated with the use of organic

bovine bone and membrane irradiated at 830 nm.

Bone

Bone repair

Rochkind

Israel
(Tel Aviv)

2004

Photomed Laser
Surg

Bone

Bone repair

Pinheiro

Brazil
(Salvador,
Bahia)

2003

Braz Dent J

Brazil
(Salvador,
Bahia)

2003

Brazil
(Salvador,
Bahia)

2003

Bone

Bone repair

Pinheiro

Bone graft

10
10

15

3
mm2

16

1200

d=
0.6
mm

"Greater degrees of new bone formation and vertical regeneration were found in
the irradiated groups than in the control group."

PubMed

"The results of the present investigation showed histological evidence of improved

amount of collagen fibers at early stages of the bone healing (15 days) and
increased amount of well organized bone trabeculae at the end of the
experimental period (30 days) on irradiated animals compared to non irradiated
ones."

PubMed

14

"The results suggest that low-power laser irradiation alone and in combination with
Bio-Oss enhances bone healing and increases bone repair."

PubMed

"We conclude that LLLT had a positive effect on the repair of bone defects
implanted with inorganic bovine bone."

PubMed

Note: The authors might have accidentally misreported radiant energy (J) as
energy density (J/cm2)

J Clin Laser Med

Surg

Effect of 830-nm laser light on the repair of bone defects grafted

with inorganic bovine bone and decalcified cortical osseus
membrane. (Oct 2003)

Rat

Effect of 830-nm laser light on the repair of bone defects grafted

with inorganic bovine bone and decalcified cortical osseous
membrane. (Dec 2003)

Rat

"The results showed more advanced repair of the irradiated groups when
compared to the non-irradiated ones.

PubMed

The repair of the irradiated group was characterized by both increased bone
formation and on the amount of collagen fibers around the graft within the cavity,
as early as the 15th day after surgery, considering the osteoconductive capacity of
the Gen-ox and the increment of the cortical repair in specimens with Gen-derm
membrane."
Note: It's not clear to me, what's the difference between the october and december
articles. They seem identical.

Bone

Bone repair

Barbos Pinheiro

J Clin Laser Med

Surg

Bone graft

830

40

"The results showed evidence of a more advanced repair on the irradiated groups
when compared to non-irradiated ones.

PubMed

The repair of irradiated groups was characterized by both increased bone

formation and amount of collagen fibers around the graft within the cavity since the
15th day after surgery, through analysis of the osteoconductive capacity of the
Gen-ox and the increment of the cortical repair in specimens with Gen-derm
membrane."
Note: The authors might have accidentally misreported radiant energy (J) as
energy density (J/cm2)

Bone

Bone repair

Barushka

Israel

1995

Bone

Effect of low-energy laser (He-Ne) irradiation on the process of

bone repair in the rat tibia.

Rat

Bone

Cell proliferation

Amid

Iran
(Tehran)

2014

J Lasers Med Sci

Effect of low level laser therapy on proliferation and differentiation

of the cells contributing in bone regeneration.

Review

Histomorphometrical analysis revealed a more rapid accumulation of reparative

new bone in the hole injury of the laser-irradiated rats.

"Following the initial screening of titles and abstracts as well as the final screening of full texts, 22 articles completely fulfilled the inclusion criteria of this
study.

PubMed

PubMed

Wavelength used in LLLT irradiation varied between 600 to 1000 nm with an energy density of 0.04-60J/cm(2) .
Although almost all studies agreed on getting positive effects from LLLT, some had opposing results."
"Low level laser with low-energy density range appears to exert a biostimulatory effect on bone tissue, enhance osteoblastic proliferation and
differentiation on cell lines used in in vitro studies. Despite the fact that many researches have been recently done on the effects of LLLT on different cell
lines, without knowing the precise mechanism and effects, we are not able to offer a clinical treatment protocol. This paper is a beginning to help further
progress and extend practical use of LLLT in future."

Bone

Cell proliferation

Huertas

Spain

2014

Biol Res Nurs

Effect and clinical implications of the low-energy diode laser on

bone cell proliferation.

In vitro
MG-63 cells

940

Bone

Cell proliferation

Mesquita-Ferrari

Brazil
(So Paulo)

2011

Indian J Exp Biol

No effect of low-level lasers on in vitro myoblast culture.

In vitro
C2C12
myoblasts

660
780

Bone

Cell proliferation

Renno

Brazil

2010

Photomed Laser
Surg

Effect of 830 nm laser phototherapy on osteoblasts grown in vitro

on Biosilicate scaffolds.

830

Bone

Cell proliferation

Renno

Brazil

2007

Photomed Laser
Surg

The effects of laser irradiation on osteoblast and osteosarcoma

cell proliferation and differentiation in vitro.

670
780
830

Bone

Cell proliferation

Martinasso

Italy

2007

Minerva Stomatol

Effect of superpulsed laser irradiation on bone formation in a

human osteoblast-like cell line.

70

0.5
1.0
1.5

1
2
3
4
5

d=
0.4
mm

3.8
6.3
10
17.5

30

10

0.5
1
5
10

LLLT increased cell proliferation.

PubMed

"There were no significant differences in cell proliferation between laser-treated

myoblasts and control cultures for any of the parameters and incubation periods."

PubMed

"Further studies are necessary to determine the correct laser parameters for
optimizing the biostirhulation of myoblasts."

10
mm2

335
/p

Despite successful seeding of bioscaffolds with osteoblasts, laser phototherapy

resulted in a reduction in cell growth compared to non-irradiated controls.

PubMed

Based on the conditions of this study, we conclude that each cell line responds
differently to specific wavelength and dose combinations.

PubMed

LLLT stimulated cell proliferation in human osteoblast-like cells and increased the
expression of proteins essential for bone formation.

PubMed

Additional info

Comment

Reply

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Bone

Cell proliferation

Stein

Israel

2005

Photomed Laser
Surg

Low-level laser irradiation promotes proliferation and

differentiation of human osteoblasts in vitro.

In vitro

632

10

0.18

Bone

Cell proliferation

Ueda & Shimizu

Japan

2001

J Oral Sci

Pulse irradiation of low-power laser stimulates bone nodule

formation.

In vitro

830

500

Bone

Cell proliferation

Ozawa

Japan

1998

Bone

Low-energy laser irradiation stimulates bone nodule formation at

early stages of cell culture in rat calvarial cells.

In vitro

830

500

Fractures

Chang

Taiwan
(Taichung)

2014

Photomed Laser
Surg

Therapeutic outcomes of low-level laser therapy for closed bone

fracture in the human wrist and hand.

Human
RCT/SB

830

60

Bone

Gene
expression

Tim

Brazil
(Sao Carlos)

2016

J Photochem
Photobiol B

Effects of low level laser therapy on inflammatory and angiogenic

gene expression during the process of bone healing: A microarray
analysis.

Rat

830

30

Bone

Gene
expression

Fernandes

Brazil

2013

J Biomed Opt

Effects of low-level laser therapy on the expression of osteogenic

genes related in the initial stages of bone defects in rats.

Rat

830

30

1.071

2.8

100

Bone

Gene
expression

Fvaro-Ppi

Brazil

2011

Photomed Laser
Surg

Low-level laser therapy induces differential expression of

osteogenic genes during bone repair in rats.

Rat

830

30

1.071

1.4

50

Bone

Implants

Obradovi

Serbia
(Ni)

2009

Lasers Med Sci

Influence of low-level laser therapy on biomaterial

osseointegration: a mini-review.

Review

Bone

Implants

Freddo

Brazil
(Porto Alegre)

2009

Lasers Med Sci

Effect of low-level laser therapy after implantation of poly-Llactic/polyglycolic acid in the femurs of rats.

Rat

Bone

Implants

Khadra M

Norway
(Oslo)

2005

Swed Dent J
Suppl

The effect of low level laser irradiation on implant-tissue

interaction. In vivo and in vitro studies.

Rat
+ in vitro

Category

Bone

0.14
0.43
1.43

Link

Results: positive / unclear/modest / negative

LLLT promoted proliferation and maturation of human osteoblasts.

PubMed

LLLT in both groups increased cell proliferation, bone nodule formation, ALP
activity and ALP gene expression. Pulsed irradion had a stronger effect.

PubMed

LLLT increased cell profliferation, ALP activity and osteocalcin gene expression.
LLLT at earlier stages of culture also led to a greater number and larger area of
bone nodules.

PubMed

"After treatment and at the follow-up, the laser group exhibited significant changes
in all of the parameters compared with the baseline (p<0.05). The results of
comparing the two groups after treatment and at the follow-up indicated significant
between-group differences among all of the parameters (p<0.05)."

PubMed

9.7

1
3
10

600

10

94

3
4
8

Our findings indicate that LLLT was efficient on accelerating the development of
newly formed bone probably by modulating the inflammatory and angiogenic gene
expression as well as COX2 and VEGF immunoexpression during the initial phase
of bone healing.

PubMed

0.028
cm2

94

1
2
3
5

"We concluded that LLLT modulated the inflammatory process and accelerated
bone repair, and this advanced repair pattern in the laser-treated groups may be
related to the higher mRNA expression of genes presented by these animals."

PubMed

0.028
cm2

47

3
6
12

Laser therapy improved bone repair in rats as depicted by differential

histopathological and osteogenic genes expression, mainly at the late stages of
recovery.

PubMed

"The utility of LLLT in biomaterial osseointegration is still unanswered, due to lack of literature and poorly understood mechanisms. It is still difficult for
one to compare studies about the action of LLLT on the osseointegration of biomaterials because the experimental models and duration of treatments
are very distinct. However, it could be concluded that LLLT may offer advantages in terms of periodontal and bone functional recovery and biomaterial
osseointegration."

PubMed

Comment: The results are quite remarkable.

Surgical bone defect

Implantation of polyL-lactic/polyglycolic
acid

685
830

2.8

35
50

d=
0.06
cm

"Results showed that the laser irradiation had had a positive photobiomodulation
effect on inflammation, confirmed by a better histologic pattern than that of the
control group at 3 days and 7 days. Semiquantitative analysis revealed that
groups A and B had a histologic score significantly greater than that of the control
group at 3 days. At 21 days, histomorphometric analysis revealed a more intense
inflammation in the red laser group than in the other groups.

PubMed

We concluded that low-level laser therapy (LLLT) has positive effects on the
photobiomodulation of inflammation in the tissues surrounding the poly-Llactic/polyglycolic acid (PLLA/PGA) bioabsorbable plate. It stimulated
vascularization, fibroblast proliferation, and collagen deposition."
1.5
3

"The following conclusions are drawn from the results of these five studies:

PubMed

LLLT can promote bone healing and bone mineralization and thus may be
clinically beneficial in promoting bone formation in skeletal defects. It may be also
used as additional treatment for accelerating implant healing in bone.
LLLT can modulate the primary steps in cellular attachment and growth on
titanium surfaces. Multiple doses of LLLT can improve LLLT efficacy, accelerate
the initial attachment and alter the behaviour of human gingival fibroblasts cultured
on titanium surfaces.
The use of LLLT at the range of doses between 1.5 and 3 J/cm2 may modulate
the activity of cells interacting with an implant, thereby enhancing tissue healing
and ultimate implant success."

Bone

In vitro

lker

Turkey
(Ankara)

2016

Lasers Med Sci

Polychromatic light-induced osteogenic activity in 2D and 3D

cultures.

In vitro

Bone

Osteoblasts

Son

Korea
(Ulsan)

2017

Lasers Med Sci

A novel combination treatment to stimulate bone healing and

regeneration under hypoxic conditions: photobiomodulation and
melatonin.

In vitro

Bone

Osteoblasts

Shin

Korea
(Yangsan)

2016

Maxillofac Plast
Reconstr Surg

Effect of low-level laser therapy on bisphosphonate-treated

osteoblasts.

Bone

Osteoblasts

Tschon

Italy
(Bologna)

2015

J Biomed Opt

Bone

Osteoblasts

Saracino

Italy

2009

Bone

Osteoclastogen
esis

Lee

Korea
(Gwangju)

Bone

Review

Pinheiro

Alzheimer's
Disease

Lu

Brain

5901500

808

80

In vitro

808

80

Photobiomodulation with low-level diode laser promotes

osteoblast migration in an in vitro micro wound model.

In vitro

915

Lasers Surg Med

Superpulsed laser irradiation increases osteoblast activity via

modulation of bone morphogenetic factors.

In vitro

904910

2016

Photomed Laser
Surg

Regulation of RANKL-Induced Osteoclastogenesis by 635-nm Light In vitro

Emitting Diode Irradiation Via HSP27 in Bone Marrow-Derived
Macrophages.

635

Brazil
(Salvador,
Bahia)

2015

BOOK: Lasers in
Dentistry: Guide
for Clinical
Practice

Bone biomodulation

Review

USA (Georgia)

2017

Neurobiol Aging

Low-level Laser Therapy for Beta-Amyloid Toxicity in Rat

Hippocampus

Rat

Photobiomodulation
+ melatonin

1
cm2

5
10
15

200

60

9
cm2

300

3
7
12

"Cell culture studies under static conditions indicated that polychromatic light
significantly stimulated bone nodule formation via the prolonged cell survival and
stimulated differentiation of MC3T3-E1 preosteoblastic cells in both TCPS and
chitosan scaffold groups."

PubMed

"Therefore, we concluded that laser irradiation could promote the effect of

melatonin on the differentiation and mineralization of MC3T3-E1 cells under
hypoxic conditions, and that this process is mediated through melatonin 1/2
receptors and PKRD/p38 signaling pathways."

PubMed

"The LLLT does not affect the OPG expression in the hFOB cell line, but it may
increase the RANKL and M-CSF expressions, thereby resulting in positive effects
on osteoclastogenesis and bone remodeling."

PubMed

"This study demonstrated that laser photobiomodulation at 915 nm promoted

wound healing mainly through stimulation of cell migration and collagen deposition
by osteoblasts."

PubMed

LLLT (904-910nm) had various effects on osteoblast-like cells.

PubMed

"The 635-nm irradiation treatment significantly increased HSP27 expression and

decreased intracellular ROS generation, as well as p38 and AKT phosphorylation,
leading to reductions in the expression of c-fos, NFATc1, and DC-STAMP and
TRAP activation and osteoclastic bone resorption in RANKL-induced BMMs.
However, in HSP27-silenced BMMs, no change was observed."

PubMed

"It is established that LLLT stimulates and accelerates bone repair, although more studies are being conducted to elucidate the mechanism of action of
laser light in the bone repair process. At present, it remains uncertain whether the stimulation of bone formation by LLLT is the result of a general effect
on mesenchymal cells or a direct stimulation of osteoblasts, or both."

Beta-amyloid
injection to
hippocampus

808

0.025
(brain)

15
(brain)

Additional info

sec

d=
1.8
mm

1
cm2

120

"LLI treatment suppressed A-induced hippocampal neurodegeneration and longterm spatial and recognition memory impairments.
Molecular studies revealed that LLI treatment:
a) restored mitochondrial dynamics, by altering fission and fusion protein levels
thereby suppressing A-induced extensive fragmentation;
b) suppressed A-induced collapse of mitochondrial membrane potential;
c) reduced oxidized mtDNA and excessive mitophagy;
d) facilitated mitochondrial homeostasis via modulation of the Bax/Bcl-2 ratio and
of mitochondrial antioxidant expression;
e) promoted cytochrome c oxidase activity and ATP synthesis;
f) suppressed A induced G6PDH and NADPH oxidase activity;
g) enhanced the total antioxidant capacity of hippocampal CA1 neurons while
reducing oxidative damage; and
h) suppressed A-induced reactive gliosis, inflammation and tau
hyperphosphorylation."

Wiley

PubMed

Pulsing = pulsed vs. continous

Comment

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---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

sec

Brain

Alzheimer's
Disease

Oron

Israel

2016

Photomed Laser
Surg

Low-Level Laser Therapy to the Bone Marrow Ameliorates

Neurodegenerative Disease Progression in a Mouse Model of
Alzheimer's Disease: A Minireview.

Mouse

Systemic effects

808

max
400

0.01

100

Results: positive / unclear/modest / negative

"MSCs from wild-type mice stimulated with LLLT showed to increase their ability to
maturate towards a monocyte lineage and to increase phagocytosis activity
towards soluble amyloid beta (A).

Link

Additional info

PubMed

Furthermore, weekly LLLT to BM of AD mice for 2 months, starting at 4 months of

age (progressive stage of AD), improved cognitive capacity and spatial learning,
as compared to sham-treated AD mice. Histology revealed a significant reduction
in A brain burden."

Brain

Alzheimer's
Disease

Purushothuman

Australia
(Sydney)

2015

Neurosci Lett

Near infrared light mitigates cerebellar pathology in transgenic

mouse models of dementia.

Mouse

Cerebellar injury

670

Brain

Alzheimer's
Disease

Farfara

Israel

2015

J Mol Neurosci

Low-level laser therapy ameliorates disease progression in a

mouse model of Alzheimer's disease.

Mouse

5XFAD transgenic
mice

???
???
???

670

20

"One month of NIr treatment mitigated the deposition of -amyloid in cerebellar

cortex of APP/PS1 mice, and the formation of neurofibrillary tangles, the
hyperphosphorylation of tau, the damage caused by oxidative stress and the
downregulation of cytochrome oxidase expression by Purkinje cells in the
cerebellar cortex of K3 mice.

PubMed

These findings show the ability of NIr to mitigate degeneration in many - probably
all - regions of the mouse brain."

d=
0.3
cm

Systemic effects

Brain

Alzheimer's
Disease

Purushothuman

Australia
(Sydney)

2014

Alzheimers Res
Ther

Photobiomodulation with near infrared light mitigates Alzheimer's

disease-related pathology in cerebral cortex - evidence from two
transgenic mouse models.

Mouse

Brain

Alzheimer's
Disease

Duggett &
Chazot

UK
(Durham)

2014

Biology and
Medicine

Low-Intensity Light Therapy (1068 nm) Protects CAD

Neuroblastoma Cells from -Amyloid-Mediated Cell Death

In vitro

Transgenic mice:
- K3
- APP/PS1

90

20

"MSCs from wild-type mice stimulated with LLLT demonstrated an increased

ability to maturate toward a monocyte lineage and to increase phagocytosis of
soluble A in vitro. Furthermore, weekly LLLT for 2 months to the BM, starting at 4
months of age (progressive stage of the disease in these 5XFAD transgenic male
mice), improved memory and spatial learning, compared to a sham-treated AD
mouse model. Histology revealed a significant reduction in A brain burden in the
laser-treated mice compared to the nonlaser-treated ones."

PubMed

"In the K3 mice, NIr treatment was associated with a reduction in

hyperphosphorylated tau, neurofibrillary tangles and oxidative stress markers (4hydroxynonenal and 8-hydroxy-2-deoxyguanosine) to near wildtype levels in the
neocortex and hippocampus, and with a restoration of expression of the
mitochondrial marker cytochrome c oxidase in surviving neurons."

PubMed

"Our measurements of NIr penetration across the fur and skull of a C57BL/6 mouse indicate that ~2.5% of transmitted light reaches the cortex."

"In the APP/PS1 mice, NIr treatment was associated with a reduction in the size
and number of amyloid- plaques in the neocortex and hippocampus."
1068

"IR1068 exposure was found to consistently significantly reduce cell death caused
by A, by up to 24%, over the range of A concentrations (1-25 M). The range of
A concentrations used would not necessarily be found in vivo."

OMICS

"The use of IR1068 as a treatment for Alzheimers disease is under investigation,

with recruitment of patients initiated in December 2010 (double-blind, placebocontrolled clinical trial). The results of these trials will enable statistically valid
conclusions to be drawn, regarding the use of IR1068 as a treatment for
neurodegenerative disease in a clinical setting."
Note: OMICS International isn't a very respected scientific publishing company,
but the article seems to be of decent quality.

Brain

Alzheimer's
Disease

Grillo

UK
(Durham)

2013

J Photochem
Photobiol B

Non-invasive infra-red therapy (1072 nm) reduces -amyloid

protein levels in the brain of an Alzheimer's disease mouse model,
TASTPM.

1072

Mouse

"Chronic IR1072 treatment of female TASTPM mice elicited significant increases

in HSP60, 70 and 105 and phosphorylated-HSP27 (P-HSP27) (50-139%),
together with a concomitant profound decrease in B-crystallin, APP, tau-P, A140 and A1-42 (43-81%) protein levels at 7 months of age. Furthermore, IR1072
treatment elicited a modest, but significant, reduction in A1-42 plaques in the
cerebral cortex."

PubMed

"IR1072 treatment provides a novel non-invasive and safe way to upregulate a

panel of stress response proteins in the brain, known to both reduce protein
aggregation and neuronal apoptosis. This approach recently entered clinical trials
for AD in the USA, and may provide a novel disease modifying therapy for a range
of neuropathologies."

Brain

Alzheimer's
Disease

Liang

China
(Guangzhou)

2012

Free Radic Biol

Med

Photobiomodulation by low-power laser irradiation attenuates Ainduced cell apoptosis through the Akt/GSK3/-catenin pathway.

In vitro

633

10

0.0012
74

"We found that Akt activated by LPLI interacted with GSK3 and phosphorylated it
on Ser9 in the presence of A(25-35), which resulted in the inhibition of GSK3.
Furthermore, LPLI increased the nuclear translocation of -catenin and enhanced
its T cell factor/lymphocyte enhancer factor-dependent transcriptional activity via
the Akt/GSK3 pathway to promote cell survival upon treatment with A(25-35.)

Brain

Alzheimer's
Disease

Zhang

China
(Guangzhou)

2012

Cell Signal

Inhibition of A(25-35)-induced cell apoptosis by low-power-laserirradiation (LPLI) through promoting Akt-dependent YAP
cytoplasmic translocation.

In vitro
PC12 cells

633

5.4

0.0069

"LPLI inhibits A2535-induced apoptosis through Akt/YAP/p73 pathway."

PubMed

Brain

Alzheimer's
Disease

Sommer AP

Germany

2012

Photomed Laser
Surg

670 nm laser light and EGCG complementarily reduce amyloid-

aggregates in human neuroblastoma cells: basis for treatment of
Alzheimer's disease?

In vitro

670

33

0.1

"In irradiated cells, A(42) aggregate amounts were significantly lower than in
nonirradiated cells."

PubMed

Brain

Alzheimer's
Disease

De Taboada

USA (CA)

2011

J Alzheimers Dis

Transcranial laser therapy attenuates amyloid- peptide

neuropathology in amyloid- protein precursor transgenic mice.

Mouse

"All TLT doses produced an increase in sAPP and a decrease in CTF levels
consistent with inhibition of the -secretase activity. In addition, TLT showed an
increase in ATP levels, mitochondrial function, and c-fos suggesting an overall
improvement in neurological function. These studies suggest that TLT is a
potential candidate for treatment of AD."

PubMed

Brain

Alzheimer's
Disease

Yang

USA
2010
(Columbia, MO)

Neuroscience

Low energy laser light (632.8 nm) suppresses amyloid- peptideinduced oxidative and inflammatory responses in astrocytes.

In vitro
Rat
astrocytes

"Our data showed that laser light at 632.8 nm suppressed A-induced superoxide
production, colocalization between NADPH oxidase gp91(phox) and p47(phox)
subunits, phosphorylation of cPLA(2,) and the expressions of IL-1 and iNOS in
primary astrocytes.

PubMed

Brain

Brain injury

Naeser

USA
(Boston, MA)

2016

Photomed Laser
Surg

Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to

Improve Cognition in Chronic Traumatic Brain Injury.

Review

Brain

Brain injury

Thunshelle &
Hamblin

USA
(Cambridge,
MA)

2016

Photomed Laser
Surg

Transcranial Low-Level Laser (Light) Therapy for Brain Injury.

Review

"We review the fundamental mechanisms at the cellular and molecular level and the effects on the brain are discussed. There are several contributing
processes that have been proposed to lead to the beneficial effects of PBM in treating TBI such as stimulation of neurogenesis, a decrease in
inflammation, and neuroprotection. Both animal and clinical trials for ischemic stroke are outlined. A number of articles have shown how transcranial
LLLT (tLLLT) is effective at increasing memory, learning, and the overall neurological performance in rodent models with TBI."

PubMed

Brain

Brain injury

Henderson TA

USA
(Centennial,
CO)

2016

Neural Regen Res Multi-watt near-infrared light therapy as a neuroregenerative

treatment for traumatic brain injury.

Perspective

"These data presented herein make an intriguing case for the potential of multi-watt NIR laser therapy as a safe and effective modality for the treatment
of TBI and possibly other neurological insults. This multi-Watt modality provides sufficient energy delivery to the skin to yield biologically meaningful
fluence at the site of brain injury (Henderson and Morries, 2015a, b; Morries et al., 2015; Tedford et al., 2015), which can be 17 cm from the scalp
surface.

PubMed

Brain

Brain injury

Xuan

USA
(Boston, MA)

2016

J Biophotonics

Repeated transcranial low-level laser therapy for traumatic brain

injury in mice: biphasic dose response and long-term treatment
outcome.

Mouse

810

0.025

Brain

Brain injury

Xuan

USA
(Boston, MA)

2015

J Biophotonics

Low-level laser therapy for traumatic brain injury in mice increases

brain derived neurotrophic factor (BDNF) and synaptogenesis.

Mouse

810

0.05

Brain

Brain injury

Naeser &
Hamblin

USA
(Boston, MA)

2015

Photomed Laser
Surg

Traumatic Brain Injury: A Major Medical Problem That Could Be

Treated Using Transcranial, Red/Near-Infrared LED
Photobiomodulation.

Review or
Editorial?

Treatments for traumatic brain injury with emphasis on

transcranial near-infrared laser phototherapy.

Review
Case series

PubMed

Our data demonstrate that LPLI has a prosurvival effect on A-induced apoptosis
and may be an effective therapeutic strategy in treating AD by targeting GSK3."

Transgenic mice
(amyloid- protein
precursor)

808

633

78

15

0.0015

162

16.2

10
cm2

3h

We demonstrated for the first time that 632.8 nm laser was capable of suppressing
cellular pathways of oxidative stress and inflammatory responses critical in the
pathogenesis in AD."

Vielight for intranasal

treatment

"Ongoing studies: Ongoing, current studies involve TBI patients who have been treated with tLED using either 26 J/cm2 per LED location on the head or
treated with intranasal only (iLED) using red (633 nm) and NIR (810 nm) diodes placed into the nostrils. The NIR iLED is hypothesized to deliver photons
to the hippocampus, and the red 633 nm iLED is believed to increase melatonin. Results have been similar to the previously published tLED study.
Actigraphy sleep data showed increased time asleep (on average one additional hour per night) after the 18th tLED or iLED treatment. LED treatments
may be performed in the home.

PubMed

Sham-controlled studies with veterans who have cognitive dysfunction from Gulf War Illness, blast TBI, and TBI/PTSD are currently ongoing."
Free full text: http://vielight.com/wp-content/uploads/2016/12/Transcranial-Red-NIR-therapy-for-Cognition-in-Chronic-TBI-Naeser-2016.pdf

Moreover, our data indicate that multi-Watt NIR laser therapy appears to induce a persistent change in neurological function (Morries et al., 2015), given
patients have maintained their clinical improvements for years after treatment. Indeed, it is possible that multi-watt NILT induces a neuroregenerative
change, based on the evidence of neurotrophin induction in animal models (e.g., Xuan et al., 2014) and the improvement of neurological function
revealed with serial functional neuroimaging (Henderson and Morries, 2015b)."

Brain

Brain injury

Morries

USA
(Lakewood,
CO)

2015

Neuropsychiatr
Dis Treat

28.3

18

d=
1cm
(?)

720

3
14

"We conclude that an excessive number of laser-treatments delivered to mice can

temporarily inhibit the process of brain repair stimulated by tPBM, but then the
inhibitory effect ceases, and brain repair can resume. The mechanism may be
temporary induction of reactive gliosis."

PubMed

36

d=
1 cm

720

1/3
/d
(?)

"The data suggest that the benefit of LLLT to the brain is partly mediated by
stimulation of BDNF production, which may in turn encourage synaptogenesis.
Moreover the pleiotropic benefits of BDNF in the brain suggest LLLT may have
wider applications to neurodegenerative and psychiatric disorders."

PubMed

"Newly funded, sham-controlled studies with red/NIR tLED and iLED for PTSD, blast-TBI and Gulf War illness are underway at the VA Boston Healthcare
System, Boston University School of Medicine, and the United States Army Research Institute of Environmental Medicine.

PubMed

In addition, a tLED study with acute TBI patients is underway through the Emergency Department at Massachusetts General Hospital."

810+
980

9000

810

1320
0

2400+

5581

10
20

"In ten patients with chronic TBI (average time since injury 9.3 years) given ten
treatments over the course of 2 months using a high-power NIR laser [...],
symptoms of headache, sleep disturbance, cognition, mood dysregulation,
anxiety, and irritability improved."

PubMed

The paper comments NEST-3: "A key factor in the interpretation of the results of NEST-3 is that, different from NEST-1, all types of stroke were included as opposed to just cortical
strokes. Continuous laser light has a limited depth of penetration (1 cm into brain tissue) which likely prevents an effect on deeper brain matter. Therefore, the lack of significant
benefits from NIR phototherapy in NEST-3 could be related to the fact that ischemic penumbra was not reached by the light (Luis DeTaboada, personal communication, January
2015). While pulsed NIR was not used in the NEST-3 study, it is estimated that pulsed NIR could penetrate up to 3 cm in depth from the cortical surface, therefore possibly
extending the therapeutic target to deeper strokes (Luis DeTaboada, personal communication, January 2015)."

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Brain

Brain injury

Brain

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Henderson&Morr ?
ies

2015

Adv Mind Body

Med

SPECT Perfusion Imaging Demonstrates Improvement of

Traumatic Brain Injury With Transcranial Near-infrared Laser
Phototherapy.

Human
Case report

810
980

Brain injury

Dong

USA
(Boston, MA)

2015

J Cereb Blood
Flow Metab

Low-level light in combination with metabolic modulators for

effective therapy of injured brain.

Mouse

810

Brain

Brain injury

Zhang

USA
(Boston, MA)

2014

J Cereb Blood
Flow Metab

Low-level laser therapy effectively prevents secondary brain injury

induced by immediate early responsive gene X-1 deficiency.

Mouse

Brain

Brain injury

Xuan

USA
(Boston, MA)

2014

J Biomed Opt

Transcranial low-level laser therapy enhances learning, memory,

and neuroprogenitor cells after traumatic brain injury in mice.

Mouse

Brain

Brain injury

Naeser

USA
(Boston, MA)

2014

J Neurotrauma

Significant improvements in cognitive performance posttranscranial, red/near-infrared light-emitting diode treatments in

chronic, mild traumatic brain injury: open-protocol study.

Human
Openprotocol
study

Brain

Brain injury

Giacci

Australia
(Adelaide &
Crawley)

2014

PLoS One

Differential effects of 670 and 830 nm red near infrared irradiation

therapy: a comparative study of optic nerve injury, retinal
degeneration, traumatic brain and spinal cord injury.

Rat

Brain

Brain injury

Xuan

USA
(Boston, MA)

2013

PLoS One

Transcranial low-level laser therapy improves neurological

performance in traumatic brain injury in mice: effect of treatment
repetition regimen.

Mouse

Brain

Brain injury

Nawashiro

Japan

2012

Photomed Laser
Surg

Focal increase in cerebral blood flow after treatment with nearinfrared light to the forehead in a patient in a persistent vegetative
state.

Case report

Brain

Brain injury

Wu

USA
(Boston, MA)

2012

Lasers Surg Med

Low-level laser therapy for closed-head traumatic brain injury in

mice: effect of different wavelengths.

Mouse

Brain

Brain injury

Quirk

USA
2012
(Milwaukee, WI)

Photomed Laser
Surg

Near-infrared photobiomodulation in an animal model of traumatic

brain injury: improvements at the behavioral and biochemical
levels.

Rat

Brain

Brain injury

Oron

Israel

2012

J Neurotrauma

Near infrared transcranial laser therapy applied at various modes

to mice following traumatic brain injury significantly reduces longterm neurological deficits.

Mouse

Brain

Brain injury

Khuman

USA
(Charlestown,
MA)

2012

J Neurotrauma

Low-level laser light therapy improves cognitive deficits and

inhibits microglial activation after controlled cortical impact in
mice.

Mouse

0.15

810

Chronic TBI patients

36

0.025

18

Results: positive / unclear/modest / negative

Link

sec

d=
1 cm

d=
1 cm

240

720

1
3

633
870

Clinical application of these levels of infrared energy for this patient with TBI
yielded highly favorable outcomes with decreased depression, anxiety, headache,
and insomnia, whereas cognition and quality of life improved. Neurological
function appeared to improve based on changes in the SPECT by quantitative
analysis.

PubMed

"We found high levels of glycolysis, reduced adenosine triphosphate generation,

and increased formation of reactive oxygen species and apoptosis in neurons
under hypoxia. Strikingly, these adverse events were reversed significantly by
noninvasive exposure of injured brain to low-level light (LLL). Low-level light
illumination sustained the mitochondrial membrane potential, constrained
cytochrome c leakage in hypoxic cells, and protected them from apoptosis,
underscoring a unique property of LLL. The effect of LLL was further bolstered by
combination with metabolic substrates such as pyruvate or lactate both in vivo and
in vitro. The combinational treatment retained memory and learning activities of
injured mice to a normal level, whereas other treatment displayed partial or severe
deficiency in these cognitive functions. In accordance with well-protected learning
and memory function, the hippocampal region primarily responsible for learning
and memory was completely protected by combination treatment, in marked
contrast to the severe loss of hippocampal tissue because of secondary damage
in control mice."

PubMed

"The low-level laser therapy (LLLT) suppressed proinflammatory cytokine

expression like interleukin (IL)-1 and IL-6 but upregulated TNF-. Moreover,
although lack of IEX-1 compromised ATP synthesis, LLLT elevated its production
in injured brain. The protective effect of LLLT may be ascribed to enhanced ATP
production and selective modulation of proinflammatory mediators. This new
closed head injury model provides an excellent tool to investigate the
pathogenesis of secondary brain injury as well as the mechanism underlying the
beneficial effect of LLLT."

PubMed

"Our study results suggest that tLLLT may improve TBI both by reducing cell death
in the lesion and by stimulating neurogenesis."

PubMed

"Each LED cluster head had a 5.35 cm diameter (9 red diodes, 633nm, and 52
NIR diodes, 870nm were embedded into each LED cluster head); 22.48cm2 in
size; 500mW total power; 22.2mW/cm2 power density; continuous wave."

PubMed

"A significant linear trend was observed for the effect of LED treatment over time
for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial
4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total
Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants
reported improved sleep, and fewer post-traumatic stress disorder (PTSD)
symptoms, if present. Participants and family reported better ability to perform
social, interpersonal, and occupational functions."
"Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result
in improvements in motor or sensory function or lesion size at 7 days (P>0.05)."

PubMed

PubMed

LED phototherapy
(23 diodes)

850

299

0.0114

20.5

0.95
cm2
/LED

1800

146

Transcranial LED might increase rCBF with some improvement of neurological

condition in severely head-injured patients.

PubMed

Comment: Parameters are well reported in a table.

665
730
810
980

808

Microgliosis

800

0.500

60

120

Mice with moderate-to-severe TBI treated with 665 and 810 nm laser (but not with
730 or 980 nm) had a significant improvement in Neurological Severity Score

PubMed

"These results show statistically significant, preclinical outcomes that support the
use of NIR treatment after TBI in effecting changes at the behavioral, cellular, and
chemical levels."

PubMed

LLLT (808nm) protected mice against traumatic brain injury (TBI).

PubMed

"Injured mice treated with 60 J/cm (500 mW/cm2 min) either transcranially or
via an open craniotomy had modestly improved latency to the hidden platform
(p<0.05 for group), and probe trial performance (p<0.01) compared to non-treated
controls. The beneficial effects of LLLT in open craniotomy mice were associated
with reduced microgliosis at 48 h (21.82.3 versus 39.24.2 IbA-1+
cells/200field, p<0.05).

PubMed

Little or no effect of LLLT on post-injury cognitive function was observed using the
other doses, a 4-h administration time point and 7-day administration of 60 J/cm.
No effect of LLLT (60 J/cm open craniotomy) was observed on post-injury motor
function (days 1-7), brain edema (24 h), nitrosative stress (24 h), or lesion volume
(14 days).
Although further dose optimization and mechanism studies are needed, the data
suggest that LLLT might be a therapeutic option to improve cognitive recovery and
limit inflammation after TBI."

870+
633

Brain

Brain injury

Naeser

USA (Boston,
MA)

2011

Photomed Laser
Surg

Improved cognitive function after transcranial, light-emitting diode

treatments in chronic, traumatic brain injury: two case reports.

Case report

Brain

Brain injury

Huang

USA
(Boston, MA)

2012

J Biophotonics

Transcranial low level laser (light) therapy for traumatic brain

injury.

Review

Brain

Brain injury

Ando

USA
(Boston, MA)

2011

PLoS One

Comparison of therapeutic effects between pulsed and continuous

wave 810-nm wavelength laser irradiation for traumatic brain injury
in mice.

Mouse

Brain

Brain injury

Moreira

Brazil

2009

J Photochem
Photobiol B

Effect of phototherapy with low intensity laser on local and

systemic immunomodulation following focal brain damage in rat.

Rat

Brain

Brain injury

Oron

Israel

2007

J Neurotrauma

Low-level laser therapy applied transcranially to mice following

traumatic brain injury significantly reduces long-term neurological
deficits.

Mouse

808

Brain

Circulation

Tian

USA
(Arlington, TX)

2016

Lasers Surg Med

Transcranial laser stimulation improves human cerebral

oxygenation.

Human

1064

Transcranial LED may improve cognition, reduce costs in TBI treatment, and be
applied at home.

Review
- Animal studies and clinical trials of transcranial-LLLT for ischemic stroke are summarized.
- Several laboratories have shown that LLLT is effective in increasing neurological performance and memory and learning in mouse models of TBI.
- There have been case report papers that show beneficial effects of transcranial-LLLT in a total of three patients with chronic TBI.
- Our laboratory has conducted three studies on LLLT and TBI in mice.
810

Cryogenic brain injury

660
780

40

0.240.4

3-5

0.04
cm2

3-5

1.2
2.4

1.2
cm2

120

PubMed
PubMed

The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was
significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover,
we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim
and tail suspension tests.

PubMed

"Thus, although some alterations of the local and systemic levels of the studied
cytokines in the cryolesioned rats were observed, at this point it is difficult to
conclude if these changes would be beneficial or deleterious to the CNS healing.
Hence, more studies are needed in order to further explore the possibility of using
laser phototherapy for preventing and/or limiting the brain damage in the traumatic
brain injury clinical outcome."

PubMed

Star: The paper was supplied with interesting photographs.

Brain

CNS

Fitzgerald

Australia
(Crawley)

2013

Rev Neurosci

Red/near-infrared irradiation therapy for treatment of central

nervous system injuries and disorders.

Review

Brain

Cognitive
performance

Grover

USA
(Denver, CO)

2016
epub

Photomed Laser
Surg

Acute Effects of Near Infrared Light Therapy on Brain State in

Healthy Subjects as Quantified by qEEG Measures.

Human

Brain

Cognitive
performance

Hwang

USA
(Austin, TX)

2016

Lasers Med Sci

Cognitive enhancement by transcranial laser stimulation and acute

aerobic exercise.

Human
RCT

0.01
0.02

3.4

0.25

13.6
cm2

"The lesion volume of the laser treated mice was significantly lower (1.4%) than
the non-treated group (12.1%). Our data suggest that a non-invasive transcranial
application of LLLT given 4 h following TBI provides a significant long-term
functional neurological benefit."

PubMed

In both experiments, transcranial laser stimulation induced an increase of

oxygenated hemoglobin concentration ([HbO2 ]) and a decrease of
deoxygenated hemoglobin concentration ([Hb]) in both cerebral hemispheres.

PubMed

"We have addressed the important issues of specification of treatment parameters, penetration of R/NIR irradiation to CNS tissues and mechanism/s,
and provided the necessary detail to demonstrate the potential of R/NIR-IT for the treatment of retinal degeneration, damage to white matter tracts of the
CNS, stroke and Parkinson's disease."

LED phototherapy
LED array (784)

903

0.0167

20

360
cm2

1064

0.250

60

13.6
cm2

"Change in reaction time significantly differed between treated and control, with a
mean of 23.8 msec improvement compared with controls (p = 0.035). Amplitude
increased an average of 0.81 V in treatment versus 0.22 V in controls and did
not reach significance."

PubMed

PubMed

"The data suggest that NIR light may have an acute effect on reaction time and
amplitude in certain subject subsets. There were no adverse events registered
across the 31 subjects in the treatment group, nor in the 18 evaluable control
group subjects."
480

"The transcranial infrared laser stimulation and acute aerobic exercise treatments
were similarly effective for cognitive enhancement, suggesting that they augment
prefrontal cognitive functions similarly."

PubMed

Additional info

Comment

Reply

 Category
Brain

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Cognitive
performance

Barrett &
Gonzalez-Lima

USA
(Austin, TX)

2013

Neuroscience

Transcranial infrared laser stimulation produces beneficial

cognitive and emotional effects in humans.

Human
RCT

nm

mW

W/cm2

J/cm2

1064

0.25

Results: positive / unclear/modest / negative

Link

sec

60

"Reaction time in a sustained-attention psychomotor vigilance task (PVT) was

significantly improved in the treated (n=20) vs. placebo control (n=20) groups,
especially in high novelty-seeking subjects.

PubMed

Performance in a delayed match-to-sample (DMS) memory task showed also a

significant improvement in treated vs. control groups as measured by memory
retrieval latency and number of correct trials.
The Positive and Negative Affect Schedule (PANAS-X), which tracks self-reported
positive and negative affective (emotional) states over time, was administered
immediately before treatment and 2 weeks after treatment. The PANAS showed
that while participants generally reported more positive affective states than
negative, overall affect improved significantly in the treated group due to more
sustained positive emotional states as compared to the placebo control group.
These data imply that transcranial laser stimulation could be used as a noninvasive and efficacious approach to increase brain functions such as those
related to cognitive and emotional dimensions."

Brain

Cognitive
performance

Rojas

USA
(Austin, TX)

2012

J Alzheimers Dis

Low-level light therapy improves cortical metabolic capacity and

memory retention.

Rat

Brain

Cognitive
performance

Michalikova

UK
(Sunderland)

2008

Neurobiol Learn
Mem

Emotional responses and memory performance of middle-aged

CD1 mice in a 3D maze: effects of low infrared light.

Mouse

Brain

Depression

Cassano

USA
(Boston, MA)

2016

Neurophotonics

Review of transcranial photobiomodulation for major depressive

disorder: targeting brain metabolism, inflammation, oxidative
stress, and neurogenesis.

Review

Brain

Depression

Disner

USA
(Austin, TX)

2016

Brain Stimul

Transcranial Laser Stimulation as Neuroenhancement for Attention Human

Bias Modification in Adults with Elevated Depression Symptoms.
RCT/SB (?)

Brain

Depression

Mohammed HS

Egypt

2016

Lasers Med Sci

Transcranial low-level infrared laser irradiation ameliorates

depression induced by reserpine in rats.

Brain

Depression

Xu

China (Jiangsu)

2016

Mol Neurobiol

Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mouse

Mice.

1072

"Experiment 1 verified that LLLT increased the rate of oxygen consumption in the
prefrontal cortex in vivo. Experiment 2 showed that LLLT-treated rats had an
enhanced extinction memory as compared to controls. Experiment 3 showed that
LLLT reduced fear renewal and prevented the reemergence of extinguished
conditioned fear responses. Experiment 4 showed that LLLT induced hormetic
dose-response effects on the metabolic capacity of the prefrontal cortex."

PubMed

"Exposure to IR appeared to have no significant effects upon exploratory activity

or anxiety responses. However, it elicited significant effects on working memory,
with the IR middle-aged mice being more considerate in their decision making,
which results in an overall improved cognitive performance which is comparable to
that of young CD-1 mice."

PubMed

"Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large
randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD."

"A significant three-way interaction between LLLT condition, ABM response, and
time indicated that right LLLT led to greater symptom improvement among
participants whose attention was responsive to ABM (i.e., attention was directed
away from negative stimuli). Minimal change in depression was observed in the
left and sham LLLT."

PubMed

PubMed

"The results suggest that larger clinical trials examining the efficacy of using
photoneuromodulation to augment cognitive training are warranted."

Rat

Biphasic dose
response

804

80
200
400

0.64
1.60
3.18

808

30

0.023

4.8
12
24

0.1256
cm2

360
(6p)

Low power (80 mW) ameliorated depressive symptoms.

High power (400 mW) exacerbated depressive symptoms.

PubMed

0.79
cm2
(??)

1800

28

"Our results revealed that LLLT effectively improved depression-like behaviors, in

the two depression mice models, by decreasing immobility duration in behavioral
despair tests.

PubMed

In addition, ATP biosynthesis and the level of mitochondrial complex IV expression

and activity were significantly elevated in prefrontal cortex (PFC) following LLLT.
Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV
levels in other tested brain regions, hippocampus and hypothalamus.
As a whole, these findings shed light on a novel strategy of transcranial LLLT on
depression improvement by ameliorating neurotransmitter abnormalities and
promoting mitochondrial function in PFC."

Brain

Depression

Salehpour

Iran (Tabriz)

2016

Lasers Surg Med

Therapeutic effects of 10-HzPulsed wave lasers in rat depression

model: A comparison between near-infrared and red wavelengths.

Brain

Depression

Wu

USA
(Bethesda, MD)

2012

Lasers Surg Med

Pulsed light irradiation improves behavioral outcome in a rat model Rat

of chronic mild stress.

Brain

Depression

Tanaka

Japan
(Oita)

2011

Brain Stimul

Infrared radiation has potential antidepressant and anxiolytic

effects in animal model of depression and anxiety.

630
810

Rat

Chronic mild stress

model

0.089
0.562

810

6001600

Rat

6.2
39.3

1.18
14.4

120

60000

0.07
cm2

120

180

1
10

"This study showed that non-invasive tLLLT using 10-Hz pulsed NIR laser light
was as effective as Citalopram and more effective than red laser in the treatment
of depressive-like behaviors and may help improve tLLLT as an alternative nonpharmacological treatments of psychological disorders such as depression."

PubMed

"TLT was comparable to fluoxetine in improving the behavioral outcome after

CMS. TLT did not cause weight loss, which is consistently seen in patients treated
with fluoxetine. This study demonstrates that TLT has potential as an effective
treatment for depression."

PubMed

"Acutely exposed rats were treated with an infrared radiation machine for one
session, whereas chronically exposed animals were treated with an infrared
radiation for 10 sessions."

PubMed

"The infrared emitter had highest emissivity values within 0.6-1.6 m and a
calculated maximal irradiation intensity of 1800-2200 mW. A polyethylene restraint
apparatus (a device that modeled the neck and the body of the animal as cylinders
and the head as an ellipsoid) was used to immobilize the head and body of the rat
during the treatment."
"Chronic infrared radiation exposure decreased indicators of depression- and
anxiety-like behavior. No significant effect on general locomotor activity was
observed. The number of BrdU-positive cells in CA1 of the hippocampus was
significantly increased in both acutely and chronically exposed infrared radiation
groups compared with the control group."
"These results indicate that chronic infrared radiation might produce
antidepressant- and anxiolytic-like effects."

Brain

Depression

Schiffer

USA
(Harvard;
Belmont, MA)

2009

Behav Brain Funct Psychological benefits 2 and 4 weeks after a single treatment with
near infrared light to the forehead: a pilot study of 10 patients with
major depression and anxiety.

Human
Pilot study

Major depression and

anxiety

Brain

Depression

Tsai

Taiwan
(Hualien)

2007

Prog
Neuropsychophar
macol Biol
Psychiatry

Infrared irradiation has potential antidepressant effect.

Mouse

Far-infrared (nonLLLT)

Biol Psychiatry

Prophylactic treatment of seasonal affective disorder (SAD) by

using light visors: bright white or infrared light?

810

0.25

300015000

60

480
(2p)

33

3600

28

"At 2-weeks post treatment 6 of 10 patients had a remission (a score </= 10) on
the HAM-D and 7 of 10 achieved this on the HAM-A."

PubMed

"This is the first study using an experimental animal design to evaluate the
potential antidepressant effect of the infrared irradiation.

PubMed

The result suggests that daily 60 min infrared irradiation for 4 weeks has potential
antidepressant effect.
The result encourages further studies applying infrared irradiation to human for the
treatment of depression, especially for those who hesitate to take antidepressants
and unable to perform the alternatives such as exercise."

Brain

Depression

Meesters

Netherlands

1999

"Almost every light fixture produces light with an infrared component. So, our data
indicate that, if light is crucial to the response, it must be that component which is
crucial. However, infrared light is beyond the visible range of the spectrum. The
720 nm filter in our light visor still transmitted some visible light. However, its
visibility was virtually negligible (0.18 lux). The conclusion of this study might
therefore be that the perception of light does not play a role in the therapeutic
mechanism. Infrared might be effective through pathways other than those
involved in perception."

Human

PubMed

"Infrared light is just as effective as bright white light. Both are more effective than
the control condition."
Comment: In this study, they used a 720nm filter for the bright light to show that
the effects of bright light might be mediated by the infrared, not visible light
wavelengths.

Brain

Energy
metabolism

Mochizuki-Oda

Japan
(Hirakata)

2002

Neurosci Lett

Effects of near-infra-red laser irradiation on adenosine

triphosphate and adenosine diphosphate contents of rat brain
tissue.

830
652

Rat

4.8

900

"These results suggest that the increase in tissue ATP content did not result from
the thermal effect, but from a specific effect of the laser operated at the 830-nm
wavelength."

PubMed

Comment 1: A strange paper, since a laser of extremely high power density was
used, and the tissue temperature was also raised significantly by ~4 celcius
degrees.
Comment 2: Red light wasn't effective in this study.

Microglia

von Leden

USA
(Bethesda, MD)

2013

Lasers Surg Med

808 nm wavelength light induces a dose-dependent alteration in

microglial polarization and resultant microglial induced neurite
growth.

In vitro

Brain

Parkinson's
disease

Johnstone

Australia &
France

2016

Front Neurosci

Turning On Lights to Stop Neurodegeneration: The Potential of

Near Infrared Light Therapy in Alzheimer's and Parkinson's
Disease.

Review

Parkinson's
disease

Reinhart

France &
Australia

2016

Neurosci Res

The behavioural and neuroprotective outcomes when 670 nm and

810 nm near infrared light are applied together in MPTP-treated
mice

Mouse

Parkinson's
disease

Reinhart

France &
Australia

2016

Near-infrared light (670 nm) reduces MPTP-induced parkinsonism

within a broad therapeutic time window.

Mouse

Brain

Brain

Brain

Exp Brain Res

Biphasic dose
response

808

50

0.2
4
10
30

"Specifically, PBM with energy densities between 4 and 30 J/cm(2) induced

expression of M1 markers in microglia. Markers of the M2 phenotype, including
CD206 and TIMP1, were observed at lower energy densities of 0.2-10 J/cm(2)"

"Red to infrared light therapy ( = 600-1070 nm), and in particular light in the near infrared (NIr) range, is emerging as a safe and effective therapy that is
capable of arresting neuronal death. Previous studies have used NIr to treat tissue stressed by hypoxia, toxic insult, genetic mutation and mitochondrial
dysfunction with much success. Here we propose NIr therapy as a neuroprotective or disease-modifying treatment for Alzheimer's and Parkinson's
patients."

MPTP

MPTP

670
+
810
670

Note: In this paper, they had 6 different active treatment groups, and all of them
fared better than the MPTP group!
0.0053
(midbrain)

0.5
(midbrain)

90

412

"In summary, irrespective of whether it was applied before, at the same time as or
after MPTP insult, NIr reduced both behavioural and structural measures of
damage by a similar magnitude."

PubMed

PubMed

NOT IN
PUBMED
YET
PubMed

"There was a broad therapeutic time window of NIr application in relation to the
stage of toxic insult, and the NIr was fast-acting and long-lasting."
Star: The paper included a photograph of LLLT application.

Brain

Parkinson's
disease

Reinhart

France &
Australia

2016

J Neurosurg

Intracranial application of near-infrared light in a hemiparkinsonian rat model: the impact on behavior and cell survival.

Mouse

6-OHDA
Light delivery into the
brain via optical fiber

Brain

Parkinson's
disease

Moro

France &
Australia

2016

Brain Res

Effects of a higher dose of near-infrared light on clinical signs and

neuroprotection in a monkey model of Parkinson's disease.

Monkey

MPTP

Brain

Parkinson's
disease

El Massri

Australia &
France

2016

Int J Neurosci

The effect of different doses of near infrared light on dopaminergic

cell survival and gliosis in MPTP-treated mice.

Mouse

MPTP

670

"In summary, when delivered at the appropriate power, delivery mode, and
dosage, NIr treatment provided both improved behavior and neuroprotection in 6OHDA-lesioned rats."

PubMed

Higher dose of 125J was not as beneficial to MPTP-treated monkeys as compared

to the lower doses of 25J and 35J.

PubMed

"In summary, we showed that neuroprotection by NIr irradiation in MPTP-treated

mice was dose-dependent; with increasing MPTP toxicity, higher doses of NIr
were required to protect cells and reduce astrogliosis."

PubMed

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

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Category

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Brain

Parkinson's
disease

El Massri

Australia &
France

2016

Exp Brain Res

Near-infrared light treatment reduces astrogliosis in MPTP-treated

monkeys.

Monkey

MPTP

"Our results showed that NIr treatment reduced dramatically (~75 %) MPTPinduced astrogliosis in both the SNc and striatum. Among microglia, however, NIr
had a more limited impact in both nuclei; although there was a reduction in overall
cell size, there were no changes in the number of microglia in the MPTP-treated
monkeys after NIr treatment."

PubMed

Brain

Parkinson's
disease

Darlot

France &
Australia

2016

Ann Neurol

Near-infrared light is neuroprotective in a monkey model of

Parkinson disease.

Monkey

MPTP

"Our findings indicate NIr to be an effective therapeutic agent in a primate model

of the disease and create the template for translation into clinical trials."

PubMed

Brain

Parkinson's
disease

Reinhart

France &
Australia

2015

Neurosci Res

810nm near-infrared light offers neuroprotection and improves

locomotor activity in MPTP-treated mice.

Mouse

MPTP
LED phototherapy

810

"Our results showed that MPTP-treated mice that were irradiated with 810nm NIr
had both greater locomotor activity (40%) and number of dopaminergic cells
(20%) than those that were not. In summary, 810nm (as with 670nm) NIr offered
neuroprotection and improved locomotor activity in MPTP-treated mice."

PubMed

Brain

Parkinson's
disease

Oueslati

Switzerland

2015

PLoS One

Photobiomodulation Suppresses Alpha-Synuclein-Induced Toxicity Rat

in an AAV-Based Rat Genetic Model of Parkinson's Disease.

Genetic model

808

28

"In this model, daily exposure of both sides of the rat's head to 808-nm nearinfrared light for 28 consecutive days alleviated -syn-induced motor impairment,
as assessed using the cylinder test. This treatment also significantly reduced
dopaminergic neuronal loss in the injected substantia nigra and preserved
dopaminergic fibers in the ipsilateral striatum."

PubMed

Brain

Parkinson's
disease

Moro

France &
Australia

2014

J Neurosurg

Photobiomodulation inside the brain: a novel method of applying

near-infrared light intracranially and its impact on dopaminergic
cell survival in MPTP-treated mice.

Mouse

MPTP

670

"Measurements showed that the NIr intensity declined as distance from the source
increased across the brain (65% per mm) but was detectable up to 10 mm away.
At neuroprotective (0.16 mW) and much higher (67 mW) intensities, the NIr
caused no observable behavioral deficits, nor was there evidence of tissue
necrosis at the fiber tip, where radiation was most intense. Finally, the
intracranially delivered NIr protected SNc cells against MPTP insult; there were
consistently more dopaminergic cells in MPTP-treated mice irradiated with NIr
than in those that were not irradiated."

PubMed

Indirect application of near infrared light induces neuroprotection

in a mouse model of parkinsonism An abscopal neuroprotective
effect

Mouse

Can phototherapy ameliorate the progression of Parkinson's

disease?

Guest
Editorial

nm

mW

W/cm2

J/cm2

0.057

0.0025
0.0050

2
cm2
(?)

100

LED phototherapy
vs
laser phototherapy
Light delivery into the
brain via optical fiber

Brain

Brain

Parkinson's
disease

Parkinson's
disease

Johnstone

Jang & Han

Australia
(Sydney)

Korea
(Gyeongbuk)

2014

2014

Neuroscience

Photomed Laser
Surg

MPTP

Results: positive / unclear/modest / negative

Link

sec

Comment: A really cool photograph is included!

670

0.05

90

"In summary, the findings suggest that treatment of a remote tissue with NIr is
sufficient to induce protection of the brain, reminiscent of the abscopal effect
sometimes observed in radiation treatment of metastatic cancer. This discovery
has implications for the clinical translation of light-based therapies, providing an
improved mode of delivery over transcranial irradiation."

Systemic effects

"In summary, emerging evidence suggests that treatment with LED or low level laser therapy (LLLT) may neuroprotect dopaminergic cells in the SNc,
by accelerating mitochondrial respiration and ATP production. Consequently, it is suggested that phototherapy may suppress the progression of
neurodegeneration or minimize the symptoms of PD.

PubMed

PubMed

Attractive as this suggestion appears, there are no human studies to support it. Moreover, light penetration through the skull may be limited, such
that it does not reach the midbrain and the limbic system of the human brain. Nevertheless, it seems reasonable to attempt phototherapy
treatment of intractable PD."

Brain

Parkinson's
disease

Moro

France
(Grenoble)

2013

BMC Neurosci

Photobiomodulation preserves behaviour and midbrain

dopaminergic cells from MPTP toxicity: evidence from two mouse
strains.

Mouse

Brain

Parkinson's
disease

Vos

Belgium

2013

PLoS One

Near-infrared 808 nm light boosts complex IV-dependent

respiration and rescues a Parkinson-related pink1 model.

Fruit fly

670

Pink1

808
730

730nm -> no effect

Brain

Parkinson's
disease

Purushothuman

Australia
(Sydney)

2013

Brain Res

The impact of near-infrared light on dopaminergic cell survival in a

transgenic mouse model of parkinsonism.

Brain

Parkinson's
disease

Shaw

Australia
(Sydney)

2012

Parkinsons Dis

Patterns of Cell Activity in the Subthalamic Region Associated with Mouse

the Neuroprotective Action of Near-Infrared Light Treatment in
MPTP-Treated Mice.

Brain

Parkinson's
disease

Quirk

USA
2012
(Milwaukee, WI)

Front Biosci (Elite

Ed)

Therapeutic effect of near infrared (NIR) light on Parkinson's

disease models.

Review

Brain

Parkinson's
disease

Peoples

Australia
(Sydney)

ISRN Neurol

Survival of Dopaminergic Amacrine Cells after Near-Infrared Light

Treatment in MPTP-Treated Mice.

Mouse

2012

Mouse

0.01
0.025

25200

Transgenic

670

90

MPTP

670

0.5

90

20

"In summary, our results revealed the neuroprotective benefits of NIr treatment
after parkinsonian insult at both cellular and behavioural levels and suggest that
Balb/c strain, due to greater penetration of NIr through skin and fur, provides a
clearer model of protection than the C57BL/6 strain."

PubMed

"We tested the hypothesis that 808 nm infrared light that effectively penetrates
tissues rescues pink1 mutants. We show that irradiating isolated fly or mouse
mitochondria with 808 nm light that is absorbed by ETC-Complex IV acutely
improves Complex IV-dependent oxygen consumption and ATP production, a
feature that is wavelength-specific. Irradiating Drosophila pink1 mutants using a
single dose of 808 nm light results in a rescue of major systemic and mitochondrial
defects."

PubMed

"Our results showed immunoreactivity for 4-HNE, 8-OHDG and AT8 within the
SNc was increased in K3 mice compared to WT, and that this increase was
mitigated by NIr. Results further showed that TH cell number was lower in K3
mice than in WT, and that this loss was mitigated by NIr. In summary, NIr
treatment reduced the oxidative stress caused by the tau transgene in the SNc of
K3 mice and saved SNc cells from degeneration. Our results, when taken together
with those in other models, strengthen the notion that NIr treatment saves
dopaminergic cells in the parkinsonian condition."

PubMed

"In summary, our results indicated that NIr had long lasting effects on the activity
of cells located deep in the brain and had repaired partially the abnormal activity
generated by the parkinsonian toxin."

PubMed

Review:
- Mitochondrial dysfunction plays a central role in PD, especially in the electron transport chain.
- This mitochondrial role allows the use of inhibitors of complex I and IV in PD models, and enhancers of complex IV activity, such as NIR light,
to be used as possible therapy.
- PD models fall into two main categories; cell cultures and animal models.
- In cell cultures, primary neurons, mutant neuroblastoma cells, and cell cybrids have been studied in conjunction with NIR light.
- Primary neurons show protection or recovery of function and morphology by NIR light after toxic insult. Neuroblastoma cells, with a gene for
mutant alpha-synuclein, show similar results.
- Cell cybrids, containing mtDNA from PD patients, show restoration of mitochondrial transport and complex I and IV assembly.
- Animal models include toxin-insulted mice, and alpha-synuclein transgenic mice. Functional recovery of the animals, chemical and
histological evidence, and delayed disease progression show the potential of NIR light in treating Parkinson's disease.

MPTP
LED phototherapy

670

0.5

90

PubMed

"In summary, we showed that NIr treatment was able to both protect
(simultaneous series) and rescue (posttreatment series) TH(+) cells of the retina
from parkinsonian insult."

PubMed

Retinal damage
(eyes)

Brain

Parkinson's
disease

Peoples

Australia
(Sydney)

2012

Parkinsonism
Relat Disord

Photobiomodulation enhances nigral dopaminergic cell survival in

a chronic MPTP mouse model of Parkinson's disease.

Mouse

MPTP
LED phototherapy

670

0.04
(scalp)
-->
0.0053
(brain)

0.5

90

10

"In summary, exposure to NIr either at the same time or well after chronic MPTP
insult saved many SNc dopaminergic cells from degeneration."

PubMed

Brain

Parkinson's
disease

Shaw

Australia
(Sydney)

2010

J Comp Neurol

Neuroprotection of midbrain dopaminergic cells in MPTP-treated

mice after near-infrared light treatment.

Mouse

LED phototherapy

670

0.04
(scalp)
-->
0.0053
(brain)

0.5

90

"In summary, our results indicate that NIr light treatment offers neuroprotection
against MPTP toxicity for dopaminergic cells in the SNc, but not in the ZI-Hyp."

PubMed

Brain

Parkinson's
disease

Trimmer

USA
(Virginia)

2009

Mol
Neurodegener

Reduced axonal transport in Parkinson's disease cybrid neurites is In vitro

restored by light therapy.
(human cells)

810

0.05

40

"The results from this study support our proposal that axonal transport is reduced
in sporadic PD and that a single, brief treatment with near-infrared light can
restore axonal transport to control levels."

PubMed

Brain

Parkinson's
disease

Ying

USA
2008
(Milwaukee, WI)

Brain Res

Pretreatment with near-infrared light via light-emitting diode

provides added benefit against rotenone- and MPP+-induced
neurotoxicity.

670

0.05

80

4
8

"Results indicate that pretreatment with NIR-LED significantly suppressed

rotenone- or MPP(+)-induced apoptosis in both striatal and cortical neurons (P<0.
001), and that pretreatment plus LED treatment during neurotoxin exposure was
significantly better than LED treatment alone during exposure to neurotoxins.

PubMed

In vitro
(striatal and
cortical
neurons)

Neurotoxins

LED phototherapy

In addition, MPP(+) induced a decrease in neuronal ATP levels (to 48% of control
level) that was reversed significantly to 70% of control by NIR-LED pretreatment.
These data suggest that LED pretreatment is an effective adjunct preventative
therapy in rescuing neurons from neurotoxins linked to PD."

Brain

Brain

Parkinson's
disease

Review

Liang

Hamblin MR

USA
2008
(Milwaukee, WI)

USA
(Boston, MA)

2016

Neuroscience

BBA Clin

Near-infrared light via light-emitting diode treatment is therapeutic

against rotenone- and 1-methyl-4-phenylpyridinium ion-induced
neurotoxicity.

In vitro

Shining light on the head: Photobiomodulation for brain disorders.

Review

MPTP

670

0.05

80

120

"Results indicated that LED treatments twice a day significantly increased cellular
ATP content, decreased the number of neurons undergoing cell death, and
significantly reduced the expressions of reactive oxygen species and reactive
nitrogen species in rotenone- or MPP+-exposed neurons as compared to
untreated ones."

PubMed

"Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured,
is degenerating, or else is at risk of dying."

PubMed

LED phototherapy

"In this transcranial PBM (tPBM) application, near-infrared (NIR) light is often applied to the forehead because of the better penetration (no hair, longer
wavelength). Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED) arrays has allowed the development
of light emitting helmets or "brain caps". This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the
key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders."

Brain

Stroke

Lee

Korea
(Yangsan)

2016

Restor Neurol
Neurosci

Pre-conditioning with transcranial low-level light therapy reduces

neuroinflammation and protects blood-brain barrier after focal
cerebral ischemia in mice.

Mouse

"LLLT significantly reduced infarct size and edema and improved neurological and
motor function 24 h after ischemic injury.

PubMed

In addition, LLLT markedly inhibited Iba-1- and GFAP-positive cells, which was
accompanied by a reduction in the expression of inflammatory mediators and
inhibition of MAPK activation and NF-B translocation in the ischemic cortex.
Concomitantly, LLLT significantly attenuated leukocyte accumulation and
infiltration into the infarct perifocal region.
LLLT also prevented BBB disruption after ischemic events, as indicated by a
reduction of Evans blue leakage and water content.
These findings were corroborated by immunofluorescence staining of the tight
junction-related proteins in the ischemic cortex in response to LLLT."

Brain

Stroke

Lapchak &
Boitano

USA
(Los Angeles,
CA)

2016

Acta Neurochir
Suppl

Transcranial Near-Infrared Laser Therapy for Stroke: How to

Recover from Futility in the NEST-3 Clinical Trial.

Review

Brain

Stroke

Zivin

USA
(San Diego,
CA)

2014

Int J Stroke

NeuroThera Efficacy and Safety Trial-3 (NEST-3): a double-blind,

randomized, sham-controlled, parallel group, multicenter, pivotal
study to assess the safety and efficacy of transcranial laser
therapy with the NeuroThera Laser System for the treatment of
acute ischemic stroke within 24 h of stroke onset.

Study
protocol

"There is especially extensive attenuation of light energy penetration across the

human calvaria, compared with animal skulls, which suggests that the power
density setting used in stroke clinical trials may not have optimally stimulated
neuroprotection and repair pathways.

PubMed

The results of our study suggest that NILT cannot be sufficiently optimized in
"small" animals and directly translated to humans because of significant variances
of skull thickness and penetration characteristics across species."

PubMed

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Brain

Stroke

Hacke

Multiple
countries

2014

Stroke

Transcranial laser therapy in acute stroke treatment: results of

neurothera effectiveness and safety trial 3, a phase III clinical end
point device trial.

Human
RCT/DB
Multicenter

Brain

Stroke

Huisa

USA
(Albuquerque,
NM)

2013

Lasers Med Sci

Incremental treatments with laser therapy augments good

behavioral outcome in the rabbit small clot embolic stroke model.

Rabbit

Embolic stroke

Brain

Stroke

Boonswang

USA
(Easton, PA)

2012

BMJ Case Rep

A new treatment protocol using photobiomodulation and

muscle/bone/joint recovery techniques having a dramatic effect on
a stroke patient's recovery: a new weapon for clinicians.

Case report

LED phototherapy

660
850

Brain

Stroke

Lapchak & De
Taboada

USA
(La Jolla, CA)

2010

Brain Res

Transcranial near infrared laser treatment (NILT) increases cortical

adenosine-5'-triphosphate (ATP) content following embolic strokes
in rabbits.

Rabbit

Dose response

808

Category

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

sec

"The study was terminated on recommendation by the Data Monitoring Committee

after a futility analysis of 566 completed patients found no difference in the primary
end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284
[49.3%] for good functional outcome; modified Rankin Scale, 0-2)."

PubMed

PubMed

1400

0.196
cm2

Pulsed vs continous
wave

"The patient in this case report experienced a dramatic recovery/rehabilitation

outcome after being treated with the treatment protocol."

PubMed

"Embolization decreased cortical ATP content in ischemic cortex by 45%

compared to naive rabbits, a decrease that was attenuated by CW NILT which
resulted in a 41% increase in cortical ATP content compared to the sham
embolized group (p>0.05). The absolute increase in ATP content was 22.5%
compared to naive rabbits.

PubMed

Following PW NILT, which delivered 5 (PW1) and 35 (PW2) times more energy
than CW, we measured a 157% (PW1 p=0.0032) and 221% (PW2 p=0.0001)
increase in cortical ATP content, respectively, compared to the sham embolized
group. That represented a 41% and 77% increase in ATP content compared to
naive control .
This is the first demonstration that embolization can decrease ATP content in
rabbit cortex and that NILT significantly increases cortical ATP content in
embolized rabbits, an effect that is correlated with cortical fluence and the mode of
NILT delivery."

Brain

Stroke

Lapchak PA

USA
(Los Angeles,
CO)

2010

Ann Med

Taking a light approach to treating acute ischemic stroke patients:

transcranial near-infrared laser therapy translational science.

Review

Brain

Stroke

Zivin

USA
(San Diego,
CA)

2009

Stroke

Effectiveness and safety of transcranial laser therapy for acute

ischemic stroke.

Human
RCT/DB

"TLT within 24 hours from stroke onset demonstrated safety but did not meet
formal statistical significance for efficacy. However, all predefined analyses
showed a favorable trend, consistent with the previous clinical trial (NEST-1)."

Acute ischemic
stroke

PubMed

Comment: In the subsequent NEST-3 trial, no benefit was found. The insufficient
dose has been suspected as the explanation for negative results.

Brain

Stroke

Lapchak

USA
(San Diego,
CA)

2008

Stroke

Safety profile of transcranial near-infrared laser therapy

administered in combination with thrombolytic therapy to
embolized rabbits.

"TLT did not significantly alter hemorrhage incidence after embolization, but there
was a trend for a modest reduction of hemorrhage volume (by 65%) in the TLTtreated group compared with controls."

Rabbit

PubMed

"TLT may be administered safely either alone or in combination with tPA because
neither treatment affected hemorrhage incidence or volume. Our results support
the study of TLT in combination with Alteplase in patients with stroke."

Brain

Stroke

Lapchak

USA
(San Diego,
CA)

2007

Neuroscience

Transcranial near-infrared light therapy improves motor function

following embolic strokes in rabbits: an extended therapeutic
window study using continuous and pulse frequency delivery
modes.

Rabbit

Brain

Stroke

Lampl

Israel
(Holon)

2007

Stroke

Infrared laser therapy for ischemic stroke: a new treatment

Human
strategy: results of the NeuroThera Effectiveness and Safety Trial-1 RCT/DB/MS
(NEST-1).

Embolic stroke
Transcranial LLLT

PubMed

"The NEST-1 study indicates that infrared laser therapy has shown initial safety
and effectiveness for the treatment of ischemic stroke in humans when initiated
within 24 hours of stroke onset. A larger confirmatory trial to demonstrate safety
and effectiveness is warranted."

PubMed

Comment: Despite the positive results, the subsequent NEST-2 and NEST-3 trials
could not verify the positive results shown here.
Note: A highly cited articly (222 on Google Scholar in 10/2016).

Brain

Stroke

Lampl

Israel
(Holon)

2007

Expert Rev
Neurother

Laser treatment for stroke.

Review

Brain

Stroke

Oron (A)

Israel
(Zerifin)

2006

Stroke

Low-level laser therapy applied transcranially to rats after

induction of stroke significantly reduces long-term neurological
deficits.

Rat

Atherothrombotic
stroke

"In vivo studies reinforced the efficacy of this technique for a better neurological and functional outcome post-stroke. The evidence is based on in vivo
animal studies of various models and one human clinical study. Although the data is very promising, some fundamental questions remain to be
answered, such as the exact mechanism along the cascade of post-stroke interconnective molecular disturbance, the optimal technique and time of
treatment, and the long-term safety aspects. The answers to these questions are expected to evolve within the next few years."

PubMed

808

PubMed

0.0075

0.9

120
/p

"Our data suggest that a noninvasive intervention of LLLT issued 24 hours after
acute stroke may provide a significant functional benefit with an underlying
mechanism possibly being induction of neurogenesis."

Transcranial LLLT

Brain

Stroke

DeTaboada

USA
(Carlsbad, CA)

2006

Lasers Surg Med

Transcranial application of low-energy laser irradiation improves

neurological deficits in rats following acute stroke.

Rat

Atherothrombotic
stroke

Note: "Application of the laser at 4 hours poststroke did not affect the neurological
outcome of the stroke-induced rats as compared with controls."
808

0.0075

0.9

120
/p

"In all three laser-treated groups, a marked and significant improvement in

neurological deficits was evident at 14, 21, and 28 days post stroke relative to the
non-treated group."

Transcranial LLLT

Brain

Stroke

Streeter

2004

Mitochondrion

Mechanisms of action of light therapy for stroke and acute

myocardial infarction.

Review

Brain

Stroke

Lapchak

USA
(San Diego,
CA)

2004

Stroke

Transcranial infrared laser therapy improves clinical rating scores

after embolic strokes in rabbits.

Rabbit

Brain

Stroke

Samosiuk NI

Russia

2003

Vopr Kurortol
Fizioter Lech Fiz
Kult

[Magnetic and laser therapy of acute ischemic stroke].

[Article in Russian]

Brain

Stroke

Leung

China
(Hong Kong)

2002

Lasers Surg Med

Treatment of experimentally induced transient cerebral ischemia

with low energy laser inhibits nitric oxide synthase activity and upregulates the expression of transforming growth factor-beta 1.

Rat

Konstantinovi

Serbia
(Belgrade)

2013

Lasers Surg Med

Transcranial application of near-infrared low-level laser can

modulate cortical excitability.

Human

PubMed

"These observations suggest that LLLT applied at different locations in the skull
and in a rather delayed-phase post stroke effectively improves neurological
function after acute stroke in rats."

PubMed

0.0075
0.025

Embolic stroke

"This study shows that laser treatment improved behavioral performance if

initiated within 6 hours of an embolic stroke and the effect of laser treatment is
durable. Therefore, transcranial laser treatment may be useful to treat human
stroke patients and should be further developed."

PubMed

Note: A highly cited article (129 on Google Scholar in 10/2016).

Brain

PubMed
60
300
600
905

0.05

3
(?)

1
cm2
spot

60

"Low energy laser could suppress the activity of NOS and up-regulate the
expression of TGF-beta1 after stroke in rats."

PubMed

"The average MEP size was significantly reduced during the first 20 minutes
following the TLS. The pattern was present in 10 (71.5%) of the participants. The
MEP size reduction correlated negatively with the motor threshold at rest."

PubMed

"TLS with NIR-LLL induced transitory reduction of the excitability of the stimulated
cortex."

Breast

Mastitis

Wang

China
(Daqing)

2014

J Vet Med Sci

Low-level laser therapy attenuates LPS-induced rats mastitis by

inhibiting polymorphonuclear neutrophil adhesion.

Rat

650

2.5

Carpal tunnel

Carpal tunnel
syndrome

Fusakul

Thailand
(Bangkok)

2014

Lasers Med Sci

Low-level laser therapy with a wrist splint to treat carpal tunnel

syndrome: a double-blinded randomized controlled trial.

Human
RCT/DB

810

50

0.03

18

15

"The results showed that LPS-induced secretion of IL-1 and IL-8 significantly
decreased after LLLT (650 nm, 2.5 mW, 30 mW/cm(2)). LLLT also inhibited
intercellular adhesion molecule-1 (ICAM-1) expression and attenuated the LPSinduced decrease of the expression of CD62L and increase of the expression of
CD11b. Moreover, LLLT also suppressed LPS-induced polymorphonuclear
neutrophils (PMNs) entering the alveoli of the mammary gland. The number of
PMNs in the mammary alveolus and the myeloperoxidase (MPO) activity were
decreased after LLLT."

PubMed

"Improvements were significantly more pronounced in the LLLT-treated group than

the placebo group especially for grip strength at 5- and 12-week follow-ups. At 12week follow-up, distal motor latency of the median nerve was significantly
improved in the LLLT group than the placebo group (p < 0.05).

PubMed

LLLT therapy, as an alternative for a conservative treatment, is effective for

treating mild to moderate CTS patients. It can improve hand grip strength and
electroneurophysiological parameter with a carry-over effect up to 3 months after
treatment for grip strength of the affected hands."
Comment: In this study, they used "red light" as the placebo treatment, but it
wasn't described accurately.

Carpal tunnel

Carpal tunnel
syndrome

Lazovic

Serbia
(Belgrade)

Carpal tunnel

Carpal tunnel
syndrome

Barbosa

Carpal tunnel

Carpal tunnel
syndrome

Tascioglu

Carpal tunnel

Carpal tunnel
syndrome

Dakowicz

2014

780

30

Low-level laser in the treatment of carpal tunnel syndrome: clinical, Human

electrophysiological, and ultrasonographical evaluation.

830

50

3
6

Comparison of the long-term effectiveness of physiotherapy

programs with low-level laser therapy and pulsed magnetic field in
patients with carpal tunnel syndrome.

904

150

50

Photomed Laser
Surg

Placebo-controlled investigation of low-level laser therapy to treat

carpal tunnel syndrome.

Human
RCT/DB

Brazil
2012
(Ribeiro Preto)

BMC
Musculoskelet
Disord

Effectiveness of low-level laser therapy for patients with carpal

Study design
tunnel syndrome: design of a randomized single-blinded controlled
trial.

Turkey
(Eskisehir)

2012

Rheumatol Int

Poland
(Bialystok)

2011

Adv Med Sci

Human
RCT
Comparison
trial

0.0382

0.785
cm2

360

20

"Significant reduction in pain, reduction in the percentage of patients with a

positive Tinel's sign, and shortening of sensory and motor latency time in the NCS
examination was observed in the experimental LLLT group (but not in the control
group)."

15

"There was no significant difference in any of the outcome measures among the
groups. With the chosen laser type and dose regimen, the results suggested that
LLLT was no more effective than placebo in CTS."

PubMed

"Although after LLL as well as PMF therapy clinical improvement was observed,
the most significant differences were registered after the second series and
persisted for up to 6 months in both groups."

PubMed

PubMed

PubMed

333

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Carpal tunnel

More info:

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Carpal tunnel
syndrome

Yagci

Turkey
(Istanbul)

2009

Clin Rheumatol

Comparison of splinting and splinting plus low-level laser therapy

in idiopathic carpal tunnel syndrome.

Human
RCT

nm

mW

W/cm2

830

30

J/cm2

8.1

Results: positive / unclear/modest / negative

10

"In the third-month control, SLLLT group had significant improvements on both
clinical and [nerve conduction study] parameters (median motor nerve distal
latency, median sensory nerve conduction velocities, BQ symptom severity scale,
and BQ functional capacity scale) while S group had only symptomatic healing
(BQ symptom severity scale). The grip strength of splinting group was decreased
significantly.

Link

sec

d=
1 cm

270

PubMed

According to clinical response criteria, in SLLLT group, five (23.8%) patients had
full and 12 (57.1%) had partial recovery; four (19%) patients had no change or
worsened. In S group, one patient (4.2%) had full and 17 (70.8%) partial recovery;
six (25%) patients had no change or worsened.
Additionally, applied laser therapy provided better outcomes on [nerve conduction
study] but not in clinical parameters in patients with CTS."
904

2.4

Carpal tunnel

Carpal tunnel
syndrome

Dincer

Turkey
(Istanbul)

2009

Photomed Laser
Surg

The effectiveness of conservative treatments of carpal tunnel

syndrome: splinting, ultrasound, and low-level laser therapies.

Human

Carpal tunnel

Carpal tunnel
syndrome

Shooshtrai

Iran
(Shiraz)

2008

Electromyogr Clin
Neurophysiol

The effects of low level laser in clinical outcome and

neurophysiological results of carpal tunnel syndrome.

Human
RCT

Carpal tunnel

Carpal tunnel
syndrome

Evcik

Turkey
(Afyonkarahisar
)

2007

Photomed Laser
Surg

Laser therapy in the treatment of carpal tunnel syndrome: a

randomized controlled trial.

Human
RCT/SB

830

450

Carpal tunnel

Carpal tunnel
syndrome

Elwakil

Egypt
(Cairo)

2007

Lasers Med Sci

Treatment of carpal tunnel syndrome by low-level laser versus

open carpal tunnel release.

Human

633

12

0.216

0.60

0.07
cm2

d=
1 cm

90

120

10

"It appeared that the combinations of US or LLL therapy with splinting were more
effective than splinting alone in treating CTS. However, LLL therapy plus splinting
was more advantageous than US therapy plus splinting, especially for the
outcomes of lessening of symptom severity, pain alleviation, and increased patient
satisfaction."

PubMed

"There was a significant improvement in clinical symptoms and hand grip in group
A (p < 0.001). Proximal median sensory latency, distal median motor latency and
median sensory latencies were significantly decreased (p < 0.001). Transcarpal
median SNCV increased significantly after laser irradiation (p < 0.001). There were
no significant changes in group B except changes in clinical symptoms (p <
0.001)"

PubMed

10

"In using LLLT, (1) there was no difference relative to pain relief and functional
capacity during the follow-up in CTS patients; (2) there were positive effects on
hand and pinch grip strengths."

PubMed

12

"The patients were evaluated clinically and by nerve conduction studies (NCSs)
about 6 months after the treatment.

PubMed

LLLT showed overall significant results but at a lower level in relation to surgery.
LLLT showed significant outcomes in all parameters of subjective complaints (p <
or = 0.01) except for muscle weakness. Moreover, LLLT showed significant results
in all parameters of objective findings (p < or = 0.01) except for thenar atrophy.
However, NCSs expressed the same statistical significance (p < or = 0.01) after
the treatment by both modalities.
LLLT has proven to be an effective and noninvasive treatment modality for CTS
especially for early and mild-to-moderate cases when pain is the main presenting
symptom."
Comment: Radiation parameters were insufficiently reported.

Carpal tunnel

Carpal tunnel
syndrome

Naeser MA

USA (Boston,
MA)

2006

Photomed Laser
Surg

Photobiomodulation of pain in carpal tunnel syndrome: review of

seven laser therapy studies.

"In this review, seven studies using photoradiation to treat carpal tunnel syndrome (CTS) are discussed: two controlled studies that observed real laser to
have a better effect than sham laser, to treat CTS; three openprotocol studies that observed real laser to have a beneficial effect to treat CTS; and two
studies that did not observe real laser to have a better effect than a control condition, to treat CTS.

Review

PubMed

In the five studies that observed beneficial effect from real laser, higher laser dosages (9 Joules, 12-30 Joules, 32 J/cm(2), 225 J/cm(2)) were used at the
primary treatment sites (median nerve at the wrist, or cervical neck area), than dosages in the two studies where real laser was not observed to have a
better effect than a control condition (1.8 Joules or 6 J/cm(2)).
The average success rate across the first five studies was 84% (SD, 8.9; total hands = 171). The average pain duration prior to successful photoradiation
was 2 years.
Photoradiation is a promising new, conservative treatment for mild/moderate CTS cases (motor latency < 7 msec; needle EMG, normal). It is costeffective compared to current treatments."

Carpal tunnel

Carpal tunnel
syndrome

Naeser

USA (Boston,
MA)

2002

Arch Phys Med

Rehabil

Carpal tunnel syndrome pain treated with low-level laser and

microamperes transcutaneous electric nerve stimulation: A
controlled study.

Human
RCT/DB
Crossover

Effect of near-infrared light on in vitro cellular ATP production of

osteoblasts and fibroblasts and on fracture healing with
intramedullary fixation.

In vitro

633
+
904

15

"Eleven mild to moderate CTS cases who failed standard medical or surgical
treatment for 3 to 30 months.""

PubMed

?
"Significant decreases in MPQ score, median nerve sensory latency, and Phalen
and Tinel signs after the real treatment series but not after the sham treatment
series. Patients could perform their previous work (computer typist, handyman)
and were stable for 1 to 3 years."
Comment: In addition LLLT, TENS treatment was also used.
Comment: Parameters were insufficiently reported.

Cells

Energy
metabolism

Quirk

USA
2016
(Milwaukee, WI)

J Clin Orthop
Trauma

Osteoblasts
Fibroblasts

660
830
or
both

"All groups gave significant increase in ATP within 5-10 min, with decay to
baseline by 45 min. 660 nm NIR was significantly more effective than 830 nm with
fibroblasts or either wavelength with osteoblasts.

PubMed

Animal study - A significant increase in the fracture healing grade in the 660 nm
group at day 14, but with no differences at day 21."

Cells

Energy
metabolism

Tsai

USA & Taiwan

2015

Photodiagnosis
Photodyn Ther

Low-level light therapy potentiates NPe6-mediated photodynamic

therapy in a human osteosarcoma cell line via increased ATP.

Cells

Energy
metabolism

Sharma

USA
(Boston, MA)

2011

Lasers Surg Med

Dose response effects of 810 nm laser light on mouse primary

cortical neurons.

Cells

Energy
metabolism

Benedicenti

Italy
(Milan)

2008

Photomed Laser
Surg

Intracellular ATP level increases in lymphocytes irradiated with

infrared laser light of wavelength 904 nm.

In vitro

In vitro

Osteosarcoma cell
line'

810
+
652

Biphasic dose
response

810

Lymphocytes

904

1.5
+
1.5
0.025

0.03
0.3
3
10
30

"Taken together, these results demonstrate that LLLT potentiates NPe6-mediated

PDT via increased ATP synthesis and is a potentially promising strategy that could
be applied in clinical PDT."

PubMed

"Light induced a significant increase in calcium, ATP and MMP at lower fluences
and a decrease at higher fluences."

PubMed

"The results suggest that LLLT at lower fluences is capable of inducing mediators
of cell signaling processes which in turn may be responsible for the beneficial
stimulatory effects of the low level laser. At higher fluences beneficial mediators
are reduced and high levels of Janus-type mediators such as ROS and NO
(beneficial at low concentrations and harmful at high concentrations) may be
responsible for the damaging effects of high-fluence light and the overall biphasic
dose response."

10

60

"The amount of ATP in irradiated cell cultures was 10.79 +/- 0.15 microg/L (SD; n
= 10), and in non-irradiated cell cultures it was 8.81 +/- 0.13 microg/L (SD; n = 10).
The average percentage increase of irradiated versus control cell cultures was
about 22.4% +/- 0.56% SD (p < 0.001)."

PubMed

"This significant increase is probably due to laser irradiation; it cannot be attributed

to any thermal effect, as the temperature during irradiation was maintained at 37.0
degrees +/- 0.5 degrees C."

Energy
metabolism

Oron

Cells

Energy
metabolism

Cells

Cells

Cells

Cells

Human neural
progenitor (NHNP)
cells

808

In vitro

HeLa cells

633

0.01

10

"The amount of ATP in the log phase of cultured cells remained at the control level
(0.79 +/- 0.09) x 10(-15) mol per cell) during the first 15 min after irradiation; it then
increased sharply and, after reaching a maximum (170.8%) 20 min after
irradiation, decreased slowly to the control level."

PubMed

[Changes in the amount of ATP in HeLa cells under the action of

He-Ne laser radiation].
[Article in Russian]

In vitro

HeLa cells

633

0.01

10

"In cells of the exponential phase of growth, the amount of ATP (basal level 8 x 10
(-16) mole/cell) starts to increase in 15 min after the irradiation with a maximum
(170% above the basal level) at 20 min, and then decreases gradually to the basal
level."

PubMed

Low intensity 635 nm diode laser irradiation inhibits fibroblastmyofibroblast transition reducing TRPC1 channel
expression/activity: New perspectives for tissue fibrosis treatment.

In vitro

Fibroblasts

635

"Low intensity irradiation with 635 5 nm diode laser inhibited TGF-1/Smad3mediated fibroblast-myofibroblast transition and this effect involved the modulation
of TRPC1 ion channels. These data contribute to support the potential anti-fibrotic
effect of LLLT and may offer further informations for considering this therapy as a
promising therapeutic tool for the treatment of tissue fibrosis."

PubMed

Increase in the nitric oxide release without changes in cell viability

of macrophages after laser therapy with 660 and 808 nm lasers.

In vitro

Macrophages

660
808

10/
30/
60

"LLLT promoted statistically significant changes in NO release and MTT value only
at the wavelength of 660 nm (p < 0.05). LLLT also promoted an increase in the NO
release and cell viability when the energy densities 64 (p = 0.04) and 214 J/cm2 (p
= 0.012), respectively, were used."

PubMed

300

"Visible light illumination increased NO concentration both in sperm and

endothelial cells. Blue light was more effective than red."

PubMed

Israel
2007
(Tel Aviv) / USA
(CA)

Photomed Laser
Surg

Ga-As (808 nm) laser irradiation enhances ATP production in

human neuronal cells in culture.

In vitro

Karu

Russia
(Troitsk)

1995

J Photochem
Photobiol B

Irradiation with He-Ne laser increases ATP level in cells cultivated

in vitro.

Energy
metabolism

Karu

Russia
(Troitsk)

1993

Biull Eksp Biol

Med.

Fibrosis

Sassoli

Italy
(Florence)

2016

Lasers Surg Med

Nitric oxide

Silva

Brazil
(Recife)

2016

Lasers Med Sci

Nitric oxide

Ankri

Israel
(Ramat Gan)

2010

Lasers Surg Med

Visible light induces nitric oxide (NO) formation in sperm and

endothelial cells.

In vitro

Sperm cells
Endothelial cells

0.05

0.05

d=
25 mm

"ATP was determined at 10 min after laser application."

PubMed

"The quantity of ATP in laser-treated cells was 7513 +/- 970 units, which was
significantly higher (p < 0.05) than the non-treated cells, which comprised 3808 +/539 ATP units."

Cell viability

Cells

600

30/
50/
100

400800

0.130

"Light induces NO formation in endothelial and sperm cells. In endothelial cells,

NO formation may explain previous results demonstrating enhanced wound
healing and pain relief following illumination. In illuminated sperm cells, NO
formation may account for the enhanced fertilization rate."

Cells

Nitric oxide

Lindgrd

Sweden
(Gothenburg)

2007

Lasers Med Sci

634

Irradiation at 634 nm releases nitric oxide from human monocytes.

"Irradiation resulted in elevated levels of NO but had no effect on iNOS or eNOS.

Irradiation also caused a decrease in levels of intracellular ROS and had no effect
on cell viability.

PubMed

Our studies indicate that irradiation at 634 nm releases NO, possibly from a
preformed store, and reduces the production of intracellular ROS without affecting
cell viability. Irradiation at 634 nm may have a wide range of clinical applications,
including a reduction in oxidative stress-mediated injury in the vasculature."
"The intracellular ATP concentration was not significantly affected by irradiation
(Fig. 5)."

Cells

Olfactory
ensheathing
cells

Byrnes

USA
(Washington)

2005

Lasers Surg Med

Low power laser irradiation alters gene expression of olfactory

ensheathing cells in vitro.

In vitro

Cells

Proliferation

Ren

China
(Hong Kong)

2016

Lasers Med Sci

Effect of diode low-level lasers on fibroblasts derived from human

periodontal tissue: a systematic review of in vitro studies.

Systematic
review

Cells

Proliferation

Marques

Brazil
(So Jos dos
Campos)

2014

Exp Biol Med

(Maywood)

Evaluation of the photobiomodulation in L929 cell culture.

In vitro

810

Inflammation
Differentation

150

0.2
68

"These results demonstrate that low and high dosages of PBM alter OEC activity,
including upregulation of a number of neurotrophic growth factors and extracellular
matrix proteins known to support neurite outgrowth. Therefore, the application of
PBM in conjunction with OEC transplantation warrants consideration as a potential
combination therapy for spinal cord injury."

"Current evidence showed that diode low-level lasers with adequate parameters stimulated the proliferation and modulated the inflammation of
fibroblasts derived from human periodontal tissue."
685
830

0.1
0.5
1
2
3
5
7
10
20
30

"Our results showed that low-level laser therapy stimulates effect when the energy
density is 5 to 3030 J/cm(2) and inhibits effects on energy density 0.1 to 3 J/cm(2).
This inhibitory effect was evidenced by the absence of dead cells labeled,
decreased cell density, and by the absorption of neutral red in intact cells."
"The present study demonstrated that LLLT has proliferative and inhibitory effects
on L929 cells, depending on the parameters chosen for irradiation, which influence
the results. It was also demonstrated that the metabolic condition of the cells
dictates the intensity response after irradiation."

PubMed

PubMed
PubMed

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Comment

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More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Cells

Proliferation

Peplow

New Zealand
(Dunedin)

2010

Photomed Laser
Surg

Laser photobiomodulation of proliferation of cells in culture: a

review of human and animal studies.

Systematic
review

Cells

Proliferation

Pires-Oliveira

Brazil
(So Paulo)

2010

Photomed Laser
Surg

Laser biomodulation on L 929 cell culture.

Cells

Proliferation

Taniguchi

Japan
(Kyoto)

2009

Lasers Surg Med

Low-energy laser irradiation promotes synovial fibroblast

proliferation by modulating p15 subcellular localization.

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

sec

"In total, 46 relevant articles were included in the review, comprising work completed on a variety of cell types."

PubMed

"Findings from studies of cells in culture clearly demonstrate the ability of laser irradiation to modulate (typically stimulate) cellular proliferation. The
relevance of some irradiation parameters remains occult and represents an important area for further research."

Biphasic dose
response

904

HIG-82 rabbit
synovial fibroblasts

660

0.05
6.00

"Irradiation of L929 cells with pulsed laser in the near infrared region (904 nm) at
two quite distinct energy densities allowed the observation of increased cell
proliferation in both cases. The result was slightly higher for an energy density of
50 mJ=cm2 than for 6 J=cm2 , as demonstrated by fluorescence microscopy. Cell
response was also found to be better 72 h after irradiation."

PubMed

Comment: The lower dose was more effective, even though the dose was 120-fold
smaller (50mJ/cm2 vs 6J/cm2).

In vitro

0.04

4.8

120

"LELI promoted HIG-82 synovial fibroblast proliferation and induced cytoplasmic

localization of cyclin-dependent kinase inhibitor p15 (INK4B/CDKN2B)."

PubMed

"Our findings suggest that cAMP may be involved in the effect of LELI on synovial
fibroblast proliferation."

Cells

Proliferation

Brondon

USA
2005
(Rochester, NY)

Lasers Surg Med

A study of the effects of phototherapy dose interval on

photobiomodulation of cell cultures.

In vitro

Human HEP-2
Murine L-929

670

Cells

Proliferation

van Breugel

Netherlands
(Utrecht)

Lasers Surg Med

Power density and exposure time of He-Ne laser irradiation are

more important than total energy dose in photo-biomodulation of
human fibroblasts in vitro.

In vitro

Human fibroblasts

633

1992

Biphasic dose
response

0.55
1.24
2.91
5.98

330
145
60
30

"Cellular response to dose frequency varies. More frequent treatments (2/24

hours) increased metabolism and proliferation in both cell lines. Further
investigation of dose fractionation in phototherapy is warranted."

PubMed

"Collagen type I production (as determined by an ELISA) was affected in the

opposite direction to cell proliferation: when the cell proliferation was increased,
collagen type I production was decreased."

PubMed

"Both stimulation and inhibition of the observed cell properties can be obtained
with the same laser on the same cells."
Comment: Increased proliferation was noted in only one of the four groups
studied.

Cells

Protection

Spitler

USA
(Irvine, CA)

2015

J Biomed Opt

Combination of low level light therapy and nitrosyl-cobinamide

accelerates wound healing.

In vitro

U2OS human
osteosarcoma cells
Mechanisms
ATP production
Oxygen consumption

Cells

Protection

Spitler & Berns

USA
(Irvine, CA)

2014

J Biomed Opt

Comparison of laser and diode sources for acceleration of in vitro

wound healing by low-level light therapy.

In vitro

Wound healing
LED phototherapy /
laser

Cells

Protection

Huang

USA
(Boston, MA)

2013

J Biophotonics

Low-level laser therapy (LLLT) reduces oxidative stress in primary

cortical neurons in vitro.

In vitro

Primary cortical
neurons

652
806
laser

1800

"LLLT-enhanced wound healing proceeded through an electron transport chain-Cox-dependent mechanism with a reduction of reactive oxygen species and
increased adenosine triphosphate production. C-ox was validated as the primary
photoacceptor by three observations: increased oxygen consumption, reduced
wound healing in the presence of sodium azide, and disassociation of cyanide, a
known C-ox ligand, following LLLT.

637
901
LED

We conclude that LLLT and NO-Cbi accelerate wound healing through two
independent mechanisms, the electron transport chain-C-ox pathway and cGMP
signaling, respectively, with both resulting in ERK1/2 activation."
652
806
(laser)

810

0.02

0.011

Cells

Protection

Sekhejane

South Africa
(Johannesburg)

2011

Photomed Laser
Surg

Irradiation at 636 nm positively affects diabetic wounded and

hypoxic cells in vitro.

In vitro

Diabetes / hypoxia /
wound

636

Cells

Protection

Hodgson

USA
2011
(Milwaukee, WI)

Photomed Laser
Surg

Effect of photobiomodulation on vinblastine-poisoned murine

HERS cells.

In vitro

Chemotherapy
(vinblastine)

670

0.05

12.8

Cells

Protection

Zungu

South Africa
(Johannesburg)

Photochem
Photobiol

Mitochondrial responses of normal and injured human skin

fibroblasts following low level laser irradiation--an in vitro study.

In vitro

Human skin
fibroblasts

633

0.003

5
16

95

Protection

Hawkins &
Abrahamse

South Africa
(Johannesburg)

Cells

Protection

Liang

Cells

Protection

Cells

2006

PubMed

"Although LLLT increases ROS in normal neurons, it reduces ROS in oxidativelystressed neurons. In both cases MMP is increased. These data may explain how
LLLT can reduce clinical oxidative stress in various lesions while increasing ROS
in cells in vitro."

PubMed

"Phototherapy resulted in hastened wound closure, increased proliferation, and

normalization of cellular function. The decrease in the different pro-inflammatory
cytokines and NF-B translocation was model and time dependent. Overall, laser
irradiation resulted in a reduction in inflammatory cytokines and directed cells into
the cell survival pathway."

PubMed

9.05
cm2

476

256

"Photobiomodulation demonstrated an improvement in proliferation and

glutathione levels in vinblastine-poisoned murine HERS cells."

PubMed

9.08
cm2

2700
9000

"The study confirmed that laser irradiation with 5 J cm(-2) stimulated an increase
in intracellular Ca2+ which resulted in an increase in MMP, ATP and cAMP, which
ultimately results in photobiomodulation to restore homeostasis of injured cells."

PubMed

Biphasic dose
response

Cells

"The laser and LED sources were found to be comparable when equal doses of
light were applied. The biological response measured was similar in most cases."

637
901
(LED)

Hydrogen peroxide /
cobalt chloride /
rotenone

2009

PubMed

Comment: Irradiation with 5 J/cm2 was beneficial, but 16 J/cm2 wasn't. Therefore
there seems to be a biphasic dose response.
633

0.5
2.5
5.0
10
16

"Results show that 5 J/cm(2) stimulates mitochondrial activity, which leads to

normalization of cell function and ultimately stimulates cell proliferation and
migration of wounded fibroblasts to accelerate wound closure. Laser irradiation
can modify cellular processes in a dose or fluence (J/cm(2)) dependent manner."

PubMed

"These results indicate that light-emitting diode pretreatment partially protects

neurons against cyanide-induced caspase-mediated apoptosis, most likely by
decreasing reactive oxygen species production, down-regulating pro-apoptotic
proteins and activating anti-apoptotic proteins, as well as increasing energy
metabolism in neurons as reported previously."

PubMed

"A single dose of 5.0 J/cm(2), and two or three doses of 2.5 J/cm(2) had a
stimulatory or positive effect on wounded fibroblasts with an increase in cell
migration and cell proliferation while maintaining cell viability, but without causing
additional stress or damage to the cells.

PubMed

Lasers Surg Med

The role of laser fluence in cell viability, proliferation, and

membrane integrity of wounded human skin fibroblasts following
helium-neon laser irradiation.

In vitro

Wounded fibroblasts

USA
2006
(Milwaukee, WI)

Neuroscience

Photobiomodulation partially rescues visual cortical neurons from

cyanide-induced apoptosis.

In vitro

Neurotoxins

Hawkins &
Abrahamse

South Africa
(Johannesburg)

Photomed Laser
Surg

Effect of multiple exposures of low-level laser therapy on the

cellular responses of wounded human skin fibroblasts.

In vitro

Biphasic dose
response

Protection

Wong-Riley

USA
2005
(Milwaukee, WI)

J Biol Chem

Photobiomodulation directly benefits primary neurons functionally

inactivated by toxins: role of cytochrome c oxidase.

In vitro

Neurotoxins

670nm LED light protected primary cultured neurons against potassium cyanide
(KCN) and tetrodotoxin (TTX).

PubMed

Cells

Protection

Wong-Riley

USA
2001
(Milwaukee, WI)

Neuroreport

Light-emitting diode treatment reverses the effect of TTX on

cytochrome oxidase in neurons.

In vitro

Neurotoxins

670nm LED light protected cultured primary neurons against tetrodotoxin (TTX).

PubMed

Cells

ROS

Chen

USA
(Boston, MA)

PLoS One

Low-level laser therapy activates NF-kB via generation of reactive

oxygen species in mouse embryonic fibroblasts.

In vitro

Mouse embronic
fibroblasts

"We conclude that LLLT not only enhances mitochondrial respiration, but also
activates the redox-sensitive NFkB signaling via generation of ROS. Expression of
anti-apoptosis and pro-survival genes responsive to NFkB could explain many
clinical effects of LLLT."

PubMed

2006

633

Multiple exposures at higher doses (16 J/cm(2)) caused additional stress, which
reduces cell migration, cell viability, and ATP activity, and inhibits cell
proliferation."

2011

810

0.003
0.03
0.3
3
30

Dose response
(biphasic?)

"However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP

levels, which indicates that LLLT also upregulates mitochondrial respiration."

Circulation

Aneurysm

Gavish

Israel
(Jerusalem)

2014

Lasers Surg Med

Arrest of progression of pre-induced abdominal aortic aneurysm in Mouse

apolipoprotein E-deficient mice by low level laser phototherapy.

Ang-II-infused Apo-E
(-/-) mice

780

2.2

540

"LLL not only prevents de novo development of AAA, but, from this study, also
arrests further progression of pre-induced AAA and its associated deterioration in
the biomechanical integrity of the aortic wall in Apo-E(-/-) mice."

PubMed

Circulation

Aneurysm

Gavish

Israel
(Jerusalem)

2012

Lasers Surg Med

Low level laser arrests abdominal aortic aneurysm by collagen

matrix reinforcement in apolipoprotein E-deficient mice.

Ang-II-infused Apo-E
(-/-) mice

780

540

"Transmural disruptions of the aorta occurred with distinct predilection for branch
orifices. In the LLLI-treated animals, the frequency of these disruptions was lower
(#branches with break points: 17 of 40 vs. 32 of 48, P = 0.023 by Chi-squared),
their size smaller (length [mm]: 0.48 0.26 vs. 0.98 1.42, P = 0.044 by ANOVA
with FPLSD), and the number of Mac-2-positive macrophages in the intramural
areas of these disruptions lower than in the non-treated control (#Macrophages/0.
01 mm(2) at break points: 11.6 7.2 vs. 26.0 15.7, P = 0.016 by Kruskal-Wallis).

PubMed

Mouse

The average size of the medial SMCs was larger reflecting a heightened synthetic
state (SMC size [m(2) ]: 463.9 61.4 vs. 354.9 71.7, P = 0.001 by ANOVA with
FPLSD).
Furthermore, at sites of transmural disruption, the %area occupied by collagen of
the overall area of attempted repair (%Col/WO) was significantly greater in the
LLLI-treated animals versus control (%Col/WO: 41 13 vs. 32 16, P = 0.009 by
ANOVA with FPLSD)."

Circulation

Aneurysm

Gavish

Israel
(Jerusalem)

2009

Cardiovasc Res

Low-level laser irradiation inhibits abdominal aortic aneurysm

progression in apolipoprotein E-deficient mice.

Mouse

Ang-II-infused Apo-E
(-/-) mice

780

0.004

540

"At 4 weeks, seven of 15 non-irradiated, but none of the 13 LLLI, mice had
aneurysmal dilatation in the suprarenal aneurysm-prone segments that had
progressed to >or=50% increase in maximal cross-sectional diameter (CSD) over
baseline (P = 0.005 by Fisher's exact test).

PubMed

The mean CSD of the suprarenal segments (normalized individually to inter-renal

control segments) was also significantly lower in irradiated animals (LLLI vs. nonirradiated: 1.32 +/- 0.14 vs. 1.82 +/- 0.39, P = 0.0002 by unpaired, two-tailed t-test)
with a 94% reduction in CSD at 4 weeks compared with baseline.
M-mode ultrasound data showed that reduced radial wall velocity seen in nontreated was significantly attenuated in the LLLI mice, suggesting a substantial
effect on arterial wall elasticity."

Circulation

Angiogenesis

de Sousa

Brazil
(Salvador,
Bahia)

2013

Lasers Med Sci

Laser and LED phototherapies on angiogenesis.

Rat

Circulation

Angiogenesis

Mirsky

Israel

2002

Antioxid Redox
Signal

Promotion of angiogenesis by low energy laser irradiation.

Rat

Circulation

Arterial
restenosis

Derkacz

Poland
(Wroclaw)

2014

Photomed Laser
Surg

Effects of intravascular low-level laser therapy during coronary

intervention on selected growth factors levels.

Human
RCT

LED phototherapy
LLLT vs LED

660
790
700
530
460

60
50
15
8
22

Myocardial infarction

804

38

Cutaneous wounds

808

1.911
1.592
0.0075
0.0040
0.0109

0.1

10
10
10
10
10

333
333
4.97
4.97
4.97

1
cm2
(area)

1.62.5
cm2

spot
size
varies

168
200
668
1250
456

7
7
7
7
7

"Quantitative results showed that green LED (530 20 nm), red LED (700 20
nm), 790 nm laser and 660 nm laser caused significant increased angiogenesis
when compared to the control group.

PubMed

It is concluded that both laser and LED light are capable of stimulating
angiogenesis in vivo on cutaneous wounds and that coherence was not decisive
on the outcome of the treatment."
"Laser irradiation caused a 3.1-fold significant increase in newly formed blood
vessels 6 days post infarction, as compared with nonirradiated rats."

PubMed

"LLLT decreases levels of TGF-1 and FGF-2 in patients undergoing coronary

intervention, which may explain smaller neointima formation."

PubMed

Note: This study seems to be based on the same patients as in the two other
Derkacz et al. studies.

Circulation

Arterial
restenosis

Derkacz

Poland
(Wroclaw)

2013

Lasers Med Sci

Effect of the intravascular low energy laser illumination during

percutaneous coronary intervention on the inflammatory process
in vascular wall.

Human
Controlled

808

"Irradiation of the lesion with low-energy laser radiation during the PCI procedure
results in a decrease in the levels of pro-inflammatory IL 1 and IL 6 as well as in
an increase in the levels of anti-inflammatory IL 10, which may result in decreased
risk for restenosis."

PubMed

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Circulation

Arterial
restenosis

Derkacz

Poland
(Wroclaw)

2010

Am J Cardiol

Usefulness of intravascular low-power laser illumination in

preventing restenosis after percutaneous coronary intervention.

Human
Controlled

808

Circulation

Arterial
restenosis

Kipshidze

USA
(New York, NY)

2001

Circulation

Effect of short pulsed nonablative infrared laser irradiation on

vascular cells in vitro and neointimal hyperplasia in a rabbit
balloon injury model.

Rabbit

1064

Category

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

sec

"Follow-up coronary angiography was performed after 6 months. The difference in

the restenosis rate was insignificant (15.0% vs 32.4%); however, significant
differences were observed in the minimal lumen diameter (2.18 0.70 vs 1.76
0.74 mm; p < 0.05), late lumen loss (0.53 0.68 vs 0.76 0.76 mm; p < 0.01), and
the late lumen loss index (0.28 0.39 vs 0.46 0.43; p < 0.005) in favor of the
laser group.

PubMed

In conclusion, the new therapy seemed effective and safe. Marked differences
between late loss, late loss index, and minimal lumen diameter were observed."
2.6
(?)

"Morphometry showed that the luminal area was significantly greater in the
arteries subjected to laser treatment (1.920.21 mm2 in the treated arteries and
0.490.09 mm2 in the control animals, P=9.11014) (Table). Similar significant
differences were demonstrated in the neointimal areas (0.760.18 and 1.850.30
mm2 in laser and control arteries, respectively, P=2.21011). The ratio
EELinj/EELref was greater in laser than control vessels (1.410.08 versus 1.090.
08, P=9.4109)."

PubMed

"The present study also shows that endoluminal NIL has a significant effect on
restenosis (Figures 5 and 6; Table)."
"When delivered endoluminally, NIL reduces neointimal hyperplasia in the rabbit
injury model. This study, however, should not be regarded as definitive preclinical
data, and further experiments in the porcine coronary model are necessary to
further establish the efficacy of this therapy. Ultimately, these data may lead to the
development of new methods for the prevention of restenosis."

Circulation

Arterial
restenosis

Kipshidze

USA
1998
(Milwaukee, WI)

J Am Coll Cardiol

Photoremodeling of arterial wall reduces restenosis after balloon

angioplasty in an atherosclerotic rabbit model.

632

Rabbit

10

180

"Endoluminal [low power red laser light] therapy was performed using a laserballoon catheter with a 200 m fiberoptic with a diffuse tip at the end to provide a
uniform distribution of light in the radial and axial directions of the balloon (Fig. 1)."

PubMed

"Morphometric analysis demonstrated that intimal area was five times greater in
the areas subjected to balloon treatment alone (25.3 1.9 mm2) than in the
balloon plus laser treatment sites (4.2 0.7 mm2)"
"Our experimental data indicate that endoluminal irradiation with [low power red
laser light] prevents restenosis after balloon angioplasty in an atherosclerotic
rabbit model. Endoluminal [low power red laser light] therapy may have a
significant role in interventional cardiology, not only to prevent restenosis after
coronary interventions but also to stabilize vascular endothelium so that
progression or redevelopment of the disease is inhibited. Randomized studies are
required to establish this as an effective clinical tool in humans."
Comment: This paper was published in a very-high impact journal (IF = 17.8). The
paper is also Open Access.

Circulation

Arterial
restenosis

Deckelbaum

USA
(New Haven,
CT)

1993

Lasers Surg Med

Photoinhibition of smooth muscle cell migration: potential therapy

for restenosis.

594600

In vitro

0.09
0.9
(single)

"We conclude that 594-600 nm light inhibits smooth muscle cell migration in vitro
and may potentially be used in vivo to decrease fibrointimal thickening following
arterial injury. This application of photoinhibition may be useful in retarding
restenosis following angioplasty."

PubMed

"R/NIR significantly increased collateral vessel number which could not be

attenuated with L-NAME.

PubMed

1.0
(daily)

Circulation

Artery
collateralization

Lohr

USA
2013
(Milwaukee, WI)

J Mol Cell Cardiol

Far red/near infrared light treatment promotes femoral artery

collateralization in the ischemic hindlimb.

670

Rabbit
Mouse
In vitro

R/NIR induced collateralization was abolished with c-PTIO.

In vitro, NO production increased in endothelial cells with R/NIR exposure, and
this finding was independent of NOS inhibition. Similarly R/NIR induced
proliferation and tube formation in a NO dependent manner.
Finally, nitrite supplementation accelerated R/NIR collateralization in wild type
C57Bl/6 mice. In an eNOS deficient transgenic mouse model, R/NIR restores
collateral development."

Circulation

Atherosclerosis

Park

Korea
(Cheongju)

2012

Lab Anim Res

Anti-hypercholesterolemic and anti-atherosclerotic effects of

polarized-light therapy in rabbits fed a high-cholesterol diet.

Rabbit

Atherosclerosis (high
cholesterol diet)

400760

60000

300
1200

"The results indicate that PLT attenuates atherosclerosis not only by lowering
blood cholesterol and LDL levels, but also by improving blood flow without adverse
effects. Therefore, it is suggested that PLT could be a safe alternative therapy for
the improvement of hypercholesterolemia and atherosclerosis."

PubMed

"Paired t-test results showed that there was a significant improvement after TCLT
with increase in the systolic and diastolic velocity of the left middle cerebral artery
(25 and 30%, respectively) and basilar artery (up to 17 and 25%), as well as a
decrease in the pulsatility index and resistance index values of the three cerebral
arteries analyzed (p < 0.05). TCD parameters showed improvement in the blood
flow on the arteries analyzed. TCLT promoted a blood and vasomotor behavior of
the basilar and middle cerebral arteries in healthy elderly women."

PubMed

"In the LG, a significant increase in GSH levels and considerable decrease in
angiostatin concentration following the LLLT were observed.

PubMed

Polarized light of
tungsten lamp (60W)

Circulation

Brain

Salgado

Brazil
(So Paulo)

2015

Lasers Med Sci

The effects of transcranial LED therapy (TCLT) on cerebral blood

flow in the elderly women.

Human

Circulation

Endothelium

Szymczyszyn

Poland
(Wroclaw)

2016

Lasers Med Sci

Effect of the transdermal low-level laser therapy on endothelial

function.

Human

Cerebral blood flow

627

808

0.07

50

1.6

10

120

20

No significant differences in levels of the VEGF, FGF, SDMA, ADMA were

observed.LLLT modifies vascular endothelial function by increasing its antioxidant
and angiogenic potential.
We found no significant differences in levels of the nitric oxide pathway
metabolites within 24 h following the LLLT irradiation."

Circulation

Circulation

Microcirculation

Microcirculation

Mak & Cheing

Maegawa

China
(Hong Kong)

2012

Japan
(Kyoto)

2000

Photomed Laser
Surg

Immediate effects of monochromatic infrared energy on

microcirculation in healthy subjects.

Human
RCT

MIRE treatment with

"Anodyne" LED pad
device

890

Lasers Surg Med

Effects of near-infrared low-level laser irradiation on

microcirculation.

Rat

Mesenteric circulation

830

720

108

22.5
cm2

1800

(60
LED)

Dose response

Circulation

Nitric oxide

Mitchell & Mack

USA
(Provo, UT)

2013

Am J Phys Med
Rehabil

Low-level laser treatment with near-infrared light increases venous

nitric oxide levels acutely: a single-blind, randomized clinical trial
of efficacy.

Human
RCT/SB

MIRE treatment with

"Anodyne" LED pad
device

"A 30-min MIRE produced a significantly greater increase in the capillar blood
velocity (CBV) and flux of the feet in the active MIRE group than in the placebo
and control groups."

PubMed

"LLLI caused potent dilation in the laser-irradiated arteriole, which led to marked
increases in the arteriolar blood flow."

PubMed

"The circulatory changes observed seemed to be mediated largely by LLLIinduced reduction of [Ca2+]i in VSMCs, in addition to the involvement of NO in the
initial phase."
890

636

"LLLT increased NO levels in venous blood draining from the treatment site in
healthy subjects. The peak increase in NO occurred 5 mins into the treatment,
after which it slowly waned. Further research is necessary to assess NO increases
with LLLT in patients with pathologies."

PubMed

4.4

"In hypertonic RBCs, LHNL irradiation may decrease the activity of energyconsuming enzymes, but increases the activity of energy-generating enzymes in
glycolysis, to improve the RBC deformability."

PubMed

"The exposure of intact RBCs to NIR light causes quaternary transitions in Hb,
dehydration of proteins and decreases the amount of physiologically inactive
methemoglobin, as detected by Raman spectroscopy. These effects are
accompanied by a lowering of the intracellular pH (pHi) and changes in the cell
membrane topography, as documented by atomic force microscopy (AFM).

PubMed

Circulation

Red blood cells

Luo

China
(Guangzhou)

2015

Lasers Med Sci

The effects of low-intensity He-Ne laser irradiation on erythrocyte

metabolism.

In vitro

633

Circulation

Red blood cells

Walski

Poland
(Wrocaw)

2015

Photochem
Photobiol Sci

Near infrared light induces post-translational modifications of

human red blood cell proteins

In vitro

7502000

Circulation

Red blood cells

Lin'kova

Russia
2008
(St. Petersburg)

Bull Exp Biol Med

Effect of low-intensity laser radiation of the red spectrum on some

properties of erythrocytes in Wistar rats.

Circulation

Red blood cells

Kujawa

Poland

2004

J Clin Laser Med

Surg

Effect of low-intensity (3.75-25 J/cm2) near-infrared (810 nm) laser

radiation on red blood cell ATPase activities and membrane
structure.

Circulation

Red blood cells

Spodaryk

Poland
(Krakow)

2001

Clin Hemorheol
Microcirc

The influence of low-power laser energy on red blood cell

metabolism and deformability.

0.69
*10^-3

600
900
1800
2700

All those changes are in line with our previous studies where alterations of the
membrane fluidity and membrane potential were attributed to NIR action on RBCs.
The rate of the above listed changes depends strictly on the dose of NIR light that
the cells receive, nonetheless it should not be considered as a thermal effect."
633

"An increase in the radiation power from 2.2 to 25 mW/cm2 was accompanied by
a decrease in the erythrocyte sedimentation rate and an increase in erythrocyte
filtration index. Radiation of 50 mW/cm2 induced abnormal erythrocyte
aggregation. Increasing the time of irradiation at power intensity of 2.2 mW/cm2
did not potentiate its effect on the blood."

PubMed

In vitro (RBC)

810

NIR LLLT changed the ATPase activities of the membrane ion pumps in the doseand fluence rate-dependent manner.

PubMed

In vitro

633
780
904

"This study revealed that the low-power laser at 632.8, 780 and 904 nm
wavelengths have little biological effects on red blood cells in vitro."

PubMed

2
cm2

300
900
1800

Comment: Since RBCs don't have mitochondria, LLLT isn't expected to have
significant effects on these cells.

Circulation

Smooth muscle
cells

Gavish

Israel
(Jerusalem)

2006

Lasers Surg Med

Low-level laser irradiation modulates matrix metalloproteinase

activity and gene expression in porcine aortic smooth muscle
cells.

780

In vitro

1
2

"LLLI stimulates SMC proliferation, stimulates collagen synthesis, modulates the

equilibrium between regulatory matrix remodeling enzymes, and inhibits proinflammatory IL-1-beta gene expression.

PubMed

These findings may be of therapeutic relevance for arterial diseases such as

aneurysm where SMC depletion, weakened extracellular matrix, and an increase
in pro-inflammatory markers are major pathologic components."

Circulation

Thrombocytope
nia

Zhang

USA
(Boston, MA)

2016

Sci Transl Med

Noninvasive low-level laser therapy for thrombocytopenia.

Mice & in
vitro

Biphasic dose
response

810

0.100

30

whole
body

300

4?

"This safe, drug-free, donor-independent modality represents a paradigm shift in

the prophylaxis and treatment of thrombocytopenia. "

PubMed

"We demonstrate here that noninvasive whole-body LLL illumination increases

platelet generation and completely cures or greatly ameliorates thrombocytopenia
caused by -irradiation (IR), ITP (induced by anti-CD41 antibody), or
chemotherapy in mice."

Circulation

Thrombocytope
nia

Yang

USA
(Boston, MA)

2016

Sci Rep

Low-level light treatment ameliorates immune thrombocytopenia.

Mice & in
vitro

LED phototherapy

830

Biphasic dose
response

0.02

36

1800

"These adverse effects of anti-CD41 antibody were all mitigated by LLLT to

varying degrees, owing to its ability to enhance mitochondrial biogenesis and
activity in megakaryocytes and preserve mitochondrial functions in platelets in the
presence of the antibody.

PubMed

The observations argue not only for contribution of mitochondrial stress to the
pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and costeffective modality of ITP."

Circulation

Vasoconstrictio
n

Gal

USA
(Boston/MA)

1992

Circulation

Percutaneous delivery of low-level laser energy reverses

histamine-induced spasm in atherosclerotic Yucatan microswine.

Microswine

633
1064

LLLT (633 or 1064nm) seemed to locally relieve vasoconstriction inYucatan

microswine.

PubMed

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Circulation

Vasorelaxation

Kihshidze

USA
(New York, NY)

2000

Photochem
Photobiol

Photoactivation of vascular iNOS and elevation of cGMP in vivo:

possible mechanism for photovasorelaxation and inhibition of
restenosis in an atherosclerotic rabbit models.

Rabbit

Aterosclerotic rabbit

630

Cosmetic
medicine

Body contouring

Caruso-Davis

USA
(Baton Rouge,
LA)

2011

Obes Surg

Efficacy of low-level laser therapy for body contouring and spot fat
reduction.

Human
RCT

LAPEX 2000
LipoLaser

635680

Category

Results: positive / unclear/modest / negative

Link

Additional info

Comment

Reply

Letter

Comment
ary

sec

"Our study demonstrated that intravascular low dose laser irradiation induces
iNOS and elevates vascular cGMP in an in vivo atherosclerotic rabbit model."

PubMed

"We think that endoluminal laser irradiation of PTCA-treated arteries modulates

relaxation, migration and prolif-eration of SMC, which in turn reduces the
incidence of restenosis."
"Cumulative girth loss after 4 weeks was 2.15 cm (0.78 2.82 vs. 1.35 2.64
cm for the control group,p < 0.05).

PubMed

A blinded evaluation of standardized pictures showed statistically significant

cosmetic improvement after 4 weeks of laser treatment."

Cosmetic
medicine

Cellulite

Jackson

USA
(Marion, IN)

2013

Lasers Surg Med

A double-blind, placebo-controlled randomized trial evaluating the

ability of low-level laser therapy to improve the appearance of
cellulite.

Human
RCT/DB

Dermatology

Herpes labialis

de Paula
Eduardo

Brazil
(So Paulo)

2014

Lasers Med Sci

Laser treatment of recurrent herpes labialis: a literature review.

Review

Green light

532

"Low-level laser therapy using green 532 nm diodes is safe and effective for
improving the appearance of cellulite in the thighs and buttocks."

"According to the literature, none of the laser treatment modalities is able to completely eliminate the virus and its recurrence. However, laser
phototherapy appears to strongly decrease pain and the interval of recurrences without causing any side effects."

PubMed

PubMed

"Photodynamic therapy can be helpful in reducing viral titer in the vesicle phase, and high-power lasers may be useful to drain vesicles. The main
advantages of the laser treatment appear to be the absence of side effects and drug interactions, which are especially helpful for older and
immunocompromised patients. Although these results indicate a potential beneficial use for lasers in the management of recurrent herpes labialis, they
are based on limited published clinical trials and case reports."

Dermatology

Herpes labialis

Dougal & Lee

UK
(Durham)

2013

Clin Exp Dermatol Evaluation of the efficacy of low-level light therapy using 1072 nm
infrared light for the treatment of herpes simplex labialis.

Human
RCT

1072

Dermatology

Herpes labialis

Muoz Sanchez

Cuba
(Cienfuegos)

2012

Photomed Laser
Surg

Human

670

The effect of 670-nm low laser therapy on herpes simplex type 1.

40

0.051

180

"The median time to healing for the active group was 129 h, compared with 177 h
for the control group, which was significant (P = 0.01)."

PubMed

2.04

0.79
cm2

40

1?

"LLLT of herpes simples virus 1 (HSV-1) appears to be an effective treatment

modality without any observed side effects."

PubMed

21
(5060p)

8.75

0.04
cm2
beam

300

10
+
5
+
5

"Based on the outcomes observed in this study, it is possible to conclude that the
preventive protocol proposed may represent an alternative treatment for patients
presenting recurrent herpes labialis infection."

PubMed

160

"Two clinical cases are described with recurrent labial herpes for which LLLT was
used. Following treatment, both patients remained symptom free during the 17month clinical follow-up period."

PubMed

7.2
10.8

3.0
4.5

30
/lip

10

"Patients in the experimental group presented a significant decrease in dimension

of herpes labialis lesions (P = 0.013) and inflammatory edema (P = 0.031). The
reduction in pain level (P = 0.051) and monthly recurrences (P = 0.076) did not
reach statistical significance. This study represents an in vivo indication that this
treatment should be further considered as an effective alternative to therapeutic
regimens for herpes labialis lesions."

PubMed

"The 1072-nm light-emitting diode device reduced cold-sore healing time to 6.3
days compared with 9.4 days for placebo (P = 0.048)."

PubMed

"The results demonstrated that a single 5 min light treatment significantly reduced
cold sore healing time by 4 days;

PubMed

1.6/
4.8
+1.2

Dermatology

Herpes labialis

Eduardo Cde

Brazil
(So Paulo)

Dermatology

Herpes labialis

Ferreira

Dermatology

Herpes labialis

de Carvalho

2012

Lasers Med Sci

Prevention of recurrent herpes labialis outbreaks through lowintensity laser therapy: a clinical protocol with 3-year follow-up.

Case series

Brazil
2011
(Rio de Janeiro)

Rev Soc Bras

Med Trop

Recurrent herpes simplex infections: laser therapy as a potential

tool for long-term successful treatment.

Case series

Brazil
(So Paulo)

Lasers Med Sci

Effect of laser phototherapy on recurring herpes labialis

prevention: an in vivo study.

Human

2010

LLLT vs aciclovir

780

70

660

100

780

60

1.75

30

0.04
cm2
(30p
/lip)

Dermatology

Herpes labialis

Hargate

UK
2006
(Middlesbrough)

Clin Exp Dermatol A randomised double-blind study comparing the effect of 1072-nm
light against placebo for the treatment of herpes labialis

Human
RCT/DB

LED phototherapy

1072

Dermatology

Herpes labialis

Dougal & Kelly

UK
(Stockton-onTees)

2001

Clin Exp Dermatol A pilot study of treatment of herpes labialis with 1072 nm narrow
waveband light

Human
Pilot study

LED phototherapy vs
aciclovir

1072

Dermatology

1072 nm light healed cold sores in 4.3 1.8 days (mean SD) as compared with
aciclovir applied five times daily, 8.5 3.0 days (P < 0.0001)."
690

80

Human
Postherpetic
Retrospective neuralgia
data

633

50

Letter

1064

Herpes labialis

Schindl &
Neumann

Austria
(Vienna)

1999

J Invest Dermatol

Low-intensity laser therapy is an effective treatment for recurrent

herpes simplex infection. Results from a randomized double-blind
placebo-controlled study.

Human
RCT

Dermatology

Herpes zoster

Chen

Taiwan
(Taipei)

2016

J Am Acad
Dermatol

Early application of low-level laser may reduce the incidence of

postherpetic neuralgia (PHN).

Dermatology

Herpes zoster

Fan & Wang

China
(Xi'an)

2015

Dermatol Surg

A Novel Treatment of Herpes Zoster Pain With Pulsed Laser

Irradiation.

0.08

48

48

1
cm2

0.81.5

600

14

"The median recurrence-free interval in the laser-treated group was 37.5 wk

(range: 2-52 wk) and in the placebo group 3 wk (range: 1-20 wk). This difference
was found to be statistically significant (p < 0.0001; Wilcoxon's Rank Sum Test). In
conclusion, we demonstrated that a total of 10 irradiations with low-intensity laser
therapy significantly lowers the incidence of local recurrence of herpes simplex
infection."

PubMed

300

3
/wk

"Applying LLLT within the first 5 days of herpes zoster eruption significantly
reduced the incidence of PHN. LLLT may have the potential to prevent PHN, but
further well-designed randomized controlled trials are required."

PubMed

1-2
?

"In summary, the authors found in the treatment of 5 herpes zoster patients that
1,064-nm Nd:YAG laser irradiation could significantly alleviate herpetic pain with
persisting effect and no apparent adverse effect."

PubMed

d=
8 mm

Comment: The parameters were poorly reported.

Dermatology

Herpes zoster

Knapp DJ

USA
(Sarasota, FL)

2013

Clin J Pain

Postherpetic neuralgia: case study of class 4 laser therapy

intervention.

Human
Case report

Dermatology

Radiation
dermatitis

Censabella

Belgium
(Hasselt)

2016

Support Care
Cancer

Photobiomodulation for the management of radiation dermatitis:

the DERMIS trial, a pilot study of MLS() laser therapy in breast
cancer patients.

Human
Pilot study

Dermatology

Radiation
dermatitis

Fife

USA
(Irvine, CA)

2010

Dermatol Surg

A randomized, controlled, double-blind study of light emitting

diode photomodulation for the prevention of radiation dermatitis in
patients with breast cancer.

Human
RCT/DB

Human

810
+
980

MLS() laser therapy

20004000

905
+
808

0.410.82

6001200

0.168

3.57.1

d=
2.5 cm

19.635
cm2

600

"Weekly laser therapy treatment over 8 weeks resulted in reduced 0 to 10 Numeric

Pain Scale score from 8 to 0, Neuropathy Pain Scale Questionnaire total score
from 39 to 4, and allodynia over a 60 cm surface area of the upper trunk and
posterior arm totally resolved, with resolution continued at 14-month follow-up."

PubMed

"Skin toxicity was equivalent between the groups before the start of LT but
significantly differed at the end of radiotherapy, with an aggravation in the control
but not in the LT group (e.g., 29 versus 3 % of RTOG grade 2 RD, respectively, P
< 0.005).

PubMed

We found no significant group differences with respect to quality of life. However,

the RISRAS subjective score decreased in the LT group only, implying a
decreased impact of RD on patients' quality of life. Finally, patients' ratings were
significantly higher for LT than for standard care."
590

35

30+

"LED photomodulation did not reduce the incidence of radiation-induced skin

reactions or interruptions in therapy. ."

PubMed

Note: DeLand published a letter, wondering why the results were so different in
this study. He suggests it might be related to the treatment parameters...
Metelitsa's commentary also mentions this issue, and also focuses on some
differences between the treatments in these two studies.

Dermatology

Radiation
dermatitis

DeLand

USA
(Lafayette, LA)

2007

Lasers Surg Med

Treatment of radiation-induced dermatitis with light-emitting diode

(LED) photomodulation.

Dermatology

Telangiectasia

Tierney & Hanke

USA
(Carmel, IN)

2009

Lasers Surg Med

Randomized controlled trial: Comparative efficacy for the treatment Human

of facial telangiectasias with 532 nm versus 940 nm diode laser.
RCT/SB (?)
Split-face

590

0.15

"In LED-treated patients, 18 (94.7%) had grade 0 or 1 reaction and 1 (5.3%) had
grade 2 reaction. Among controls, 4 (14.3%) had a grade 1 reaction, 24 (85.7%)
had a grade 2 or 3 reaction. One LED-treated patient (5.3%) and 19 controls
(67.9%) had to interrupt treatment."

PubMed

Note: Results are very interesting, but parameters are poorly reported.

Green light vs LLLT

532
940

"Pain associated with the laser treatment was rated as significantly less for the
940 nm wavelength relative to the 532 nm wavelength. Erythema post-treatment
was significantly less with 940 nm relative to 532 nm. Significant crusting and
swelling were only reported with the 532 nm wavelength.

PubMed

The mean percentage improvement with the 940 nm wavelength (63.0%) was
greater than that achieved with the 532 nm wavelength (47.8%) (P<0.05).
On photographic evaluation, 940 nm was significantly more efficacious for larger
caliber vessels than 532 nm. Both wavelengths were equally efficacious for
smaller caliber vessels."

Development

Embryogenesis

Lim

USA
(Bloomington,
IN)

2008

J Biochem Mol
Toxicol

Attenuation of TCDD-induced oxidative stress by 670 nm

photobiomodulation in developmental chicken kidney.

Chicken

Development

Embryogenesis

Yeager

USA
(Bloomington,
IN)

2006

Photomed Laser
Surg

Brief report: embryonic growth and hatching implications of

developmental 670-nm phototherapy and dioxin co-exposure.

Chicken

670

LED phototherapy

670

500
min

0.05
min

Dioxin

Development

Embryogenesis

Yeager

USA
(Bloomington,
IN)

2006

J Biochem Mol
Toxicol

670 nanometer light treatment attenuates dioxin toxicity in the

developing chick embryo.

Development

Embryogenesis

Yeager

USA
(Bloomington,
IN)

2006

Photomed Laser
Surg

Survivorship and mortality implications of developmental 670-nm

phototherapy: dioxin co-exposure.

10
cm2
(beam
)

20

670

"The biochemical indicators of oxidative and energy stress in the kidney were
reversed by daily phototherapy, restoring ATP and glutathione contents and
increasing antioxidant enzyme activities to control levels. Photobiomodulation also
normalized the level of lipid peroxidation increased by TCDD exposure. The
results of this study suggest that 670 nm photobiomodulation may be useful as a
noninvasive treatment for renal injury resulting from chemically induced cellular
oxidative and energy stress."

PubMed

"Size and hatching times suggest that the hatching success and preparedness of
chicks developmentally exposed to dioxin concentrations above the lethality
threshold is improved by 670-nm LED treatment administered throughout the
gestation period, but the relationship may be complicated by an LED-oil
interaction."

PubMed

"Our study demonstrates that 670 nm phototherapy can mitigate the oxidative
stress and energy deficit resulting from developmental exposure to TCDD while
reducing TCDD-induced embryo mortality. Moreover, LED treatment restores
hepatic enzyme activities to control levels in TCDD-exposed embryos. The
effective attenuation of TCDD-induced embryo toxicity by LED treatment could
extend to mitigating the effects of other teratogens that induce oxidative and
energy stress."

PubMed

Comment: According to the figure, LLLT seemed to increase mortality at some

dioxin dosages... I wonder why this isn't mentioned in the abstract.

Chicken

670

"LED therapy decreased the embryonic mortality rate by 41%, resulting in

increased embryonic survival and improved hatching success in eggs exposed to
200 ppt dioxin. However, at sub-lethal dioxin concentrations and in oil-treated
controls, LED therapy slightly increased mortality."

PubMed

Chicken

670

20

"These results indicate that 670-nm phototherapy by itself does not adversely
affect developing embryos and may improve the hatching survival rate."

PubMed

20.4
40.8

"The blood plasma fructosamine level of diabetic mice irradiated with 20.4 J/cm(2)
was significantly lower than for nonirradiated controls, whereas that for diabetic
mice irradiated with 40.8 J/cm(2) was not significantly different than for
nonirradiated controls."

PubMed

"Irradiation of left inguinal region in diabetic mice with 810 nm laser has potential
to ameliorate diabetes as shown by decreased blood plasma fructosamine."

PubMed

Development

Embryogenesis

Yeager

USA
(Bloomington,
IN)

2005

Photomed Laser
Surg

Effects of 670-nm phototherapy on development.

Diabetes
mellitus

Glycation

Peplow & Baxter

New Zealand
(Dunedin)

2014

Lasers Surg Med

Defining a therapeutic window for laser irradiation (810 nm) applied Mouse
to the inguinal region to ameliorate diabetes in diabetic mice.

LED phototherapy

810

Diabetes
mellitus

Glycation

Peplow & Baxter

New Zealand
(Dunedin)

2013

Lasers Surg Med

Testing infrared laser phototherapy (810 nm) to ameliorate

diabetes: irradiation on body parts of diabetic mice.

810

Mouse

Comment: Irradiation of other parts wasn't helpful. The total effect is probably quite
negligible.

Diabetes
mellitus

Glycemia

Fukuoka

Brazil
(So Paulo)

2016

J Biophotonics

Low-power laser irradiation in salivary glands reduces glycemia in

streptozotocin-induced diabetic female rats.

Rat

Irradiation of salivary
glands

660

70

22.4

20

1.13
cm2
area

320

"LPLI probably reduced the hyperglycemia in diabetes by improving the insulin

resistance in these animals"

PubMed

Comment: A surprising results. I think it should be repeated.

0.028
cm2
spot

Diabetes
mellitus

Ulcers and
wounds

TchanqueFossuo

USA
(Mather, CA)

2016

J Drugs Dermatol

Low-level Light Therapy for Treatment of Diabetic Foot Ulcer: A

Review of Clinical Experiences.

Review

"LLLT is an emerging and promising treatment modality to current alternatives that are costly and have shown limited success. Based upon the published
evidence, we envision additional research may allow for stronger recommendation with LLLT for treatment of DFU."

PubMed

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Diabetes
mellitus

Ulcers and
wounds

TchanqueFossuo

USA
(Mather, CA)

2016

Wound Repair
Regen

A systematic review of low-level light therapy for treatment of

diabetic foot ulcer.

Systematic
review

Diabetes
mellitus

Ulcers and
wounds

Carvalho

Brazil
(Teresina)

2016

Rev Esc Enferm

USP

Low-level laser therapy and Calendula officinalis in repairing

diabetic foot ulcers.

Human
RCT

Diabetes
mellitus

Ulcers and
wounds

Mathur

India
(Indore)

2016

Lasers Med Sci

Low-level laser therapy as an adjunct to conventional therapy in

the treatment of diabetic foot ulcers.

Human
RCT

Diabetes
mellitus

Ulcers and
wounds

Maltese

UK
(London)

2015

Diabetes Care

A pilot study to evaluate the efficacy of class IV lasers on

Letter
nonhealing neuroischemic diabetic foot ulcers in patients with type
2 diabetes.
Human

Category

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

658

30

660

Nonhealing foot ulcer

0.05

Link

Additional info

sec

"This systematic review reports that LLLT has significant potential to become a portable, minimally invasive, easy-to-use, and cost effective modality for
treatment of DFU. To enthusiastically recommend LLLT for treatment of DFU, additional studies with comparable laser parameters, screening period to
exclude rapid healers, larger sample sizes and longer follow-up periods are required. We envision future stringent RCTs may validate LLLT for treatment
of DFU."

PubMed

12.566
mm2

80

12

"We conclude that LLLT isolated or in combination with Calendula officinalis oil is
effective in relieving pain due to its anti-inflammatory action, and in reducing the
total area of ulcers by stimulating neovascularization and accelerating cell
proliferation, thereby contributing to improving possible morbidities that may occur
as consequence of Diabetes Mellitus."

PubMed

d=
2 cm

60
/p?

15

"Percentage ulcer area reduction was 37 9% in the LLLT group and 15 5.4% in
the control group (p < 0.001)."

PubMed

"Within the 12-week follow-up, four of five laser-treated patients (80%) had a
complete ulcer resolution (most ulcers healed after 4.6 weeks). In the control
group, no ulcer healing occurred by week 12."

PubMed

4 :s

"an advanced class IV laser (emitting four wavelengths)"

Comment: Parameters were not reported.

Diabetes
mellitus

Ulcers and
wounds

Houreld NN

Diabetes
mellitus

Ulcers and
wounds

Feitosa

South Africa
(Johannesburg)

2015

Brazil
(So Paulo)

2015

Photomed Laser
Surg

Healing of diabetic ulcers using photobiomodulation.

Acta Cir Bras

Effects of the Low-Level Laser Therapy (LLLT) in the process of

healing diabetic foot ulcers.

A good mini-review on studies of diabetic wound/ulcer healing and LLLT/PBM.

Editorial

PubMed

"If this treatment modality is to become better recognized for the healing of diabetic ulcers, larger, well controlled clinical studies with
statistically significant results are required. There is a definite need to generate new treatment modalities to improve diabetic wound
healing, and photobiomodulation has an unmistakable place in this"
633

Human

30

80

12

"There was a significant decrease in the size of the wound when compared to the
control group (p<0.05). The pain was also reported as having an intense
improvement in the treated group."

PubMed

"The low-level laser treatment seems to be an efficient method, viable, painless

and of low costs concerning the tissue repair ulcers in a diabetic foot."

Diabetes
mellitus

Ulcers and
wounds

Minatel

Brazil
2009
(Ribeiro Preto)

Lasers Surg Med

Phototherapy promotes healing of chronic diabetic leg ulcers that

failed to respond to other therapies.

Human
RCT/DB

LED phototherapy

660
+
890

500

0.1

"By day 90, 58.3% of group two ulcers had healed fully and 75% had achieved 90100% healing. In contrast, only one "placebo" treated ulcer healed fully by day 90;
no other ulcer attained > or =90% healing."

PubMed

From Enwemeka's 2011 paper "The Relevance of Accurate Comprehensive Treatment Parameters in Photobiomodulation":
"For example, the significance of two parameterstotal energy and total cumulative dosewhich hitherto were either ignored or unaccounted for, is vividly illustrated by a recent
report7 involving what was considered to be placebo phototherapy.

[Also see additional info]

In this example, the investigators had two identical treatment applicators; the only difference being that all but 1 of the 36 diodes in the placebo applicator were disabled, reducing
the irradiance to <1.0mW/cm2; whereas the output of the real treatment applicator was kept at 100mW/cm2. As expected, treatment with the real applicator prompted faster healing
of treated ulcers from the very beginning of therapy. Overall, it gave better results than the placebo treatment. However, the small amount of light emitted by the placebo applicator
was not totally ineffective as was anticipated. Indeed, after the initial 45 days of treatment during which placebo-treated ulcers worsened, the ulcers began to heal virtually as nicely
as those in the real treatment group did from the very beginning. This finding suggests that once the total amount of energy, that is, energy delivered at each treatment session
multiplied by the total number of treatments, reached a certain threshold, the so-called placebo treatment began to engender positive healing."

Diabetes
mellitus

Ulcers and
wounds

Al-Watban FA

Saudi Arabia
(Riyadh)

2009

Photomed Laser
Surg

Laser therapy converts diabetic wound healing to normal healing.

Rat

Wavelength
comparison
Green light therapy

Diabetes
mellitus

Ulcers and
wounds

Diabetes
mellitus
Diabetes
mellitus

Dose
response

Insufficient
dosage

532
633
810
980

143
140
200
200

0.0204
0.0156
0.0222
0.0222

510872

272

0.0136

0.0664

10600

300

Schindl

Austria
(Vienna)

1998

Diabetes Care

Low-intensity laser irradiation improves skin circulation in patients

with diabetic microangiopathy.

Human
RCT/DB

Diabetic
microangiopathy

633

30

Kazemikhoo

Iran
(Tehran)

2016

Lasers Med Sci

Modifying effect of intravenous laser therapy on the protein

expression of arginase and epidermal growth factor receptor in
type 2 diabetic patients.

Human

Intravenous laser
therapy

630

1.5

Gralczyk

Poland
(Bydgoszcz)

2016

Lasers Med Sci

Low-level laser irradiation effect on endothelial cells under

conditions of hyperglycemia.

In vitro

Lundeberg

Sweden

1991

Ann Plast Surg

Low-power HeNe laser treatment of venous leg ulcers.

Human

5/
10/
20/
30

1-36
min

3
/wk

4.5-20
cm2
(area)

30

d=
5 mm

633

PubMed

Star: A remarkably huge study with 893 rats!

3000

"After a single transcutaneous low-intensity laser irradiation, a statistically

significant rise in skin temperature was noted (P < 0.001 by ANOVA for repeated
measurements), whereas in the sham-irradiated control group, a slight but
significant drop in temperature (P < 0.001) was found."

PubMed

1800

"In conclusion, laser therapy may have a beneficial effect for diabetic patients via
decreasing arginase expression and activation of the NOS/NO pathway which
increases NO production and vasodilation, and decreasing EGFR expression
which may reduce neuroinflammation and its secondary damages."

PubMed

"It is considered that adverse effects of hyperglycemia on vascular endothelial

cells may be corrected by the action of LLLT, especially with the wavelength of
830 nm. It leads to the reduction of TNF- concentration in the supernatant and
enhancement of cell proliferation."

PubMed

"There were no significant differences in the proportion of healed ulcers or ulcer

area in the HeNe group compared with the placebo group."

PubMed

635
830

Venous leg ulcers

"In this induced-diabetes model, wound and burn healing were improved by 40.3%
and 45%, respectively, in 633-nm laser dosimetry experiments, and diabetic
wound and burn healing was accelerated by phototherapy. This indicates that the
healing rate was normalized in the phototherapy-treated diabetic rats."

24

Tuner: "In this study, a 6 mW HeNe laser or a placebo HeNe laser was used to
treat leg ulcers twice weekly for 12 weeks. The stated dose was 4 J/cm2. The area
of the ulcers varied from 3 cm2 to 32 cm2.
To achieve the stated dose, the treatment time of each session of therapy would
thus have had to vary from 33 minutes to 6 hours. It is questioned that the patients
really would have been treated for 6 hours."
[For more information, see additional info]

Edema

Paw

Chagas

Brazil
(So Jos dos
Campos)

2015

Lasers Med Sci

Expression of mPGES-1 and IP mRNA is reduced by LLLT in both

subplantar and brain tissues in the model of peripheral
inflammation induced by carrageenan.

Rat

Inflammatory paw
edema by
carrageenan

660

7.5

"LLLT was able to reduce both mPGES-1 and IP mRNA expression in subplantar
and brain tissues."

PubMed

"LLLT (7.5 J/cm(2)) reduced significantly the COX-2 mRNA expression both in the
subplantar (~2.5-fold) and brain (4.84-9.67-fold) tissues. The results show that
LLLT is able to reduce COX-2 mRNA expression. It is possible that the
mechanism of LLLT decreasing hyperalgesia is also related to its effect in
reducing the COX-2 expression in the CNS."

PubMed

"Our results suggest that LLLT was able to produce both anti-inflammatory and
pro-inflammatory effects depending on to the site and moment of irradiation."

PubMed

"A pronounced swelling of the rat paw was observed 4 h after treatment with
carrageenan in comparison to the control group. Edema formation was decreased
by LLLT with wavelengths of both 660 and 684 nm (Fig. 1)."

PubMed

Hyperalgesia

Edema

Paw

Prianti

Brazil
(So Jos dos
Campos)

2014

Lasers Med Sci

Low-level laser therapy (LLLT) reduces the COX-2 mRNA

expression in both subplantar and total brain tissues in the model
of peripheral inflammation induced by administration of
carrageenan.

Rat

Carrageenan-induced
paw edema

660

30

Edema

Paw

Meneguzzo

Brazil
(So Paulo)

2013

Lasers Med Sci

Prevention and treatment of mice paw edema by near-infrared lowlevel laser therapy on lymph nodes.

Mouse

Inflammatory paw
edema

830

100

35

10

PBM vs diclofenac
LLLT on lymph nodes

Edema

Paw

Albertini

Brazil
(So Jos dos
Campos)

2008

Photomed Laser
Surg

Cytokine mRNA expression is decreased in the subplantar muscle

of rat paw subjected to carrageenan-induced inflammation after
low-level laser therapy.

Rat

Inflammatory paw
edema by
carrageenan

660
684

7.5

"Both the 660 nm and 684 nm laser groups had 30%-40% lower mRNA
expression for cytokines TNF-alpha, IL-1beta, and IL-6 in the paw muscle tissue
than the carrageenan-only control group.
Cytokine measurements were made 3 h after laser irradiation of the paw muscle,
and all cytokine differences between the carrageenan-only control group and the
LLLT groups were statistically significant (p < 0.001)."
Comment: The results are quite notable and interesting.

Edema

Edema

Paw

Paw

Albertini

Albertini

Brazil
(So Jos dos
Campos)

2007

Brazil
(So Jos dos
Campos)

2007

Inflamm Res

J Photochem
Photobiol B

COX-2 mRNA expression decreases in the subplantar muscle of rat Rat

paw subjected to carrageenan-induced inflammation after low level
laser therapy.

Inflammatory paw
edema by
carrageenan

660
684

Anti-inflammatory effects of low-level laser therapy (LLLT) with two Rat

different red wavelengths (660 nm and 684 nm) in carrageenaninduced rat paw edema.

Inflammatory paw
edema by
carrageenan

660
684

Edema
COX-2 mRNA

PubMed

"Taken together, these results suggest that LLLT may be a new alternative
therapy in the treatment of inflammatory disorders, probably activated by a
mechanism involving the reduction of COX-2 expression."
30

0.030

7.5

0.785
cm2

196

"The 660 nm and 684 nm laser groups developed significantly (p<0.01) less
edema (0.58 ml [SE+/-0.17] ml and 0.76 ml [SE+/-0.10] respectively) than the
control group (1.67 ml [SE+/-0.19]) at 4h after injections.

PubMed

(area)
Similarly, both laser groups showed a significantly lower number of inflammatory
cells in the muscular and conjunctive sub-plantar tissues than the control group.
We conclude that both 660 nm and 684 nm red wavelengths of LLLT are effective
in reducing edema formation and inflammatory cell migration when a dose of 7.5
J/cm(2) is used."

Edema

Paw

Albertini

Brazil
(So Paulo)

2004

J Photochem
Photobiol B

Effects of different protocol doses of low power gallium-aluminumarsenate (Ga-Al-As) laser radiation (650 nm) on carrageenan
induced rat paw ooedema.

Rat

Inflammatory paw
edema

650

1
2.5
(5)

80

4.007.68

88
+
35
+
35

PBM vs diclofenac

Eyes

Merry

Canada
(Toronto)

2016

Acta Ophthalmol

Photobiomodulation reduces drusen volume and improves visual

acuity and contrast sensitivity in dry age-related macular
degeneration.

Human
Case series
(n=42)

Dry age-related
macular degeneration
LED phototherapy
(Warp10 +
Gentlewaves)

670

+
590
+
790

+
4
+
0.6

0.050.08

+
0.1

9
/
3wk

"The ED that produced an anti-inflammatory effect were 1 and 2.5 J/cm(2),

reducing the oedema by 27% (P<0.05) and 45.4% (P<0.01), respectively. The ED
of 2.5 J/cm(2) produced anti-inflammatory effects similar to those produced by the
cyclooxigenase inhibitor sodium diclofenac at a dose of 1 mg/kg. In
adrenalectomized animals, the laser irradiation failed to inhibit the oedema."

PubMed

"Significant improvement in mean BCVA of 5.90 letters (p < 0.001) was seen on
completion of the 3-week treatment and 5.14 letters (p < 0.001) after 3 months.
Contrast sensitivity improved significantly (log unit improvement of 0.11 (p = 0.02)
at 3 weeks and 3 months (log unit improvement of 0.16 (p = 0.02) at three cycles
per degree. Drusen volume decreased by 0.024 mm3 (p < 0.001) and central
drusen thickness was significantly reduced by a mean of 3.78 m (p < 0.001),
while overall central retinal thickness and retinal volume remained stable."

PubMed

"This is the first study demonstrating improvements in functional and anatomical

outcomes in dry AMD subjects with PBM therapy. These findings corroborate an
earlier pilot study that looked at functional outcome measures. The addition of
anatomical evidence contributes to the basis for further development of a noninvasive PBM treatment for dry AMD."

Eyes

Gueven

Australia
(Hobart)

2016

Mitochondrion

Targeting mitochondrial function to treat optic neuropathy.

Review

"Far-red to near-infrared (FR/NIR) light therapy aims to directly alter mitochondrial function non-invasively by light exposure, typically applied by a laser
diode with a defined wavelength."

PubMed

"Thus, in light of the limited but encouraging evidence from comparatively small studies, larger studies are currently planned or ongoing to establish the
therapeutic potential of this therapy."

Eyes

Eyes

Roy

Osborne

USA
(Boston, MA)
Spain
(Oviedo)

2016

2016

Am J Pathol

Mitochondrion

Mechanistic Insights into Pathological Changes in the Diabetic

Retina : Implications for Targeting Diabetic Retinopathy
Visual light effects on mitochondria: The potential implications in
relation to glaucoma.

Review

"Significantly, laboratory studies show that increasing the normal amount of natural red light reaching rat RGC mitochondria in situ, subjected to
ischemia, proved to be beneficial. A challenge now is to test whether extra red light delivered to the human retina can slow-down RGC loss in glaucoma.
Such a methodology has also the advantage of being non-invasive. One very exciting possibility might be in the production of a lens where solar UV light
is converted to add to the amount of natural red light entering the eye."

PubMed

Review

"Significantly, laboratory studies show that increasing the normal amount of natural red light reaching rat RGC mitochondria in situ, subjected to
ischemia, proved to be beneficial. A challenge now is to test whether extra red light delivered to the human retina can slow-down RGC loss in glaucoma.
Such a methodology has also the advantage of being non-invasive. One very exciting possibility might be in the production of a lens where solar UV light
is converted to add to the amount of natural red light entering the eye."

PubMed

"The method by which the dose was calculated is therefore questionable. No indication is given of the method of treatment. If a scanning laser with an unexpanded beam was used,
the power density would have been about 0.15 W/cm2. If the beam was expanded to a diameter capable of illuminating the whole area of the ulcer at once, the power density when
treating the largest ulcer would have been about 0.00019 W/cm2, which is close to the level of moonlight. Unless more parameters are accounted for, it is impossible to evaluate this
study. The possibility of performing a double blind study with red light is also questionable. The authors have been reluctant to answer questions on this paper."

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Eyes

Kaynezhad

UK
(London)

2016

Exp Eye Res

Optical monitoring of retinal respiration in real time: 670 nm light

increases the redox state of mitochondria.

Rat

670

3.5

Eyes

Rezaei Kanavi

Iran
(Tehran)

2016

Exp Eye Res

Short-term effects of extremely low-frequency pulsed

electromagnetic field and pulsed low-level laser therapy on rabbit
model of corneal alkali burn.

Rabbit

810

100

Category

Subcategory

Results: positive / unclear/modest / negative

Link

Additional info

sec

300
0.5

1800

28

"Retinae of aged rats exposed to 670 nm for 5 mins showed consistent

progressive increases in oxidation of COX 5 mins post exposure."

PubMed

"he defect area was significantly less in the ELF, LLLT, and ELF + LLLT groups
than in the control group (P < 0.005), and was comparable with that of the
[medical therapy] group."

PubMed

"However, the histopathological results showed that LLLT was superior to

magnetic therapy in terms of lower intensity of corneal inflammation, and LLLT
had a lower rate of keratocyte loss than medical treatment."
"Short-term LLLT is a noninvasive and safe treatment method that effectively
improves the healing of corneas with alkali burns."
Comment: Parameters were insufficiently reported.

Eyes

Geneva (Ivayla)

USA
(Syracuse, NY)

2016

Int J Ophthalmol

Photobiomodulation for the treatment of retinal diseases: a review.

"The literature supports the conclusion that the low-cost and non-invasive nature of PBM, coupled with the first promising clinical reports and the
numerous preclinical-studies in animal models, make PBM well-poised to become an important player in the treatment of a wide range of retinal
disorders.

Review

PubMed

Nevertheless, large-scale clinical trials will be necessary to establish the PBM therapeutic ranges for the various retinal diseases, as well as to gain a
deeper understanding of its mechanisms of action."

Retinal injury

"Investigations in rodent models of methanol-induced ocular toxicity, light damage, retinitis pigmentosa and age-related macular degeneration have
demonstrated the PBM attenuates photoreceptor cell death, protects retinal function and exerts anti-inflammatory actions."

Eyes

Eells

USA & Australia 2016

Adv Exp Med Biol

Near-Infrared Photobiomodulation in Retinal Injury and Disease.

Review

Eyes

Del OlmoAguado

Spain
(Oviedo)

2016

Acta Ophthalmol

Red light of the visual spectrum attenuates cell death in culture

and retinal ganglion cell death in situ.

Rat

Eyes

Chu-Tan

Australia
(Canberra)

2016

Int J Photoenergy

Efficacy of 670 nm Light Therapy to Protect against Photoreceptor

Cell Death Is Dependent on the Severity of Damage

Rat

Light-induced
damage

670

Eyes

Beirne

UK (Cardiff)

2016

Photochem
Photobiol

Red Light Treatment in an Axotomy Model of Neurodegeneration.

Ex vivo
(mouse)

Optic nerve injury

(axotomy)

670

630

0.06

Ivandic & Ivandic

Germany
(Heidelberg)

2015

Photomed Laser
Surg

Effects of Photobiomodulation Therapy on Patients with Primary

Open Angle Glaucoma: A Pilot Study.
[RETRACTED ARTICLE]

780

Human

10

0.3

PubMed

9
18
36
90

180
360
720
1800

"670 nm light exhibited a biphasic response in its amelioration of cell death in lightinduced degeneration in vivo. Lower light damage intensities required lower doses
of 670 nm light to reduce TUNEL cell death. At higher damage intensities, the
highest dose of 670 nm light showed protection. In vitro, the Seahorse XFe96
Extracellular Flux Analyzer revealed that 670 nm light directly influences
mitochondrial metabolism by increasing the spare respiratory capacity of
mitochondria in 661 W photoreceptor-like cells in light damaged conditions. Our
findings further support the use of 670 nm light as an effective treatment against
retinal degeneration as well as shedding light on the mechanism of protection
through the increase of the mitochondrial spare respiratory capacity."

Hindawi

31.7

528

"The results demonstrate the ability of 670 nm light to partially prevent ex vivo
dendropathy in the mouse retina, suggesting that it is worth exploring as a
treatment option for dendropathy-associated neurodegenerative diseases,
including glaucoma and Alzheimer's disease."

PubMed

30

"Poor visual acuity ( 20/25), initially found in 24 of 63 eyes (38.1%), improved in

17 (70.8%) eyes and did not change in 7 eyes (29.2%)."

PubMed

LED phototherapy

Eyes

PubMed

"Low, non-toxic levels of red light focussed on the retina for a short period of time
are sufficient to attenuate an insult of raised IOP to the rat retina. Since
mitochondrial dysfunctions are thought to play a major role in ganglion cell death
in glaucoma, we propose the potential use of red light therapy for the treatment of
the disease."

10
limbus
+
90
bulbus

3
mm2

+
90

"Mean IOP dropped from 24.9 14.9 to 15.0 6.5 mm Hg (-39.7%, p < 0.001)."
"Visual fields were either fully restored, improved by at least 10 degrees, or
remained unchanged in 32, 29, and 2 of 63 eyes (51%, 46%, and 3%),
respectively."
"Mean M-VEP latency was reduced by 13.5 msec (-8%, p < 0.001); mean
amplitude increased by +677 nV (+14%, p < 0.001). Adverse effects were not
observed. No changes were noted in control eyes."
"This first small series of cases indicated that photobiomodulation might be a safe
approach to lower IOP and to improve visual acuity and fields in eyes with POAG."
RETRACTION NOTICE:
"The second author of the article, Dr. Tomislav Ivandic, notified the Journal that
inaccuracies in the reported parameters were discovered after publication of the
article as a consequence of the information being translated from German (the
authors' native language) into English. As a very serious repercussion of this error,
Dr. Ivandic states that, 'Further studies or application based on these false doses
would probably harm the eye.'
The first-named author of the article, Dr. Boris Ivandic, disagrees with this
declaration and states that, 'there is no mistake in the dose calculations using the
parameters 10mW power, 3mm2 beam spot area as well as 30 or 90 sec time of
irradiation, respectively.'
Photomedicine and Laser Surgery is dedicated to upholding the integrity of the
science it publishes. As a result of this irreconcilable dispute between the authors,
the editorial leadership of the Journal is officially retracting this article from the
literature in an effort to reduce any potential for iatrogenic injury in the event that
the erroneous information was used to study or treat other patients.
The authors regret this very unfortunate circumstance."

Eyes

Sun

China
(Shanghai)

2015

Lasers Med Sci

Pre-exposure to low-power diode laser irradiation promotes

cytoprotection in the rat retina.

Rat

(Preconditioning)

670

60

34.27

60

"Pre-exposure to a 60-mW (34.27 J/cm(2) on the retina) power laser irradiation

stimulates a hyperexpression of Hsp70 together with a hypoexpression of cleaved
caspase 3 in rat retina, which may suggest a cellular protective effect."

PubMed

Higher-power laser induced some apoptosis but no other injury: "No retinal
hemorrhage, necrosis, atrophy, or detachment was observed microscopically with
HES staining 20 h after irradiation of 80 mW (44.88 J/cm2 on the retina)."

Eyes

Saliba

USA
(Ohio &
Michigan)

2015

PLoS One

Photobiomodulation Mitigates Diabetes-Induced Retinopathy by

Direct and Indirect Mechanisms: Evidence from Intervention
Studies in Pigmented Mice.

Mouse

Eyes

Fuma

Japan

2015

Mol Vis

Photobiomodulation with 670 nm light increased phagocytosis in

human retinal pigment epithelial cells.

In vitro
(human)

Eyes

Calaza

UK
(London)

2015

Neurobiol Aging

Mitochondrial decline precedes phenotype development in the

complement factor H mouse model of retinal degeneration but can
be corrected by near infrared light.

Mouse

Eyes

Koev K

Bulgaria
(Sofia)

2015

Acta
Ophthalmologica

Aplication of low-level Laser therapy (LLLT) in patients with

Retinitis Pigmentosa (RP)
[Abstract]

Human
Case series

Eyes

Gkotsi

UK
(London)

2014

Exp Eye Res

Recharging mitochondrial batteries in old eyes. Near infra-red

increases ATP.

Mouse

Diabetic eye

670

0.0203

Age-related macular
degeneration

670

0.04

4.86

240

70

670nm light protected against retinopathy (in streptozotocin-induced diabetes).

90

"Near infrared (NIR) increases ATP and reduces inflammation. [...] In summary,
we provide evidence for a mitochondrial basis for this disease in mice and correct
this with simple light exposure known to improve mitochondrial function."

PubMed

180

10

"There was a statistically significant increase in visual acuity (p < 0.001, end of
study versus baseline) for RP patients for the period of 3 years after the LLLT. The
mid-peripheral absolute concentric scotoma in RP was reduced after LLLT. No
side effects were observed during the therapy."

Wiley

90

PubMed

PubMed

633

"This study shows that LLLT may be a novel long-lasting therapeutic option for
RP. This is highly effective treatment that improves visual acuity for a long time."

Age-related macular
degeneration

670

0.04

"When 12 month old mice were exposed to 670 nm for 90 s 7 times spaced over
84 h at an energy level of 40 mW/cm2 there was significant increase in retinal ATP
of just under 20% from around 14,000 to 17,000 pm/mg (P < 0.05. Fig. 1B)."

PubMed

"In light of all these factors, it is likely that this treatment will benefit retinal disease.
But this need not be confined to the eye, as declining ATP is a feature of all
ageing tissues."

Eyes

Giacci

Australia
(Adelaide &
Crawley)

2014

PLoS One

Differential effects of 670 and 830 nm red near infrared irradiation

therapy: a comparative study of optic nerve injury, retinal
degeneration, traumatic brain and spinal cord injury.

Rat

Light-induced
damage

670
830

3.4
2.7

180

60+

670nm (red light) had better effect on retina than 830nm (near-infrared).

PubMed

[PBM protected eyes from light-induced retinal damage.]

PubMed

"Daily PBM treatment for only 80 s per treatment twice daily caused a significant
reduction in focal retinal thickening in all 4 treated eyes. No adverse effects
attributable to therapy were noted by the patients or study investigators during the
study period."

PubMed

"Animals of the FL group showed a significant reduction in the outer nuclear layer
thickness and cell count in addition to the total thickness of the retina. LL group
which were exposed to 670 nm LED prior to exposure to fluorescent light showed
a significant decrease in the degree of damage."

PubMed

"Preconditioning the retina with saffron or PBM reduced photoreceptor death,

preserved the population of surviving photoreceptors and reduced the
upregulation of GFAP in Mller cells. At the daily dose of saffron used (1 mg/kg),
protection was detectable at 2 d, increasing to 10 d. At the daily dose of PBM used
(5 J/cm(2) at 670 nm) protection was detectable at 5 d, increasing to 7-10 d."

PubMed

Red light ameliorated lesions of diabetic retinopathy in vivo and reduced oxidative
stress and cell death in vitro.

PubMed

Preconditioning

Eyes

Di Marco

Italy
(L'Aquila)

PLoS One

Combining neuroprotectants in a model of retinal degeneration: no

additive benefit.

Rat

Light-induced
damage

670

4-4.5

Eyes

Tang

USA
2014
(Cleveland, OH)

Br J Ophthalmol

Photobiomodulation in the treatment of patients with non-centerinvolving diabetic macular oedema.

Human
Case series

Diabetic macular
edema

670

25
(?)
(closed
eye)

160

Eyes

Ahamed Basha

India
(Chennai)

Ann Anat

Protective effect of light emitting diode phototherapy on

fluorescent light induced retinal damage in Wistar strain albino
rats.

Rat

Light-induced
damage

670

360

2014

2014

0.025

LED phototherapy

Eyes

Marco

Italy
(L'Aquila)

2013

Am J
The time course of action of two neuroprotectants, dietary saffron
Neurodegener Dis and photobiomodulation, assessed in the rat retina.

Rat

Light-induced
damage

670

Preconditioning

Rat
+ In vitro

Diabetic eye

670

Eyes

Tang

USA
(Ohio)

2013

Invest Ophthalmol Low-intensity far-red light inhibits early lesions that contribute to
Vis Sci
diabetic retinopathy: in vivo and in vitro.

Eyes

RodrguezSantana &
Santana-Blank

Venezuela
(Caracas)

2013

Photomed Laser
Surg

Laser photobiomodulation as a potential multi-hallmark therapy for Guest

age-related macular degeneration.
Editorial

Eyes

Natoli

Australia
(Canberra)

2013

PLoS One

670nm photobiomodulation as a novel protection against

retinopathy of prematurity: evidence from oxygen induced
retinopathy models.

Mouse & Rat

Oxygen-induced
damage & Lung
damage

670

Eyes

Kokkinopoulos I

UK (London)

2013

J Photochem
Photobiol B

670 nm LED ameliorates inflammation in the CFH/ mouse neural

retina

Mouse

Retinal inflammation
(complement factor H
deficiency)

670

0.025

240

30
or
70

"[N]ew research is needed to ascertain whether it may improve the lives of millions of people who currently have or will develop AMD."

0.04

PubMed

180

7
/
18

"670 nm light reduced neovascularisation, vaso-obliteration and abnormal

peripheral branching patterns of retinal vessels in OIR. The neural retina was also
protected against OIR by 670 nm light exposure. OIR-exposed animals had
severe lung pathology, including haemorrhage and oedema, that was significantly
reduced in 670 nm+OIR light-exposed animals."

PubMed

90

"These regimes significantly reduced activated macrophage number, TNF-alpha

and MIF protein expression levels. Immuno-reactivity to C3, C3b and calcitonin, all
markers of inflammatory status were also altered. Finally, innate immune proteins,
TLR 2 and 4, showed a marked decrease in protein expression."

PubMed

In most of 670nm eye studies, LED devices Warp 10 and Warp 75 by Quantum Devices were used.

Comment

Reply

 Category
Eyes

Subcategory

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Kokkinopoulos

UK (London)

2013

Neurobiol Aging

Age-related retinal inflammation is reduced by 670 nm light via

increased mitochondrial membrane potential.

Mouse

Age-related macular
degeneration

670

Begum

UK

2013

PLoS One

Treatment with 670 nm light up regulates cytochrome C oxidase

expression and reduces inflammation in an age-related macular
degeneration model.

Mouse

Age-related macular
degeneration

670

Results: positive / unclear/modest / negative

90

"Aged mice were exposed to only five 90-second exposures over 35 hours. This
significantly increased mitochondrial membrane polarization and significantly
reduced macrophage numbers and tumor necrosis factor (TNF)-alpha levels, a
key proinflammatory cytokine. Three additional inflammatory markers were
assessed; complement component 3d (C3d), a marker of chronic inflammation
and calcitonin, and a systemic inflammatory biomarker were significantly reduced.
Complement component 3b (C3b), a marker of acute inflammation, was not
significantly altered."

360

28

Link

Additional info

sec

0.04

PubMed

"These results provide a simple route to combating inflammation in an aging

population with declining visual function and may be applicable to clinical
conditions where retinal inflammation is a key feature."

Eyes

"Exposed animals had significant increase in cytochrome c oxidase (COX), which

is a mitochondrial enzyme regulating oxidative phosphorylation.

PubMed

"Mice were exposed to 670 nm for 6 minutes twice a day for 14 days in the form of supplemented environmental light."

There was a significant reduction in complement component C3, an inflammatory

marker in the outer retina.
Vimetin and glial fibrillary acidic protein (GFAP) expression, which reflect retinal
stress in Muller glia, were also significantly down regulated.
There were also significant changes in outer retinal macrophage morphology."

Eyes

Albarracin

Australia
(Canberra)

2013

BMC Neurosci

670 nm light mitigates oxygen-induced degeneration in C57BL/6J

mouse retina.

Mouse

Eyes

Rutar

Australia
(Canberra)

2012

J
Neuroinflammatio
n

670-nm light treatment reduces complement propagation following

retinal degeneration.

Rat

Gopalakrishnan
S

USA
2012
(Milwaukee, WI)

DISSERTATION
(University of
WisconsinMilwaukee)

Photobiomodulation in Inherited Retinal Degeneration

Rat

Eyes

Oxygen-induced
damage

670

0.06

670

P23H transgenic

180

"Pretreatment with 670 nm red light reduced expression of markers of oxidative

stress and C3, and slowed, but did not prevent, photoreceptor loss over the time
course of hyperoxia exposure."

PubMed

180

"Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and
complement propagation in the degenerating retina. These findings have
relevance to the cellular events of complement activation underling the
pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive
anti-inflammatory therapy."

PubMed

830 nm PBM exerted a robust retinoprotective effect compared to 670 nm PBM in

the P23H transgenic rat model.

UWM

830
670

Star: The dissertation contains a lot of details and photographs. Worth a read.
670

Eyes

Albarracin &
Valter

Australia
(Canberra)

2012

Photochem
Photobiol

670 nm red light preconditioning supports Mller cell function:

evidence from the white light-induced damage model in the rat
retina.

Eyes

Albarracin &
Valter

Australia
(Canberra)

2012

Adv Exp Med Biol

Treatment with 670-nm light protects the cone photoreceptors from Rat
white light-induced degeneration.

Rat

Light-induced
damage

670

Eyes

Koev

Bulgaria
(Sofia)

2012

Acta Ophthalmol

Two year follow-up of low-level laser therapy (LLLT) in patients

with age-related macular degeneration (AMD)
[ABSTRACT]

Human

AMD

633

0.06

180

0.0001
(?)

180

Abstract only

Red light pretreatment ameliorated the light-induced alterations in the expression

of Mller-cell specific markers for structure, stress, metabolism and inflammation.

PubMed

Damaging effects of white light on the photoreceptor population, function and

structure were ameliorated by red light.

PubMed

"Visual acuity remained unchanged in all patients in the control group. There was
a statistically significant increase in visual acuity (p<0.001, end of study versus
baseline) for AMD patients for the period of 2 years after the treatment. The
edema and hemorrhage in the patients with progressive, exudative AMD
significantly decreased. No side effects were observed during the therapy. The
prevalence of metamorphopsia, scotoma in AMD group was reduced."

Wiley

In most of 670nm eye studies, LED devices Warp 10 and Warp 75 by Quantum Devices were used.

Comment: The results are quite similar to Ivandic's. The dose seems very low.
Parameters are incompletely reported.

Eyes

Ivandic & Ivandic

Germany
(Heidelberg)

2012

Photomed Laser
Surg

Low-level laser therapy improves visual acuity in adolescent and

adult patients with amblyopia.

Human

Amblyopia

780

7.5

0.77

Eyes

Koev

Bulgaria
(Sofia)

2011

Proc SPIE

He-Ne low level laser therapeutic applications for treatment of

corneal trauma
[Proceedings article]

Human

Foreign body in the

cornea (corneal
trauma)

633

0.0001
(?)

Eyes

Albarracin

Australia
(Canberra)

2011

Invest Ophthalmol Photobiomodulation protects the retina from light-induced

Vis Sci
photoreceptor degeneration.

Rat

Light-induced
damage

670

0.06

Eyes

Qu

China (Sichuan) 2010

Adv Exp Med Biol

Near-infrared light protect the photoreceptor from light-induced

damage in rats.

Rat

Light-induced
damage

670

Eyes

Natoli

Australia

2010

Mol Vis

Gene and noncoding RNA regulation underlying photoreceptor

protection: microarray study of dietary antioxidant saffron and
photobiomodulation in rat retina.

Rat

Eyes

Koev

Bulgaria
(Sofia)

2010

Acta Medica
Bulgarica

He-Ne low level laser therapeutic applications for treatment of

acute iridocyclitis

Human

3
mm2

3
avg

"Visual acuity improved in 90% of the eyes treated with LLLT (p<0.001),
increasing by three or more lines in 56.2% and 53.6% of the eyes with amblyopia
caused by ametropia and strabismus, respectively. The treatment effect was
maintained for at least 6 months. The mean M-VEP amplitude increased by 1207
nV (p<0.001) and mean latency was reduced by 7 msec (p=0.14). No changes
were noted in the control group."

PubMed

"LLLT led to a significant improvement in visual acuity in adolescent and adult

patients with amblyopia caused by ametropia or strabismus."

Device: Mediray 04

180

180

50

670

0.06

632

0.0001

180

"For irradiated eyes by LLLT, we have found that the healing period is shortened
significantly by 42 % (p<0,001). Our results revealed that LLLT application is
appropriate and perspective for recovery therapy after corpus alienum corneae
extraction."

SPIE

Red light attenuated histopathological alterations and abolished microglial invasion

of the retina.

PubMed

A red LED was protective against light-induced retinal damage.

PubMed

In this study, they also investigated the effects of LLLT on gene expression.

PubMed

10

"For irradiated eyes by LLLT, we have found that the healing period is shortened
signi cantly by 40 % (p<0,001)"

PDF

Comment: The parameters were very poorly reported. Even treatment time is
unknown.

Eyes

Ivandic

Germany
(Heidelberg)

2009

Photomed Laser
Surg

"In this study of a case series we examined the potential use of LILI as a tool to
determine the individual physiological IOP. The aim was to differentiate between
normoand hypertensive eyes by classifying changes in IOP after irradiation of the
limbus area of the eye with a weak laser."

Early diagnosis of ocular hypertension using a low-intensity laser

irradiation test.

PubMed

"We report here for the first time that LILI of the limbus area of the eye may lower
the IOP. The laser power used here does not cause thermal damage and may well
reach the ciliary body and the trabecular meshwork as previously shown."
"A study limitation is the lack of long-term observations after LILI. It is currently
unknown, how long the effects of a single LILI treatment last."
"The largest decrease in IOP (
26%) was observed in eyes with a pathological
baseline IOP of >21 mm Hg which exhibited ocular hypertension without damage.
However, LILI also decreased IOP in most eyes (73%) with a 'normotensive'
baseline IOP reaching a mean level of 14.1 mm Hg in this group, which is in
agreement with the accepted population-based normative IOP."
"The diagnostic 'LILI test' introduced here, may be particularly useful to detect
latent ocular hypertension in eyes with apparently normotensive but potentially
nonphysiological IOP, if ocular hypertension is associated with an open angle.
Eyes with ocular hypertension may be at risk of developing glaucoma later on.
Untreated ocular hypertension leads to glaucoma in 9.5% of cases."

Eyes

Rojas

USA
(Austin, TX)

2008

J Neurosci

Neuroprotective effects of near-infrared light in an in vivo model of

mitochondrial optic neuropathy.

Rat

Optic neuropathy
(rotenone)

633

0.002

3.6

d=
4.4 cm
(?)

1800

3-7

LED phototherapy

"Rotenone induced a decrease in visual function, as determined by changes in the

dark-adapted illuminance sensitivity threshold, escape latency and rate of
successful trials in a two-choice visual task, compared with vehicle-treated
controls. Behavioral impairment correlated with a decrease in retinal and visual
pathway metabolic activity, retinal nerve fiber layer thickness and ganglion cell
layer cell density.

PubMed

These changes were prevented by NIL treatments in a dose-dependent manner.

Whole-brain cytochrome oxidase and superoxide dismutase activities were also
increased in NIL-treated subjects in a dose-dependent manner, suggesting an in
vivo transcranial effect of NIL. In whole-brain membrane isolates, NIL prevented
the rotenone-induced decrease in cell respiration.
The results show that NIL treatment can effectively prevent the neurotoxic effects
of rotenone and that it might be used in the treatment of neurodegenerative
disorders associated with mitochondrial dysfunction."

Eyes

Eyes

Ivandic & Ivandic

Germany

2008

Eells

USA
2003
(Milwaukee, WI)

Photomed Laser
Surg

Low-level laser therapy improves vision in patients with agerelated macular degeneration.

Human
Age-related macular
Retrospective degeneration
data

780

Proc Natl Acad

Sci U S A

Therapeutic photobiomodulation for methanol-induced retinal

toxicity.

Rat

670

Methanol toxicity

7.5

0.3

d=
3 mm

40

LLLT improved visual acuity in 162/182 (95%) of eyes with cataracts and 142/146
(97%) of eyes without cataracts. The prevalence of metamorphopsia, scotoma,
and dyschromatopsia was reduced. In patients with wet AMD, edema and
bleeding improved. The improved vision was maintained for 3-36 mo after
treatment. No adverse effects were observed .

PubMed

144

"Our studies document a significant recovery of rod- and cone-mediated function

in LED-treated, methanol-intoxicated rats. We further show that LED treatment
protected the retina from the histopathologic changes induced by methanolderived formate. These findings provide a link between the actions of
monochromatic red to near-IR light on mitochondrial oxidative metabolism in vitro
and retinoprotection in vivo."

PubMed

"An increase of intraocular pressure was recorded at a dose of 0.1 J/cm2 (4.5 min)
and higher; morphological study showed dilated, well-filled and newly formed
vessels in the ciliary body and iris, as well as edema and destruction of the
external layers of the retina. Exposure to a dose of 0.05 J/cm2 and lower did not
lead to destruction of ocular structures and increase of intraocular pressure."

PubMed

LED phototherapy

890?

Eyes

Prokof'eva

Russia

1996

Vestn Oftalmol

[Effects of low-intensity infrared laser irradiation on the eye (an

experimental study)].
[Article in Russian]

Rabbit

Eyes

Belkin &
Schwartz

Israel
(Ramat Gan)

1994

Surv Ophthalmol

Ophthalmic effects of low-energy laser irradiation.

Review

Eyes

Sokolovskii

Russia

1990

Oftalmol Zh

[The stimulating effect of helium-neon laser radiation on rabbit

eyes].
[Article in Russian]

Rabbit

633

Eyes

Shmyreva

Russia

1989

Oftalmol Zh

[The mechanism of action of laser stimulation of the eye].

[Article in Russian]

Human

633

Comment: They reported harmful effects with a suspiciously low dose...

"This review outlines the reported effects of low-energy laser irradiation on nonophthalmological tissues and organs, including those of the nervous
system, with special emphasis on the optic nerve. It also details the ophthalmic phenomena induced by low-energy laser irradiation and examines claims
of its therapeutic efficacy in several eye diseases, such as keratitis, glaucoma and macular degeneration."
0.008

600

10

PubMed

Comment: Very low dose was used... Is it even possible to see such a low-power
laser ray?

PubMed

"The mechanism of action of helium-neon laser stimulation has been studied in 26

eyes of 15 patients with dystrophic diseases of the eye and on the ground of 63
lymphangiographic investigations of the same patients.

PubMed

It was found that low-energy helium-neon laser stimulation (0.05-0.5 mWt/cm2)

has a positive effect on restoration of visual functions. Lymphangiographic
investigations have revealed a new biological phenomenon--activation of disturbed
lymphatic flow under the action of a specially organized laser radiation. The results
obtained confirm the earlier hypothesis (M. M. Krasnov et al., 1982) that under the
action of laser radiation a normal physiologic system purifying the retina from
disintegrated products is engaged into action."

Not a RCT.

Comment

Reply

 Category
Fertility and
genitals

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Dyssmenorrhea

Shin

Korea
(Yangsan)

2012

Arch Gynecol
Obstet

Skin adhesive low-level light therapy for dysmenorrhoea: a

randomized, double-blind, placebo-controlled, pilot trial.

Human
RCT/DB

nm

mW

W/cm2

J/cm2

610

Results: positive / unclear/modest / negative

Link

Additional info

sec

0.001

1200

"The pain reduction rate was 83 % in the active LLLT group, whereas there was
only a slight and temporary reduction in pain in the placebo LLLT group. Changes
of VAS within 6 months of LLLT showed statistical significance (p = 0.001) over
placebo control."

PubMed

"In conclusion, this study supported our hypothesis that the direct cause of
dysmenorrhoea might not be changes in bioactive substances, such as hormone
imbalance, a decrease in serotonin levels or excessive prostaglandin production,
but the abnormal function of parts of smooth muscles in the uterus secondary to
long-term deficient blood supply into smooth muscle tissue caused by disease or
stress. This study also suggests that skin adhesive LLLT administered to
acupuncture points might be an effective, simple, safe non-pharmacological
method for the treatment of dysmenorrhoea. This study also shows the possibility
that even low-level light stimulation on acupuncture points can relax smooth
muscles of internal organs through meridians.
To the best of our knowledge, this is the first study on the treatment of
dysmenorrhoea with skin adhesive LLLT administered to acupuncture points."

Fertility and
genitals

Infertility

Karu TI

Russia

2012

Photomed Laser
Surg

Lasers in infertility treatment: irradiation of oocytes and

spermatozoa.

Guest
Editorial

Fertility and
genitals

Sperm motility

Siqueira

Brazil
(So Paulo)

2016

Lasers Med Sci

Effects of photobiomodulation therapy (PBMT) on bovine sperm

function.

In vitro

PubMed
Bovine sperm

633

5
7.5
10

300
600

"Results showed significant effects depending on power while using 10 min of

irradiation on motility parameters and mitochondrial potential. However, no effect
was observed using 5 min of irradiation, regardless of power applied."

PubMed

"In conclusion, PBMT is effective to modulate bovine sperm function. The

effectiveness is dependent on the interaction between power applied and duration
of irradiation, showing that these two parameters simultaneously influence sperm
function.
In this context, when using the same fluency and energy with different
combinations of power and time of exposure, we observed distinct effects,
revealing that biological effects should be also based on simple parameters rather
than only composite parameters such as fluency, irradiance and energy. Laser
irradiation of frozen/thawed bovine semen led to an increase on mitochondrial
function and motility parameters that could potentially improve fertility rates."

Fertility and
genitals

Sperm motility

Ban Frangez

Slovenia
(Ljubljana)

2015

Lasers Med Sci

Photobiomodulation with light-emitting diodes improves sperm

motility in men with asthenozoospermia.

In vitro

Human sperm

850

LED phototherapy

625
+
660
+
850

"This finding confirmed that photobiomodulation using LED improved the sperm
motility in asthenozoospermia regardless of the wavelength."

PubMed

Comment: Interesting result, since blue light was effective too.

470
625
+
660
+
470

Fertility and
genitals

Sperm motility

Fernandes

Brazil
(So Paulo)

2015

Fertility and
genitals

Sperm motility

Salman Yazdi

Iran
(Tehran)

2014

Fertility and
genitals

Sperm motility

Drozdov

Russia
(Vladivostok)

2014

PLoS One

The effect of low-level laser irradiation on sperm motility, and

integrity of the plasma membrane and acrosome in cryopreserved
bovine sperm.

In vitro

Bovine spern

Lasers Med Sci

Effect of 830-nm diode laser irradiation on human sperm motility.

In vitro

Human sperm

830

Dokl Biochem
Biophys

Influence of low-intensity red diode and laser radiation on the

locomotor activity of sea urchin sperm.

In vitro

Sea urchin sperm

650

Biphasic dose
response
4
6
10

0.09
0.25
0.75

0.00007
0.07

"We conclude that LLLI may exert beneficial effects in the preservation of live
sperm. A dose of 4 joules prior to cryopreservation was more effective than a dose
of 6 joules in preserving sperm motility."

PubMed

"Sperm motility of the control groups significantly decreased after 30, 45 and 60
min of irradiation, while those of irradiated groups remained constant or slightly
increased by passing of time. Significant increases have been observed in doses
of 4 and 6 J/cm(2) at the times of 60 and 45 min, respectively. SCD test also
revealed a non-significant difference."

PubMed

"In this study, we showed that lowintensity red light diode and laser radiation affect
the locomotor activity of sea urchin sperms, 25 times increasing the per centage
of active cells depending on the time elapsed after exposure."

PubMed

"The results showed that different output powers affected dog semen motility
parameters differently. The highest output power showed the most intense effects.
Significant changes in the structure of the motile sperm subpopulation were linked
to the different output powers used."

PubMed

"Average path velocity (VAP), linear coefficient (Lin) and beat cross frequency
(BCF) were statistically and significantly different when compared to the control.
The functional tests also showed a significant difference.

PubMed

0.003
635

Fertility and
genitals

Sperm motility

Corral-Baqus

Spain

2009

Lasers Med Sci

The effect of low-level laser irradiation on dog spermatozoa

motility is dependent on laser output power.

In vitro

Dog sperm

655

Fertility and
genitals

Sperm motility

Corral-Baqus

Spain
(Reus)

2005

Lasers Med Sci

Effect of 655-nm diode laser on dog sperm motility.

In vitro

Dog sperm

655

0.29
6.8
15.4
33.1
49.7

3.34

2700

4
6
10

At these parameters, the 655-nm continuous-wave diode laser improves the

speed and linear coefficient of the sperm."

Fertility and
genitals

Fertility and
genitals

Testicle

Testicle

Alves

Al-Ebady

Brazil
(Pirassununga)

Iraq

2016

2014

Lasers Med Sci

Int J Adv Res

Low-level laser therapy to recovery testicular degeneration in

rams: effects on seminal characteristics, scrotal temperature,
plasma testosterone concentration, and testes histopathology.

Ram

The effect of expose the rat testis to low level laser light on
changing serum LH and testosterone levels

Rat

Biphasic dose
response

808

30

28
56

(total
dose
during
study)

Biphasic dose
response

660

50

4
12

30

670
808

200

360

1800

Toxicity

Fertility and
genitals

Testicle

Ahn

Korea
(Cheonan)

2013

Biomed Res

The effects of low level laser therapy (LLLT) on the testis in

elevating serum testosterone level in rats.

Rat

"Thus, in concern to the results, it is possible to conclude that LLLT at energy of

28 J/cm2 , 808 nm of wavelength, and 30 mW of power output can induce semen
injuries and increase the quantities of cells in seminiferous tubule when detected
32 days after LLLT treatment. However, this increase did not occur in a long time
after the therapy and in animals that did not present testicular degeneration. LLLT
in this condition is not efficient to increase serum testosterone concentration, and
consequently, it is not efficient to stimulate Leydig cells. It is an evident need for
further studies investigating the effect of LLLT in testicular degeneration with other
protocols and other methods to measure its biostimulatory effects."

PubMed

"The results showed that there was significant (P<0.05) decrease in serum LH
level in group when compared with group and control, while serum T levels
were not significantly higher between groups, and there was clear
histopathological changes in right testes seminiferous tubules of group which
exposed to 12 joules of laser light."

IJAR

"Our results showed that the rate of tissue penetration was significantly higher in
the 808 nm wavelength group as compared with the 670 nm wavelength group
(P<0.05); serum T level was not significantly higher in the experimental groups as
compared with the control group; but serum T level was significantly elevated in
the 670 nm wavelength group on day 4. Thus the LLLT using a 670-nm diode
laser was effective in increasing serum T level without causing any visible
histopathological side effects.

PDF

In conclusion, the LLLT might be an alternative treatment modality to the

conventional types of testosterone replacement therapy."
Comment: This finding was published in a very-low impact journal, not indexed by
PubMed.

Fertility and
genitals

Testicle

Taha & Valojerdi

Iran (Tehran)

2004

Lasers Surg Med

Quantitative and qualitative changes of the seminiferous

epithelium induced by Ga. Al. As. (830 nm) laser radiation.

Rat

28.05
46.80

Toxicity
(with high dose)

15

Biphasic dose
response

"The number of germ cells specially the pachytene spermatocytes and elongated
spermatids increased after 28.05 J/cm(2) laser radiation. Ultrastructural features of
germ and Sertoli cells in this group were similar to that of control; while laser
irradiation at 46.80 J/cm(2) had a destructive effect on the seminiferous epithelium
such as dissociation of immature spermatids and evident ultrastructural changes
in them."

PubMed

"Moreover, it was revealed that low doses of laser light have a biostimulatory
effect on the spermatogenesis and may provide benefits to the patients with
oligospermia and azoospermia."

Fibromyalgia

da Silva

Brazil
(So Paulo)

2015

Trials

Effects of exercise training and photobiomodulation therapy

(EXTRAPHOTO) on pain in women with fibromyalgia and
temporomandibular disorder: study protocol for a randomized
controlled trial.

Study
protocol

Fibromyalgia

Ruaro

Brazil
(Guarapuava)

2014

Lasers Med Sci

Low-level laser therapy to treat fibromyalgia.

Human
RCT

PubMed

670

20

0.57

0.035
cm2
(spot)

126

12

"LLLT provided relief from fibromyalgia symptoms in patients and should be further
investigated as a therapeutic tool for management in fibromyalgia."

PubMed

Comment: This paper reported very slightly positive results. Parameters were
reported very poorly and there is a formatting error in the table showing treatment
results.

PubMed

"Our results suggest that LLLT has both short- and long-term effectiveness in the
treatment of fibromyalgia."

IOS Press

1
cm2
(area)

905

Fibromyalgia

Fernndez
Garca

Spain
(Almera)

2011

Reumatol Clin

Using a laser based program in patients diagnosed with

fibromyalgia

Human
RCT

Fibromyalgia

Armagan

Turkey
(Eskisehir)

2006

J Back
Musculoskelet
Rehabil

Long-term efficacy of low level laser therapy in women with

fibromyalgia: A placebo-controlled study

Human
RCT

Fibromyalgia

Gr

Turkey
(Diyarbakir)

2002

Rheumatol Int

Effects of low power laser and low dose amitriptyline therapy on

clinical symptoms and quality of life in fibromyalgia: a single-blind,
placebo-controlled trial.

Human
RCT/SB

904

11.2

11.2

Gr

Turkey
(Diyarbakir)

2002

Lasers Med Sci

Efficacy of low power laser therapy in fibromyalgia: a single-blind,

placebo-controlled trial.

Human
RCT/SB

904

Flatworms

Dugesia tigrina

Wu & Persinger

Canada
(Ontario)

2011

J Photochem
Photobiol B

Increased mobility and stem-cell proliferation rate in Dugesia

tigrina induced by 880nm light emitting diode.

Dugesia
tigrina

880

Flatworms

Dugesia tigrina

Lopes

Brazil
(So Jos dos
Campos)

2009

Braz J Biol

A study of low power laser on the regenerative process of Girardia

tigrina (Girard,1850) (Turbellaria; Tricladida; Dugesiidae).

Dugesia
tigrina

660

Fibromyalgia

1
cm2

180
/t.p.

10

"Our study suggests that both amitriptyline and laser therapies are effective on
clinical symptoms and QOL in fibromyalgia and that Ga-As laser therapy is a safe
and effective treatment in cases with FM. Additionally, the present study suggests
that the Ga-As laser therapy can be used as a monotherapy or as a
supplementary treatment to other therapeutic procedures in FM."

PubMed

t.p. = tender point

1
cm2

180
/t.p.

10

"Our study suggests that laser therapy is e#ective on pain, muscle spasm,
morning sti#ness, and total tender point number in fibromyalgia and suggests that
this therapy method is a safe and e#ective way of treatment in the cases with
fibromyalgia."

PubMed

t.p. = tender point

"These findings suggest that non-coherent light sources with power-densities

about 1000 times lower than contemporary low-power laser settings remain
effective in generating photobiostimulation effects and warrants further
investigation on stem-cell proliferation induced by near-infrared light emitting
diodes."

PubMed

"The head fragment after 1 minute of irradiation presented a better organized

tissue scheme, when compared with the other treatments. Aspects of the body
fragments submitted to 3 minutes of light treatment were very similar to fragments
that had not been injured. It can be concluded that there are changes in the quality
of regeneration when treated with low power laser under the conditions mentioned
above."

PubMed

0.01

3.3

60
180

14

Comment

Reply

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Dugesia tigrina

de Souza

Brazil
(So Jos dos
Campos)

2005

J Photochem
Photobiol B

Low power laser radiation at 685 nm stimulates stem-cell

proliferation rate in Dugesia tigrina during regeneration.

Dugesia
tigrina

685

35

Fluorescent
lamps

Ahamed

India

2016

Lasers Med Sci

Effect of LED photobiomodulation on fluorescent light induced

changes in cellular ATPases and Cytochrome c oxidase activity in
Wistar rat.

Rat

670

Gastroenterol Atrophic
gastritis
ogy

Yang

China
(Zhangjiakou)

2005

Sheng Wu Yi Xue
Gong Cheng Xue
Za Zhi

[Effects of He-Ne laser on gastric mucosa in rat with chronic

atrophic gastritis].
[Article in Chinese]

Rat

Biphasic dose
response

633

Gastroenterol Atrophic
gastritis
ogy

Shao

China
(Zhangjiakou)

2005

World J
Gastroenterol

Effects of He-Ne laser irradiation on chronic atrophic gastritis in

rats.

Rat

Biphasic dose
response

633

Gastroenterol Colitis
ogy

Zigmond

Israel
(Tel Aviv)

2014

Photomed Laser
Surg

Low-level light therapy induces mucosal healing in a murine model

of dextran-sodium-sulfate induced colitis.

Mouse

Biphasic dose
response

440
660
850

Category
Flatworms

0.025

Results: positive / unclear/modest / negative

Link

sec

whole
animal
(?)

360

"A remarkable increase in stem cells counts for the fourth day of regeneration was
observed when the regenerating worms was stimulated by the laser radiation. Our
findings encourage further research works on the influence of optical radiation
onto stem cells and tissue regeneration."

PubMed

"This study demonstrates the protective effect of 670 nm LED pre exposure on
cellular enzymes against fluorescent light induced change."

PubMed

Note: See also the another paper from this group, in the Eyes-category.

0.008

3.36
4.80
6.24

d=
1 cm

420
600
780

20

"Compared with untreated group, the gastric mucosa of 3.36J x cm(-2) He-Ne
laser group was significantly thicker (P < 0.01), the inflammatory cells of gastric
mucosa were decreased (P < 0.05), the morphology, structure and volume of the
cells were restored or nearly normal and the expressions of cyclinD1 were higher
(P < 0.05). In a word, small dose He-Ne laser (3.36 J x cm(-2)) has a good
adjuvant therapeutic effect on rat's CAG."

PubMed

20

"After 3.36 J/cm(2) dose of He-Ne laser treatment for 20 d, the secretion of gastric
acid was increased (P<0.05), the thickness of gastric mucosa was significantly
thicker than that in model control group (P<0.01), the gastric mucosal inflammation
cells were decreased (P<0.05). Morphology, structure and volume of the parietal
cells all recuperated or were closed to normal."

PubMed

Comment: In higher dose groups, no benefit was noted.

"The three wavelengths used demonstrated efficacy, and a clear dose-response
curve was observed for one of the wavelengths (850 nm). On day 11,
colonoscopic scoring in the sham-treated mice increased from 7.91.3 to 12.22.
2, while activity in all treated groups remained stable."

PubMed

Note: In another study (J Gastroenterol Hepatol 2014 Apr;29(4):749-56), bright

light therapy with 1000lux alleviated colitis compared to 200lux light, while 2500lux
didn't have a beneficial effect.

Gastroenterol Ulcerative colitis

ogy

Dubinkin &
Mimrikova

Russia

1999

Complex treatment of non-specific ulcerative colitis with low-level

HeNe laser used transanally

Human

633

Gene
expression

Tim

Brazil

2016

J Photochem
Photobiol B

Effects of low level laser therapy on inflammatory and angiogenic

gene expression during the process of bone healing: A microarray
analysis.

Rat

830

Gene
expression

Houreld

South Africa
(Johannesburg)

2014

J Photochem
Photobiol B

Expression of genes in normal fibroblast cells (WS1) in response

to irradiation at 660nm.

In vitro

660

["81 patients (average age 42) with non-specific ulcerous colitis were treated with
trans-anal HeNe laser. After 10-12 sessions 72% of the patients noted a reduction
of pain and the stool became rare. Coloscopy showed that the mucous membrane
regenerated repidly with an increased vascular picture."]
30

2.8

0.011

d=
0.6
mm

94

4
(?)

Our findings indicate that LLLT was efficient on accelerating the development of
newly formed bone probably by modulating the inflammatory and angiogenic gene
expression as well as COX2 and VEGF immunoexpression during the initial phase
of bone healing.

PubMed

"This study aimed to profile 84 genes in response to irradiation at 660nm."

PubMed

"A total of 76 genes were regulated by laser irradiation, 43 genes were upregulated while 33 genes were down-regulated.
Irradiation of WS1 cells at 660nm modulates the expression of genes involved in
collagen production, cellular adhesion, remodelling and spreading, the
cytoskeleton, inflammatory cytokines and chemokines, growth factors and
molecules involved in signal transduction."

Masha

Gene
expression

South Africa
(Johannesburg)

2013

Photomed Laser
Surg

660

Low-intensity laser irradiation at 660 nm stimulates transcription of

genes involved in the electron transport chain.

"LILI upregulated cytochrome c oxidase subunit VIb polypeptide 2 (COX6B2),

cytochrome c oxidase subunit VIc (COX6C), and pyrophosphatase (inorganic) 1
(PPA1) in diabetic wounded cells;

PubMed

COX6C, ATP synthase, H+transporting, mitochondrial Fo complex, subunit B1

(ATP5F1), nicotinamide adenine dinucleotide (NADH) dehydrogenase
(ubiquinone) 1 alpha subcomplex, 11 (NDUFA11), and NADH dehydrogenase
(ubiquinone) Fe-S protein 7 (NDUFS7) in wounded cells;
and ATPase, H+/K+ exchanging, beta polypeptide (ATP4B), and ATP synthase,
H+ transporting, mitochondrial Fo complex, subunit C2 (subunit 9) (ATP5G2) in
ischemic cells."
"LILI at 660 nm stimulates the upregulation of genes coding for subunits of
enzymes involved in complexes I and IV and ATP synthase."

Peplow

Gene
expression

Safavi

Gene
expression

General

Laser

Rola

New Zealand
(Dunedin)

Iran

Poland
(Wroclaw)

2011

2008

2014

Photomed Laser
Surg

Lasers Med Sci

Adv Clin Exp Med

Laser photobiomodulation of gene expression and release of

growth factors and cytokines from cells in culture: a review of
human and animal studies.

Systematic
review

Effects of low-level He-Ne laser irradiation on the gene expression

of IL-1beta, TNF-alpha, IFN-gamma, TGF-beta, bFGF, and PDGF in
rat's gingiva.

Rat

The Use of Low-Level Energy Laser Radiation in Basic and Clinical

Research.

Review

"A total of 17 relevant papers were included in the review, comprising studies on a variety of cell types. Considerable variation occurred in research
design, methodology, and irradiation parameters employed, limiting comparison of research findings between studies."

PubMed

"Results demonstrated that laser irradiation at green, red, or infrared wavelengths at a range of dosage parameters can cause significant changes in the
cellular gene expression and release of these mediators, and that such effects depend upon wavelength and radiant exposure."
633

5.1

7.5

68
mm2

300

"The case and control groups did not have a significant difference in the gene
expression of TNF-alpha and bFGF (P > 0.05)."

PubMed

"These findings suggest that low-level He-Ne laser irradiation decreases the
amount of inflammation and accelerates the wound healing process by changing
the expression of genes responsible for the production of inflammatory cytokines."
"Areas in which LLLT is used are: regenerative medicine (for healing wounds and ulcers); aesthetic medicine (to improve appearance of scars); dentistry
(to accelerate healing of implants); physiotherapy (to reduce chronic pain syndromes), orthopedics (in bone healing) and cardiology (as a prevention of
restenosis after percutaneous coronary intervention).

PubMed

This paper discusses the medical applications of LLLT which are used in daily clinical practice as well as those used in basic science."

General

LED

Lim S

Korea
(Cheonan)

General

LED

Desmet

USA
2006
(Milwaukee, WI)

2011

J Soc Inf Disp

Phototherapy and the benefits of LEDs

Photomed Laser
Surg

Clinical and experimental applications of NIR-LED

photobiomodulation.

Review

LED phototherapy

"Radiation from LEDs have been reported beneficial for treating many kinds of minor diseases in our body. UV, blue, green, red, and IR radiation from
LEDs has been found effective in curing skin diseases such as psoriasis, vitiligo, atopic dermatitis (eczema), reducing pain, generating collagen and
elastics cells, killing acne bacteria, treating hair growth, etc"

Wiley

"NIR-LED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production.

PubMed

NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of
methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos.
Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients.
The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue
repair in vivo.
NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction."

Hair

Keene

USA
(Tucson, AZ)

2016

Exp Dermatol

Illuminating current pitfalls in optimal photobiomodulation device

development and assessment for treating hair loss.

Commentary

Hair

Mignon

UK &
Netherlands

2016

Exp Dermatol

Photobiomodulation devices for hair regrowth and wound healing:

a therapy full of promise but a literature full of confusion.

Review

Parameters

"Photobiomodulation has been established as a credible treatment modality for a variety of medical conditions including hair loss. Despite recently
published RCTs, there is reason to believe optimal wavelengths and dosing have yet to be identified. Addressing the identified challenges will hopefully
achieve the full potential of PBM for hair loss patients. In the meantime, recommendation of PBM devices to treat hair loss may be premature."

PubMed

"The aim of this review was to seek greater clarity and rationality specifically for the selection of optical parameters for studies on hair regrowth and
wound healing. Our investigation of 90 reports published between 1985 and 2015 revealed major inconsistencies in optical parameters selected for
clinical applications."

PubMed

"Furthermore, special attention needs to be paid when conducting studies for hair regrowth, aiming for double-blind, placebo-controlled randomized
clinical trials as the gold standard for quantifying hair growth."

Hair

Gupta & Foley

Canada
(Toronto &
London,
Ontario)

2016

Dermatol Surg

A Critical Assessment of the Evidence for Low-Level Laser

Therapy in the Treatment of Hair Loss.

Systematic
review

Hair loss treatment

"There are a number of unanswered questions about the optimum treatment regimen, including maintenance treatment and the long-term consequences
of LLLT use."

PubMed

Hair

Afifi

USA (Miami,
FL)

2016

Lasers Surg Med

Low-level laser therapy as a treatment for androgenetic alopecia.

Systematic
review

Androgenetic
alopecia

"The majority of studies covered in this review found an overall improvement in hair regrowth, thickness, and patient satisfaction following LLLT therapy.
Although we should be cautious when interpreting these findings, LLLT therapy seems to be a promising monotherapy for AGA and may serve as an
effective alternative for individuals unwilling to use medical therapy or undergo surgical options."

PubMed

Hair

Sheen

Taiwan
(Taipei)

2015

Lasers Surg Med

Visible red light enhances physiological anagen entry in vivo and

has direct and indirect stimulative effects in vitro.

In vitro

Anagen entry

630

Hair

Olivieri

Italy
(Spilamberto)

2015

Vet Dermatol

Efficacy of low-level laser therapy on hair regrowth in dogs with

noninflammatory alopecia: a pilot study.

Dog

Alopecia, noninflammatory

470
+
685
+
830

208

200

25
cm2
(area)

80

8
(?)

"These results suggest that hair follicles respond to visible light in vivo. Red light
may promote physiological telogen to anagen transition by directly stimulating
outer root sheath keratinocytes and indirectly by enhancing epithelialmesenchymal interaction in vitro."

PubMed

"By morphometry, the area occupied by hair follicles was 18% in the treated
sample and 11% in the untreated one (11%)"

PubMed

"Haired follicles were (per area) 93% in the treated sample and only 9% in the
control sample."

800

Comment: Article has some nice photographs of the LLLT device/treatment and
the effects.

Hair

Munck

Brazil &
Switzerland

2014

Hair

Lanzafame

USA
2014
(Rochester, NY)

Int J Trichology

Use of low-level laser therapy as monotherapy or concomitant

therapy for male and female androgenetic alopecia.

Human
Androgenetic
Retrospective alopecia
data
HairMax Laser Comb
()

655

Lasers Surg Med

The growth of human scalp hair in females using visible red light
laser and LED sources.

Human ()
RCT/DB

655

Androgenetic
alopecia

60

"LLLT represents a potentially effective treatment for both male and female AGA,
either as monotherapy or concomitant therapy."

PubMed

"LLLT of the scalp at 655 nm significantly improved hair counts in women with
androgenetic alopecia at a rate similar to that observed in males using the same
parameters."

PubMed

TOPHAT655 device

Hair

Gupta & Daigle

Canada
(Toronto)

2014

J Dermatolog
Treat

The use of low-level light therapy in the treatment of androgenetic

alopecia and female pattern hair loss.

Review

Androgenetic
alopecia

Hair

Avci

USA
(Boston, MA)

2014

Lasers Surg Med

Low-level laser (light) therapy (LLLT) for treatment of hair loss.

Review

Hair loss

Wikramanayake

USA
(Miami, FL)

2013

Lasers Med Sci

Low-level laser treatment accelerated hair regrowth in a rat model

of chemotherapy-induced alopecia (CIA).

Mouse

Chemotherapyinduced
alopecia

Hair

PubMed
LLLT for hair growth in both men and women appears to be both safe and effective. The optimum wavelength, coherence and dosimetric parameters
remain to be determined.
655

"Taken together, our results demonstrated that LLL treatment significantly

accelerated hair regrowth after CIA without compromising the efficacy of
chemotherapy in our rat model."

PubMed
PubMed

Star: Results are very interesting, and a photograph is supplied.

Comment: Parameters were poorly reported.

Hair

Lanzafame

USA
2013
(Rochester, NY)

Lasers Surg Med

The growth of human scalp hair mediated by visible red light laser
and LED sources in males.

Human ()
RCT/DB

Androgenetic
alopecia
TOPHAT655 device

655

60

"LLLT of the scalp at 655 nm significantly improved hair counts in males with
androgenetic alopecia."

PubMed

Additional info

Comment

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First author

Country

Year

Journal

Title

Hair

Kim

Korea
(Seongnam)

2013

Dermatol Surg

Low-level light therapy for androgenetic alopecia: a 24-week,

Human
randomized, double-blind, sham device-controlled multicenter trial. RCT/DB

Androgenetic
alopecia

Hair

Ghanaat M

USA
(Brooklyn, NY)

2010

South Med J

Types of hair loss and treatment options, including the novel lowlevel light therapy and its proposed mechanism.

Review

Hair loss

"There are several theories and minimal clinical evidence of the safety and efficacy of LLLT, although most experts agree that it is safe. More in vitro
studies are necessary to elucidate the mechanism and effectiveness at the cellular level, and more controlled studies are necessary to assess the role of
this new treatment in the general population."

PubMed

Hair

Avram

USA
(New York, NY)

2007

J Cosmet Laser
Ther

The current role of laser/light sources in the treatment of male and

female pattern hair loss.

Review

Hair loss

"Despite aggressive marketing and centers claiming great success in the treatment of hair loss there is little scientific data supporting laser/light sources
in hair loss."

PubMed

Category

Subcategory

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

Additional info

sec

"After 24 weeks of treatment, the LLLT group showed significantly greater hair
density than the sham device group. Mean hair diameter improved statistically
significantly more in the LLLT group than in the sham device group. Investigator
global assessment showed a significant difference between the two groups, but
that of the subject did not."

PubMed

"The authors believe that, while seemingly safe, there are no controlled, peer-reviewed studies validating current devices for hair loss and that all
patients should be medically evaluated for any hair loss by a physician specialist to rule out other underlying medical conditions or the etiology of hair
loss."
Note: This was written in 2007, before the randomized trials started appearing in the literature.

Yamazaki

Hair

Japan
(Tokyo)

2003

Int J Dermatol

Linear polarized infrared irradiation using Super Lizer is an

effective treatment for multiple-type alopecia areata.

Human

Alopecia areata

6001600

For irratiated lesions, the success was 7/15. For non-irratiated, 0/15.

Hearing

Auditory
neuropathy

Lee

Korea
(Cheonan)

2016

Neurosci Lett

Photobiomodulation by laser therapy rescued auditory neuropathy

induced by ouabain.

Gerbil

Ouabain-induced
auditory neuropathy

Super Lizer (SL) (Tokyo Iken, Tokyo, Japan), a medical instrument operating on polarized linear light, provides a high output (1.8 W) of infrared radiation (6001600 nm) capable
of penetrating into deep subcutaneous tissue. It was designed and manufactured in Japan, and has been used to good effect in orthopedics and anesthesiology for the treatment of
arthralgia and neuralgia.57 Some dermatologists have recently begun treating skin ulcers in a similar way.8 In this study, we evaluated SL as an alternative to drug therapy in the
treatment of AA.

[See additional info for details about Super Lizer]

Super Lizer
808

200

0.909

720

3272

0.22
cm2

3600

"Ouabain application increased the ABR thresholds increase, while the use of
ouabain plus laser produced lower threshold compared to the ouabain group.

PubMed

Hematoxylin and Eosin staining of cochlea mid-modiolar sections in animals

treated with ouabain showed damaged spiral ganglion cells, neurofilaments, and
post synaptic puncta. Ouabain plus laser group showed higher number of spiral
ganglion cells, higher density of neurofilaments, and higher number post synaptic
puncta counts compared with ouabain application group."
Star: Parameters were well reported, and a good-quality photograph was supplied.

Hearing

Hearing loss

Tamura

Japan
(Saitama)

2016

Brain Res

Photobiomodulation rescues the cochlea from noise-induced

hearing loss via upregulating nuclear factor B expression in rats.

Rat

Noise-induced
hearing loss

808

2.9

0.165

26

Hearing

Hearing loss

Lee

Korea
(Cheonan)

2016

PeerJ

Simultaneous bilateral laser therapy accelerates recovery after

noise-induced hearing loss in a rat model.

Rat

Noise-induced
hearing loss

808

185

0.165

594

Hearing

Hearing loss

Tamura

Japan
(Saitama)

2015

Neurosci Lett

Low-level laser therapy for prevention of noise-induced hearing

loss in rats.

Rat

Noise-induced
hearing loss

808

0.110
0.165

Hearing

Hearing loss

Rhee

Korea
(Cheonan)

2013

J Biomed Opt

Effect of low-level laser treatment on cochlea hair-cell recovery

after ototoxic hearing loss.

Rat

Gentamicin-induced
hearing loss

830

0.9

35.642.8

d=
2 mm

1800

"These data suggest that PBM activates NF-B to induce protection against
inducible nitric oxide synthase-triggered oxidative stress and caspase-3-mediated
apoptosis that occur following noise-induced hearing loss."

PubMed

2700

0.22
cm2

3600

15

"Both bilateral and unilateral laser therapy decreased the hearing threshold after
noise overstimulation in the rat model. The bilateral laser therapy group showed
faster functional recovery at all tested frequencies compared with the unilateral
laser therapy group."

PubMed

162194

0.22
cm2

Star: Parameters were well reported in a table.

1800

"Our findings suggest that LLLT has cytoprotective effects against NIHL via the
inhibition of iNOS expression and apoptosis."

PubMed

3600

10

"Hearing was significantly improved by laser irradiation. After LLLT treatment, both
the hearing threshold and hair-cell count significantly improved."

PubMed

Star: Parameters were well reported, and some photographic material was
supplied.

Hearing

Hearing loss

Goodman

USA
(Iowa city, IA)

2013

ISRN Otolaryngol

The effect of low-level laser therapy on hearing.

635
532

Human
RCT/DB

7.5

300

"No statistically significant differences were found between groups for any of the
auditory tests. Additionally, no clinically significant differences were found in any
individual subjects."

PubMed

Comment: Parameters were poorly reported.

Hearing

Hearing loss

Rhee

Korea
(Cheonan)

2012

J Biomed Opt

Effect of low-level laser treatment on cochlea hair-cell recovery

after acute acoustic trauma.

Rat

Hearing

Meniere's
disease

Teggi

Italy
(Milan)

2008

Photomed Laser
Surg

Efficacy of low-level laser therapy in Mnire's disease: a pilot

study of 10 patients.

Human
Pilot study

Hearing

Tinnitus

Park

Korea
(Cheonan)

2013

Neurosci Lett

Trans-canal laser irradiation reduces tinnitus perception of

salicylate treated rat.

Rat

Noise-induced
hearing loss

830

0.10.165

3600

12

1200

180

1800

"Our findings suggest that low-level laser irradiation promotes recovery of hearing
thresholds after acute acoustic trauma."

PubMed

Comment: Parameters were insufficiently reported.

650

High dose LLLT

830

6
@
tymp.
memb

1
cm2

0.165

"In our experience, LLLT seems to prevent vertigo spells in MD, although results
indicate that it has a slower action than betahistine. Dose-dependent therapeutic
effects could explain the last result. In our opinion, increased blood flow in the
inner ear is the main mechanism leading to the therapeutic results."

PubMed

"Therapeutic effect of LLLT is demonstrated in animal tinnitus model by means of

GPIAS. Further experimental studies are needed to find possible mechanisms and
better methods to improve LLLT efficacy."

PubMed

Comment: Parameters were poorly reported.

Hearing

Tinnitus

Dehkordi

Iran
(Mashhad)

2015

Ear Nose Throat J Effect of low-level laser therapy in the treatment of cochlear
tinnitus: a double-blind, placebo-controlled study.

650

Human
RCT/DB

1200

20

"We conclude that 5-mV laser therapy with a wavelength of 650 nm is no better
than placebo for improving hearing thresholds overall or for treating tinnitus with
regard to age, sex, environmental noise level, and the duration of tinnitus."

PubMed

References by Tunr:
Bjorne A, Agerberg G. Reduction in sick leave and costs to society of patients with Mnires disease after treatment of temporomandibular and cervical spine disorders: A
controlled 6-year cost-benefit study. Cranio. 2003; 21 (2): 136-143.

Jan Tunr: "Not arguing against the results of this paper, but a problem with most
studies trying to treat tinnitus with laser light is the lack of proper diagnosis of the
patients. Quite a few of these have a somatosensory background (the problem is
basicly muscluar). Irradiation into the ear will then have no effect."

Bernhardt O, Gesch D, Schwahn C, Bitter K et al. Signs of temporomandibular disorders in tinnitus patients and in a population-based group of volunteers: results of the Study of
Health in Pomerania. J Oral Rehabil. 2004; 31 (4): 311-319.
Levine RA, Abel M, Cheng H. CNS somatosensory-auditory interactions elicit or modulate tinnitus. Exp Brain Res. 2003; 153 (4): 643-648.

[See additional info for Tunr's references]

Tullberg M, Ernberg M. Long-term effect on tinnitus by treatment of temporomandibular disorders: a two-year follow-up by questionnaire. Acta Odontol Scand. 2006; 64 (2): 89- 96.

Hearing

Tinnitus

Salahaldin

Qatar
(Doha)

2012

ISRN Otolaryngol

Low-level laser therapy in patients with complaints of tinnitus: a

clinical study.

Human

650

Hearing

Tinnitus

Teggi

Italy
(Milan)

2009

Audiol Neurootol

Transmeatal low-level laser therapy for chronic tinnitus with

cochlear dysfunction.

Human
RCT/DB

650

Hearing

Tinnitus

Hahn

Czech Republic
(Prague)

2008

Int Tinnitus J

Multimodal therapy for chronic tinnitus.

Human

Hearing

Tinnitus

Cuda & De Caria

Italy
(Piacenza)

2008

Int Tinnitus J

Effectiveness of combined counseling and low-level laser

stimulation in the treatment of disturbing chronic tinnitus.

Human
RCT

Hearing

Tinnitus

Gungor

Turkey
(Istanbul)

2008

J Laryngol Otol

Effectiveness of transmeatal low power laser irradiation for chronic Human

tinnitus.
RCT/DB

650

650

6
@
tymp.
memb

1
cm2

1200

900

90

"Over half of the patients (56.9%) had some form of improvement in their tinnitus
symptoms. Mild improvement was reported in 33.8% of patients, moderate
improvement was reported in 16.9%, and full improvement was reported in
6.15%."

PubMed

"Soft laser therapy demonstrated no efficacy as a therapeutic measure for

tinnitus."

PubMed

"None of the treatment modalities had an objective correlate of improvement,

though improvement was reported by a visual analog scale."

PubMed

"The THI scores improved in the entire sample after treatment but more
significantly in the group receiving low-level laser stimulation. From the point of
view of clinical classification, approximately 61% of irradiated patients had tinnitus
severity decreased by one class, in comparison to 35% of the placebo group."

PubMed

"The loudness, duration and degree of annoyance of tinnitus were improved,

respectively, in up to 48.8, 57.7 and 55.5 per cent of the patients in the active laser
group. No significant improvement was observed in the placebo laser group."

PubMed

Jan Tunr: "A problem with most studies trying to treat tinnitus with laser light is
the lack of proper diagnosis of the patients. Quite a few of these have a
somatosensory background (the problem is basicly muscluar). Irradiation into the
ear will then have no effect."

Hearing

Tinnitus

Tauber

Germany
(Munich)

2003

Lasers Med Sci

Transmeatal cochlear laser (TCL) treatment of cochlear

dysfunction: a feasibility study for chronic tinnitus.

Human
Pilot study

635
830

7.8
20

Hearing

Tympanic
membrane

Maleki

Iran
(Tehran)

2013

J Laryngol Otol

Effect of local irradiation with 630 and 860 nm low-level lasers on

tympanic membrane perforation repair in guinea pigs.

Guinea pig

630
+
860

30
+
100

14.6

1.0
cm2

60

Hearing

Bartos

USA
(Boston, MA)

2016

J Biophotonics

Pre-conditioning with near infrared photobiomodulation reduces

In vitro
inflammatory cytokines and markers of oxidative stress in cochlear
hair cells.

100

Hearing

Rhee

Korea
(Cheonan)

2012

Lasers Med Sci

Effect of low-level laser therapy on cochlear hair cell recovery after

gentamicin-induced ototoxicity.

3600

Cochlear hair cells

treated with
gentamicin or LPS

810

0.03

810

0.008

0.48

"After a follow-up period of six months tinnitus loudness was attenuated in 13 of 35

irradiated patients, while two of 35 patients reported their tinnitus as totally absent.
Hearing threshold levels and middle ear function remained unchanged."

PubMed

"The results show that the combined application of 630 and 860 nm lasers had a
significant effect on the healing of tympanic membrane perforation, and on the
prevention of thick fibrotic or atelectatic neomembrane formation."

PubMed

"We report a decrease of inflammatory cytokines and stress levels resulting from
NIR applied to HEI-OC1 auditory cells before treatment with gentamicin or
lipopolysaccharide."

PubMed

"These results suggest that LLLT may promote hair cell survival following
gentamicin damage in the cochlea."

PubMed

LED phototherapy

Heart

CABG surgery

Kazemi Khoo

Iran (Tehran)

2014

J Lasers Med Sci

Application of Low-Level Laser Therapy Following Coronary Artery

Bypass Grafting (CABG) Surgery.

In vitro

Cochlear hair cells

treated with
gentamicin

Comment: Parameters are contradictory. I guess that fluence is actually 48 J/cm2,

not 0.48.
810

Human

500

1
cm2

"It is concluded that low-level laser irradiation after CABG surgery could decrease
cardiac cellular damage and help accelerate the repair of cardiac tissue postoperatively."

PubMed

Comment: Parameters insufficiently reported.

Heart

Cardiomyocytes

Zhang

USA
2009
(Milwaukee, WI)

J Mol Cell Cardiol

Near infrared light protects cardiomyocytes from hypoxia and

reoxygenation injury by a nitric oxide dependent mechanism.

"Our results demonstrate that exposure to NIR at the time of reoxygenation

protects neonatal rat cardiomyocytes and HL-1 cells from injury, as assessed by
lactate dehydrogenase release and MTT assay. Similarly, indices of apoptosis,
including caspase 3 activity, annexin binding and the release of cytochrome c from
mitochondria into the cytosol, were decreased after NIR treatment.

In vitro

PubMed

NIR increased NO in cardiomyocytes, and the protective effect of NIR was

completely reversed by the NO scavengers carboxy-PTIO and oxyhemoglobin, but
only partially blocked by the NO synthase (NOS) inhibitor L-NMMA.
Mitochondrial metabolism, measured by ATP synthase activity, was increased by
NIR, and NO-induced inhibition of oxygen consumption with substrates for
complex I or complex IV was reversed by exposure to NIR.
Taken together these data provide evidence for protection against hypoxia and
reoxygenation injury in cardiomyocytes by NIR in a manner that is dependent
upon NO derived from NOS and non-NOS sources."

Heart

Heart

Coronary
arteries

Coronary
arteries

Plass

Plass

Austria
(Vienna)

Austria
(Vienna)

2012

2012

Ann Thorac Surg

Lasers Surg Med

Light-induced vasodilation of coronary arteries and its possible

clinical implication.

Low-level-laser irradiation induces photorelaxation in coronary

arteries and overcomes vasospasm of internal thoracic arteries.

In vitro

In vitro

LED phototherapy

680
(laser)

Dose response
Biphasic dose
response

670
(LED)
680

1.5
2.5
5
10

"Vessels exposed to either light source showed a remarkable as well as

comparable photorelaxation at definite energy densities. This effect is mediated by
an intracellular nitric oxide-dependent mechanism. As LED sources are of small
size, simple, and inexpensive build-up, they may be used during routine coronary
artery bypass surgery to ease suturing of anastomosis by target vessel
vasodilation."

PubMed

"Macroscopic healthy LAD exposed to [low-level laser irradiation] revealed

significant photorelaxation. With the administration of [low-level laser irradiation,
73% of the maximal obtainable effect by an endothelium-dependent vasodilator
could be reached. Furthermore, [low-level laser irradiation] has the potential to
overcome vasospasms of [internal thoracic arteries."

PubMed

"TinniTool (Adisma) is a diode laser delivering continuous-wave laser light with a wavelength of 650 nm."

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Heart

Gene
expression

Khanna

USA
1999
(Milwaukee, WI)

Cardiovasc Radiat Augmentation of the expression of proangiogenic genes in

Med
cardiomyocytes with low dose laser irradiation in vitro.

In vitro

633

Heart

Heart failure

Hentschke

Brazil
(Porto Alegre)

2016
epub

Lasers Med Sci

Maximal oxygen uptake and exercise tolerance are improved in

rats with heart failure subjected to low-level laser therapy
associated with resistance training.

Rat

Heart

Heart failure

Bublitz

Brazil

2016

Lasers Med Sci

Acute effects of low-level laser therapy irradiation on blood lactate

and muscle fatigue perception in hospitalized patients with heart
failure-a pilot study.

Human
RCT

Heart

Heart failure

Capalonga

Brazil
(Porto Alegre)

2016

Lasers Med Sci

Light-emitting diode therapy (LEDT) improves functional capacity

in rats with heart failure.

Rat

Heart

Review

Liu & Zhang

China
(Beijing)

2016

Photomed Laser
Surg

Low-Level Laser Irradiation Precondition for Cardiac Regenerative

Therapy.

Review

Heart

Heart failure

Biasibetti

Brazil
(Porto Alegre)

2014

Lasers Med Sci

The influence of low-level laser therapy on parameters of oxidative

stress and DNA damage on muscle and plasma in rats with heart
failure.

Rat

Heart failure markers

660

20

0.571

Heart

Heart failure

Hentschke

Brazil
(Porto Alegre)

2013

Lasers Med Sci

Low-level laser therapy improves the inflammatory profile of rats

with heart failure.

Rat

Heart failure

660

20

Heart

MI

Blatt

Israel

2016

Photomed Laser
Surg

Low-Level Laser Therapy to the Bone Marrow Reduces Scarring

and Improves Heart Function Post-Acute Myocardial Infarction in
the Pig.

Pig

MI

808

Heart

MI

Carlos

Brazil
(So Paulo)

2016

Life Sci

Role of low-level laser therapy on the cardiac remodeling after

Systematic
myocardial infarction: A systematic review of experimental studies. Review

MI

Heart

MI

Quirk

USA
2014
(Milwaukee, WI)

Photomed Laser
Surg

Cardioprotection from ischemia-reperfusion injury by near-infrared

light in rats.

Ischemia-reperfusion

Year

Journal

Dose response

Results: positive / unclear/modest / negative

Link

Additional info

sec

"We observed that a dose-dependent increase in cardiomyocytes proliferation can

be obtained with [low power red laser light] and that there is a significant increase
in VEGF and TGF-beta mRNA expression by cardiomyocytes."

PubMed

"These data may have significant importance leading to the establishment of new
methods for myocardial photoangiogenesis and photoregeneration as well as in
vitro proliferation of cardiac myocytes."
850

300

Heart failure

808

100

LED phototherapy

850

50

8.33

8.8

61.25

0.012
cm2

29

32

28

0.250

15

0.2
cm2

60
/point

40

"LLLT associated with [resistance training] improved oxygen uptake and exercise
tolerance compared with [resistance training] alone in [heart failure] rats."

PubMed

LLLT was associated with decreased perceived exercion, but functional capacity
wasn't improved.

PubMed

"Sham and LEDT-HF groups showed higher relative values than the Control-HF
group, respectively, for distance covered (27.7 and 32.5 %), time of exercise test
(17.7 and 20.5 %), and speed (13.6 and 12.2 %)."

PubMed

n = 20

Note: In this paper, the "sham" group does not refer to sham-therapy, but instead
to sham-HF.
"LLLI preconditioning provides a promising approach to maximize the efficacy of cardiac cell-based therapy. Although many studies have reported
possible molecular mechanisms involved in LLLI preconditioning, the exact mechanisms are still not clearly understood."
0.21
1.47

0.035
cm2
(/p)

10.5
73.5
(2p)

10

(?)

PubMed

0.571

3
21

0.035
cm2

5.25
36.8

10

"LLLT showed systemic and skeletal muscle anti-inflammatory effects in rats with
HF."

PubMed

0.01
(BM)

1
(BM)

d=
8 mm

100

"LLLT application to BM in the porcine model for MI caused a significant reduction

in scarring, enhanced angiogenesis and functional improvement both in the acute
and long term phase post-MI."

PubMed

Systemic effect

Rat

"The reduction in infarct size is a major finding. The LLLT cardioprotection may be mediated by several molecular and cellular mechanisms. Although
these results are exciting, there are many limitations that must be resolved before LLLT clinical trials."
670

0.03
(heart)

18

600

"NIR application had no effect on the function of the nonischemic isolated heart,
and had no effect on infarct size when applied during global ischemia.

LED phototherapy
LED cluster

Heart

MI

Keszler

USA
2014
(Milwaukee, WI)

Front Physiol

Far red/near infrared light-induced protection against cardiac

ischemia and reperfusion injury remains intact under diabetic
conditions and is independent of nitric oxide synthase.

Mouse

Diabetic mice

PubMed

3
21

PubMed
PubMed

In the in vivo model, NIR commencing immediately before reperfusion decreased

infarct size by 40%, 33%, 38%, and 77%, respectively, after regional ischemic
periods of 30, 20, 15, and 10 min."
670

0.170

300

"Here we tested the hypothesis that NIR elicits protection in a diabetic mouse
model where other cardioprotective interventions such as pre- and
postconditioning fail, and that the protection is independent of nitric oxide synthase
(NOS).

Dose response
LED phototherapy
LED array

PubMed

NIR reduced infarct size dose dependently. Importantly, NIR-induced protection

was preserved in a diabetic mouse model (db/db) and during acute
hyperglycemia, as well as in endothelial NOS(-/-) mice and in wild type mice
treated with NOS inhibitor L-NAME."
"Irradiation at 660 nm yields the highest release of NO, while at longer
wavelengths a dramatic decrease of NO release can be observed."
"NIR is cardioprotective in the presence of diabetes or hyperglycemia."
"In summary, NIR applied during reperfusion protects the myocardium against
infarction in an NO-dependent, but NOS-independent mechanisms, whereby
mitochondria may be a target of NO released by NIR, leading to reduced reactive
oxygen species generation during reperfusion. This unique mechanism preserves
protection even during diabetes where other protective strategies fail."
Comment: Beam area was not reported. According to the paper, LED array was
used, so it's likely the area was large.

Heart

MI

Manchini

Brazil
(So Paulo)

2014

PLoS One

Amelioration of cardiac function and activation of antiinflammatory vasoactive peptides expression in the rat
myocardium by low level laser therapy.

Rat

MI

660

15

1.1

Heart

MI

Yang

China
(Zhengzhou)

2013

Photomed Laser
Surg

Effect of low-level laser irradiation on oxygen free radicals and

ventricular remodeling in the infarcted rat heart.

Rat

MI

635

0.0076

Heart

MI

Yang

China (Beijing)

2011

Photomed Laser
Surg

Low-level laser irradiation alters cardiac cytokine expression

following acute myocardial infarction: a potential mechanism for
laser therapy.

Rat

MI

635

0.006

Heart

MI

Tuby

Israel

2011

Lasers Surg Med

Induction of autologous mesenchymal stem cells in the bone

marrow by low-level laser therapy has profound beneficial effects
on the infarcted rat heart.

Rat

MI
Systemic effect

804

Heart

MI

Zhang

China (Beijing)

2010

J Cell Mol Med

Low level laser irradiation precondition to create friendly milieu of

infarcted myocardium and enhance early survival of transplanted
bone marrow cells.

Rat

MI

804

Heart

MI

Lohr

USA
2009
(Milwaukee, WI)

J Mol Cell Cardiol

Enhancement of nitric oxide release from nitrosyl hemoglobin and

nitrosyl myoglobin by red/near infrared radiation: potential role in
cardioprotection.

Rabbit

Heart

MI

Tuby

Israel

2009

Photomed Laser
Surg

Implantation of low-level laser irradiated mesenchymal stem cells

into the infarcted rat heart is associated with reduction in infarct
size and enhanced angiogenesis.

Rat

MI
MSCs

Heart

MI

Tuby

Israel

2006

Lasers Surg Med

Modulations of VEGF and iNOS in the rat heart by low level laser
therapy are associated with cardioprotection and enhanced
angiogenesis.

Rat

MI
Angiogenesis

804

Heart

MI

Yaakobi

Israel

2001

Lasers Surg Med

Long-term effect of low energy laser irradiation on infarction and

reperfusion injury in the rat heart.

Rat

MI

804

38

Heart

MI

Oron

Israel

2001

Lasers Surg Med

Attenuation of infarct size in rats and dogs after myocardial

infarction by low-energy laser irradiation.

Rat, Dog

MI

810
(rat)

38

0.005

810
(dog)

400

22.5

0.785
cm2

0.96

0.8

60

"Our data suggest that LLLT diminishes the acute inflammation in the
myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI
and increases vasoactive peptides expression and nitric oxide (NO) generation."

PubMed

125

"LLLI could cause OFR accumulation, reduce infarct size, increase ventricular wall
thickness, and attenuate the formation of collagen fibers, suggesting the beneficial
effects of LLLI on improvement of VR after MI."

PubMed

0.8
cm2

150

"Although LLLI did not improve the damaged heart function, it did reduce the
infarct area expansion."

PubMed

0.01

d=
1.8 cm

100

"Infarct size and ventricular dilatation were significantly reduced (76% and 75%,
respectively) in the laser-treated rats 20 minutes post-MI as compared to the
control-non-treated rats at 3 weeks post-MI. There was also a significant 25-fold
increase in cell density of c-kit+ cells in the infarcted area of the laser-treated rats
(20 minutes post-MI) as compared to the non-laser-treated controls."

PubMed

0.01

d=
1.8 cm

100

"After LLLI precondition, increased VEGF and GRP78 expression, as well as the
enhanced SOD activity and inhibited MDA production, was observed. Compared
with BMSC transplantation and culture media injection group, although there was
no difference in the improved heart function and myogenic differentiation, LLLI
precondition significantly enhanced early cell survival rate by 2-fold, decreased the
apoptotic percentage of implanted BMSCs in infarcted myocardium and thus
increased the number of newly formed capillaries. Taken together, LLLI
precondition could be a novel non-invasive approach for intraoperative cell
transplantation to enhance cell early survival and therapeutic potential."

PubMed

"As shown in Figure 5B, exposure of the rabbit cardiac preparation to 60 mW/cm2
(11 J) of 670 nm light, in the absence of nitrite, at the time of reperfusion resulted
in a significant reduction in infarct size whereas a lower power radiation (3
mW/cm2, 0.5J) was ineffective. Interestingly, when low dose radiation (3 mW/cm2)
was combined with low-dose nitrite (0.4 mg/kg) a synergistic effect was observed
suggesting that R/NIR is able to potentiate the cardioprotective effects of nitrite."

PubMed

[Star: interesting results!]

670

804/81
0 (?)

0.003
0.06

0.05

0.5
11

d=
1.8 cm
(?)

20

"The findings of the present study provide the first evidence that LLLT can
significantly increase survival and/or proliferation of MSCs post-implantation into
the ischemic/infarcted heart, followed by a marked reduction of scarring and
enhanced angiogenesis. The mechanisms associated with this phenomenon
remain to be elucidated in further studies."

PubMed

0.008
@
heart

0.96

d=
2 cm

120

"It is concluded that VEGF and iNOS expression in the infarcted rat heart is
markedly upregulated by LLLT and is associated with enhanced angiogenesis and
cardioprotection."

PubMed

0.0045

0.27
+
0.81

1.1
cm2

60

1
+
1

LLLT decreased infarct size and increased HSP70 and angiogenesis.

PubMed

Star: The article was quite extensive, with multiple measurements of infarct sizes
at different time points.

1.1
cm2

LLLT protected against myocardial infarction. In rats, a bi-phasic dose response

was noted.

3.0
cm2

Infarct size decrease according to energy densities (in rats)

2.5 mW/cm2 ---> 14 %
6 mW/cm2 -----> 62 % (significant)
20 mW/cm2 ------> 2.8

PubMed

(other experiments were also done)

Heart

MI

Oron

Israel

2001

Circulation

Low-energy laser irradiation reduces formation of scar tissue after

myocardial infarction in rats and dogs.

Rat, Dog

MI

Heart

MI

Ad & Oron

Israel

2001

Int J Cardiol

Impact of low level laser irradiation on infarct size in the rat

following myocardial infarction.

Rat

MI

Heart

MI

Whittaker &
Patterson

USA (LA,
California)

2000

Lasers Surg Med

Ventricular remodeling after acute myocardial infarction: effect of

low-intensity laser irradiation.

Rat

MI

Heart

MI

Whittaker (Peter)

USA (LA,
California)

1999

Lasers Surg Med

Laser-mediated reversal of cardiac expansion after myocardial

infarction.

Rat

MI
LLLT? ( = 1320 nm)

Heart

Russian
research

Moshkovska &
Mayberry

UK
(Leicester)

2005

Postgrad Med J

It is time to test low level laser therapy in Great Britain.

Review

Heart

Transplants

Lukes

Sweden
(Gteborg)

2005

Transplant Proc

Singlet oxygen energy illumination during moderate cold ischemia

prolongs the survival of concordant hamster xeno-heart
transplants.

Rat

803

ATP content in the ischemic zone was 7.6-fold higher in LLLT rats. Infarct size
was 52% reduced in dogs. NIR (803nm) was used.

PubMed

"The infarct size (expressed as percent of total left ventricle area) of the LI rats
was 10.1+/-5.8, which was significantly lower (65%; P<0.01) than the infarct size
of NLI rats which was 28.7+/-9.6."

PubMed

780

"Laser-treated fibroblasts occupied more area than controls. Hearts receiving the
10 mW treatment had smaller volumes than sham hearts. Laser treatment
reduced infarct thinning and preserved arterial lumen area; however, collagen was
not increased and inflammation was inhibited."

PubMed

1320
(?)

"Cavity volume was reduced by laser treatment (0.72 +/- 0.07 ml vs. 0.54 +/- 0.05
ml; P= 0.044). In addition, treatment resulted in thicker scars, a leftward shift of the
heart's electrical axis, and straightening of collagen fibers."

PubMed

"Low level laser therapy (LLLT) has been used in Eastern Europe and Asia for the treatment of a wide range of conditions for many years. Its continued
acceptance in these populations reflects the efficacy with which it is regarded both by clinicians and their patients. Although there have been a
substantial number of reports on its clinical benefit and some practitioners have used the technique in North America and Australasia it has yet to be
subjected to detailed assessment through randomised clinical trials."

PubMed

Comment: An interesting review, focusing especially in Russian studies on LLLT and heart disease. Many of the cited studies seem to be based on
intravenous LLLT.
634

"The graft survival of SOE-illuminated ischemic hamster xenografts was 2.34 +/0.56 versus 1.15 +/- 0.37 days in the control group (P < .05). All hearts displayed
immediate graft function versus 70% in the controls (NS)."

PubMed

"SOE illumination at lambda 634 nm during moderate cold ischemia (+4 degrees
C) can improve the survival of concordant hamster xeno-heart transplants. The
exact mechanism(s) are currently unknown, but the effect might in part be exerted
by a combination of reduced production of ROS and increased oxidative
phosphorylation."

Immunity

Neutrophils

Cerdeira

Brazil&USA

2016

J Biophotonics

Low-level laser therapy stimulates the oxidative burst in human

neutrophils and increases their fungicidal capacity.

In vitro

PubMed

= 1320 nm <-- is it LLLT anymore?

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Immunity

Mast cells

de Carvalho
Monteiro

Brazil
(Salvador,
Bahia)

2011

Photomed Laser
Surg

Effect of LED red and IR Photobiomodulation in tongue mast cells

in Wistar rats: histological study.

Rat

850
630

Immunity

Monocytes

In vitro

660

670

Category

nm

mW

W/cm2

J/cm2

sec

21.9

73

Chen

Taiwan
(Kaohsiung)

2014

Mediators Inflamm Effects of low-level laser therapy on M1-related cytokine

expression in monocytes via histone modification.

Immunity

Lee

Korea
(Seoul)

2011

J Photochem
Photobiol B

Enhancement of cutaneous immune response to bacterial infection

after low-level light therapy with 1072 nm infrared light: a
preliminary study.

Immunity

Vilela

Brazil
(Salvador,
Bahia)

2012

J Photochem
Photobiol B

Influence of the HPA axis on the inflammatory response in

cutaneous wounds with the use of 670-nm laser
photobiomodulation.

Rat

2017
epub

Lasers Med Sci

Effects of low-level laser irradiation on human blood lymphocytes

in vitro.

In vitro

Whole blood
irradiation

405
589
780

Whole blood
irradiation

660

Immunity

Lymphocytes

Al Musawi

Malaysia
(Pulau Pinang)

Immunity

Lymphocytes

Stadler

USA
2000
(Rochester, NY)

Lasers Surg Med

In vitro effects of low-level laser irradiation at 660 nm on peripheral

blood lymphocytes.

In vitro

Immunity

Macrophagelike cells

Fernandes

Brazil
(So Paulo)

2015

J Photochem
Photobiol B

Photobiomodulation with 660-nm and 780-nm laser on activated

J774 macrophage-like cells: Effect on M1 inflammatory markers.

In vitro

Immunity

Macrophages
(alveolar)

Souza

Brazil
(So Paulo)

2014

J Photochem
Photobiol B

Low-level laser therapy suppresses the oxidative stress-induced

glucocorticoids resistance in U937 cells: relevance to cytokine
secretion and histone deacetylase in alveolar macrophages.

In vitro

Immunity

Macrophages
(alveolar)

de Lima

Brazil
(So Paulo)

2010

Photomed Laser
Surg

Low-level laser therapy associated to N-acetylcysteine lowers

macrophage inflammatory protein-2 (MIP-2) mRNA expression and
generation of intracellular reactive oxygen species in alveolar
macrophages.

In vitro

Immunity

Macrophages

Lu

China
(Guangzhou)

2016

Int J Biochem Cell Photo-enhancement of macrophage phagocytic activity via Rac1Biol

mediated signaling pathway: Implications for bacterial infection.

Results: positive / unclear/modest / negative

Our results lead us to conclude that both red and IR-LED light caused increased
mast cell degranulation and that IR-LED light resulted in a greater number of mast
cells.

Link

PubMed

PubMed

0.03

"Decreases in the number of CD45-positive inflammatory cells and in the total

numbers of CD8- and CD45-positive cells were observed in histological sections
of adrenalectomized animals subjected to laser biomodulation at 24h. Similar
results were observed for distribution of total lymphocytes in blood (p<0.05). The
action of 670 nm laser does not depend exclusively on HPA axis. It is believed that
corticosteroid-promoting enzymes liberated in non-adrenal tissues may influence
immune response under the influence of this type of phototherapy."

PubMed

36
54
72
90

"At a wavelength of 589 nm and fluence of 72 J/cm2, irradiation of whole blood

samples showed a significant increase in CD45 lymphocytes and natural killer
(NK) (CD16, CD56) cells, but no significant changes in CD3 T lymphocytes, Tsuppressor (CD3, CD8) cells, T-helper (CD3, CD4) cells, and CD19 B
lymphocytes when compared with their non-irradiated counterparts. Our results
clearly demonstrate that NK cell count is altered by irradiation, which ultimately
affects the whole lymphocyte count significantly."

PubMed

05.0

"Lymphocyte proliferation was significantly higher (P<0.05) as expressed by a

Stimulation Index in samples irradiated in the presence of whole blood compared
with lymphocytes irradiated after isolation from whole blood. Free radical and lipid
peroxide production also increased significantly when samples were irradiated in
the presence of red blood cells."

PubMed

"The present study supports the hypothesis that one mechanism for the
photobiostimulation effect after irradiation at 660 nm is the reaction of light with
hemoglobin, resulting in oxygen radical production."
660

15

7.5

20

780

70

2.6

1.5

"Both lasers were able to reduce TNF- and iNOS expression, and TNF- and
COX-2 production, although the parameters used for 780 nm laser provided an
additional decrease. 660 nm laser parameters resulted in an up-regulation of IL-6
expression and production.

PubMed

These findings imply a distinct, time-dependent modulation by the two different

sets of laser parameters, suggesting that the best modulation may involve more
than one combination of parameters."
"LLLT and dexa inhibited the LPS-stimulated U937 cells cytokines, but dexa effect
disappeared with H2O2. With TSA, the LLLT was less effective on H2O2/LPS
stimulated- U937 cells cytokines. Dexa failed on H2O2/LPS- induced HDAC, while
LLLT restored the HDAC and the dexa effect. LLLT plus prostaglandin E2 (PGE2)
increased cyclic adenosine monophosphate (cAMP) and potentiated the laser
action on oxidative stress-induced cytokine. LLLT reduced the PI3K and its effects
on cytokine and HDAC was suppressed with LY294002.

PubMed

In situations of corticoid resistance, LLLT acts decreasing the cytokines and

HDAC through the activation of the protein kinase A via the inhibition of PI3K."

Mouse
+ in vitro

660

Listeria infection

30

252

"LLLT attenuated the MIP-2 mRNA expression and intracellular ROS generation
after LPS or H(2)O(2). When the AM were pretreated with NAC, the laser effect
was potentiated. BMS 205820 suppresses the effect of LLLT on MIP-2 mRNA
expression and ROS generation, stimulated by LPS or H(2)O(2). On NF-B
transcription factor, both the LLLT and NAC reduced this protein in the AM
exposed to LPS or H(2)O(2). The synergistic effect between LLLT and NAC on the
reduction the NF-B was also evidenced."

PubMed

1
2
4

300
300
300

PubMed

633

300

"Here, we demonstrated for the first time that LPLI enhanced the phagocytic
activity of macrophages by stimulating the activation of Rac1. The overexpression
of constitutively activated Rac1 clearly enhanced LPLI-induced phagocytosis,
whereas the overexpression of dominant negative Rac1 exerted the opposite
effect. The phosphorylation of cofilin was involved in the effects of LPLI on
phagocytosis, which was regulated by the membrane translocation and activation
of Rac1.

(in
vivo)

(periton
eal
cavity)

633

4.5

0.0033
0.0066
0.0133

(in
vitro)

0.785
cm2

Furthermore, the photoactivation of Rac1 was dependent on the Src/PI3K/Vav1

pathway. The inhibition of the Src/PI3K pathway significantly suppressed LPLIinduced actin polymerization and phagocytosis enhancement.
Additionally, LPLI-treated mice exhibited increased survival and a decreased
organ bacterial load when challenged with Listeria monocytogenes, indicating that
LPLI enhanced macrophage phagocytosis in vivo."
"These findings highlight the important roles of the Src/PI3K/Vav1/Rac1/cofilin
pathway in regulating macrophage phagocytosis and provide a potential strategy
for treating phagocytic deficiency via LPLI."

Immunity

Macrophages

Gavish

Israel
(Jerusalem)

2008

Lasers Surg Med

Irradiation with 780 nm diode laser attenuates inflammatory

cytokines but upregulates nitric oxide in lipopolysaccharidestimulated macrophages: implications for the prevention of
aneurysm progression.

In vitro

780

Immunity

Monocytic cells
(U937)

Spoto

Italy
(Chieti)

2016

J Biol Regul
Homeost Agents

Effect of low energy light irradiation by light emitting diode on

U937 cells.

In vitro

880

0.002

2.2

"LLLI reduced gene expression of MCP-1, IL-1alpha, IL-10 (P<0.01), IL-1beta, and
IL-6 (P<0.05) when cells were stimulated by 1 microg/ml LPS. LLLI reduced LPSinduced secretion of MCP-1 over non-irradiated cells by 17+/-5% and 13+/-5% at
12 hours (0.1 and 1 microg/ml LPS; P<0.01 and P=0.05, respectively), and
reduced IL-1beta by 22+/-5% and 25+/-9% at 24 hours (0.1 and 1 microg/ml LPS,
P=0.01 and P=0.06, respectively)."

PubMed

"These properties of LLLI [...] may be of profound therapeutic relevance for arterial
diseases such as aneurysm where inflammatory processes and weakening of the
matrix structure of the arterial wall are major pathologic components."
"We demonstrate that LED exposure, in the presence or absence of
lipopolysaccharide (LPS), activates cell degranulation, increased expression of
Interleukin-8 (IL-8) and modulation of beta galactosidase activity.

PubMed

Evidence shows that the well-known pro-inflammatory nuclear factor kappa-lightchain-enhancer of activated B cells (NF-kB) and the apoptotic marker
(caspase3/cleaved-caspase3 ratio) are up-regulated in response to a
proinflammatory biochemical pathway."

Immunity

Sepsis

Yu

USA
1997
(Rochester, NY)

Lasers Surg Med

Improvement of host response to sepsis by photobiomodulation.

Rat

630

Infections

Bacteria

Silva

Brazil
(Petrolina)

2013

An Bras Dermatol

Low level laser therapy (AlGaInP) applied at 5J/cm2 reduces the

proliferation of Staphylococcus aureus MRSA in infected wounds
and intact skin of rats.

Rat

658

Infections

Bacteria

Lubart

Israel
(Ramat Gan)

2011

Laser Ther

A possible mechanism for the bactericidal effect of visible light.

Review

Infections

Bacteria

Lipovsky

Israel
(Ramat Gan)

2010

Lasers Surg Med

Visible light-induced killing of bacteria as a function of wavelength: In vitro

implication for wound healing.

0.02

d=
5 cm

"LI significantly improved ex-vivo lymphocyte proliferation of cells from septic rats
(179.7 +/- 17.2 vs. 129.5 +/- 7.8; P < 0.01) and enhanced survival in septic rats
(79% vs. 42%; P < 0.001). LI significantly stimulated lymphocyte proliferation in
the presence of mitogenic stimuli and enhanced lymphocyte ATP synthesis (P <
0.05)."

PubMed

"LI improves the host immune response and survival rate in sepsis in an animal
model. Our studies suggest that LI may be useful as an adjuvant therapy for
sepsis."
5

"The laser (AlGaInP), with a dose of 5J/cm2 in both intact skin and in wounds of
rats infected with Staphylococcus aureus MRSA, is shown to reduce bacterial
proliferation."

"Phototoxic effects were found to involve induction of high amounts of reactive oxygen species (ROS) by the bacteria while low amounts of ROS may
promote their

PubMed

PubMed

"Intense blue light, preferably at 415nm, is better than red light for bacteria killing."

Red light vs blue light

400500
500800

Infections

Bacteria

Lipovsky

Israel
(Ramat Gan)

2008

Lasers Surg Med

A possible mechanism for visible light-induced wound healing.

In vitro

Infections

Fungal

Seyedmousavi

Iran
(/Netherlands)

2014

Photomed Laser
Surg

Effects of low-level laser irradiation on the pathogenicity of

Candida albicans: in vitro and in vivo study.

In vitro
In vivo (mice,
n=110)

Infections

Staphylococcus

Ma

China (Tianjin)

2012

Lasers Med Sci

Antiinflammatory effect of low-level laser therapy on

Staphylococcus epidermidis endophthalmitis in rabbits.

Rabbit

400800

120

685
830

Endophthalmitis

632

10

8
(2)

d=
1 cm

"ROS production following blue (400-500 nm) light illumination was found to be
higher than that of red (500-800 nm). Within the blue range, light of 415 nm
induced more ROS than 455 nm, which correlated with results obtained for the
reduction in colony count of S. aureus and E. coli following illumination using equal
intensities of these two wavelengths."

PubMed

"Illumination with white light, 120 J/cm(2), caused a reduction of 62%, 83%, and
56% in the colony count of E. coli 1313, S. aureus 195 and S. marcescens,
respectively, though no reduction in the viability of P. aeruginosa 1316 was
demonstrated. The phototoxic effect was found to involve induction of ROS
production by the bacteria. It was also found that illumination of S. aureus 195 and
E. coli 1313 in the presence of pyocyanin, known to be secreted by P. aeruginosa,
had a stronger bactericidal effect compared to illumination alone."

PubMed

LLLT improved the survival of infected mice dose-dependently. both 685nm and
830nm were effective.

PubMed

"As an adjunct to vancomycin therapy to treat S. epidermidis endophthalmitis,

LLLT has an antiinflammatory effect similar to that of dexamethasone."

PubMed

"Bees exposed to insecticide and daily to 670nm light showed corrected ATP
levels and significantly improved mobility allowing them to feed. Physiological
recordings from eyes revealed that light exposure corrected deficits induced by the
pesticide. Overall, death rates in bees exposed to insecticide but also given
670nm light were indistinguishable from controls."

PubMed

LLLT vs
dexamethasone

Insect health

Bumblebee

Powner

UK
(London)

2016

PLoS One

Improving Mitochondrial Function Protects Bumblebees from

Neonicotinoid Pesticides.

Bumblebee

Imidaclopride toxicity

670

"Treatment with 670nm on control bees also resulted in a significant improvement

in survival over controls (P<0.01), similar to data from fruit flies exposed to this
light [15]"
"Hence, we show that deep red light exposure that improves mitochondrial
function, reverses the sensory and motor deficits induced by Imidacloprid."

Insect health

Fruit fly

Begum

UK
(London)

2015

Biol Lett

Near-infrared light increases ATP, extends lifespan and improves

mobility in aged Drosophila melanogaster.

Fruit fly

670

"Here, we expose fruitflies daily to 670 nm radiation, revealing elevated ATP and
reduced inflammation with age. Critically, there was a significant increase in
average lifespan: 100-175% more flies survived into old age following 670 nm
exposure and these had significantly improved mobility."

PubMed

Additional info

Comment

Reply

 Category

Subcategory

Intravascular
LLLT

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Huang

Taiwan
(Taipei)

2012

Photomed Laser
Surg

Effects of intravascular laser irradiation of blood in mitochondria

dysfunction and oxidative stress in adults with chronic spinal cord
injury.

Human
RCT/SB

Stasinopoulos

Cyprus
(Nicosia)

2016

Lasers Med Sci

LLLT for the management of patients with ankylosing spondylitis.

nm

mW

W/cm2

J/cm2

633

2.04

14.4

7347

Human
RCT/SB

820

30

0.06

27
(6p)

810

100

1
3
6
10

Spinal cord injury

patients

Link

Results: positive / unclear/modest / negative

0.196
mm2

3600

15

"At day 15 of therapy, the study group revealed a significantly higher mitochondrial
DNA (mtDNA) copy number, white blood cell adenosine triphosphate (WBC ATP)
synthesis, and total antioxidant capacity (TAC) with significantly reduced
malondialdehyde (MDA), than did the sham group."

0.5
cm2

900
(6p)

12

"The results suggested that after an 8-week treatment and after a follow-up, the
combination of LLLT and passive stretching exercises decreased pain more
effectively than placebo LLLT along with the same passive stretching exercises in
patients with nkylosing spondylitis"

PubMed

0.028
cm2

10
30
60
100

"This result was corroborated by cell counting showing the reduction of

polymorphonuclear cells at the inflammatory site. Vascular extravasation was
significantly inhibited at the higher dose of energy of 10 J. Both COX-1 and 2 gene
expression were significantly enhanced by laser irradiation while PGE(2)
production was inhibited. Low-level laser therapy operating at 810 nm markedly
reduced inflammatory signs of inflammation but increased COX-1 and 2 gene
expression."

PubMed

LLLT was highly effective in treating inflammatory arthritis in this model. Longer
illumination times were more effective than short times regardless of total fluence
or irradiance.

PubMed

Additional info

Comment

Reply

Comment

Reply

sec

PubMed

Star: The results are quite intriguing. This is interesting work.

Joints

Ankylosing
spondylitis

Joints

Arthritis

Pallotta

Brazil
(So Paulo)

2012

Lasers Med Sci

Infrared (810-nm) low-level laser therapy on rat experimental knee

inflammation.

Rat

Joints

Arthritis

Castano

USA
(Boston, MA)

2007

Lasers Surg Med

Low-level laser therapy for zymosan-induced arthritis in rats:

Importance of illumination time.

Rat

Joints

Arthritis

Brosseau

Canada
(Ontario)

2000

J Rheumatol

Low level laser therapy for osteoarthritis and rheumatoid arthritis:

a metaanalysis.

Metaanalysis

Acute knee arthritis

810

0.005
0.05

50
150
300
500

3
30

"LLLT should be considered for short term relief of pain and morning stiffness in RA, particularly since it has few side effects.

PubMed

For OA, the results are conflicting in different studies and may depend on the method of application and other features of the LLLT.
Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques. New trials on LLLT should
make use of standardized, validated outcomes.
Despite some positive findings, this metaanalysis lacked data on how effectiveness of LLLT is affected by 4 factors: wavelength, treatment duration of
LLLT, dosage, and site of application over nerves instead of joints. There is a need to investigate the effects of these factors on effectiveness of LLLT for
RA and OA in randomized controlled clinical trials."

Joints

Joints

Joints

Crystalopathy

Crystal
arthropathy

Haemophilic
arthropathy

Rubio

Soriano

El-Shamy &
Abdelaal

Argentina
(Crdoba)
Argentina
(Rosario)

Egypt
(Giza)

2009

2006

2016
epub

Photomed Laser
Surg
Photomed Laser
Surg

Disabil Rehabil

Inflammatory and oxidative stress markers in experimental

crystalopathy: their modification by photostimulation.
Photobiomodulation of pain and inflammation in microcrystalline
arthropathies: experimental and clinical results.

Efficacy of pulsed high-intensity laser therapy on pain, functional

capacity, and gait in children with haemophilic arthropathy.

Arthritis, exp
crystalopathy

633

Rat

Crystal arthropathy

633

Human
RCT

Acute gouty arthritis

Rat

3
5

fibrinogen
"Inflammatory and oxidative stress markers in experimental crystalopathy are
positively modified by photobiostimulation."

d=
2 mm

40
/point

"Fibrinogen, prostaglandin E(2), and TNF(alpha) concentrations in the rats injected

with crystals and treated with laser decreased significantly as compared with the
groups injected with crystals without treatment."

PubMed

"Both laser therapy and diclofenac achieved rapid pain relief in patients with acute
gouty arthritis without significant differences in efficacy. Laser therapy was more
effective than diclofenac in patients with chronic pyrophosphate arthropathy and in
patients with chronic apatite deposition disease."
1500

Human
RCT

"Children in the laser group showed significant improvement in pain, functional

capacity, and gait parameters compared to those in the placebo group (p < 0.05)."

PubMed

Comment 1: Parameters were somewhat poorly reported. Even wavelength was

not mentioned.
Comment 2: However, results are encouraging. This isn't the first time that
Egyptian researchers report very good results for the diseases they are treating
with "HILT".

Joints

Meniscus

Malliaropoulos

Greece
(Thessaloniki)

2013

Lasers Med Sci

Low-level laser therapy in meniscal pathology: a double-blinded

placebo-controlled trial.

904

Human
RCT/DB

240

0.24

100.8
/knee

~1
cm2

420
/knee

"The pain decreased approximately by 65 % 4 weeks after LLLT and by 22 % in

the placebo group."

PubMed

"Treatment with LLLT was associated with a significant decrease of symptoms

compared to the placebo group: it should be considered in patients with meniscal
tears who do not wish to undergo surgery."

Joints

Osteoarthritis

Kim

Korea
(Daegu)

2016

J Phys Ther Sci

The effects of high intensity laser therapy on pain and function in

patients with knee osteoarthritis.

1.5

Human
Controlled

300

"The comparison of the two groups showed that the high intensity laser therapy
group had statistically significant lower scores in both the visual analogue scale
and the Korean Western Ontario and McMaster Universities Osteoarthritis Index
than the conservative physical therapy group."

PubMed

"High intensity laser therapy is considered an effective non-surgical intervention

for reducing pain in patients with knee osteoarthritis and helping them to perform
daily activities."
Comment: The important parameters were not reported (wavelength, power
output, spot size etc).

Joints

Osteoarthritis

Saudi Arabia
(Al-Kharj)

2016
epub

Lasers Med Sci

905

Radiological and biochemical effects (CTX-II, MMP-3, 8, and 13) of

low-level laser therapy (LLLT) in chronic osteoarthritis in Al-Kharj,
Saudi Arabia.

25

12

1
cm2
/p

480

"After 4- and 8-week treatment, active laser group shows more significant
difference (p < 0.001) in all the parameters than the placebo laser group (p >
0.05). Our results show that low-level laser therapy was more efficient in reducing
pain and improving cartilage thickness through biochemical changes."

PubMed

(8p)
Star: In this study, the improvement in LLLT versus placebo is huge. Maybe they
found some good parameters for the treatment of knee osteoarthritis?

Joints

Joints

Osteoarthritis

Osteoarthritis

Youssef

Tomazoni

Saudi Arabia
(Dammam)
Brazil
(So Paulo)

2016

2016

J Lasers Med Sci

J Biomed Opt

Effect of Laser Therapy on Chronic Osteoarthritis of the Knee in

Older Subjects.
Isolated and combined effects of photobiomodulation therapy,
topical nonsteroidal anti-inflammatory drugs, and physical activity
in the treatment of osteoarthritis induced by papain.

27
48

Human
RCT
Rat

3
6

Osteoarthritis
induced by papain

"It can be concluded that addition of LLLT to exercise training program is more
effective than exercise training alone in the treatment of older patients with chronic
knee OA and the rate of improvement may be dose dependent, as with 6 J/cm(2)
or 3 J/cm(2)."

PubMed

"The results of this study indicate that PBMT is the most effective therapy in
stopping disease progression, and improving inflammatory conditions observed in
OA."

PubMed

"The results from the present study indicate that treatment with PBMT is more
effective in modulating the inflammatory process underlying OA when compared
with the other therapies tested."

PubMed

"We conclude that photobiomodulation therapy was able to promote the reduction
of proinflammatory cytokines such as TNF- and CINC-1, to reduce the gene and
protein expression of the bradykinin receptor (B1 and B2), as well as increasing
the stimulus response threshold of pressure in an experimental model of acute
osteoarthritis."

PubMed

PBM vs NSAID

Joints

Osteoarthritis

Tomazoni

Brazil
(So Paulo)

2016

Lasers Med Sci

Effects of photobiomodulation therapy, pharmacological therapy,

and physical exercise as single and/or combined treatment on the
inflammatory response induced by experimental osteoarthritis.

Rat

Knee osteoarthritis
induced by papain
PBM vs NSAID

Joints

Osteoarthritis

de Oliveira

Brazil
(So Paulo)

2016

Lasers Med Sci

Photobiomodulation therapy in the modulation of inflammatory

mediators and bradykinin receptors in an experimental model of
acute osteoarthritis.

Rat

Joints

Osteoarthritis

Huang

China
(Chengdu)

2015

Osteoarthritis
Cartilage

Effectiveness of low-level laser therapy in patients with knee

osteoarthritis: a systematic review and meta-analysis.

Metaanalysis

Osteoarthritis
induced by papain

808

50

1.78

4*

144

"Based on seven studies, the SMD in visual analog scale (VAS) pain score right after therapy (RAT) (within 2 weeks after the therapy) was not
significantly different between LLLT and control (SMD = -0.28 [95% CI = -0.66, 0.10], I(2) = 66%). No significant difference was identified in studies
conforming to the World Association of Laser Therapy (WALT) recommendations (four studies) or on the basis of OA severity."

PubMed

"Our findings indicate that the best available current evidence does not support the effectiveness of LLLT as a therapy for patients with KOA."
Note: A comment was published by a group of researchers, criticizing the meta-analysis for several different reasons. Huang's group also published a
reasonable reply.

Joints

Osteoarthritis

Atik OS

Turkey
(Ankara)

2015

Photomed Laser
Surg

Can we treat knee osteoarthritis with photomedicine?

"Although many studies using laser therapy have been conducted to decrease pain and improve function, the beneficial effects of photomedicine are still
controversial. This is probably because of lacking or heterogeneous data on laser type (HeNe, GaAs, GaAsAl), wavelength (632, 785, 810, 830, 850,
890, 904 nm), laser mode (continuous, pulsed), distance of probe from skin, irradiation points (28 points), duration of treatment (20 sec to 7 min), mean
power out (30800 mW), energy density (0.21848 J cm2 ), irradiation energy per point (0.136 J), spot size (0.028 0.0451 cm2 ), number of sessions,
and site of application of photobiomodulation.

Guest
Editorial

PubMed

On the other hand, until the last decade, the target tissue for the treatment of knee osteoarthritis was cartilage. Recently, this has been changed,
because of new data demonstrating that the pathogenesis involves not only cartilage but also subchondral bone and other soft tissues, including synovial
tissue in the joints."
"As mentioned by Lanzafame, overselling the attributes and benefits of photobiomodulation must be avoided; our path forward is best paved with careful
research and methodical testing of parameters and treatment paradigms, coupled with honest evaluation of the results, both positive and negative.2"

Joints

Osteoarthritis

Wang

China
(Chengdu)

2014

Lasers Med Sci

Effects of low-level laser therapy on joint pain, synovitis, anabolic,

and catabolic factors in a progressive osteoarthritis rabbit model.

830

Rabbit

1.5

24

"The histological assessment of pain and synovitis showed that at least 6-week
intermittent irradiation of LLLT could relief knee pain and control synovium
inflammation."

PubMed

"Gross morphologic inspection and histological evaluation showed that 6 weeks of

LLLT could decrease cartilage damage of medical femoral condyle and 8 weeks of
LLLT could decrease cartilage damage of medical and lateral femoral condyles
and medical tibial plateau."
"Gene expression analysis revealed two results: At least 6 weeks of LLLT could
decrease production of catabolic factors, for example, interleukin 1 (IL-1),
inducible nitric oxide synthase (iNOS), and MMP-3, and slow down the loss of
anabolic factors, mainly TIMP-1."
"Eight weeks of LLLT treatment could slow down the loss of collagen II, aggrecan,
and anabolic factors, mainly transforming growth factor beta (TGF-)."
"The study suggests that LLLT plays a protective role against cartilage
degradation and synovitis in rabbits with progressive OA by virtue of the regulation
of catabolic and anabolic factors in the cartilage."
Comment: It seems the results were quite modest.

Joints

Osteoarthritis

dos Santos

Brazil
(So Paulo)

2014

Lasers Med Sci

Comparative analysis of two low-level laser doses on the

expression of inflammatory mediators and on neutrophils and
macrophages in acute joint inflammation.

Rat

Papain-induced joint
inflammation

808

50

1.78
1.78

2
4

71.4
142.8

0.028
cm2

48
80

"Both laser modalities were efficient in reducing cellular inflammation and

decreasing the expression of IL-1 and IL-6. However, the 2-J treatment led to
more reduction in TNF- than the 4-J treatment. A single application of LLLT with
2 J was more efficient in modulating inflammatory mediators and inflammatory
cells."

PubMed

808

50
100

1.78
3.57

142.4

0.028
cm2

80
40

"Laser treatment with 50 mW was more efficient than 100 mW in reducing cellular
inflammation, and decreased the expression of IL-1 and IL-6. However, the 100
mW treatment led to a higher reduction of TNF compared with the 50 mW
treatment."

PubMed

890

6240

2400

Biphasic dose
response

Joints

Osteoarthritis

Alves

Brazil
(So Paulo)

2013

Arthritis Res Ther

Effect of low-level laser therapy on the expression of inflammatory

mediators and on neutrophils and macrophages in acute joint
inflammation.

Rat

Papain-induced joint
inflammation
Biphasic dose
response

Joints

Osteoarthritis

Hsieh

Taiwan
(Taipei)

2012

J Orthop Sports
Phys Ther

Therapeutic effects of short-term monochromatic infrared energy

therapy on patients with knee osteoarthritis: a double-blind,
randomized, placebo-controlled study.

Human
RCT/PB

MIRE treatment with

"Anodyne" LED pad
device

Star: In this paper, parameters are nicely reported in a table.

83.2

"Short-term MIRE therapy provided no beneficial effects to body functions,

activities, participation, and quality of life in patients with knee OA."
Comment: Because of the biphasic dose response, this dose might have been too
high by a few orders of magnitude...

PubMed

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Joints

Osteoarthritis

Hsieh

Taiwan
(Taipei)

2012

Arch Phys Med

Rehabil

Short-term effects of 890-nanometer radiation on pain, physical

Human
activity, and postural stability in patients with knee osteoarthritis: a RCT/PB
double-blind, randomized, placebo-controlled study.

Joints

Osteoarthritis

Bjordal

Norway
(Bergen)

2007

BMC
Musculoskelet
Disord

Short-term efficacy of physical interventions in osteoarthritic knee

pain. A systematic review and meta-analysis of randomised
placebo-controlled trials.

Metaanalysis
Rabbit

Category

Study type Sub-category 2 /

animal model
MIRE treatment with
"Anodyne" LED pad
device

nm

mW

W/cm2

J/cm2

sec

890

6240

41.6
/knee

2400

Results: positive / unclear/modest / negative

"Short-term 890-nm radiation therapy for patients with knee OA provided no

beneficial effect in improving pain, physical activity, and postural stability."

Link

Additional info

Comment

Reply

Comment

Reply

PubMed

Comment: Because of the biphasic dose response, this dose might have been too
high by a few orders of magnitude...
"Low level laser therapy (LLLT) offered clinically relevant pain relieving effects of [...] 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus
placebo control.

PubMed

In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to [...] 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS."

Osteoarthritis

Cho

Korea
(Gwangju)

2004

In vivo

Effect of low-level laser therapy on osteoarthropathy in rabbit.

Joints

Rheumatoid
arthritis

Alves

Brazil
(So Paulo)

2013

Lasers Med Sci

Low-level laser therapy in different stages of rheumatoid arthritis: a Rat

histological study.

Collagen-induced RA

780

Joints

Rheumatoid
arthritis

Zhang

Japan
(Matsudo)

2011

Laser Ther

Reduction of CXCR4 expression in Rheumatoid Arthritis Rat Joints

by low level diode laser irradiation.

Collagen-induced RA

830

Joints

300

28

75

7
14

"These results suggest that LLLT was effective in the treatment of chemicallyinduced OA."

PubMed

Note: The authors did not report wavelength or dose.

Rat

22

0.10

1.65
/p

7.7

0.214
cm2

500

"We observed that LLLT both at early and late RA progression stages significantly
improved mononuclear inflammatory cells, exudate protein, medullary
hemorrhage, hyperemia, necrosis, distribution of fibrocartilage, and chondroblasts
and osteoblasts compared to RA group (p < 0.05). We can conclude that LLLT is
able to modulate inflammatory response both in early as well as in late
progression stages of RA."
"CIA significantly increased swelling in the rat hind-paw and LLLI reduced the CIAinduced swelling."

PubMed

"Decreased CXCR4 expression may be one of the mechanisms in LLLI-mediated

reduction of RA inflammation."

Joints

Rheumatoid
arthritis

Yamaura

USA
(Boston, MA)

2009

Lasers Surg Med

Low level light effects on inflammatory cytokine production by

rheumatoid arthritis synoviocytes.

In vitro

(human
synoviocytes)

810

"Radiation at 810 nm (5 J/cm(2)) given before or after TNF-alpha decreases the

mRNA level of TNF-alpha and IL-1beta in RA synoviocytes.

PubMed

This treatment using 25 J/cm(2) also decreases the intracellular levels of TNFalpha, IL-1beta, and IL-8 protein but did not affect the levels of seven other
cytokines/chemokines.
TNF-alpha-induced activation of NF-kappaB is not altered by 810 nm radiation
using 25 J/cm(2)."

Joints

Rheumatoid
arthritis

Hall

UK

1994

Br J Rheumatol

Low level laser therapy is ineffective in the management of

rheumatoid arthritic finger joints.

Human
RCT

Hand arthritis
Single probe vs
cluster probe

Joints

Septic arthritis
(experimental)

Araujo

Brazil
(Cascavel)

2013

ISRN Rheumatol

Effects of Low-Level Laser Therapy, 660 nm, in Experimental

Septic Arthritis.

Rat

Kidney

Diabetic kidney

Lim

USA
(Bloomington,
IN)

2010

J Photochem
Photobiol B

Effects of low-level light therapy on streptozotocin-induced

diabetic kidney.

Rat

820

40

880&
870&
950&
820

60
total

0.4

3.6
/joint

36

0.1
cm2

90
/joint

12

"Using these irradiation parameters the efficacy of LLLT is ineffective."

PubMed

Star: Parameters were well reported.

4.527

660

0.1
cm2
*
31

180
/hand

"It was found that nociception increases in the right knee. There was a lack of
results for the seeding of the synovial fluid. The morphological analysis showed
slight recovery areas in the articular cartilage and synovia; however, there was the
maintenance of the inflammatory infiltrate."

PubMed

"The parameters used were not effective in the nociception reduction, even with
the slight tissue recovery due to the maintenance of inflammatory infiltrate, but
produced no change in the natural history of resolution of the infectious process."

LED phototherapy

670

0.035

10.5

300

70

cytochrome oxidase activity, cytochrome oxidase expression, serum BUN,

serum creatinine, BUN/creatinine ratio, 8-hydroxy-2'-deoxyguanosine in kidney

PubMed

"LLLT may be broadly applicable to ameliorate kidney complications induced by

diabetes that disrupt antioxidant defense mechanisms."

Kidney

Fibrosis

Oliveira

Brazil
(Juiz de Fora)

2012

Photomed Laser
Surg

Low-level laser therapy decreases renal interstitial fibrosis.

Rat

UUO --> renal

interstitial fibrosis

780

Kidney

Glomerulonephr
itis

Yamata

Japan
(Kobe)

2013

Lasers Med Sci

Low-level laser therapy improves crescentic glomerulonephritis in

rats.

Rat

Glomerulonephritis
(crescentic)

830

30

0.75

22.5

4
mm2

270

220

2.27
cm2

250

14

"For the first time, we showed that LLLT had a protective effect regarding renal
interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can
prevent tubular activation and transdifferentiation, which are the two processes
that mainly drive the renal fibrosis of the UUO model."

PubMed

Note: See comment&reply of this paper. They discuss the mechanism a little bit.

0.88

500

"Histological observations indicated that LLLT suppressed crescent formation and

infiltration of ED1+ macrophages and CD8+ lymphocytes into the glomeruli. LLLT
attenuated the levels of IL-1 and TNF- messenger RNA in the renal cortex.

PubMed

Externally directed LLLT suppresses the activity of rat anti-GBM crescentic

glomerulonephritis in rats. LLLT has the potential to be used for direct treatment of
glomerulonephritis."
Star: Parameters were well reported.

Kidney

Ischemia

Asghari

Iran
(Tehran)

2016

USA
(Bloomington,
IN)

2011

Lasers Med Sci

Effect of photobiomodulation on ischemia/reperfusion-induced

renal damage in diabetic rats.

Rat

Acceleration of the meckel syndrome by near-infrared light

therapy.

Rat

Diabetic rats

685

15

3.2

0.28
cm2

Effects of photobiomodulation:

PubMed

GSH, SOD, CAT

BUN, MDA, MPO, NO, creatinine, histological injury
"The results of present investigation revealed that PBM attenuated kidney damage
induced by renal IR in diabetic rats."

Kidney

Meckel
syndrome

Lim

Nephron Extra

Meckel syndrome

640690

"LED phototherapy initiated after the onset of symptoms was detrimental to MKSinduced pathology.

LED phototherapy

Kidney

Metabolic
syndrome

Ucero

Spain

2013

Photochem
Photobiol

Laser therapy in metabolic syndrome-related kidney injury.

Rat

Kidney injury

785

Larynx

Reflux laryngitis

Marinho

Brazil
(So Cristvo)

2014

Lasers Med Sci

Potential anti-inflammatory effect of low-level laser therapy on the

experimental reflux laryngitis: a preliminary study.

Rat

Experimental reflux
laryngitis

780

70

70

4.2

105

Reflux laryngitis

Marinho

Brazil
(So Cristvo)

2013

J Photochem
Photobiol B

Potentiated anti-inflammatory effect of combined 780 nm and 660

nm low level laser therapy on the experimental laryngitis.

Rat

Experimental reflux
laryngitis
Combined
wavelengths

0.04
cm2

180

(3p)
(*3p)

Combined
wavelengths

Larynx

PubMed

NIR stimulates CCO thereby increasing the kidney's need for oxygen. We
hypothesize that cystic compression of the vasculature impairs oxygen availability
and the enhanced CCO activity produces more radicals, which are not sufficiently
detoxified by the increased CAT activity."
blood pressure
glomerular filtration rate

PubMed

"In conclusion, we demonstrated that 105-J/cm2 infrared laser irradiation is

potentially useful to control reflux laryngitis secondary to nasogastric intubation by
reducing the influx of neutrophils to the injured area and improving the reparative
collagenization of the laryngeal tissues."

PubMed

"Therefore, we suggest that low-level laser is a promising therapy to be used in

treatment of reflux-induced laryngitis."
780

70

1.75

2.1

17.5

40

1.00

1.2

10.0

0.04
cm2

30
(3p)

or
780+
660

- || - || -

"In conclusion, we demonstrated that the combined 17.5 J/cm2 at 780 nm and
10.0 J/cm2 at 660 nm successfully modulated early inflammatory response in
experimental model of nasogastric intubation-induced reflux laryngitis. The
possible mechanism involves the reduction in neutrophil infiltration, modulation of
mast cells degranulation, and improved granulation tissue formation and collagen
deposition in the injured area."

PubMed

[Star: Parameters were very well reported - and the combined wavelength
experiment was interesting.]

660
840

LED
technology

Lim

Korea
(Chungnam)

2015

Mol Cryst Liq

Cryst

Red/Infrared LED Unit with Moderate Light Intensity and Low Heat
Generation for Personal Phototherapy Applications

Lichen planus

Cafaro

Italy

2014

Lasers Med Sci

Clinical evaluation of the efficiency of low-level laser therapy for

oral lichen planus: a prospective case series.

Case series

980

Lichen planus

Gambino

Italy

2013

Ann Stomatol
(Roma)

LLLT in combination with non-surgical periodontal therapy in

patients with gingival oral lichen planus: a pilot study.

Case series

980

Bublitz

Brazil
(Santos)

2014

Lasers Med Sci

Low-level laser therapy prevents degenerative morphological

changes in an experimental model of anterior cruciate ligament
transection in rats.

Rat

Effect of low-level laser therapy on healing of medial collateral

ligament injuries in rats: an ultrastructural study.

Rat

Ligaments

ACL injury

Ligament transection

300

808

10
50

633

0.01
1.20

0,28
cm2

3.73

15

Biphasic dose
response

"A new phototherapy unit for personal and home application is developed based
on red and infrared LEDs."

Taylor&Fra
ncis

82 lesions were treated, and LLLT seemed to reduce the clinical score and pain.
No control group.

PubMed

LLLT appeared to have some benefits. However, there was no control group.
Parameters weren't reported.

PubMed

"Initial signs of tissue degradation were observed in CG. Interestingly, lasertreated animals presented a better tissue organization, especially at the fluence of
10 J/cm(2). Furthermore, laser phototherapy was able of modulating some of the
aspects related to the degenerative process, such as the prevention of
proteoglycans loss and the increase in cartilage area. However, LLLT was not
able of modulating chondrocytes proliferation and the immunoexpression of
markers related to inflammatory process (IL-1 and MMP-13).

PubMed

This study showed that 808 nm laser, at both fluences, prevented features related
to the articular degenerative process in the knees of rats after ACLT."

Ligaments

MCL injury

Delbari

Iran
(Tehran)

2007

Photomed Laser
Surg

Dose response

3.14
mm2

1
120

21

"On day 12, the fibril dimension of group 2 and their density were higher than of
groups 1 and 3."

PubMed

"Although we could not find significant difference between density of fibrils of laser
groups and other groups, the p value shows a difference almost at the range of
significance (p = 0.059)."

Ligaments

MCL injury

Bayat

Iran
(Tehran)

2005

Photomed Laser
Surg

Low-level laser therapy improves early healing of medial collateral

ligament injuries in rats.

Rat

Dose response

633

10

0.01
1.20

3.14
mm2

1
120

21

"The ultimate tensile strength (UTS) of group 2 on day 12 was significantly higher
than that of groups 1 and 3."

PubMed

Comment: The dose of 0.01J/cm2 was ineffective, while 1.20J/cm2 was effective.
Too small dose does often have no effect.

Ligaments

MCL injury

Ng

China
(Hong Kong)

2004

Lasers Surg Med

Comparison of single and multiple applications of GaAlAs laser on

rat medial collateral ligament repair.

Rat

Ligaments

MCL injury

Fung

China
(Hong Kong)

2003

Lasers Surg Med

Effects of a therapeutic laser on the ultrastructural morphology of

repairing medial collateral ligament in a rat model.

Rat

Ligaments

MCL injury

Fung

China
(Hong Kong)

2002

Lasers Surg Med

Therapeutic low energy laser improves the mechanical strength of

repairing medial collateral ligament.

Rat

Liver

Diabetes

Lim

USA
(Bloomington,
IN)

2009

J Biochem Mol
Toxicol

Effects of low-level light therapy on hepatic antioxidant defense in

acute and chronic diabetic rats.

Rat

Single vs multiple
treatments

Diabetic rats
LED phototherapy

660

8.8

31.6

660

8.8

31.6
63.2

450
900

300

14
70

670

0.05

1
9

"Multiple laser therapy improves the normalized strength and stiffness of repairing
rat MCLs at 3 weeks after injury. The multiple treatments seem to be superior to a
single treatment when the cumulative dosages are comparable between the two
modes of application."

PubMed

"Single application of low energy laser therapy increases the collagen fibril size of
healing MCLs in rats."

PubMed

"The UTS of laser and sham groups were comparable."

PubMed

"Light treatment was ineffective as an antioxidant therapy in chronic diabetes, but

light treatment for 18 days in acutely diabetic rats resulted in the normalization of
hepatic glutathione reductase and superoxide dismutase activities and a
significant increase in glutathione peroxidase and glutathione-S transferase
activities. The results of this study suggest that 670 nm photobiomodulation may
reduce, at least in part, acute hepatic oxidative stress by enhancing the
antioxidant defense system in the diabetic rat model."

PubMed

Light therapy also didn't affect blood glucose levels. ATP and CCO activity were
increased.

= 785 nm (770-795)
"Transcutaneous therapeutic LLLT of kidney tissue"

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

sec

Liver

Liver cirrhosis

Oliveira-Junior

Brazil
(So Paulo)

2013

Photochem
Photobiol

Low-level laser therapy ameliorates CCl4-induced liver cirrhosis in

rats.

Rat

Liver cirrhosis (CCl4)

830

35

2.5
(?)

426

Liver

Liver
regeneration

Arajo

Brazil
(So Paulo)

2015

Lasers Med Sci

Low-power laser irradiation fails to improve liver regeneration in

elderly rats at 48 h after 70 % resection.

Rat

Hepatectomy

633

Category

Results: positive / unclear/modest / negative

10

aspartate aminotransferase (P < 0.001)

alkaline phosphatase (P < 0.001)
gamma-glutamyl transferase (P < 0.001)
lactate dehydrogenase (P < 0.01) activity, as well as
total proteins (P < 0.05) and
globulins (P < 0.01)
number of cirrhotic areas
collagen accumulation
hepatic inflammatory infiltrate
CCl(4)-increased number of Kupffer cells (P < 0.05) and
hepatic stellate cells (P <

Link

Additional info

PubMed

"We conclude that LLLT presents beneficial effects on liver function and structure
in an experimental model of CCl(4)-induced cirrhosis."
3.6

0.97

d=
1.6 cm

900

"this study demonstrated that the main molecular pathway, i.e.

PubMed

HGF/MetAkt and Erk 1/2PCNA,

involved in the hepatic regeneration process was not improved by LPLI in elderly
hepatectomized rats, which in turn rules out LPLI as an adjuvant therapy, as
observed in this protocol of liver regeneration evaluation (i.e. at 48 h after 70 %
resection), in elderly"

Liver

Liver
regeneration

Arajo

Brazil
(So Paulo)

2013

Lasers Med Sci

Liver regeneration following partial hepatectomy is improved by

enhancing the HGF/Met axis and Akt and Erk pathways after lowpower laser irradiation in rats.

Rat

Hepatectomy -> Liver

regeneration

633

3.3

0.065

Liver

Liver
regeneration

Oron

Israel

2010

Photomed Laser
Surg

Enhanced liver regeneration following acute hepatectomy by lowlevel laser therapy.

Rat

Hepatectomy -> Liver

regeneration

804/
810
(?)

max
400

0.005

Liver

Liver
regeneration

Castro-e-Silva

Brazil
(Sao Carlos)

2007

Braz J Med Biol

Res

The use of light-emitting diodes to stimulate mitochondrial

function and liver regeneration of partially hepatectomized rats

Rat

Hepatectomy -> Liver

regeneration

630

10
140

180
2400

590

15

300

22.5

150

LED phototherapy vs
laser

Liver

Liver
regeneration

Oliveira

Brazil
2006
(Ribeiro Preto)

Acta Cir Bras

The effect of laser on remanescent liver tissue after 90%

hepatectomy in rats.

Rat

Hepatectomy -> Liver

regeneration

660

30

900

0.6

d=
2 cm

60

"Our results show that LPLI can improve liver regeneration as shown by increased
HGF protein expression and the phosphorylation levels of Met, Akt, and Erk 1/2
accompanied by higher levels of the PCNA and Ki-67 protein in the remnant livers.
In summary, our results suggest that LPLI may play a clinical role as a simple,
fast, and easy-to-perform strategy in order to enhance the liver regenerative
capacity of a small liver remnant after hepatectomy."

PubMed

BrdU positive cells per area in the regenerating regions of the livers
The density of the newly formed blood vessels and c-kit immunopositive cells in
the regenerating area

PubMed

"In conclusion, the present results suggest that LED irradiation promotes biological
stimulatory effects during the early stage of liver regeneration and that LED is as
effective as laser light, independent of the coherence, divergence and cromaticity."

SciELO

"Laser did not cause hepatic injuries additional to the partial hepatectomy and
perhaps led to a benefit by stimulating the proliferative activity."

PubMed

Comment: Parameters were poorly reported.

Liver

Liver
regeneration

Melo

Brazil
(Sergipe)

2005

Dig Dis Sci

Enhancement of liver regeneration by the association of Hyptis

pectinata with laser therapy.

Rat

Hepatectomy -> Liver

regeneration

590

Liver

Minimal hepatic
encephalopathy

Arias

Spain

2016

Lasers Med Sci

Low-light-level therapy as a treatment for minimal hepatic

encephalopathy: behavioural and brain assessment.

Rat

LED phototherapy

670

40

0.05

240

10
cm2

180

Cytochrome oxidase

"The present study shows that the association of the aqueous extract of Hyptis
pectinata leaves at 200 mg/kg with intraoperative laser therapy can stimulate liver
regeneration and cause a reduction in liver mitochondrial respiratory function
without altering its phosphorylative activity."

PubMed

"Taking these findings into account, an improvement in the PH + LLLT group due
to LLLT treatment should show not only a correct acquisition of the behavioural
task, indicated by the behavioural differences between PH and PH + LLLT and
their absence when compared to the SHAM group, but also a decrease in C.O.,
due to an improvement in the enzyme activity produced by the LLLT treatment,
and similarities between brain networks."

PubMed

"Interestingly, decreases in C.O. activity in the PH + LLLT group, compared to the other groups, were found in most of the evaluated brain structures. How can we explain this
decrease when LLLT is said to improve cytochrome c oxidase activity?
Firstly, we are not evaluating a single dose and looking for the peak effect 24 h later [7]. Instead, our aim is to study an accumulative effect of LLLT in order to reproduce the effect of
a distributed treatment. Therefore, we expected to observe the beneficial effects of the treatment, rather than a single-event effect.
Secondly, we are studying this treatment based on performance on a behavioural task. It is important to know that under behavioural conditions, previous studies have shown
differential metabolic brain activity during the acquisition of a spatial task [12], during different post-task periods [34] and due to contextual changes during the performance of a fear
conditioning task [35]. These studies illustrate that as soon as an animal acquires the behavioural criterion, metabolic brain requirements are decreased and tend to spare cortical
structures.

[For more information, read additional info]

Thirdly, it has been shown that the action of the LLLT potentially reaches all brain regions, but will selectively enhance those with higher energy demands due to task-dependent
activation. This effect could be due to the previously demonstrated fact that light absorption by cytochrome oxidase is maximized in the presence of a mixed valence enzyme state
that is more likely to be found with higher respiratory chain electron flow [7]. In turn, this condition is expected to occur in states of increased energy consumption, such as those of
neuronal networks activated during a particular task."

LLLT: past
and future
LLLT: past
and future

Anders

USA
(Bethesda, MD)

2015

Photomed Laser
Surg

Low-level light/laser therapy versus photobiomodulation therapy.

Editorial

"In summary, photobiomodulation therapy is an accurate and specific term for this effective and important application of light. Universal use of this term
would reduce, and potentially eliminate, confusion in the field and in both the scientific and lay literature. This would engender a unified, positive image to
showcase the exciting clinical applications photobiomodulation therapy can offer for various medical applications."

PubMed

Moore KC

UK
(Oldham)

2013

Photomed Laser
Surg

Photomedicine: the early years.

Guest
Editorial

"It wasnt until the mid-1980s that low-powered lasers began to make an impact in the Western world. This was mainly because of the influence of Toshio
Ohshiro from the Japan Medical Laser Laboratory (JMLL) in Tokyo, Japan.

PubMed

Ohshiro was the catalyst who helped develop low-level laser therapy (LLLT), as it was to become known. He described these early years in his own
guest editorial for PMLS, with the establishment of the International Laser Therapy Association (ILTA) and the publication of its journal Laser Therapy,
and in 1994 the formation of the World Association for Laser Therapy (WALT)."
"Confusing terminology was rife, with different authors referring to their equipment as being 'low power,' 'low dose,' or 'low energy.' Terms such as 'soft
laser,' 'mid laser,' and even 'cool laser' further confused the issue."
"It was Ohshiro who focused attention on LLLT, but even then, others still used the terms 'low energy light irradiation (LELI),' 'low intensity light irradiation
(LILI),' 'biostimulation,' 'photobio-activation,' and 'photobio-modulation,' before the now currently accepted terms 'laser therapy,' 'light therapy,' and the allembracing 'photomedicine' became the norm. 'Photobio-activation' was the preferred term in these early years, until it was pointed out that excessive
therapy could lead to inhibition, after which photobio-modulation became popular."
"Many congress reports in these early days were anecdotal with poor research. Even published articles on clinical trials omitted the full details of
dosimetry, thus rendering the trials unable to be reproduced. But even more damaging were claims for therapeutic benefit that was unsubstantiated by
experimental and clinical research, which led to health insurers refusing funding and in the United States, the Food and Drug Administration (FDA)
remained skeptical. This led to a critical response from some scientific establishments."

LLLT: past
and future

Arany PR

2012

Photomed Laser
Surg

Photobiomodulation: poised from the fringes.

LLLT: past
and future

Karu, Pyatibrat &

Kalendo

2001

Toxicol Lett

Donors of NO and pulsed radiation at lambda = 820 nm exert

effects on cell attachment to extracellular matrices.

Karu &
Afanas'eva

1995

Dokl Akad Nauk

[Cytochrome c oxidase as the primary photoacceptor upon laser

exposure of cultured cells to visible and near IR-range light].
[Article in Russian]

LLLT: past
and future

USA
(Boston, MA)

LLLT: past
and future

Tadakuma T

Japan

1993

Keio J Med

Possible application of the laser in immunobiology.

LLLT: past
and future

Bakeeva

Russia

1993

Mol Biol (Mosk).

[Formation of gigantic mitochondria in human blood lymphocytes

under the effect of an He-Ne laser].
[Article in Russian]

Editorial

PubMed
820

3.54

8120

10170

Nitric oxide donors can prevent the effects of LLLT.

PubMed

First paper suggesting the importance of cytochrome c oxidase.

PubMed

"Although much more research needs to be done, there are enough experimental and clinical data to show that the laser, and LLLT in particular,
has a possibly exciting role both in immunobiological therapy for diseases of the immune system, and to activate and boost the normal reaction
of the immune system components against harmful foreign bodies."

Review

633

"Reconstruction of mitochondria from ultrathin sections through the whole

lymphocyte showed that 1 h after the irradiation the number of mitochondria was
reduced to 9-12 compared to 40-45 in the control cells.

PubMed
PubMed

In the irradiated lymphocytes 2-4 branching giant mitochondria were revealed

instead of small discrete mitochondria in the control cells. Other 6-7 mitochondria
were found to retain their shape and volume.
It is suggested that the giant mitochondria are formed by fusion of small
mitochondria. Formation of giant mitochondria may reflect the increase in the
energy exchange level."

1992

J Photochem
Photobiol B

Effects of visible and near-infrared lasers on cell cultures.

In vitro
(fibroblasts)

Mester E

1985

Lasers Surg Med

The biomedical effects of laser application.

Review

LLLT: past
and future

Lobko, Karu &

Letokhov

1985

Biofizika

[Is the coherence of low-intensity laser light essential for its effect
on biological objects?].
[Article in Russian]

LLLT: past
and future

Sato

Germany

1984

Andrologia

The effects of laser light on sperm motility and velocity in vitro.

In vitro

Passarella

Italy
(Bari)

1984

FEBS Lett

Increase of proton electrochemical potential and ATP synthesis in

rat liver mitochondria irradiated in vitro by helium-neon laser.

In vitro

LLLT: past
and future

LLLT: past

Lubart

Israel

360
632
780

and future

LLLT: past
and future

"It is suggested that low-level laser therapy in the visible and in the near-infrared
region is due to cell respiration stimulation by either the endogenous porphyrins in
the cell, or by the cytochromes."

PubMed

This paper briefly reviews the authors' experimental and clinical use of lasers over a 20-year period, during which laser effects on 15 biological systems
were studied. Low-energy laser radiation was found to have a stimulating effect on cells, and high-energy radiation had an inhibiting effect. The
application of lasers to stimulate wound healing in cases of nonhealing ulcers is recommended.

PubMed

647

Rat liver mitochondria

633

0.5
1.0
2.0
4.0
8.0
32
15

80
80
80
80
80
160

It means that the role of coherent interaction processes is negligible. This

conclusion is confirmed by the experimental results obtained with living cells of
different types.

PubMed

"Total sperm motility increased after Laser irradiation at 4 J/cm2, 8 J/cm2 and 32
J/cm2 respectively with respect to control. However, no influence on sperm
velocity was demonstrated after Laser irradiation. This observation suggests that
Laser light stimulates non-motile live spermatozoa."

PubMed

First paper showing increased ATP after LLLT irradiation.

PubMed

"This paper clearly shows that the irradiation of isolated rat liver mitochondria in
vitro by low power He-Ne laser causes an increase in membrane potential, proton
gradient and ATP synthesis."

LLLT: past
and future

Karu

Russia

1984

Vopr Kurortol
Fizioter Lech Fiz
Kult

[Phototherapy of gastric and duodenal peptic ulcer patients based

on cell stimulation with low-intensity red light].
[Article in Russian]

Human

LLLT: past
and future

Salet

France
(Paris)

1979

Exp Cell Res

A study of beating frequency of a single myocardial cell. III. Laser

micro-irradiation of mitochondria in the presence of KCN or ATP.

In vitro

530

LLLT was already being studied in humans in 1984.

PubMed

An ancient paper showing cellular changes in myocardial cell, after green light
irradiation. The authors suspect that the changes might be related to ATP
production. The authors discuss the effects of light on animals.

PubMed

"If our inferences concerning ATP involvement are valid, this emphasizes the
similarities between mitochondria and bacteria, especially Halobacteria, which are
able to produce ATP on light illumination"
Note: A wavelength of typical LLLT range (600-1100nm) was not used.
[Also see additional info]

LLLT: past
and future

Mester

Hungary

1968

Acta Chir Acad

Sci Hung

Lasers in clinical practice.

Review?

PubMed

LLLT: past
and future

Mester

Hungary

1968

Radiobiol
Radiother (Berl).

[The effect of laser beams on the growth of hair in mice].[Article in

German]

Mouse

PubMed

"The stimulation with visible light of heart in toto is well stablished [20-221. To the best of our knowledge, this point was reported for the first time by Arvanitaki & Chalazonitis who
demonstrated that the action spectrum for stimulating Helix pomatia heart has the same shape than the absorption spectrum of mitochondria [20]. Light can also change the beating
rate of heart cells in tissue culture, a good model for investigating this effect"

Comment

Reply

 Category

Subcategory

LLLT: past

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Mester

Hungary

1968

Langenbecks
Arch Chir

[Studies on the inhibiting and activating effects of laser beams].

[Article in German]

In vitro & in
vivo ??

Mester E

Hungary

1966

Orv Hetil

[The use of the laser beam in therapy].

[Article in Hungarian]

Storz

Germany
(Homburg)

2016

Photodermatol
Photoimmunol
Photomed

Photobiomodulation Therapy in breast cancer-related

lymphedema: a randomized placebo-controlled trial.

and future

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

Additional info

sec

"Laser beams of low energy were tested on four biological systems and were
found to promote the cell functions. Higher radiant energy causes inhibition.
Repeated small doses of radiation have a cumulative effect. The knowledge of
these facts is essential if any therapeutic use is intended."

PubMed

Original title: "Untersuchungen ber die hemmende bzw. frdernde Wirkung der
Laserstrahlen"
Comment: It is nice that parameters were considered already in the sixties!

LLLT: past
and future

Lymphedema

First scientific paper on LLLT?

Human
RCT/DB

LED phototherapy
LED array (16)

980

640

0.0081
4

384

4.89

78.54
cm2

600

"PBMT using a compactly designed treatment regime in combination with a cluster

laser device did not significantly improve quality of life, pain scores, grip strength
and limb volume over the time course."

PubMed

"A too high amount of total energy applied per point could be a possible
explanation for our results. Its particularly worth mentioning, that we increased the
energy dose in order to cut the total amount of sessions. So its hard to determine,
whether the applied doses are really too high or whether the amount of sessions is
simply insufficient. [...] We assume that in treating chronic conditions such as
lymphedema, the application of our chosen energy dose and density simply
constituted a too strong stimulus in a too short time frame."
Star: The parameters and treatment methods were exceptionally well reported in a
table.

Jang

Lymphedema

Korea
(Incheon &
Seoul)

2016

Lasers Med Sci

Anti-inflammatory and lymphangiogenetic effects of low-level laser

therapy on lymphedema in an experimental mouse tail model.

904

Mouse

0.025

1.5

0.2
cm2

600
(10p)

12

"The thickness of the tail rapidly increased until 6 days in the laser and sham
groups. The mice in the laser group showed a significantly decreased thickness
compared with the sham group at 10 and 12 days. Immunohistochemistry assay
revealed that LLLT reduced inflammation and induced new lymphatic vessel
growth. qPCR showed that expressions of VEGFR3 were (p = 0.002) increased in
the laser group. These results suggest that LLLT has anti-inflammatory and
lymphangiogenetic effects for the management of lymphedema."

PubMed

"Moderate-strength evidence supports LLLT in the management of BCRL, with clinically relevant within-group reductions in volume and pain immediately
after conclusion of LLLT treatments. Greater reductions in volume were found with the use of LLLT than in treatments without it."

PubMed

(/p)

Lymphedema

Smoot

USA
(San Francisco,
CA)

2015

J Cancer Surviv

Effect of low-level laser therapy on pain and swelling in women

with breast cancer-related lymphedema: a systematic review and
meta-analysis.

Metaanalysis

Lymphedema

Hwang

Korea

2015

J Phys Ther Sci

Complex decongestive physical therapy and low-level laser

therapy for the treatment of pediatric congenital lymphedema: a
case report.

Human
Case report

Lymphedema

E Lima

Brazil
2014
(Rio de Janeiro)

Lasers Med Sci

Low-level laser therapy in secondary lymphedema after breast

cancer: systematic review.

Systematic
review

USA
(Nashville, TN)

Oncol Nurs Forum A pilot randomized trial evaluating low-level laser therapy as an
alternative treatment to manual lymphatic drainage for breast
cancer-related lymphedema.

PubMed
"Of the 41 articles identified, four were considered to be of high methodological quality (score 5).

PubMed

The low-level laser in the axillary region was performed in all studies. The control group was not similar across studies. The results presented showed
that there was a reduction in limb volume in the group subjected to low-power laser when compared with other treatments.
No studies have evaluated the risk of metastasis or relapse in the irradiated areas. Because no studies have included the complex physical therapy as
the comparison group, we cannot claim that laser treatment is the best efficacy or effectiveness in lymphedema treatment after breast cancer. No studies
have evaluated the hypothesis that the LLLT can increase the risk of recurrence or metastasis. Therefore, the questions about the safety of this
procedure in cancer patients remain."

Ridner

Lymphedema

2013

Human
RCT

Comparison trial

904

1200

"No statistically significant between-group differences were found in volume

reduction; however, all groups had clinically and statistically significant reduction in
volume. No group differences were noted in psychological and physical symptoms
or QOL; however, treatment-related improvements were noted in symptom burden
within all groups. Skin improvement was noted in each group that received LLLT."

PubMed

"LLLT with bandaging may offer a time-saving therapeutic option to conventional

MLD. Alternatively, compression bandaging alone could account for the
demonstrated volume reduction."
"Lasers may provide effective, less burdensome treatment for lymphedema."
Comment: Parameters were very poorly reported.

Omar

Lymphedema

Egypt
(Giza)

2012

Support Care
Cancer

A systematic review of the effect of low-level laser therapy in the

management of breast cancer-related lymphedema.

"There is moderate to strong evidence for the effectiveness of LLLT for the management of BCRL from five small studies of acceptable methodological
quality.

Systematic
review

PubMed

A dose of 1-2 J/cm(2) per point applied to several points covering the fibrotic area can reduce limb volume following BCRL.
Further well-designed, large-scale studies are required to determine more precisely how effective LLLT may be in BCRL."

Lymphology

Changes in tissue water and indentation resistance of

lymphedematous limbs accompanying low level laser therapy
(LLLT) of fibrotic skin.

Human

PubMed

USA
2011
(Pittsburgh, PA)

Support Care
Cancer

The short-term effects of low-level laser therapy in the

management of breast-cancer-related lymphedema.

Human
Observationa
l

"Patients with BCRL received additional benefits from LLLT when used in
conjunction with standard lymphedema treatment. These benefits include
reduction in limb circumference, pain, increase in range of motion and scar
mobility. Additionally, two cycles of LLLT were found to be superior to one in this
study."

PubMed

Ahmed Omar

Egypt
(Cairo)

2011

J Surg Res

Treatment of post-mastectomy lymphedema with laser therapy:

double blind placebo control randomized study.

Human
RCT/DB

904

1.5

0.2
cm2

Lau&Cheing

China
(Hong Kong)

2009

Photomed Laser
Surg

Managing postmastectomy lymphedema with low-level laser

therapy.

Human
RCT/SB

808
+
905

144
cm2

Kozanoglu

Turkey
(Adana)

2009

Clin Rehabil

Efficacy of pneumatic compression and low-level laser therapy in

the treatment of postmastectomy lymphoedema: a randomized
controlled trial.

Human
RCT

904

1.5

Lymphedema

Mayrovitz &
Davey

USA
(Lauderdale,
FL)

Lymphedema

Dirican

Lymphedema
Lymphedema
Lymphedema

2011

Kaviani

Iran
(Tehran)

2006

Lasers Med Sci

Low-level laser therapy in management of postmastectomy

lymphedema.

Human

890

Lymphedema

Carati

Australia
(Adelaide)

2003

Cancer

Treatment of postmastectomy lymphedema with low-level laser

therapy: a double blind, placebo-controlled trial.

Human
RCT/DB

904

Lymphedema

Piller&Thelander

Australia
(Adelaide)

1998

Lymphology

Treatment of chronic postmastectomy lymphedema with low level

laser therapy: a 2.5 year follow-up.

Human
Case series

Abrahamse H

South Africa
(Johannesburg)

2015

Photomed Laser
Surg

Stimulation of Cellular Proliferation and Migration: Is It a Viable

Measure of Photobiomodulation?

Guest
Editorial

Editorial

2.1

36

"Laser treatment was found to be effective in reducing the limb volume, increase
shoulder mobility, and hand grip strength in approximately 93% of patients with
postmastectomy lymphedema."

PubMed

1200

12

"LLLT was effective in the management of PML, and the effects were maintained
to the 4 wk follow-up."

PubMed

1200

12

"Group II had better long-term results than group I. Low-level laser might be a
useful modality in the treatment of postmastectomy lymphoedema."

PubMed

Comment: Parameters were poorly reported.

Lymphedema

Mechanisms

1.5

0.2
cm2
16

"Reduction in limb circumference was detected in both groups, although it was

more pronounced in the laser group up to the end of 22nd week. Desire to
continue treatment at each session and baseline score in the laser group was
greater than in the sham group in all sessions. Pain reduction in the laser group
was more than in the sham group except for the weeks 3 and 9. No substantial
differences were seen in other two parameters between the two treatment
groups."

PubMed

"Two cycles of laser treatment were found to be effective in reducing the volume of
the affected arm, extracellular fluid, and tissue hardness in approximately 33% of
patients with postmastectomy lymphedema at 3 months after treatment."

PubMed

"The data suggest that laser treatment, at least initially, improved most objective
and subjective parameters of arm lymphedema."

PubMed

"In vitro studies have shown an increase in cellular migration, proliferation, viability, collagen production, ATP, cyclic adenosine monophosphate (cAMP),
cytochrome c oxidase activity, nitric oxide, growth factors, mitochondrial membrane potential and gene regulation, and a decrease in matrix
metalloproteinases (MMPs) apoptosis and pro-inflammatory cytokines, to name but a few.

PubMed

Cellular proliferation studies using new, well-researched and established assays including ATP luminescence, MTT assays, trypan blue staining, and a
variety of additional measures, have now become a hallmark of analyzing the cellular effects of photobiomodulation, and rightfully so, considering the
intricate mechanisms involved in this process.
As a first-level monitoring method to determine the cellular effects of photobiomodulation, viability and proliferation analysis seems perfectly sound.
However, caution should be exercised in the inference of this outcome. Proliferation and viability studies should never be used as the only method of
monitoring photobiomodulation, and must be accompanied by more sensitive and specific investigation that includes the molecular mechanisms
associated with cell growth."

Mechanisms

Editorial

Karu T

Russia
(Troitsk)

2010

Photomed Laser
Surg

Mitochondrial mechanisms of photobiomodulation in context of

new data about multiple roles of ATP.

"It is generally accepted that the mitochondria are the initial site of light action in cells, and cytochrome c oxidase (the terminal enzyme of the
mitochondrial respiratory chain) is the responsible molecule. Mixed-valence copper components of cytochrome c oxidase, CuA and CuB, are believed to
be the photoacceptors."

Guest
Editorial

PubMed

"ATP activation of P2 receptors (subtypes P2X and P2Y) can produce different cellular effects. A recent article by Anders et al. 17 demonstrated that
P2Y2 and P2Y11 receptors were expressed in the irradiated at l 810-nm normal human neural progenitor cells in vitro. It appeared that the irradiation
could be used as a replacement for growth factors. This line of research opens a new understanding of the complicated mechanisms of LLLT."

Mechanisms

Editorial

Enwemeka CS

USA
2006
(Milwaukee, WI)

Photomed Laser
Surg

The place of coherence in light induced tissue repair and pain

modulation.

"Indeed, evidence from specially designed studies indicate that coherent and noncoherent light of identical wavelength, intensity, and irradiation dose
provide the exact same biological response,3 an observation which continues to gain support from recent studies.46"

Editorial

PubMed

"Coherence may influence light distribution in tissue, and it can be demonstrated that lasers produce light speckles or pockets of intense light within
tissues; noncoherent monochromatic and polychromatic lights do not.7 However, this physical difference has not been shown to produce any additional
benefits in favor of treatment with lasers."
"All said, at least for now, the conclusion must be drawn that we lack the scientific evidence needed to support the assertion that coherence plays a role
in producing the benefits derived from therapeutic light."

Mechanisms

Original
research

Amaroli

Italy
(Genoa)

2016

Photomed Laser
Surg

An 808-nm Diode Laser with a Flat-Top Handpiece Positively

Photobiomodulates Mitochondria Activities.

In vitro

"Our data show for the first time that even the higher fluences (64 J/cm2-1 W),
similar to the low fluences, can photobiostimulate the mitochondria respiratory
chain without uncoupling them and can induce an increment in the ATP
production.

Bovine liver
mitochondria
Flat-top handpiece

PubMed

These results suggest that the negative effects of higher fluences observed to
date are not unequivocally due to higher fluence per se but might be a
consequence of the irradiation carried by handpieces with a Gaussian profile."

Mechanisms

Original
research

Wang

USA (Texas)

2016

Sci Rep

Interplay between up-regulation of cytochrome-c-oxidase and

hemoglobin oxygenation induced by near-infrared laser.

"For the first time, we demonstrated that 1064nm laser can induce significant
increases of CCO and HbO concentrations in a dose-dependent manner over
time, as compared with placebo treatment. In addition, [CCO] and [HbO]
displayed a clear linear relationship as the dose of LLLT increased. "

Human

PubMed

"These results demonstrate the tremendous potential of broadband NIRS as a

non-invasive, in vivo means to study mechanisms of photobiomodulation and
perform treatment evaluations of LLLT. "

Mechanisms

Original
research

Wang

USA
(Boston, MA)

2016

Biochim Biophys
Acta

Photobiomodulation of human adipose-derived stem cells using

810nm and 980nm lasers operates via different mechanisms of
action.

In vitro

Stem cells
980nm --> calcium
channels, TRPV1,
TRPC

810
980

0.03
0.3
1
3
5
10
20

"The use of NIR wavelengths such as 810nm is reasonably well accepted to

stimulate mitochondrial activity and ATP production via absorption of photons by
cytochrome c oxidase. However, the mechanism of action of 980nm is less well
understood."
[See additional info]

PubMed

"Both wavelengths showed a biphasic dose response, but 810nm had a peak dose response at 3J/cm2 for stimulation of proliferation at 24h, while the peak dose for 980nm was 10100 times lower at 0.03 or 0.3J/cm2. Moreover, 980nm (but not 810nm) increased cytosolic calcium while decreasing mitochondrial calcium. The effects of 980nm could be blocked
by calcium channel blockers (capsazepine for TRPV1 and SKF96365 for TRPC channels), which had no effect on 810nm.
To test the hypothesis that the chromophore for 980nm was intracellular water, which could possibly form a microscopic temperature gradient upon laser irradiation, we added cold
medium (4C) during the light exposure, or pre-incubated the cells at 42C, both of which abrogated the effect of 980nm but not 810nm. We conclude that 980nm affects
temperature-gated calcium ion channels, while 810nm largely affects mitochondrial cytochrome c oxidase."

Comment

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More info:

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Subcategory

First author

Country

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

sec

Mechanisms

Original
research

Tang

USA (Bethesda, 2016

MD)

J Periodontal Res

Laser-activated transforming growth factor-1 induces human defensin 2: implications for laser therapies for periodontitis and
peri-implantitis.

In vitro

810

1
2.5
4
5.5
7.5

300

Mechanisms

Original
research

Quirk & Whelan

USA
2016
(Milwaukee, WI)

Photomed Laser
Surg

Effect of Red-to-Near Infrared Light on the Reaction of Isolated

Cytochrome c Oxidase with Cytochrome c.

In vitro

Category

Year

TGF-1
Periodontium & periimplantitis

660
670
830

Results: positive / unclear/modest / negative

Link

"Laser-activated TGF-1 signaling and induced expression of HBD-2, both of

which are individually capable of promoting healing in tissues adjacent to highpower surgical laser applications."

PubMed

"The oxidation of cytochrome c by isolated CCO has not been shown to be

affected by R-NIR irradiation, whether applied prior to or concurrently with the
enzymatic assays. This lack of effect by R-NIR calls into question the CCO activity
model of R-NIR photobiomodulation."

PubMed

Additional info

Comment

"There could still be a role for CCO in R-NIR-PBM. Although the activity may not
be affected, it may be possible that R-NIR reception by CCO in some manner
results in increased expression of the same enzyme. It is difficult, however, to
envision how such a result could be achieved. Perhaps CCO modulation by R-NIR
does not affect the rate of cytochrome c oxidation, but rather increases its
efficiency by increasing the proton pumping rate per electron transferred, as
argued in a study of isolated rat liver mitochondria. This could improve the
production of adenosine triphosphate (ATP), with all of the implied cellular
benefits."
"We have only studied one part of the CCO reaction. In this work, the other
substrate, oxygen, is considered to be saturating and not rate limiting. It is
possible that the kinetics of the reduction of oxygen by CCO may be affected by
R-NIR even if the cytochrome c oxidation may not. It is our intention to study
oxygen uptake in a respiration chamber using the Clark electrode technique."
Comment: Still, the in vitro setting with isolated CCO, instead of a living cell, could
possibly explain these results. Hopefully we get some clarity about the mechanism
during the following years.

Mechanisms

Original
research

Ball

USA
(Boulder, CO)

2011

J Photochem
Photobiol B

Low intensity light stimulates nitrite-dependent nitric oxide

synthesis but not oxygen consumption by cytochrome c oxidase:
Implications for phototherapy.

In vitro

590

Mechanisms

Original
research

Heger

Netherlands
(Amsterdam)

2010

J Photochem
Photobiol B

Absence of 633-nm laser irradiation-induced effects on glucose

phosphorylation by hexokinase.

In vitro

633

"By using a series of bandpass filters and light emitting devices (LEDs) we have
determined that maximal stimulation of Cco/NO activity is achieved by exposure to
light whose central wavelength is 590 14 nm. This wavelength of light stimulates
Cco/NO synthesis at physiological nitrite concentrations.

PubMed

These findings raise the interesting possibility that low intensity light exerts a
beneficial effect on cells and tissues by increasing NO synthesis catalyzed by Cco
and offer a new explanation for the increase in NO bioavailability experienced by
tissue exposed to light."
"No differences in reaction rates between the NROF-irradiated and control groups
were found at either temperature."

PubMed

Comment

Note: Amat published a critical comment to this paper.

Mechanisms

Original
research

Anders

USA
(Bethesda, MD)

2008

IEEE J Sel Top

Light Supports Neurite Outgrowth of Human Neural Progenitor
Quantum Electron Cells In Vitro: The Role of P2Y Receptors

810

In vitro

150

0.05
0.10

0.2
0.2

4
2

"The data presented here establish the neuritogenic potential of light on NHNPCs
in a growth factor and serum-free environment. Based on these findings, we
propose that the light caused an increase in ATP that acted through P2Y receptors
and downstream signaling pathways leading to neurite outgrowth."

IEEE

Note: A correction has been published. The Figure 4 (especially images D, E and
F) was incorrect.

Mechanisms

Original
research

Arany

India
(Karnataka)

2007

Wound Repair
Regen

Activation of latent TGF-beta1 by low-power laser in vitro

correlates with increased TGF-beta1 levels in laser-enhanced oral
wound healing.

Rat

Wound healing

Mechanisms

Original
research

Karu

Russia
(Troitsk)

2005

Photomed Laser
Surg

Exact action spectra for cellular responses relevant to

phototherapy.

In vitro

HeLa cells

904

10

300

"For the preliminary experiments, NHNPCs were plated on slides and treated with light once a day for three days and grown for a total of seven days in three separate experiments
using the following laser parameters:
1) wavelengths: 458.6, 477, 488.7, 515, 646, 660, 780, 807, 810, and 975 nm;
2) doses (810 nm light, at 50 mW/cm2 ): 0.005, 0.01, 0.02, 0.05, 0.1, 0.2, 0.5, 1, 2, 4, and 6 J/cm2 ; and
3) power density (810 nm light): 1, 3, 10, 30, 50, and 100 mW/cm2 .
For each of the three experiments, the diameter of the laser(s) spot size was 10 mm corresponding to an area of 0.785 cm2"

"Low-power laser irradiation is capable of activating the latent TGF-beta1 complex

in vitro and its expression pattern in vivo suggests that TGF-beta play a central
role in mediating the accelerated healing response."

PubMed

"The peak positions are between 613.5 and 623.5 nm (in one spectrum, at 606
nm), in the red maximum.

PubMed

The far-red maximum has exact peak positions between 667.5 and 683.7 nm in
different spectra.
Two near infrared maxima have peak positions in the range 750.7-772.3 nm and
812.5-846.0 nm, respectively."

Mechanisms

Original
research

Amat

Spain
(Reus)

Mechanisms

Original
research

Lanzafame

Mechanisms

Original
research

Greco

2005

J Photochem
Photobiol B

Modification of the intrinsic fluorescence and the biochemical

In vitro
behavior of ATP after irradiation with visible and near-infrared laser ATP
light.
irradiation

USA
2004
(Rochester, NY)

Photomed Laser
Surg

Temperature-controlled 830-nm low-level laser therapy of

experimental pressure ulcers.

Mouse

Italy
(Bari)

Lasers Surg Med

Helium-Neon laser irradiation of hepatocytes can trigger increase

of the mitochondrial membrane potential and can stimulate c-fos
expression in a Ca2+-dependent manner.

In vitro

Specific helium-neon laser sensitivity of the purified cytochrome c

oxidase.

In vitro

655
830

200

"In conclusion, visible and near-infrared light modifies the biochemical behavior of
ATP in the hexokinase reaction and the fluorescence intensity of the molecule
thus altering the Mg2+ binding strength to the oxygen atoms in the phosphate
group."

PubMed

Note: Heger et al published a paper which claimed to disprove these findings.

However, they used different parameters (9-fold lower irradiance), which could
explain the different results.

2001

Isolated hepatocytes

633

0.012

0.24

633

0.01

Isolated liver
mitochondria

LLLT improved wound healing compared to control. The effect was noted also in
the temperature-controlled group, so the benefit isn't caused by the thermal effects
of LLLT.

PubMed

"As a result of irradiation, increase of the mitochondrial membrane potential was

found to occur in irradiated hepatocytes both in the presence or in the absence of
CaCl2. The hyperpolarization of the mitochondrial membrane is assumed to cause
an increase in mitochondrial Ca2+ uptake that was measured in isolated
mitochondria. Finally, an increase in c-fos expression was found in irradiated
hepatocytes when incubated in the presence of CaCl2."

PubMed

"This paper gives additional information on the mechanism by which He-Ne laser
light, either directly or in a cascade-like effect dependent on increase in cell Ca2+,
can cause cell stimulation."

Mechanisms

Original
research

Pastore

Italy
(Campobasso)

2000

Int J Radiol Biol

"Cytochrome c oxidation catalysed by COX was affected by He-Ne laser

irradiation of the purified enzyme."

PubMed

"This study shows that purified COX is a specific target of He-Ne laser light;
therefore, COX may be considered to be a mitochondrial photo-acceptor."

Mechanisms

Original
research

Yu

USA
1997
(Rochester, NY)

Photochem
Photobiol

Photomodulation of oxidative metabolism and electron chain

enzymes in rat liver mitochondria.

In vitro

Isolated liver
mitochondria

660

0.01

0.6
1.2
1.8
2.4
4.8

"Photoirradiation significantly increased oxygen consumption (0.6 J/cm2 and 1.2

J/cm2, P < 0.05), phosphate potential, and the energy charge (1.8 J/cm2 and 2.4
J/cm2, P < 0.05) of rat liver mitochondria and enhanced the activities of NADH:
ubiquinone oxidoreductase, ubiquinol: ferricytochrome C oxidoreductase and
ferrocytochrome C: oxygen oxidoreductase (0.6 J/cm2, 1.2 J/cm2, 2.4 J/cm2 and
4.8 J/cm2, P < 0.05).

Isolated hepatocytes

633

0.012

0.24

"Irradiation resulted in an enhancement in cytosolic free Ca2+ concentration that

requires the presence of Ca2+ in the phase outside hepatocytes; consistently an
increase in cell membrane potential was measured correlated with it."

PubMed

0.056

"Three-dimensional reconstruction of mitochondria from ultrathin sections trough

the whole lymphocyte showed that the number of mitochondria was reduced to 912 in the irradiated cells compared with 40-45 in the control cells. In the irradiated
lymphocytes, 2-4 giant branching mitochondria were also observed among small
discrete mitochondria."

PubMed

"While no change in ATP synthase kinetics was observed as a result of ADP

irradiation, adenine nucleotides proved to be sensitive to He-Ne laser irradiation
when their interaction with ADP/ATP carrier and adenylate kinase was
considered."

PubMed

"Both cytosolic and mitochondrial protein synthesis increased as a result of

irradiation, as demonstrated by the measurement of hepatocytes previously
treated with chloramphenicol and cycloheximide respectively.

PubMed

PubMed

The activities of succinate ubiquinone oxidoreductase, ATPase, and lactate

dehydrogenase were not affected by photoirradiation."
Note: A highly cited article (238 in Google Scholar in 10/2016).

Mechanisms

Original
research

Vacca

Italy
(Bari)

1997

Biochem Mol Biol

Int

The irradiation of hepatocytes with He-Ne laser causes an increase

of cytosolic free calcium concentration and an increase of cell
membrane potential, correlated with it, both increases taking place
in an oscillatory manner.

In vitro

Mechanisms

Original
research

Manteifel

Russia
(Troitsk)

1997

J Photochem
Photobiol B

Ultrastructural changes in chondriome of human lymphocytes after In vitro

irradiation with He-Ne laser: appearance of giant mitochondria.

Mechanisms

Original
research

Gagliardi

Italy
(Bari)

1997

Biochem Mol Biol

Int

A novel property of adenine nucleotides: sensitivity to helium-neon In vitro

laser in mitochondrial reactions.

Mechanisms

Original
research

Vacca

Italy
(Bari)

1996

J Photochem
Photobiol B

Increase in cytosolic and mitochondrial protein synthesis in rat

hepatocytes irradiated in vitro by He-Ne laser.

In vitro

633

Isolated hepatocytes

633

0.01

633

0.007
0.012

0.24

Coherence

An initial investigation showed that stimulation of protein synthesis also occurred

in hepatocytes irradiated with a non-coherent radiation source (fluence, 0.24 J cm
(-2))."

Mechanisms

Original
research

Pastore

Italy
(Campobasso)

1994

Biochem Mol Biol

Int

Increase in <--H+/e- ratio of the cytochrome c oxidase reaction in

mitochondria irradiated with helium-neon laser.

In vitro

Isolated liver
mitochondria

633

Mechanisms

Original
research

Greco

Italy
(Bari)

1991

J Photochem
Photobiol B

Helium-neon laser irradiation of rat liver mitochondria gives rise to

a new subpopulation of mitochondria: isolation and first
biochemical characterization.

In vitro

Isolated liver
mitochondria

Mechanisms

Original
research

Greco

Italy
(Bari)

1989

Biochem Biophys
Res Commun

Increase in RNA and protein synthesis by mitochondria irradiated

with helium-neon laser.

In vitro

Mechanisms

Original
research

Passarella

Italy
(Bari)

1988

Biochem Biophys
Res Commun

Increase in the ADP/ATP exchange in rat liver mitochondria

irradiated in vitro by helium-neon laser.

In vitro

Mechanisms

Rapid
communication

Santana-Blank

Venezuela
(Caracas)

2013

Photomed Laser
Surg

Photobiomodulation of aqueous interfaces: finding evidence to

support the exclusion zone in experimental and clinical studies.

Rapid
Communicati
on

The author suggests that some of the effects of photobiomodulation might happen by increasing "EZ water" in the cells.

PubMed

Review

Freitas &
Hamblin

Brazil&USA

2016

IEEE J Sel Top

Proposed Mechanisms of Photobiomodulation or Low-Level Light
Quantum Electron Therapy

Review

"Photobiomodulation also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread
acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has
been gained in this area, which will be summarized in this review."

IEEE

Mechanisms

Isolated liver
mitochondria

10

"A low, but statistically significant increase in the oxygen uptake was found, as
polarographically measured, in the presence of rotenone and antimycin A, with
ascorbate and TMPD used as substrate pair. Measurements were also made both
of the electron transfer and of proton pumping activity: as a result of a major
stimulation in the proton pumping activity, about 55% increase of <--H+/e- ratio
was found in irradiated mitochondria."

PubMed

633

In the irradiated sample, two bands were observed, one corresponding to normal
mitochondria and the other to atypical mitochondria.

PubMed

633

"Following mitochondrial irradiation, both the rate and amount of incorporation of

alpha-[32P]UTP and L-[35S]methionine, used to monitor RNA and protein
synthesis respectively, proved to increase. Electrophoretic analysis made of the
synthesis products clearly shows that He-Ne laser irradiation stimulates the
synthesis of all mitochondrial transcription and translation products."

PubMed

633

"As a result of experiments carried out with mitochondria loaded with either ATP or
ADP, the increase in the activity of the ADP/ATP translocator is here proposed to
depend on the increase in the electrochemical proton gradient which occurs owing
to irradiation of mitochondria."

PubMed

See additional information (on the right).

"One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light
into the near-infrared region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial
membrane potential, and adenosine triphosphate production.
Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium (Ca2+) to enter the cell.
After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO, and Ca2+, leading to activation of transcription
factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic
proteins, and antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT."

Correction

Reply

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Mechanisms

Review

Arany PR

USA
(Buffalo, NY)

2016

J Dent Res

Craniofacial Wound Healing with Photobiomodulation Therapy:

New Insights and Current Challenges.

Review

Mechanisms

Review

Sommer AP

Germany

2015

Ann Transl Med

A mechanism for ultrasound/light-induced biostimulation.

(Review)

Category

Alternative ideas

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

Additional info

sec

"Despite significant volumes of scientific literature from clinical and laboratory studies noting the phenomenological evidence for this innovative therapy,
limited mechanistic insights have prevented rigorous and reproducible PBM clinical protocols. This article briefly reviews current evidence and focuses on
gaps in knowledge to identify potential paths forward for clinical translation with PBM therapy with an emphasis on craniofacial wound healing. PBM
offers a novel opportunity to examine fundamental nonvisual photobiological processes as well as develop innovative clinical therapies, thereby
presenting an opportunity for a paradigm shift from conventional restorative/prosthetic approaches to regenerative modalities in clinical dentistry."

PubMed

1) Sommer critisizes Karu's research: [See additional info]

PubMed

2) Sommer suggests LLLT and ultrasound have similar mechanisms

3) Sommer suggests that LLLT improves the rotation of ATPase by reducing the viscosity of the nanoscopic interfacial water layers within and around the
ATP synthase.

Sommer: "In our opinion, the cytochrome enzyme mechanism is not capable to explain the enhancement of the action of the ATP synthase. First, red or near-infrared (NIR) light is
practically not absorbed by the chromophore of cytochrome c oxidase (it is a porphyrin ring with an absorption maximum at 550 nm). [...] There exist experiments showing that the
concentration of cytochrome c oxidase increases slightly upon illumination with NIR light. However, these results are not understood and they do not prove any connection between
cytochrome c oxidase and ATP synthase."
However, in 2004, Karu had already mentioned that Recent experimental absorption studies in the red-NIR region (2729) do not contradict the suggestions made by Karu and
Afanasyeva (26).] <--- [Photochem Photobiol. 2004 Sep-Oct;80(2):366-72.]

Mechanisms

Review

Sommer AP

Germany

2015

Ann Transl Med

Tuning the mitochondrial rotary motor with light.

(Review)

Sommer offers some unique thoughts on LLLT mechanisms, pulsing, dose response, etc... However, his views haven't been commented by other
researchers in the LLLT/PBM field.

PubMed

Mechanisms

Review

Passarella &
Karu

Italy & Russia

2014

J Photochem
Photobiol B

Absorption of monochromatic and narrow band radiation in the

visible and near IR by both mitochondrial and non-mitochondrial
photoacceptors results in photobiomodulation.

Review

"We describe whether and how mitochondria can interact with monochromatic and narrow band radiation in the red and near IR optical regions with
dissection of both structural and functional effects likely leading to photobiostimulation. Moreover we also report that a variety of biomolecules localized in
mitochondria and/or in other cell compartments including cytochrome c oxidase, some proteins, nucleic acids and adenine nucleotides are light sensitive
with major modifications in their biochemistry.

PubMed

Mechanisms

Review

Hong P Kim

Korea

2014

Biomol Ther
(Seoul)

Lightening up Light Therapy: Activation of Retrograde Signaling

Pathway by Photobiomodulation

Review

Mechanisms

Review

Farivar

Iran

2014

J Lasers Med Sci

Biological effects of low level laser therapy.

Review

All together the reported investigations show that the elucidation of the mechanism of the light interaction with biological targets still remains to be
completed, this needing further research, however the light sensitivity of a variety of molecules strongly suggests that photobiomodulation could be used
in both in photomedicine and in biotechnology."

Mechanisms

Review

Agrawal

USA
(Boston, MA)

2014

Dose Response

Pre-conditioning with low-level laser (light) therapy: light before

the storm.

Review

Mechanisms

Review

Wu & Xing

China
(Guangzhou))

2013

Laser Photon Rev

Intracellular signaling cascades following light irradiation

Review

PubMed
PubMed
Preconditioning

Brain

Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a
pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack.

PubMed

"Low-level light therapy (LLLT) using red to near-infrared (NIR) (6301000 nm) light has gained attention in recent years as a therapy in ophthalmology,
neurology, dermatology, dentology, and regenerative medicine[...]"

Wiley

Includes an interesting comparison of LLLT and methylene blue.

PubMed

Mechanisms

Review

Rojas &
Gonzalez-Lima

USA
(Austin, TX)

2013

Biochem
Pharmacol

Neurological and psychological applications of transcranial lasers

and LEDs

Review

Mechanisms

Review

Prindeze

USA
(Washington)

2013

Exp Biol Med

(Maywood)

Mechanisms of action for light therapy: a review of molecular

interactions.

Review

PubMed

Mechanisms

Review

Liebert

Australia

2013

Med Hypotheses

Protein conformational modulation by photons: a mechanism for

laser treatment effects.

Review

PubMed

Mechanisms

Review

Kushibiki

Japan
(Tokorozawa)

2013

Int J Mol Sci

Regulation of miRNA expression by low-level laser therapy (LLLT)

and photodynamic therapy (PDT).

Review

Mechanisms

Review

Chung

USA
(Boston, MA)

2012

Ann Biomed Eng

The nuts and bolts of low-level laser (light) therapy.

Review

Mechanisms

Review

Quirk & Whelan

USA
2011
(Milwaukee, WI)

Photomed Laser
Surg

Near-infrared irradiation photobiomodulation: the need for basic

science.

Mechanisms

Review

Poyton & Ball

USA
(Colorado)

Discov Med

Therapeutic photobiomodulation: nitric oxide and a novel function

of mitochondrial cytochrome c oxidase.

PubMed
A highly-cited LLLT overview.

PubMed

"One thing that is missing in all of these pre-clinical and clinical studies is a proper investigation into the basic science of the NIR-PBM phenomenon.
Although there is much discussion of the uses of NIR, there is very little on how it actually works. As far as explaining what really happens, we are
basically left to resort to saying light enters, then a miracle happens, and good things come out! Clearly, this is insufficient, if for no other reason than
our own intellectual curiosity. But beyond that, we can not hope to truly develop this extremely promising treatment to its highest potential without some
understanding of what is actually happening inside the 'black box'"

PubMed

"Although early studies identified mitochondrial cytochrome c oxidase as an endogenous photoreceptor for photobiomodulation, the cellular and
molecular mechanisms underlying photobiomodulation have not been clear.

Review

"At the heart of the matter is the question of enzyme kinetics. As it is generally agreed that the cellular target for the NIR is the enzyme CCO, an understanding of how the light
affects its kinetic properties is the most logical place to start. At this point, there appears to be only one study directly addressing this question. An increase in the observed kinetic
constant for the reaction of CCO with cytochrome c was observed at high enzyme/substrate ratios when the enzyme was irradiated with 630-nm laser light. In contrast, a lowering of
the kinetic constant occurred at low enzyme/substrate ratios. A mechanistic interpretation of these results was not offered."
"In sum, we feel that the time is right to move aside from limiting ourselves to studying only the downstream results of NIR-PBM, and aggressively pursue avenues leading to a basic
understanding of the underlying science."

[See additional info for more quotes]

2011

Tuner has also written about this topic http://www.laserannals.com/2015/09/05/preconditioning-laser-phototherapy/

PubMed

"First, nitric oxide has been implicated.

Second, cytochrome c oxidase, an enzyme known to reduce oxygen to water at the end of the mitochondrial respiratory chain, has been shown to have a new enzymatic activity-the reduction of nitrite to nitric oxide. This nitrite reductase activity is elevated under hypoxic conditions but also occurs under normoxia.

Three recent findings provide important new insight: [See additional info]
From these findings, we propose that cytochrome c oxidase functions in photobiomodulation by producing nitric oxide, a signaling molecule which
can then function in both intra- and extracellular signaling pathways. We also propose that the effectiveness of photobiomodulation is under the
control of tissue oxygen and nitrite levels."

And third, low intensity light enhances nitric oxide synthesis by cytochrome c oxidase without altering its ability to reduce oxygen."

Mechanisms

Review

Karu & Pyatibrat

Russia
(Troitsk)

2011

IUBMB Life

Gene expression under laser and light-emitting diodes radiation for Review
modulation of cell adhesion: Possible applications for
biotechnology.

"Cell adhesion and proliferation can be increased by irradiation with light of certain wavelengths (maxima in action spectrum are 619, 675, 740, 760, and
820 nm) or decreased when the activity of photoacceptor (cytochrome c oxidase in mitochondrial respiratory chain) is inhibited by chemicals before the
irradiation. This modality allows controlling the number of attached and/or proliferating cells. Possible biotechnology applications of this method are
outlined."

PubMed

Mechanisms

Review

Huang

USA & China

2011

Dose Response

Biphasic dose response in low level light therapy - an update.

Review

Shows preliminary evidence that too high dose might inhibit the beneficial effects of LLLT.

PubMed

Mechanisms

Review

Tafur

USA
(San Diego,
CA)

2010

Photomed Laser
Surg

Biophoton detection and low-intensity light therapy: a potential

clinical partnership.

Review

Mechanisms

Review

Karu T

Russia
(Troitsk)

2010

IUBMB Life

Multiple Roles of Cytochrome c Oxidase in Mammalian Cells Under

Action of Red and IR-A Radiation

Review

The evidence linking LLLT to cytochrome c oxidase function.

PDF

Mechanisms

Review

Hashmi

USA
(Boston, MA)

2010

PM R

Role of low-level laser therapy in neurorehabilitation.

Review

A highly-cited article on LLLT.

PubMed

Mechanisms

Review

Lane N

UK

2009

Nature

Cell biology: power games.

News feature
(Review)

Nick Lanes news article in Nature journal. An interesting piece of news focusing on cytochrome oxidase.

PubMed

Mechanisms

Review

Gao & Xing

China
(Guangzhou)

2009

J Biomed Sci

Molecular mechanisms of cell proliferation induced by low power

laser irradiation.

Review

"Low power laser irradiation (LPLI) promotes proliferation of multiple cells, which (especially red and near infrared light) is mainly through the activation of
mitochondrial respiratory chain and the initiation of cellular signaling.

PubMed

PubMed

Recently, the signaling proteins involved in LPLI-induced proliferation merit special attention, some of which are regulated by mitochondrial signaling."
[Also see additional info]

"Hepatocyte growth factor receptor (c-Met), a member of tyrosine protein kinase receptors (TPKR), is phosphorylated during LPLI-induced proliferation, but tumor necrosis factor
alpha (TNF-alpha) receptor has not been affected.
Activated TPKR could activate its downstream signaling elements, like Ras/Raf/MEK/ERK, PI3K/Akt/eIF4E, PI3K/Akt/eNOS and PLC-gamma/PKC pathways.
Other two pathways, DeltaPsim/ATP/cAMP/JNK/AP-1 and ROS/Src, are also involved in LPLI-induced proliferation. LPLI-induced cell cycle progression can be regulated by the
activation or elevated expressions of cell cycle-specific proteins.

Note: A highly cited article (279 on Google Scholar in 10/2016).

Furthermore, LPLI induces the synthesis or release of many molecules, like growth factors, interleukins, inflammatory cytokines and others, which are related to promotive effects of
LPLI."

Mechanisms

Review

Tafur & Mills

USA
(La Jolla, CA)

2008

Photomed Laser
Surg

Low-intensity light therapy: exploring the role of redox

mechanisms.

Review

"The mitochondrial electron transport chain has been shown to be photosensitive to red and near-infrared (NIR) light. Although the underlying
mechanisms have not yet been clearly elucidated, mitochondrial photostimulation has been shown to increase ATP production and cause transient
increases in reactive oxygen species (ROS). In some cells, this process appears to participate in reduction/oxidation (redox) signaling."

PubMed

Mechanisms

Review

Karu TI

Russia
(Troitsk)

2008

Photochem
Photobiol

Mitochondrial signaling in mammalian cells activated by red and

near-IR radiation. K

Review

"Experimental data about modulation of elements of mitochondrial retrograde signaling by the irradiation (mitochondrial membrane potential DeltaPsi(m),
reactive oxygen species ROS, Ca(2+), NO, pH(i), fission-fusion homeostasis of mitochondria) are reviewed. The terminal enzyme of the mitochondrial
respiratory chain cytochrome c oxidase is considered as the photoacceptor. Functions of cytochrome c oxidase as a signal generator as well as a signal
transducer in irradiated cells are outlined."

PubMed

Mechanisms

Review

Yeager

USA
(IN)

2007

Med Hypotheses

Melatonin as a principal component of red light therapy.

Review

Mechanisms

Review

Amat

Spain

2006

J Photochem
Photobiol B

The electric field induced by light can explain cellular responses to

electromagnetic energy: a hypothesis of mechanism.

Review

Mechanisms

Review

Eells

USA
2004
(Milwaukee, WI)

Mitochondrion

Mitochondrial signal transduction in accelerated wound and retinal

healing by near-infrared light therapy.

Review

An old, yet good, review on LLLT.

PubMed

Mechanisms

Review

Karu TI

Russia
(Troitsk)

1999

J Photochem
Photobiol B

Primary and secondary mechanisms of action of visible to near-IR

radiation on cells.

Review

A highly cited LLLT review (965 in Google Scholar in 10/2016).

PubMed

Mechanisms

Review

Laakso

Australia

1993

Aust J Physiother

Factors affecting Low Level Laser Therapy.

Review

A very old, yet good, review on LLLT.

PubMed

Mechanisms

Review

Kitchen &
Partridge

1991

Physiotherapy

A Review of Low Level Laser Therapy: Part I: Background,

Physiological Effects and Hazards

Review

Mechanisms

Review

Karu TI

1989

Health Phys

Photobiology of low-power laser effects.

Review

Russia
(Troitsk)

Melatonin

PubMed

Link
"Quantitative studies have been performed to determine the action of low-intensity visible monochromatic light on various cells (E. coli, yeasts, HeLa,
Chinese hamster fibroblasts and human lymphocytes); also irradiation conditions (wavelength, dose and intensity) conducive to vital activity stimulation
have been examined.

PubMed

Respiratory chain components are discussed as primary photoacceptors. The possible ways for photosignal transduction and amplification are
discussed. It is proposed that enhanced wound healing due to irradiation with low-intensity visible laser light (He-Cd, He-Ne and semiconductor lasers) is
due to the increasing proliferation of cells."

Mechanisms

Review

Belkin &
Schwartz

Israel
(Ramat Gan)

1989

Health Phys

New biological phenomena associated with laser radiation.

"Low-energy laser irradiation produces significant bioeffects. These effects are manifested in biochemical, physiological and proliferative phenomena in
various enzymes, cells, tissues, organs and organisms.

Review

PubMed

Examples are given of the effect of He-Ne laser irradiation in preventing the post-traumatic degeneration of peripheral nerves and the postponement of
degeneration of the central nervous system. The damage produced by similar radiant exposures to the corneal epithelium and endothelium is also
described.
It is suggested that the mechanism of laser/tissue interaction at these low levels of radiant exposure is photochemical in nature, explaining most of the
characteristics of these effects. These low-energy laser bioeffects are of importance on a basic scientific level, from a laser safety aspect and as a
medical therapeutic modality."

Mechanisms

Review

Karu TI

Russia
(Troitsk)

1988

Lasers Life Sci

Molecular Mechanism of the Therapeutic Effect of Low-Intensity

Laser Radiation

Review

Mechanisms

Review

Smith KC

1981

J Invest Dermatol

Photobiology and photomedicine: the future is bright.

Review

Mechanisms

Review

Lane (Nick)

UK

Muscle

Action potential

Comelekoglu

Turkey
(Mersin)

2002

(none)

Are mitochondria the alpha and omega of retinal disease?

Review

Lasers Surg Med

Electrophysiologic effect of gallium arsenide laser on frog

gastrocnemius muscle.

Frog

Muscle

Atrophy

Rochkind &
Shainberg

Israel
(Ramat Gan)

2013

Photomed Laser
Surg

Protective effect of laser phototherapy on acetylcholine receptors

and creatine kinase activity in denervated muscle.

Rat

Muscle

Cachexia (burn)

Martins

Brazil
(Santos)

2015

Acta Cir Bras

Low-level laser therapy modulates musculoskeletal loss in a skin

burn model in rats.

Rat

PDF
History of light therapy. Not related to LLLT.

Link

Retinal diseases

PDF
904

Muscle denervation

633

35

808

30

1800
3.57

1.44

50

d=
0.028
mm
(?)

48

14

"This study revealed that at the different repetition rate and exposure time, low
energy GaAs laser does not have any significant effect on frog gastrocnemius
action potential."

PubMed

"In the early stages of muscle atrophy, laser phototherapy may preserve the
denervated muscle by maintaining CK activity and the amount of AChR."

PubMed

"Low-level laser therapy had positive effects on gastrocnemius muscle, improving

tissue muscle morphology, increasing cross sectional area and MyoD
immunoexpression."

PubMed

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Muscle

Energy
metabolism

Nguyen

USA
(Gainesville,
FL)

2014

Mitochondrion

Effect of near-infrared light exposure on mitochondrial signaling in

C2C12 muscle cells.

In vitro

Biphasic dose
response

808
+
980

8.14
14.85
22.8
29.6

Muscle

Energy
metabolism

Hayworth

USA
(Austin, TX)

2010

Photochem
Photobiol

In vivo low-level light therapy increases cytochrome oxidase in

skeletal muscle.

Rat

Cytochrome oxidase

660

10.8
21.6
32.4

Category

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

Additional info

sec

"Repeated NIR light exposure (4 days) appeared to elevate oxidative stress and
increase the upstream mitochondrial regulatory proteins AMPK (3.1-fold), p38
(2.8-fold), PGC-1 (19.7%), Sirt1 (26.8%), and reduced RIP140 (23.2%), but
downstream mitochondrial regulation/content (Tfam, NRF-1, Sirt3, cytochrome c,
ETC subunits) was unaltered.

PubMed

Our data indicates that NIR light alters mitochondrial biogenesis signaling and may
represent a mechanistic link to the clinical benefits."

LED phototherapy
LED cluster (149x)

1200
2400
3600

"The findings showed for the first time that in vivo LLLT induced a dose- and fiber
type-dependent increase in cytochrome oxidase in muscle fibers. LLLT was
particularly effective at enhancing the aerobic capacity of intermediate and red
fibers.

PubMed

The findings suggest that LLLT may enhance the oxidative energy metabolic
capacity of different types of muscle fibers, and that LLLT may be used to
enhance the aerobic potential of skeletal muscle."

Muscle

Energy
metabolism

Ferraresi

Brazil
(So Carlos)

2015

Photochem
Photobiol

Low-level laser (light) therapy increases mitochondrial membrane

potential and ATP synthesis in C2C12 myotubes with a peak
response at 3-6 h.

630
+
850

In vitro
C2C12
myotubes

"LEDT employed a cluster of LEDs with 20 red (630 10 nm, 25 mW) and 20
near-infrared (850 10 nm, 50 mW) delivering 28 mW cm(2) for 90 s (2.5 J cm(2))
with analysis at 5 min, 3 h, 6 h and 24 h post-LEDT.

PubMed

LEDT-6 h had the highest MMP, followed by LEDT-3 h, LEDT-24 h, LEDT-5 min
and Control with significant differences.
The same order (6 h > 3 h > 24 h > 5 min > Control) was found for ATP with
significant differences. A good correlation was found (r = 0.89) between MMP and
ATP.
These data suggest an optimum time window of 3-6 h for LEDT stimulate muscle
cells."
Comment: The increase in ATP levels at 6h was quite huge. Interesting.

Muscle

Energy
metabolism

AlbuquerquePontes

Brazil
(So Paulo)

2015

Photochem
Photobiol

Effect of pre-irradiation with different doses, wavelengths, and

application intervals of low-level laser therapy on cytochrome c
oxidase activity in intact skeletal muscle of rats.

660
830
905

Rat
Biphasic
dose
response (?)

50
50
50

1/3/10
1/3/10
1/3/10

0.028
cm2

20/
60/
200

"Our results show that LLLT increased (p < 0.05) cytochrome c oxidase
expression mainly with the following wavelengths and doses: 660 nm with 1 J, 830
nm with 3 J, and 905 nm with 1 J at all time points."

PubMed

"We conclude that LLLT can increase cytochrome c oxidase activity in intact
skeletal muscle and that it contributes to our understanding of how LLLT can
enhance performance and protect skeletal muscles against fatigue development
and tissue damage."
Comment: At some time points, the Cox expression was lower than in control
group. It doesn't seem the result is as straightforward as the abstract makes it
seem...

Muscle

Energy
metabolism

Larkin-Kaiser

Canada
(Calgary)

2015

J Athl Train

Near-infrared light therapy to attenuate strength loss after

strenuous resistance exercise.

Human
Crossover

Muscle

Energy
metabolism

Xu

China
(Guangzhou)

2008

Photomed Laser
Surg

Low-intensity laser irradiation improves the mitochondrial

dysfunction of C2C12 induced by electrical stimulation.

In vitro

Muscle

Muscle

Muscle

Exercise

Exercise

Exercise

De Marchi

Vanin

Aver Vanin

Brazil
(Caxias do Sul)

Brazil
(So Paulo)

Brazil
(So Paulo)

2017
epub

2016

2016

Lasers Med Sci

Lasers Med Sci

Photomed Laser
Surg

Does photobiomodulation therapy is better than cryotherapy in

muscle recovery after a high-intensity exercise? A randomized,
double-blind, placebo-controlled clinical trial.

Human
RCT/DB

What is the best moment to apply phototherapy when associated

to a strength training program? A randomized, double-blinded,
placebo-controlled trial : Phototherapy in association to strength
training.

Human
RCT/DB

800
+
970

Biphasic dose
response

LED phototherapy
LED cluster (34+35)

360

810

660
+
850

0.33
1.338
2.646
5.358
8.22
11.22
14.16

340
+
1050

41.7

Pre-Exercise Infrared Low-Level Laser Therapy (810 nm) in Skeletal Human

Muscle Performance and Postexercise Recovery in Humans, What RCT/DB
Is the Optimal Dose? A Randomized, Double-Blind, PlaceboControlled Clinical Trial.

Dose response

13.8
cm2

30

"Our data (as shown in Fig. 2) suggest that doses of 0.338.22 J/cm2 do no harm
to the mitochondrial function of normal cells, while doses of 11.2214.16 J/cm2
are beyond the point at which PBM is beneficial, and such doses can actually
worsen cellular function (p  0.01), a finding consistent with that of the study done
by Lavi et al.

PubMed

DOMS, CK (serum), TBARS (serum), oxidative damage (serum), MVC (postexercise)

PubMed

"The clinical impact of these findings is clear because they demonstrate that the
use of phototherapy is more effective than the use of cryotherapy for muscle
recovery, additionally cryotherapy decreases PBMT efficacy."

640
+
875
+
905

810

PubMed

Our current research also showed that LIL irradiation at doses of 0.338.22 J/cm2
had a photobiomodulating effect on C2C12 myotubes, as manifested by the
improvement of mitochondrial function compared with 75 min of electrical
stimulation (p  0.01), and that LIL doses of 0.33 and 1.338 J/cm2 reversed the
dysfunctional state induced by the electrical stimulation, as shown in Fig. 2."

(0.2
/LED)

LED phototherapy
LED+LLLT cluster

"Applied to skeletal muscle before resistance exercise, NIR light therapy

effectively attenuated strength loss. Therefore, NIR light therapy may be a
beneficial, noninvasive modality for improving muscle function during rehabilitation
after musculoskeletal injury. However, future studies using higher treatment doses
are warranted."

"Volunteers from group treated with phototherapy before and placebo after training
sessions showed significant (p < 0.05) changes in MVC and 1-RM tests for both
exercises (leg extension and leg press) when compared to other groups.

PubMed

With an apparent lack of side effects and safety due to no thermal damage to the
tissue, we conclude that the application of phototherapy yields enhanced strength
gains when it is applied before exercise"
1000

60
180
300

60
180
300

"Pre-exercise LLLT, mainly with 50 J dose, significantly increases performance

and improves biochemical markers related to skeletal muscle damage and
inflammation."

PubMed

"However, LLLT had no effect in decreasing DOMS. No differences (p > 0.05)

were found for 30 J dose in any of the outcomes measured."
Comment: Since six sites were irradiated, 50J group refers to the 300J total dose.

Muscle

Exercise

Fritsch

Brazil
(Porto Alegre)

2016

Lasers Med Sci

Effects of low-level laser therapy applied before or after plyometric

exercise on muscle damage markers: randomized, double-blind,
placebo-controlled trial.

Human
RCT/DB

LED phototherapy
LED cluster (5)

810

Muscle

Exercise

Ferraresi

Brazil
(So Carlos)

2016

Am J Phys Med
Rehabil

Effects of Light-Emitting Diode Therapy on Muscle Hypertrophy,

Gene Expression, Performance, Damage, and Delayed-Onset
Muscle Soreness: Case-control Study with a Pair of Identical
Twins.

Human
RCT
Twin study

LED phototherapy

850

1000

240

210

75

15

36

"In summary, the LLLT protocol used in this study had no effect on strength fall
induced by muscle damage; then, caution is needed for recommending
phototherapy to reduce this functional impairment. However, LLLT applied both
before and after plyometric exercise was able to reduce the muscular echo
intensity, indicating a reduced inflammatory response mediated by phototherapy.
In addition, our findings suggest a slight effect (not statistically significant) on
muscle soreness, which might seem too small for most individuals but can make a
crucial difference for high-performance athletes."

PubMed

"Compared with placebo, LEDT increased the maximal load in exercise and
reduced fatigue, creatine kinase, and visual analog scale.

PubMed

Gene expression analyses showed decreases in markers of inflammation

(interleukin 1) and muscle atrophy (myostatin) with LEDT.
Protein synthesis (mammalian target of rapamycin) and oxidative stress defense
(SOD2 [mitochondrial superoxide dismutase]) were up-regulated with LEDT,
together with increases in thigh muscle hypertrophy."
"Light-emitting diode therapy can be useful to reduce muscle damage, pain, and
atrophy, as well as to increase muscle mass, recovery, and athletic performance
in rehabilitation programs and sports medicine."

Muscle

Exercise

Rossato

Brazil
(Florianpolis)

2016

Lasers Med Sci

Effect of pre-exercise phototherapy applied with different cluster

probe sizes on elbow flexor muscle fatigue.

Human
RCT/DB
Crossover

Muscle

Exercise

Malta Ede

Brazil
(Rio Claro)

2016

Lasers Med Sci

Acute LED irradiation does not change the anaerobic capacity and
time to exhaustion during a high-intensity running effort: a doubleblind, crossover, and placebo-controlled study : Effects of LED
irradiation on anaerobic capacity and performance in running.

Human
RCT/DB
Crossover

Muscle

Exercise

Larkin-Kaiser

Canada
(Calgary)

2016

Lasers Med Sci

Photobiomodulation delays the onset of skeletal muscle fatigue in

a dose-dependent manner.

Human
RCT

Muscle

Exercise

Nampo

Brazil
(So Cristvo)

2016

Lasers Med Sci

Effect of low-level phototherapy on delayed onset muscle

soreness: a systematic review and meta-analysis.

Metaanalysis

LED phototherapy
LED cluster (33 or 9)

670
+
880
+
950
660
+
850

Biphasic dose
response (?)

810
(20%)
+
980
(80%)

600
(10p)

2000
4000

240
480

20
40

1.72
cm2
spot

120

"In both large and small cluster probes (according parameters tested in this study)
led to reduced fatigue in elbow flexor muscles, without difference between them."

PubMed

"In summary, LEDT after a high-intensity running effort did not alter the
MAODALT, metabolic energy pathways, or high-intensity running performance."

PubMed

"The 240-J dose significantly extended TTF by 26 % (p = 0.032) compared with

the sham dose. TTF for the 240-J dose was strongly associated with a decrease in
muscle fatigue (R (2) = 0.54, p = 0.024). Our findings show that a 240-J dose of
NIR light therapy is efficacious in delaying the onset and extent of muscle fatigue
during submaximal isometric positioning tasks. Our findings suggest that NIR light
therapy may be used as an ergogenic aid during functional tasks or post-injury
rehabilitation."

PubMed

Comment: The 480J dose was less effective.

"We identified 15 studies involving 317 participants. Meta-analyses were limited by substantial heterogeneity.

PubMed

Compared to the placebo group, reduction in CK levels was only observed when LASERtherapy was applied before an exercise protocol (standardized
mean difference = -0.66; 95 % CI = -1.30, -0.02).
No between-group difference in edema, range of movement and strength were detected when phototherapy was applied before or after exercise.
Evidence from this review suggests that low-level phototherapy may not have substantial effect in the treatment of skeletal muscle injury and pain caused
by exercise. Definitive conclusions are limited due to the small number of included studies in each meta-analysis, disparities across the included studies
and small sample sizes."

Muscle

Exercise

Ferraresi

Brazil
(So Paulo)

2016

J Biophotonics

Photobiomodulation in human muscle tissue: an advantage in

sports performance?

Review

Parameters
Optimal Dose

"This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The
parameters used were categorized into those with positive effects or no effects on muscle performance and recovery."

PubMed

"Searches retrieved 533 studies, of which 46 were included in the review (n = 1045 participants). Studies used single laser probes, cluster of laser
diodes, LED clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase
muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be
permitted in athletic competition by international regulatory authorities."
Comment: The review also has some photos and interesting figures related to studied light doses in different trials.

Muscle

Exercise

Zagatto

Brazil
(Bauru)

2016

Lasers Med Sci

Effects of low-level laser therapy on performance, inflammatory

markers, and muscle damage in young water polo athletes: a
double-blind, randomized, placebo-controlled study.

Human
RCT/DB

810

Muscle

Exercise

Miranda

Brazil
(So Paulo)

2016

J Athl Train

Using Pre-Exercise Photobiomodulation Therapy Combining

Super-Pulsed Lasers and Light-Emitting Diodes to Improve
Performance in Progressive Cardiopulmonary Exercise Tests.

Human
Crossover

640
+
875
+
905

Muscle

Exercise

Toma

Brazil

2016

Lasers Med Sci

Low level laser therapy associated with a strength training

program on muscle performance in elderly women: a randomized
double blind control study.

Human
RCT/DB

100

3.57

48

107.14

0.028
cm2

30
/p
(18p)

Muscle performance

808

100

"In conclusion, LLLT resulted in a non-significant, but small to moderate effect on

inflammatory and muscle damage markers and a moderate effect on performance
in water polo players. In addition, the lack of positive results could be due to the
small area covered by irradiation and this should be considered in future studies."

PubMed

"The combination of lasers and LEDs increased the time, distance, and pulmonary
ventilation and decreased the score of dyspnea during a cardiopulmonary test."

PubMed

LLLT seemed a little bit better than the control, but is it clinically/statistically
relevant (between-the-group)?

PubMed

n = 48

Comment

Reply

 Category
Muscle

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Exercise

Pinto

Brazil
(So Paulo)

2016

J Strength Cond
Res

Photobiomodulation Therapy Improves Performance and

Accelerates Recovery of High-Level Rugby Players in Field Test: A
Randomized, Crossover, Double-Blind, Placebo-Controlled Clinical
Study.

Human
RCT/DB

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

Additional info

Comment

sec

"Photobiomodulation therapy significantly (p 0.05) improved the average time of

sprints and fatigue index in BST. Photobiomodulation therapy significantly
decreased percentage of change in blood lactate levels (p 0.05) and perceived
fatigue (p 0.05).

PubMed

Pre-exercise PBMT with the combination of super-pulsed laser (low-level laser),

red LEDs, and infrared LEDs can enhance performance and accelerate recovery
of high-level rugby players in field test.
This opens a new avenue for wide use of PBMT in real clinical practice in sports
settings."

Muscle

Exercise

Perini

Brazil
(Porto Alegre)

2016

Lasers Med Sci

Long-term low-level laser therapy promotes an increase in maximal Rat

oxygen uptake and exercise performance in a dose-dependent
manner in Wistar rats.

"The 61.2 J/cm(2)-LLLT group increased VO2basal (~40 %), VO2max (~24 %),
VCO2max (~17 %), and distance covered (~34 %) after LLLT application on the
skeletal muscle. No significant results were found comparing before and after
conditions for the studied variables considering P-LLLT and 8.7 J/cm(2)-LLLT
groups.

Dose response

PubMed

The LLLT promoted in a dose-dependent manner an increase in oxygen

consumption uptake and a performance increment of male Wistar rats."
Comment: Parameters were well reported.

Muscle

Exercise

de Paiva

Brazil
(So Paulo)

2016

Lasers Med Sci

Photobiomodulation therapy (PBMT) and/or cryotherapy in skeletal

muscle restitution, what is better? A randomized, double-blinded,
placebo-controlled clinical trial.

Human
RCT/DB

Restitution after
exercise
GameDay device

Muscle

Exercise

Leal-Junior

Brazil
(So Paulo)

2015

Lasers Med Sci

Effect of phototherapy (low-level laser therapy and light-emitting

diode therapy) on exercise performance and markers of exercise
recovery: a systematic review with meta-analysis.

905
+
875
+
640

"We conclude that PBMT used as single treatment is the best modality for
enhancement of post-exercise restitution, leading to complete recovery to baseline
levels from 24 h after high-intensity eccentric contractions."

"From 13 RCTs with acceptable methodological quality (6 of 10 items), 12 RCTs irradiated phototherapy before exercise, and 10 RCTs reported
significant improvement for the main outcome measures related to performance.

Metaanalysis

PubMed

PubMed

The time until exhaustion increased significantly compared to placebo by 4.12 s (95% CI 1.21-7.02, p < 0.005) and the number of repetitions increased
by 5.47 (95% CI 2.35-8.59, p < 0.0006) after phototherapy.
Heterogeneity in trial design and results precluded meta-analyses for biochemical markers, but a quantitative analysis showed positive results in 13 out
of 16 comparisons.
The most significant and consistent results were found with red or infrared wavelengths and phototherapy application before exercises, power outputs
between 50 and 200 mW and doses of 5 and 6 J per point (spot).
We conclude that phototherapy (with lasers and LEDs) improves muscular performance and accelerate recovery mainly when applied before exercise."

Muscle

Exercise

Francisco Cde

Brazil
(So Carlos)

2015

Trials

Evaluation of acute effect of light-emitting diode (LED)

phototherapy on muscle deoxygenation and pulmonary oxygen
uptake kinetics in patients with diabetes mellitus: study protocol
for a randomized controlled trial.

Study
protocol

Diabetic patients

Muscle

Exercise

Ferraresi

Brazil
(So Carlos)

2015

Lasers Med Sci

Light-emitting diode therapy (LEDT) before matches prevents

increase in creatine kinase with a light dose response in volleyball
players.

Human
RCT/DB

LED phototherapy
LED cluster

630
+
850

"The main objective of this study is to evaluate the acute effects of muscular preconditioning using LED phototherapy on pulmonary oxygen uptake, muscle
oxygenation, heart rate, and arterial pressure dynamics during dynamic moderate
exercise. We hypothesize that phototherapy may be beneficial to optimize aerobic
fitness in the DM population."

PubMed

"LEDT prevented significant increases of CK in blood in athletes when applied

before official matches with a light dose response of 210-315 J, suggesting
athletes might consider applying LEDT before competition."

PubMed

Nampo et al published a brief criticism of this paper:

"Due to the fragilities we pointed above, we agreed that the validity of this paper
does not allow safe conclusions. To produce valid and meaningful results, we
recommend to increase sample size, evaluate functional outcomes to establish
clinical relevance, evaluate better established indicators of muscle damage (i.e.,
imaging), and do better data reporting."

Muscle

Exercise

Ferraresi

Brazil
(So Carlos)

2015

Physiother Theory Muscular pre-conditioning using light-emitting diode therapy

Pract
(LEDT) for high-intensity exercise: a randomized double-blind
placebo-controlled trial with a single elite runner.

Human
(n=1)

LED phototherapy
LED cluster

850

50

37.5

15

"LEDT improved the speed of the muscular VO2 adaptation (-9 s), decreased O2
deficit (-10 L), increased the VO2 from the slow component phase (+348 ml min
(-1)), and increased the time limit of exercise (+589 s)."

PubMed

Note: A photograph is supplied, but it is black-and-white.

Muscle

Exercise

Ferraresi

Brazil
(So Carlos)

2015

Lasers Med Sci

Time response of increases in ATP and muscle resistance to

fatigue after low-level laser (light) therapy (LLLT) in mice.

Mouse

LED phototherapy
LED cluster

630
+
850

500
+
1000

0.08

7.2

45
cm2

90

"LEDT-6 h was the subgroup with the highest ATP content in soleus and
gastrocnemius compared to all subgroups (P < 0.001). In addition, mice in LEDT-6
h group performed more repetitions in the fatigue test (P < 0.001) compared to all
subgroups: LEDT-sham and LEDT-5 min (~600 %), LEDT-3 h (~200 %), and
LEDT-24 h (~300 %). A high correlation between the fatigue test repetitions and
the ATP content in soleus (r = 0.84) and gastrocnemius (r = 0.94) muscles was
observed.

(skin)
cluster

PubMed

LEDT increased ATP content in muscles and fatigue resistance in mice with a
peak at 6 h. Although the time response in mice and humans is not the same,
athletes might consider applying LEDT at 6 h before competition."

Muscle

Exercise

Ferraresi

Brazil
(So Paulo)

2015

J Biophotonics

Light-emitting diode therapy in exercise-trained mice increases

muscle performance, cytochrome c oxidase activity, ATP and cell
proliferation.

Mouse

LED phototherapy
LED cluster

630
850

0.08

7.3

90

"Six bi-daily training sessions LEDT-After and LEDT-Before-After regimens more

than doubled muscle performance and increased ATP more than tenfold. The
effectiveness of LEDT on improving muscle performance and recovery suggest
applicability for high performance sports and in training programs."

PubMed

Star: Parameters are well reported. Results are interesting. A photograph is

supplied.

Muscle

Exercise

Amadio

Brazil
(So Paulo)

2015

Lasers Med Sci

808

The action of pre-exercise low-level laser therapy (LLLT) on the

Rat
expression of IL-6 and TNF- proteins and on the functional fitness
of elderly rats subjected to aerobic training.

"These results suggest that laser therapy in conjunction with aerobic training may
provide a therapeutic approach for reducing the inflammatory markers (IL-6 and
TNF-), however, LLLT without exercise was not able to improve physical
performance of aged rats."

PubMed

Comment: Exercise was beneficial, but the importance of LLLT seems

unclear/minimal.

Muscle

Exercise

Assis

Brazil
(Santos)

2015

Braz J Phys Ther

Effect of low-level laser therapy (808 nm) on skeletal muscle after

endurance exercise training in rats.

Rat

Muscle

Exercise

Kakihata

Brazil
(Cascavel)

2015

Einstein (Sao
Paulo)

Influence of low-level laser therapy on vertical jump in sedentary

individuals.

Human

660

Muscle

Exercise

da Costa Santos

Brazil
(Londrina)

2014

Lasers Med Sci

LED therapy or cryotherapy between exercise intervals in Wistar

rats: anti-inflammatory and ergogenic effects.

Rat

940

160

Muscle

Exercise

Borges

Brazil
(Jequie)

2014

Lasers Med Sci

Light-emitting diode phototherapy improves muscle recovery after

a damaging exercise.

630

300

0.0095

"Both trained groups showed significant increase in speed compared to the CG.
The TLG demonstrated a significantly reduced lactate level, increased tibialis
anterior (TA) fiber cross-section area, and decreased TA fiber density."

PubMed

"The low intensity laser on the triceps surae, in sedentary individuals, had no
significant effects on the variables evaluated."

PubMed

"The [passive rest] group presented a high frequency of necrosis, but the LED
group had fewer necrotic areas. Edema formation was prevented, and fewer areas
of inflammatory cells were observed in the LED group. The time to exhaustion was
greater in both the LED and Cryo groups, without differences in CK levels. CRP
was decreased in LED animals. We conclude that LED therapy and cryotherapy
can improve performance, although LED therapy is more efficient in preventing
muscle damage and local and systemic inflammation."

PubMed

Comment: Results are very interesting. Parameters weren't well reported, though.
20.4

1.77
cm2

120

"Our results showed that the muscle soreness, muscle strength loss, and ROM
impairments were significantly reduced up to 96 h after a damaging eccentric
exercise bout for the LEDT group compared with the PLACEBO group.

PubMed

A single LEDT (630 nm) intervention immediately after a damaging eccentric

exercise bout was effective in terms of attenuating the muscle soreness and
muscle strength loss and ROM impairments."

Muscle

Exercise

de Brito Vieira

Brazil
(Natal)

2014

Photomed Laser
Surg

Use of low-level laser therapy (808 nm) to muscle fatigue

resistance: a randomized double-blind crossover trial.

Human
RCT/DB
Crossover

808

100

Muscle

Exercise

Dos Reis

Brazil
(Campo
Grande)

2014

Photomed Laser
Surg

Effects of pre- or post-exercise low-level laser therapy (830 nm) on

skeletal muscle fatigue and biochemical markers of recovery in
humans: double-blind placebo-controlled trial.

Human
RCT/DB

830

360

0.0028
cm2

(6 *
60)

Muscle

Exercise

da Silva Alves

Brazil
(Santos)

2014

Lasers Med Sci

Acute effects of low-level laser therapy on physiologic and

electromyographic responses to the cardiopulmonary exercise
testing in healthy untrained adults.

Human
RCT/DB
Crossover

850

Muscle

Exercise

Santos

Brazil
(So Paulo)

2014

Lasers Med Sci

Effects of pre-irradiation of low-level laser therapy with different

doses and wavelengths in skeletal muscle performance, fatigue,
and skeletal muscle damage induced by tetanic contractions in
rats.

Rat

660
830
905

100
/diod
e

14
/site

1/3/10

"LLLT group increased RM (52%; p=0.002) with a small EFI for the vastus
medialis (p=0.004) and rectus femoris (p=0.004)."

PubMed

"The number of repetitions (p=0.8965), RM (p=0.9915), and duration of fatigue

(p=0.8424) were similar among the groups. Post-fatigue laser treatment
significantly decreased the serum lactate concentration relative to placebo
treatment (p<0.01) and also within the group over time (after 5 min vs. after 10 and
15 min, p<0.05 both). The CK level was lower in the post-fatigue laser group (p<0.
01)."

PubMed

"The LLLT acutely increases exercise performance in healthy untrained adults

probably due to increased O2 extraction by peripheral muscles without causing a
significant impact on muscle fatigue."

PubMed

"Several LLLT doses showed some positive effects on peak force and time to
decay for one or more contractions, but in terms of total work, only 3 J/660 nm and
1 J/905 nm wavelengths prevented significantly (p < 0.05) the development of
skeletal muscle fatigue"
"Optimal doses of LLLT significantly delayed the development skeletal muscle
performance and protected skeletal muscle tissue against damage. Our findings
also demonstrate that optimal doses are partly wavelength specific and,
consequently, must be differentiated to obtain optimal effects on development of
skeletal muscle fatigue and tissue preservation.
Our findings also lead us to think that the combined use of wavelengths at the
same time can represent a therapeutic advantage in clinical settings."

Muscle

Exercise

Felismino

Brazil
(Natal)

2014

Lasers Med Sci

Effect of low-level laser therapy (808 nm) on markers of muscle

damage: a randomized double-blind placebo-controlled trial.

Human
RCT/DB

808

100

35.7

1
/point

357.14

40
(4p)

"In conclusion, the LLLT attenuated CK activity 72 h after the muscle damage
protocol but did not have a positive effect on the recovery of strength
performance."

PubMed

Muscle

Exercise

Paolillo

Brazil
(So Carlos)

2014

Lasers Surg Med

Low-level laser therapy associated with high intensity resistance

training on cardiac autonomic control of heart rate and skeletal
muscle remodeling in wistar rats.

Rat

780

15

0.0375

0.15
/p

3.8

10

"The main results of the present study found that LLLT in conjunction with HIT
increased MMP-2 gene expression and some HRV indices. It also appears LLLT
has independent positive effects on HRV."

PubMed

Muscle

Exercise

Baroni

Brazil
(Porto Alegre)

2014

Eur J Appl Physiol Effect of low-level laser therapy on muscle adaptation to knee
extensor eccentric training.

810

1000

"Subjects from [training + LLLT group] reached significantly higher percent

changes compared to subjects from [training group] for sum of muscles'
thicknesses (15.4 vs. 9.4%), isometric peak torque (20.5 vs. 13.7%), and eccentric
peak torque (32.2 vs. 20.0%)."

PubMed

Human
RCT

Muscle growth
LLLT cluster

(5 *
200)

240

30
/p
(8p)

14

Star: Interesting results. A topic worth investigating.

Comment: LLLT spot size or energy density was not reported.

Muscle

Exercise

de Oliveira

Brazil
(So Paulo)

2014

Trials

What is the ideal dose and power output of low-level laser therapy
(810 nm) on muscle performance and post-exercise recovery?
Study protocol for a double-blind, randomized, placebo-controlled
trial.

Study
protocol

"Our intention, is to determine optimal laser therapy application parameters

capable of slowing down the physiological muscle fatigue process, reducing
injuries or micro-injuries in skeletal muscle stemming from physical exertion and
accelerating post-exercise muscle recovery."

PubMed

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Muscle

Exercise

Antonialli

Brazil
(So Paulo)

2014

Lasers Med Sci

Phototherapy in skeletal muscle performance and recovery after

exercise: effect of combination of super-pulsed laser and lightemitting diodes.

Human
RCT/DB

Muscle performance
and recovery
LED phototherapy
LED cluster

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

sec

905
+
875
+
670

"Pre-exercise phototherapy with combination of low-level laser and LEDs, mainly

with 30 J dose, significantly increases performance, decreases DOMS, and
improves biochemical marker related to skeletal muscle damage."

PubMed

Comment: The parameters are quite complex in this study - read the full text for
further information.
Star: An interesting paper with parameters well reported and good outcome!

Muscle

Exercise

Gomes

Brazil
(So Paulo)

2014

Trials

Efficacy of pre-exercise low-level laser therapy on isokinetic

muscle performance in individuals with type 2 diabetes mellitus:
study protocol for a randomized controlled trial.

Study
protocol

Muscle

Exercise

Higashi

Brazil
(Santos)

2013

Photomed Laser
Surg

Effects of low-level laser therapy on biceps braquialis muscle

fatigue in young women.

Human
RCT
Crossover

Biceps braquialis

Blood lipids,
cholesterol

Muscle

Exercise

Aquino

Brazil
(So Carlos)

2013

Lasers Med Sci

Low-level laser therapy (LLLT) combined with swimming training

improved the lipid profile in rats fed with high-fat diet.

Rat

Muscle

Exercise

Borsa

USA
(Gainesville,
FL)

2013

J Athl Train

Does phototherapy enhance skeletal muscle contractile function

and postexercise recovery? A systematic review.

Systematic
review

Brazil
(Santos)

2013

Effect of 808 nm low-level laser therapy in exercise-induced

skeletal muscle fatigue in elderly women.

Human
RCT/DB
Triple-blinded
Crossover

Muscle

Exercise

Toma

Lasers Med Sci

808

100

35.7

7
/p

70
/p

(8p)
830

9.4
(2p)

"The purpose of this randomized clinical trial is to evaluate the efficacy of preexercise LLLT on the performance of the quadriceps muscle (peak torque, total
muscle work, maximum power and fatigue index - normalized by body mass) in
individuals with DM-2. The study will support the practice of evidence-based to the
use of LLLT in improving muscle performance in Individuals with DM-2. Data will
be published after the study is completed."

PubMed

"No statistical differences were found for eletromyographic fatigue and blood
lactate values between groups. Mean numbers of elbow flexion-extension
repetitions were 22.6 7.58 after placebo, and 25.1 9.89 after active LLLT
group, but these differences were not statistically significant (p=0.342)."

PubMed

"LLLT decreased the total cholesterol (p < 0.05), triglycerides (p < 0.01), lowdensity lipoprotein cholesterol (p < 0.05), and relative mass of fat tissue (p < 0.05),
suggesting increased metabolic activity and altered lipid pathways. The
combination of exercise and LLLT increased the benefits of exercise alone.
However, LLLT without exercise tended to increase body weight and fat content."

PubMed

"In total, 12 randomized controlled trials met the inclusion criteria. However, we excluded data from 2 studies, leaving 32 data sets from 10 studies."

PubMed

"Exposing skeletal muscle to single-diode and multidiode laser or multidiode LED therapy was shown to positively affect physical performance by
delaying the onset of fatigue, reducing the fatigue response, improving postexercise recovery, and protecting cells from exercise-induced damage."
808

100

"The results showed no difference in the slope comparing placebo LLLT and
active LLLT groups (p = 0.293). However, a significant difference was observed in
the number of repetitions between groups, after active LLLT, subjects
demonstrated significantly higher number of repetitions (p = 0.047). In this study,

PubMed

LLLT was efficient in increasing the mean number of repetitions during knee
flexion-extension exercise, although results have not shown delay
electromyographic fatigue."

Muscle

Exercise

Patrocinio

Brazil
(So Carlos)

2013

Photomed Laser
Surg

Effect of low-level laser therapy (808 nm) in skeletal muscle after

resistance exercise training in rats.

Rat

Muscle

Exercise

de Almeida

Brazil
(So Paulo)

2012

Lasers Med Sci

Red (660 nm) and infrared (830 nm) low-level laser therapy in
skeletal muscle fatigue in humans: what is better?

Human
RCT
Crossover

Muscle

Exercise

Vieira

Brazil
(Natal)

2012

Lasers Med Sci

Effects of low-level laser therapy (808 nm) on isokinetic muscle

performance of young women submitted to endurance training: a
randomized controlled clinical trial.

660
830

50

Human
RCT

808

360

Wavelength
comparison

17.85

20
/
muscl
e

"Analysis demonstrated that TGL demonstrated significantly reduced resting

lactate level and decreased muscle glycogen depletion than the animals that were
exercised only, and significantly increased the cross-section area of TA muscle
fibers compared with thoseo in the other groups."

PubMed

"The mean peak force was significantly greater (p < 0.05) following red (12.14%)
and infrared LLLT (14.49%) than following placebo LLLT, and the mean average
force was also significantly greater (p < 0.05) following red (13.09%) and infrared
LLLT (13.24%) than following placebo LLLT. There were no significant differences
in mean average force or mean peak force between red and infrared LLLT.

PubMed

We conclude that both red than infrared LLLT are effective in delaying the
development skeletal muscle fatigue and in enhancement of skeletal muscle
performance."
18
/limb

(6 *
60)

Muscle

Exercise

De Marchi

Brazil
(Caxias do Sul)

2012

Lasers Med Sci

Low-level laser therapy (LLLT) in human progressive-intensity

running: effects on exercise performance, skeletal muscle status,
and oxidative stress.

Human
RCT/DB
Crossover

810

Muscle

Exercise

Leal Junior

Brazil
(So Paulo)

2011

Lasers Med Sci

Comparison between cold water immersion therapy (CWIT) and

light emitting diode therapy (LEDT) in short-term skeletal muscle
recovery after high-intensity exercise in athletes--preliminary
results.

Human
RCT/DB
Crossover

660
+
850

Muscle

Exercise

Ferraresi

Brazil
(So Carlos)

2011

Lasers Med Sci

Effects of low level laser therapy (808 nm) on physical strength

training in humans.

Human
RCT

808

200

30
/point

30
/point

"The results suggest that an endurance training program combined with LLLT
leads to a greater reduction in fatigue than an endurance training program without
LLLT. This is relevant to everyone involved in sport and rehabilitation."

PubMed

"Compared to placebo, active LLLT significantly increased exercise performance

(VO(2 max) p = 0.01; time to exhaustion, p = 0.04) without changing the aerobic
and anaerobic thresholds. LLLT also decreased post-exercise lipid (p = 0.0001)
and protein (p = 0.0230) damages, as well as the activities of SOD (p = 0.0034),
CK (p = 0.0001) and LDH (p = 0.0001) enzymes. LLLT application was not able to
modulate CAT activity.

PubMed

The use of LLLT before progressive-intensity running exercise increases exercise

performance, decreases exercise-induced oxidative stress and muscle damage,
suggesting that the modulation of the redox system by LLLT could be related to
the delay in skeletal muscle fatigue observed after the use of LLLT."

360

21.42

50.4

214.3

(6 *
60)

0.028
cm2

140

24

beam
(?)

"There were no significant differences in the work performed during the three
Wingate tests (p > 0.05). All biochemical parameters increased from baseline
values (p < 0.05) after the three exercise tests, but only active LEDT decreased
blood lactate levels (p = 0.0065) and CK activity (p = 0.0044) significantly after
treatment. There were no significant differences in CRP values after treatments."

PubMed

"The TLG subjects showed an increase of 55% in the 1RM leg-press test, which
was significantly higher than the increases in the TG subjects (26%, P = 0.033)
and in the CG subjects (0.27%, P < 0.001).

PubMed

The TLG was the only group to show an increase in muscle performance in the
isokinetic dynamometry test compared with baseline.
The increases in thigh perimeter in the TLG subjects and TG subjects were not
significantly different (4.52% and 2.75%, respectively; P = 0.775).
Strength training associated with LLLT can increase muscle performance
compared with strength training only."
Comment: In the paper they report beam area as 0.0028 cm2, but since many
other papers from Brazil have been 0.028, it is possible that they are misreporting
something here.

Muscle

Exercise

de Almeida

Brazil
(So Paulo)

2011

Photochem
Photobiol

Low-level laser therapy improves skeletal muscle performance,

decreases skeletal muscle damage and modulates mRNA
expression of COX-1 and COX-2 in a dose-dependent manner.

Rat

Electrical stimulation
of muscle

904

15

1.0
3.0

"The 1.0 and 3.0 J groups showed significant enhancement (P < 0.01) in total
work performed in six tetanic contractions compared with control group.

PubMed

All laser groups, except the 3.0 J group, presented significantly lower postexercise CK activity than control group.
Additionally, 1.0 J group showed increased COX-1 and decreased COX-2 mRNA
expression compared with control group and 0.1, 0.3 and 3.0 J laser groups (P <
0.01)."
Comment: Parameters were raported in a nice way.

Muscle

Exercise

Demura

Japan
(Kanazawa)

2011

J Physiol
Anthropol

Effect of linear polarized near-infrared light irradiation and light

exercise on muscle performance.

Muscle

Exercise

Sussai

Brazil
(Campo
Grande)

2010

Lasers Med Sci

Muscle

Exercise

Leal Junior

Norway
(Bergen)

2010

Eur J Appl Physiol Effect of low-level laser therapy (GaAs 904 nm) in skeletal muscle
fatigue and biochemical markers of muscle damage in rats.

Low-level laser therapy attenuates creatine kinase levels and

apoptosis during forced swimming in rats.

Super Lizer

6001600

Rat

Swimming

660

Rat

Biphasic dose
response

904

Human

100

133.3

0.1
0.3
1.0
3.0

"In conclusion, skin and muscle temperatures increased significantly with the
active and passive warm-ups selected in this study. However, muscle strength,
muscle power, and controlled force-exertion performance did not improve with
either warm-up."

PubMed

"There was a significant difference in CK levels between groups (P < 0.0001) as

well as between the 24 h and 48 h levels in the control group, whereas there was
no significant intra-group difference in the LLLT group at the same evaluation
times."

PubMed

"We conclude that pre-exercise irradiation with a laser dose of 1.0 J and 904 nm
wavelength significantly delays muscle fatigue and decreases post-exercise blood
lactate and CK in this rat model."

PubMed

Note: The first author is from Brazil. The last author is from Norway. Maybe this
was some kind of collaboration project.

Muscle

Exercise

Baroni

Brazil
(Porto Alegre)

2010

Eur J Appl Physiol Low level laser therapy before eccentric exercise reduces muscle
damage markers in humans.

Human

LLLT cluster (5)

810

1000

"In conclusion, LLLT treatment before eccentric exercise was effective in terms of
attenuating the increase of muscle proteins in the blood serum and the decrease
in muscle force."

PubMed

Muscle

Exercise

Baroni

Brazil
(Porto Alegre)

2010

Photomed Laser
Surg

Effect of light-emitting diodes therapy (LEDT) on knee extensor

muscle fatigue.

Human
RCT/DB
Crossover

LED cluster (34+35)

660
+
850

340
+
1050

"LEDT treatment produced a smaller maximal isometric torque decrease after

high-intensity concentric isokinetic exercise, which is consistent with an increase
in performance."

PubMed

Muscle

Exercise

Leal Junior

Brazil
(So Paulo)

2010

J Orthop Sports
Phys Ther

Effects of low-level laser therapy (LLLT) in the development of

exercise-induced skeletal muscle fatigue and changes in
biochemical markers related to postexercise recovery.

Human

LLLT cluster (5)

810

200

"Active LLLT increased the number of repetitions by 14.5% (mean +/- SD, 39.6 +/4.3 versus 34.6 +/- 5.6; P = .037) and the elapsed time before exhaustion by 8.0%
(P = .034), when compared to the placebo treatment.

PubMed

30

The biochemical markers also indicated that recovery may be positively affected
by LLLT, as indicated by postexercise blood lactate levels (P<.01), creatine kinase
activity (P = .017), and C-reactive protein levels (P = .047), showing a faster
recovery with LLLT application prior to the exercise."

Muscle

Exercise

Leal Junior

Brazil
(Caxias do Sul)

2009

Lasers Surg Med

Effect of cluster multi-diode light emitting diode therapy (LEDT) on

exercise-induced skeletal muscle fatigue and skeletal muscle
recovery in humans.

Human
RCT/DB
Crossover

LED phototherapy
LED cluster (69)

660
+
850

"Active LEDT increased the number of biceps humeri contractions by 12.9%

(38.60 [SD +/-9.03] vs. 34.20 [SD +/-8.68], P = 0.021) and extended the elapsed
time to perform contractions by 11.6% (P = 0.036) versus placebo.

PubMed

In addition, post-exercise levels of biochemical markers decreased significantly

with active LEDT: Blood Lactate (P = 0.042), Creatine Kinase (P = 0.035), and CReative Protein levels (P = 0.030), when compared to placebo LEDT."

LLLT vs LED
LED phototherapy
LED cluster

810
vs
660+
850

Muscle

Exercise

Leal Junior

Brazil
(Caxias do Sul)

2009

Photomed Laser
Surg

Comparison between single-diode low-level laser therapy (LLLT)

and LED multi-diode (cluster) therapy (LEDT) applications before
high-intensity exercise.

Human
RCT/DB
Crossover

Muscle

Exercise

Leal Junior

Brazil
(Caxias do Sul)

2009

Lasers Med Sci

Effect of 830 nm low-level laser therapy applied before highintensity exercises on skeletal muscle recovery in athletes.

Human
RCT/DB
Crossover

830

100

Muscle

Exercise

Leal Junior

Brazil
(Caxias do Sul)

2009

Lasers Med Sci

Effect of 830 nm low-level laser therapy in exercise-induced

skeletal muscle fatigue in humans.

Human
RCT/DB
Crossover

830

100

3-4

0.0028
cm2
(?)
0.0028
cm2

200

"In this experimental set-up, only the active LEDT probe decreased post-exercise
CK levels after the Wingate cycle test. Neither performance nor blood lactate
levels were significantly affected by this protocol of pre-exercise LEDT or LLLT."

PubMed

"LLLT irradiation before the Wingate test seemed to inhibit an expected postexercise increase in CK level and to accelerate post-exercise lactate removal
without affecting test performance."

PubMed

"After active LLLT the mean number of repetitions was significantly higher than
after placebo irradiation [mean difference 4.5, standard deviation (SD) +/- 6.0, P =
0.042], the blood lactate levels increased after exercises, but there was no
significant difference between the treatments.

PubMed

We concluded that 830 nm LLLT can delay the onset of skeletal muscle fatigue in
high-intensity exercises, in spite of increased blood lactate levels."

Muscle

Exercise

Leal Junior

Brazil
(Caxias do Sul)

2008

Photomed Laser
Surg

Effect of 655-nm low-level laser therapy on exercise-induced

skeletal muscle fatigue in humans.

Human
RCT/DB

655

5
/p

500

"Compared to the first session (on day 1), the mean number of repetitions
increased significantly by 8.5 repetitions (+/- 1.9) in the active LLLT group at the
second session (on day 8), while in the placebo LLLT group the increase was only
2.7 repetitions (+/- 2.9) (p = 0.0001)."

PubMed

Additional info

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---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Muscle

Exercise

Demura

Japan
(Kanazawa)

2008

J Hum Ergol
(Tokyo)

Effect of linear polarized near-infrared light irradiation on muscle

fatigue recovery after repeated handgrip exercise.

Human

Super Lizer

Muscle

Exercise

Lopes-Martins

Brazil
(So Paulo)

2006

J Appl Physiol
(1985)

Effect of low-level laser (Ga-Al-As 655 nm) on skeletal muscle

fatigue induced by electrical stimulation in rats.

Rat

Biphasic dose
response

Muscle

Muscle activity

Vasso

Brazil
(Santos)

2016

Lasers Med Sci

Effects of photobiomodulation on the fatigue level in elderly

women: an isokinetic dynamometry evaluation.

Human
RCT/DB

Muscle

Muscle activity

Kelencz

Brazil
(Paraiba)

2010

Photomed Laser
Surg

Effect of low-power gallium-aluminum-arsenium noncoherent light

(640 nm) on muscle activity: a clinical study.

Human

Category

LED phototherapy

nm

mW

W/cm2

J/cm2

808

100

7
/point

640

116

1.044
2.088
3.132

Results: positive / unclear/modest / negative

Link

sec

6001600

"It is inferred that PL-irradiation maintains a high skin temperature and blood flow,
but it may not contribute to recover muscle contraction performance in muscle
fatigue."

PubMed

0.5
1.0
2.5

"Laser groups receiving 0.5 and 1.0 J/cm2 showed significant increases in mean
performed work compared with both the control group and their first contraction
values."

PubMed

250

"Muscle performance was evaluated using an isokinetic dynamometer. The results

showed that photobiomodulation was able of reducing muscle fatigue by a
significant increase of electromyographic fatigue index (EFI) (p = 0.047) and
decreasing significantly lactate concentration 6 min after the performance of the
fatigue protocol (p = 0. 0006) compared the placebo laser session. However, the
photobiomodulation was not able of increasing muscle performance measured by
the isokinetic dynamometer."

PubMed

"It was concluded that LED can be used as a clinical tool to increase muscle
activity (1.044 J per point) and to prevent fatigue (2.088 J per point), without
change in the muscle force."

PubMed

"We observed a subsequent improvement in atrophy that was most prominent

after 4 weeks in the groups that received P1 protein, but which also was present
after 8 weeks in the groups that received LLLT."

PubMed

0.522
cm2

/point

Muscle

Muscle atrophy

Muniz

Brazil
2015
(Ribeiro Preto)

Muscle Nerve

Properties of the tibialis anterior muscle after treatment with laser

therapy and natural latex protein following sciatic nerve crush.

780

Rat

30

0.75

1.8

15

0.04
cm2

60

"Treatment using only P1 proved most efficient, revealing a negative interaction

between P1 and LLLT."
Comment: Parameters were well reported.

Muscle

Muscle atrophy

Silva-Couto

Brazil
(So Carlos)

2012

Rev Bras Fisioter

Effects of low-level laser therapy after nerve reconstruction in rat

denervated soleus muscle adaptation.

Rat

Muscle

Muscle fatigue

Lopes-Martins

Brazil
(So Paulo)

2016

Photomed Laser
Surg

Laser Therapy and Muscle Fatigue: A Promising Research Area.

Muscle

Muscle fatigue

Gorgey

USA
(Indianapolis,
IN)

2008

Photomed Laser
Surg

The effect of low-level laser therapy on electrically induced muscle

fatigue: a pilot study.

Human
RCT
Crossover

Muscle

Muscle
inflammation

Mantineo

Portugal
(Coimbra)

2014

J Biomed Opt

Low-level laser therapy on skeletal muscle inflammation:

evaluation of irradiation parameters.

Rat

Nerve injury

660
780

"LLLT applied to the nerve post-reconstruction was ineffective in delaying

degenerative changes to the slow-twitch denervated muscles and in functional
recovery in rats."

PubMed
PubMed

Cytokine-induced
muscle inflammation

808

500

830
980

10
20
30
40
50

Pulsing vs continuous

3
7

300
600

"LLLT did not attenuate muscle fatigue evoked by NMES, but this needs to be
further addressed in human studies and clinical settings. The lack of significant
findings could be explained by the small sample size and the selection of LLLT
parameters."

PubMed

"Our results show treatment effects, particularly for irradiation with the 830-nm
laser.

PubMed

At day 6, the concentration of all measured proinflammatory cytokines in the 30

and 40 mW groups was significantly lower than for the control group. IL-6
concentration was reduced for all treatment groups and TNF- for all but the 50mW group.

Biphasic dose
response

The number of inflammatory cells in muscle tissue samples was also significantly
lower in all treatment groups when compared to the control animals"

Muscle

Muscle injury

Ribeiro

Brazil
(So Paulo)

2015
epub

Lasers Surg Med

The effect of low-level laser therapy (LLLT) applied prior to muscle

injury.

780

Rat

40

3.2
(8p)

10

0.04
cm2

80
(8p)

"LLLT applied prior to muscle injury led to a reduction in myonecrosis and

inflammatory cells, an increase of blood vessels and immature muscle fibers. An
increase in MMP-2 activity and a decrease in collagen deposition were also found,
with a better collagen organization and distribution."

PubMed

"LLLT applied immediately prior to injury had positive effects during the muscle
regeneration process."
Star: Parameters were well reported!

Muscle

Muscle injury

Ozaki

Brazil
(Campinas)

2016

Lasers Med Sci

Analysis of photobiomodulation associated or not with platelet-rich Rat

plasma on repair of muscle tissue by Raman spectroscopy.

Muscle

Muscle injury

de Melo

Brazil
(So Paulo)

2016

Lasers Med Sci

Light-emitting diode therapy increases collagen deposition during

the repair process of skeletal muscle.

Rat

Muscle

Muscle injury

Ribeiro

Brazil
(So Paulo)

2016

PLoS One

Red and Infrared Low-Level Laser Therapy Prior to Injury with or

without Administration after Injury Modulate Oxidative Stress
during the Muscle Repair Process.

Rat

Muscle

Muscle injury

Takhtfooladi

Iran

2016

Lasers Med Sci

Evaluation of low-level laser therapy on skeletal muscle ischemiareperfusion in streptozotocin-induced diabetic rats by assaying
biochemical markers and histological changes.

Rat

Muscle

Muscle injury

Morais

Brazil
(Araatuba)

2016

Lasers Med Sci

Strength training prior to muscle injury potentiates low-level laser

therapy (LLLT)-induced muscle regeneration.

Rat

Muscle

Muscle injury

Alves

Brazil
(So Paulo)

2014

Am J Phys Med
Rehabil

Effects of low-level laser therapy on skeletal muscle repair: a

systematic review.

Systematic
review

Brazil
(So Paulo)

2014

Lasers Med Sci

What is the best treatment to decrease pro-inflammatory cytokine

release in acute skeletal muscle injury induced by trauma in rats:
low-level laser therapy, diclofenac, or cryotherapy?

Rat

637

25

0.25

850

30

3.2

660
780

40

3.2

Muscle injury
Diabetes

650

30

1.8

1
cm2

Muscle regeneration

660

35

4.9
(?)

0.028
cm2

Cryoinjury

31.85

d=
1 mm

10

LED phototherapy
10

1-2

14

"It is concluded that either PBM or PRP, and the association of both, was able to
reduce the oxidative stress promoted by injury and modulate collagen production
at the site of the injury. Furthermore, although both treatments individually were
effective for repairing the damage caused by muscle injury, the association of both
demonstrated a better histological aspect."

PubMed

"LED therapy at 850 nm induced a significant reduction in inflammation,

decreased MMP-2 activity, and increased the amount of immature muscle and
collagen fibers during the muscle repair process following acute injury."

PubMed

"The administration of red and infrared laser therapy at different times positively
modulates the activity of antioxidant enzymes and reduces stress markers during
the muscle repair process."

PubMed

"LLLT has a beneficial effect on the IR muscle injury treatment in the diabetic rats"

PubMed

"Cryolesion induced massive muscle degeneration associated with inflammatory

infiltrate. Prior ST improved skeletal regeneration 14-days after cryolesion and
potentiated the regenerative response to LLLT."

PubMed

"Seventeen of the 36 original articles on LLLT and muscle injuries met the inclusion criteria and were critically evaluated.

PubMed

The main effects of LLLT were a reduction in the inflammatory process, the modulation of growth factors and myogenic regulatory factors, and increased
angiogenesis. The studies analyzed demonstrate the positive effects of LLLT on the muscle repair process, which are dependent on irradiation and
treatment parameters.
The findings suggest that LLLT is an excellent therapeutic resource for the treatment of skeletal muscle injuries in the short-term."

Muscle

Muscle injury

de Almeida

Muscle trauma

904

60

1.67

Inflammation

1
3
6
9

17
50
100
150

"LLLT with 1 J dose significantly decreased (p < 0.05) IL-1, IL-6, and TNF-
levels compared to non-treated injured group as well as diclofenac and
cryotherapy groups."

PubMed

For inflammation marker reduction, the 1J dose was the most efficient (a biphasic
dose response)!

Biphasic dose
response
PBM vs diclofenac

Muscle

Muscle injury

Brunelli

Brazil
(Campinas)

2014

Lasers Med Sci

The effects of 780-nm low-level laser therapy on muscle healing

process after cryolesion.

780

Rat

10
50

"The G10 and G50 during the 7 days showed a significant reduction (p < 0.05) of
lesion area compared to the CG, without differences between groups treated for
14 and 21 days.

PubMed

The G10 showed an increase of the amount of vessels after 14 days compared to
the G50, but not in relation to controls. With regard to the immunohistochemical
analyses of the MyoD factor, the G10 and G50 during the 7 days showed higher
concentrations of immunomarkers than controls."

Muscle

Muscle injury

Alves

Brazil
(So Paulo)

2014

Lasers Med Sci

Modulating effect of low level-laser therapy on fibrosis in the repair Rat

process of the tibialis anterior muscle in rats.

780

40

Muscle

Muscle injury

Silveira

Brazil
(Cricima)

2013

Lasers Med Sci

Effects of low-level laser therapy (GaAs) in an animal model of

muscular damage induced by trauma.

904

40

0.400

10

0.04
cm2

10

"The results revealed that LLLT induced a reduction in inflammatory infiltrate and
myonecrosis after 1 day, an increase in the number of blood vessels after 3 and 7
days as well as an increase in the number of immature muscle fibers and MMP-2
gelatinase activity after 7 days.

PubMed

In conclusion, LLLT has a positive effect on the inflammatory process, MMP2

activity and collagen organization and distribution in the repair process of rat
skeletal muscle."

Rat

2.5
(5p)

0.10
cm2

spot

Muscle

Muscle

Muscle injury

Muscle injury

Luo

de Paiva
Carvalho

China
(Suzhou)

Brazil
(So Paulo)

2013

2013

Lasers Med Sci

Photochem
Photobiol

Effects of low-level laser therapy on ROS homeostasis and

expression of IGF-1 and TGF-1 in skeletal muscle during the
repair process.

Rat

Effects of low-level laser therapy (LLLT) and diclofenac (topical

and intramuscular) as single and combined therapy in
experimental model of controlled muscle strain in rats.

Rat

635

0.0175

0.4
cm2

"LLLT accelerated the muscular healing by significantly decreasing superoxide

anion production, TBARS levels, the activity of SOD, and hydroxyproline content.

PubMed

The data strongly indicate that increased ROS production and augmented
collagen synthesis are elicited by traumatic muscular injury, effects that were
significantly decreased by LLLT."
1200

10

"The results showed that LLLT markedly promoted the regeneration of muscle and
reduced scar formation.

PubMed

LLLT also significantly enhanced muscle SOD activity and significantly decreased
muscle MDA levels 1, 2, and 3 days after injury."

PBM vs diclofenac

810

100

"LLLT showed better effects than TD and ID regarding PGE2 levels and walking
track analysis (P < 0.05)."

PubMed

"We can conclude that LLLT has more efficacy than topical and intramuscular
diclofenac in treatment of muscle strain injury in acute stage."

Muscle

Muscle injury

Frana

Brazil
(So Paulo)

2013

Lasers Med Sci

Effect of laser therapy on skeletal muscle repair process in diabetic Rat

rats.

Diabetic rats

780

Muscle

Muscle injury

de Almeida

Brazil
(So Paulo)

2013

Photochem
Photobiol

Low-level laser therapy and sodium diclofenac in acute

Rat
inflammatory response induced by skeletal muscle trauma: effects
in muscle morphology and mRNA gene expression of inflammatory
markers.

Muscle trauma

810

1.6

10
/point

"On day 14, the LLLT group was in the remodeling phase; the D group was still in
the proliferative phase, with fibrosis, chronic inflammation, and granulation tissue;
and the D-LLLT group was in an intermediary state in relation to the two previous
groups.

PubMed

Under polarized light, on day 14, the LLLT and D-LLLT groups had organized
collagen bundles in the perimysium, whereas the diabetic groups exhibited
fibrosis."

Inflammation

100

3.57

1
3
9

10
30
90

PBM vs diclofenac
Muscle injury

Rodrigues

Brazil
(So Carlos)

2013

J Photochem
Photobiol B

Low-level laser therapy (LLLT) (660nm) alters gene expression

during muscle healing in rats.

Rat

PubMed

"All LLLT doses also decreased (P < 0.05) COX-2 compared to injury group at all
time points, and to diclofenac group at 24 h after trauma. In addition, LLLT
decreased (P < 0.05) TNF- compared both to injury and diclofenac groups at all
time points. LLLT mainly with dose of 9 J is better than topical application of
diclofenac in acute inflammation after muscle trauma."

Biphasic dose
response

Muscle

"LLLT with all doses improved morphological aspects of muscle tissue, showing
better results than injury and diclofenac groups."

For inflammation marker reduction, the 1J dose was the most efficient (a biphasic
dose response)!
660

10
50

"Irradiated groups presented less inflammatory process than control group after 14
and 21 days.
Cox-2 levels were downregulated in all irradiated groups after 7, 14 and 21 days.
On day 7, both treated groups had a downregulation of Vegf levels, and an
upregulation after 14 and 21 days, mainly with 50J/cm(2).
The MyoD levels were upregulated with high dose in all periods and with low dose
after 21 days.
Myogenin expression was downregulated in both treated groups after 7 days, and
was upregulated with 10J/cm(2) after 21 days."

PubMed

Additional info

Comment

Reply

 Category
Muscle

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Muscle injury

Assis

Brazil
(So Carlos)

2013

Lasers Med Sci

Low-level laser therapy (808 nm) contributes to muscle

regeneration and prevents fibrosis in rat tibialis anterior muscle
after cryolesion.

Rat

808

30

3.8

1.4

180

Cryolesion

Results: positive / unclear/modest / negative

"LLLT significantly reduced the lesion percentage area in the injured muscle (p<0.
05), increased mRNA levels of the transcription factors MyoD and myogenin (p<0.
01) and the pro-angiogenic vascular endothelial growth factor (p<0.01).

Link

sec

0.785
mm2

47

PubMed

Moreover, LLLT decreased the expression of the profibrotic transforming growth

factor TGF- mRNA (p<0.01) and reduced type I collagen deposition (p<0.01).
These results suggest that LLLT could be an effective therapeutic approach for
promoting skeletal muscle regeneration while preventing tissue fibrosis after
muscle injury."

Muscle

Muscle injury

Fernandes

Brazil
(So Paulo)

2013

Lasers Med Sci

Effect of photobiomodulation on expression of IL-1 in skeletal

muscle following acute injury.

Rat

Acute injury

660

Muscle

Muscle injury

Rodrigues

Brazil
(So Carlos)

2013

J Rehabil Res
Dev

Effects of 660 nm low-level laser therapy on muscle healing

process after cryolesion.

Rat

Cryolesion

660

Muscle

Muscle injury

Pertille

Brazil
(Piracicaba)

2012

Rev Bras Fisioter

Evaluation of muscle regeneration in aged animals after treatment

with low-level laser therapy.

Rat

(Sarcopenia)

830

Muscle

Muscle injury

Silva

Brazil
(So Paulo)

2012

Lasers Med Sci

GaAs 904-nm laser irradiation improves myofiber mass recovery

during regeneration of skeletal muscle previously damaged by
crotoxin.

Mouse

Crotoxin

904

20

0.500

30

0.04
cm2

10

"In conclusion, LLLT was able to decrease IL-1 expression during the skeletal
muscle repair following an acute injury."

PubMed

10
50

"Histopathological findings revealed a lower inflammatory process in the lasertreated groups after 7 d. After 14 d, irradiated animals at both fluences showed
higher granulation tissue, new muscle fibers, and organized muscle structure.
After 21 d, full tissue repair was observed in all groups. Moreover, irradiated
animals at both fluences showed smaller necrosis area in the first experimental
period evaluated."

PubMed

"Considering the morphological and molecular analyzes performed, as well as the

parameters used, it may be concluded that low-level laser therapy affects muscle
regeneration of aged animals through its anti-inflammatory effects alone, as the
results did not demonstrate an effect on the contents of the proteins studied."

PubMed

Comment: The results suggest that LLLT increased the recovery of cross sectional
area of muscles quite markedly, but the authors claim there was no difference.
Maybe it's a matter of statistical significance.
1.5
3.0

"GaAs laser at a dose of 3 J, but not 1.5 J, significantly increased the CSA of
regenerating myofibers and reduced the PIMA and the area density of
intramuscular connective tissue of CTX-injured muscles."

PubMed

"Our results suggest that GaAs laser treatment at a dose of 3 J improves skeletal
muscle regeneration by accelerating the recovery of myofiber mass."

Muscle

Muscle injury

Assis

Brazil
(So Carlos)

2012

Lasers Surg Med

Low-level laser therapy (808 nm) reduces inflammatory response

and oxidative stress in rat tibialis anterior muscle after cryolesion.

808

Rat

30

0.0038

1.4

180

0.785
mm2

47

"LLLT reduced oxidative and nitrative stress in injured muscle, decreased lipid
peroxidation, nitrotyrosine formation and NO production, probably due to reduction
in iNOS protein expression.

PubMed

Moreover, LLLT increased SOD gene expression, and decreased the

inflammatory response as measured by gene expression of NF-k and COX-2 and
by TNF- and IL-1 concentration."

Muscle

Muscle injury

de Souza

Brazil
(So Paulo)

2011

Lasers Med Sci

Phototherapy with low-level laser affects the remodeling of types I

and III collagen in skeletal muscle repair.

Rat

Cryoinjury

660

20

0.0005
(?)

Muscle

Muscle injury

Baptista

Brazil
(So Paulo)

2011

Photomed Laser
Surg

Influence of laser photobiomodulation on collagen IV during

skeletal muscle tissue remodeling after injury in rats.

Rat

Cryoinjury

660

20

0.500

0.2

0.04
cm2

10

10

"InGaAlP diode laser within the power parameters and conditions tested had a
biostimulatory effect at the regenerative and fibrotic phases of the skeletal muscle
repairs, by promoting angiogenesis, reducing myonecrosis, and inducing types I
and III collagen synthesis, following cryoinjury in rat."

PubMed

"It was demonstrated that LLLT promotes an increase in collagen IV

immunolabeling in skeletal muscle in the first 7 days after acute trauma caused by
cryoinjury, but does not modify the duration of the tissue-repair process.

PubMed

Even with LLLT, the injured muscle tissue needs 21 days to achieve the same
state of organization as that in the noninjured muscle."

Muscle

Muscle injury

Mesquita-Ferrari

Brazil
(So Paulo)

2011

Lasers Med Sci

Effects of low-level laser therapy on expression of TNF- and TGF in skeletal muscle during the repair process.

Rat

660

Muscle

Muscle injury

Lakyov

Slovakia
(Kosice)

2010

Lasers Surg Med

Low-level laser therapy for protection against skeletal muscle

damage after ischemia-reperfusion injury in rat hindlimbs.

Rat

670

Muscle

Muscle injury

Liu

China
(Wuman)

2009

Photomed Laser
Surg

Effects of low-level laser irradiation on rat skeletal muscle injury

after eccentric exercise.

Rat

Exercise-induced
muscle injury

20

0.500

0.04

633

0.04
cm2

10

"LLLT caused a decrease in TNF- mRNA expression at 1 and 7 days following

injury and in TGF- mRNA expression at 7 days following cryoinjury in comparison
to the control group."

PubMed

"LLLT confers a protective effect against early inflammatory tissue response,

further atrophy, and necrosis of the muscle and it stimulates neovascularization
after I/R injury."

PubMed

"He-Ne laser irradiation at 43 J/cm2 inhibited muscle inflammation, significantly

enhanced muscle SOD activity and significantly reduced serum CK activity and
muscle MDA level at both 24 and 48 h after exercise, whereas the irradiation at 12
or 28 J/cm2 slightly inhibited muscle inflammation and significantly reduced serum
CK activity at 48 h after exercise only (P<0.05)."

PubMed

12
28
43

Dose response

"The photobiomodulation was dose-dependent, and the 43 J/cm2 dose was the
most efficient among the doses used."

Rat

Surgically induced
injury

785

75

810

400

2.7

0.3
cm2

36

1-4

"Quantitative data showed that the number of both polymorphonuclear and

mononuclear leukocytes in the inflammatory infiltrate at the injury site was smaller
in the ILI(1), ILI(2), and ILI(4) subgroups compared with their respective control
subgroups (IN(1), IN(2), and IN(4)) for sessions 1, 2, and 4, respectively (p <
0.05)."

Muscle

Muscle injury

Cressoni

Brazil
(So Paulo)

2008

Photomed Laser
Surg

The effects of a 785-nm AlGaInP laser on the regeneration of rat

anterior tibialis muscle after surgically-induced injury.

Muscle

Muscle injury

Avni

Israel
(Tel Aviv)

2005

Photomed Laser
Surg

Protection of skeletal muscles from ischemic injury: low-level laser Rat

therapy increases antioxidant activity.

Muscle

Muscle injury

Bibikova

1994

Anat Embryol
(Berl).

Enhancement of angiogenesis in regenerating gastrocnemius

muscle of the toad (Bufo viridis) by low-energy laser irradiation.

Angiogenesis

Red light (632.8nm) promotes angiogenesis in the injured zone.

PubMed

Muscle

Muscle injury

Bibikova & Oron

1993

Anat Rec

Promotion of muscle regeneration in the toad (Bufo viridis)

gastrocnemius muscle by low-energy laser irradiation.

Muscle injury
regeneration

Young myofibers in the laser-irradiated muscles populated 15.5% +/- 7.9% and
65.0% +/- 9.5% of the injured area at 9 and 14 days of muscle regeneration,
respectively, while in control muscles these structures were not evident at 9 days
and made up only 5.3% +/- 2.9% of the traumatized area at 14 days postinjury.

PubMed

Muscle

Muscle injury

Weiss & Oron

1992

Anat Embryol
(Berl).

Enhancement of muscle regeneration in the rat gastrocnemius

muscle by low energy laser irradiation.

It is concluded that He-Ne laser irradiation during the regeneration process

promotes muscle maturation in the injured zone following partial excision of the rat
gastrocnemius muscle.

PubMed

Muscle

Myopathy

Macedo

Brazil
(Campinas)

2015

PLoS One

Low-Level Laser Therapy (LLLT) in Dystrophin-Deficient Muscle

Cells: Effects on Regeneration Capacity, Inflammation Response
and Oxidative Stress.

"Together, these results suggest that the laser treatment improved regenerative
capacity and decreased inflammatory response and oxidative stress in dystrophic
muscle cells, indicating that LLLT could be a helpful alternative therapy to be
associated with other treatment for dystrophinopathies."

PubMed

Muscle

Myopathy

Silva

Brazil
(So Paulo)

2015

Lasers Med Sci

Pre-exercise low-level laser therapy improves performance and

Mouse
levels of oxidative stress markers in mdx mice subjected to muscle
fatigue by high-intensity exercise.

"The mdx mice treated with LLLT showed significantly lower levels of creatine
kinase (CK) and oxidative stress than mdx mice that underwent forced highintensity exercise on a treadmill.

PubMed

PubMed

"With regard to the regeneration of muscle fibers following injury, only after the
fourth treatment session was it possible to find muscle precursor cells such as
myoblasts and some myotubes in the ILI(4) subgroup."
"It was found that laser irradiation markedly protects skeletal muscles from
degeneration following acute I-R injury. This was evident by significantly (p < 0.05)
higher content of creatine phosphokinase activity and lower (p < 0.05) activity of
acid phosphatase in the LLLT-treated muscles relative to the injured non-irradiated
ones.

PubMed

The content of antioxidants and heat shock proteins was also higher (p < 0.05) in
the LLLT-treated muscles relative to that of injured non-irradiated muscles."

Muscle injury
regeneration
In vitro

Mdx muscle cells

830

Mdx mice

808

30

1071

107

0.028
cm2

100

The activities of the antioxidant enzyme superoxide dismutase (SOD) were higher
in control mdx mice than in WT mice.
LLLT also significantly reduced the level of this marker. LLLT had a beneficial
effect also on the skeletal muscle performance of mdx mice."

Muscle

Myopathy

Leal-Junior

Brazil & UK &

Norway

2014

PLoS One

Superpulsed low-level laser therapy protects skeletal muscle of

mdx mice against damage, inflammation and morphological
changes delaying dystrophy progression.

Muscle

Myopathy

Dvila

Argentina
(Crdoba)

2011

Laser Ther

Low level laser therapy on experimental myopathy.

Mouse

Mdx mice

904

15

Experimental
myopathy

633
904

5
12

0.075

1.005

5.025

0.2
cm2
(area)

67

70

60
47

10
10

"Irradiation of superpulsed LLLT on successive days five times per week for 14
weeks decreased morphological changes, skeletal muscle damage and
inflammation in mdx mice. This indicates that LLLT has potential to decrease
progression of Duchenne muscular dystrophy."

PubMed

Star: The parameters were well reported, and the article was well written. A
photograph of LLLT treatment was included.
9.5
9.5

"In the present work, LLLT caused great changes in inflammatory biomarkers, with
decreased levels of NO in rats with experimental myopathies and significant
muscle recovery."

PubMed

Comment: Parameters were reported incompletely.

Muscle

Myopathy

Servetto

Argentina
(Crdoba)

2010

Lasers Surg Med

Evaluation of inflammatory biomarkers associated with oxidative

stress and histological assessment of low-level laser therapy in
experimental myopathy.

Muscle

Review

Leal-Junior EC

Brazil
(So Paulo)

2015

Photomed Laser
Surg

Photobiomodulation therapy in skeletal muscle: from exercise

performance to muscular dystrophies.

Muscle

Sarcopenia

Corazza

Brazil
(Piracicaba)

2013

Lasers Med Sci

Phototherapy and resistance training prevent sarcopenia in

ovariectomized rats.

Rat

Experimental
myopathy

633
904

5
12

9.5
9.5

60
47

7
7

"LLLT caused significant changes in inflammatory biomarkers and oxidative

stress: decreased levels of fibrinogen, L-citrulline and SOD as opposed to the
increase of NO in rats with experimental myopathies and significant muscle
recovery."

PubMed

Comment: Parameters were reported incompletely. Laser spot size wasn't

reported. However, results are interesting.

Guest Editorial

Rat

Ovaryectomized rats

"On the other hand, skeletal muscle performance and exercise recovery are novel and recent areas of research in the photobiomodulation field. Since
the first clinical trial was published in 20083 several studies have reported positive effects of photobiomodulation with red3,4 and infrared wavelengths4
8 and both with low-level laser therapy (LLLT)38 and light emitting diode therapy (LEDT).912 Interestingly, different kinds of exercises were employed
in these studies, such as: repeated contractions,3,5,6,8,10 isometric sustained contraction,4,11,12 cycling,9 and running.7 These reports increase the
evidence supporting use of photobiomodulation therapy for improvement of performance and also to accelerate recovery of functional and biochemical
markers related to exercise restitution."
850

100

120

0.5
cm2

600

"Significant increases (p < 0.05) were noted for the muscle volume of the T (68.1
19.7%), the L (74.1 5.1%), and the LT (68.2 11.5%) groups compared to the C
group (60.4 5.5%).

PubMed

PubMed

There were also significant increases in the concentrations of IGF-1, IL-1, and
TNF- in the muscles of the treated groups (p < 0.05)."

Muscle

Spasticity

das Neves

Brazil
(So Jos dos
Campos)

2016

Lasers Med Sci

Effects of low-level laser therapy (LLLT 808 nm) on lower limb

spastic muscle activity in chronic stroke patients.

Human
DB

Stroke patients

808

100

127.39

0.0314
cm2

40

"After the real LLLT intervention, we observed significant reduction in the visual
analogue scale for pain intensity (p = 0.0038), increased time to onset of muscle
fatigue (p = 0.0063), and increased torque peak (p = 0.0076), but no significant
change in the root mean square (RMS) value (electric signal in the motor unit
during contraction, as obtained with surface electromyography).

PubMed

Our results suggest that the application of LLLT may contribute to increased
recruitment of muscle fibers and, hence, to increase the onset time of the spastic
muscle fatigue, reducing pain intensity in stroke patients with spasticity, as has
been observed in healthy subjects and athletes."

Muscle

Spasticity

dos Reis

Brazil
(Urbanova)

2015

Lasers Med Sci

Immediate effects of low-intensity laser (808 nm) on fatigue and

strength of spastic muscle.

Human
DBB

808

100

"After application of LILT, we found increased torque as well as decreased in

lactate level in patients with spasticity."

PubMed

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Nerves

CNS

Ashworth

Australia
(Crawley)

2016

BMC Neurosci

Comparative assessment of phototherapy protocols for reduction

of oxidative stress in partially transected spinal cord slices
undergoing secondary degeneration.

In vitro

Spinal cord

660
860

Nerves

CNS

Ng & Chu

China
(Hong Kong)

2014

J Chiropr Med

Treatment of Bell's Palsy Using Monochromatic Infrared Energy: A

Report of 2 Cases.

Human
Case series

Bell's palsy

890

Category

nm

mW

W/cm2

J/cm2

1800

MIRE treatment with

"Anodyne" LED pad
device

Bell's palsy

830

HILT vs LLLT

1064

CNS

Alayat

Egypt
(Cairo)

2014

Lasers Med Sci

Efficacy of high and low level laser therapy in the treatment of

Bell's palsy: a randomized double blind placebo-controlled trial.

Human
RCT

Nerves

Cranial

Buchaim

Brazil
(Marilia)

2016

Lasers Med Sci

The new heterologous fibrin sealant in combination with low-level

laser therapy (LLLT) in the repair of the buccal branch of the facial
nerve.

Rat

Nerves

Cranial

Snyder

USA
(Bethesda, MD)

2002

Lasers Surg Med

Quantitation of calcitonin gene-related peptide mRNA and neuronal Rat

cell death in facial motor nuclei following axotomy and 633 nm low
power laser treatment.

Axotomy

633

Nerves

Cranial

Anders

USA
(Bethesda, MD)

1993

Lasers Surg Med

Low power laser irradiation alters the rate of regeneration of the rat Rat
facial nerve.

Nerve injury

361
457
514
633
720
1064

Nerves

Diabetic
neuropathy

Cg

India
(Manipal)

2015

Laser Ther

Efficacy of low level laser therapy on painful diabetic peripheral

neuropathy.

830

30

80

10

80

10

0.259

0.116
cm2

8.5
40

Link

PubMed

Additional info

Comment

"The acute case received 19 treatments in 6 weeks. He reported an improvement

of 95%. The chronic case received a total of 45 treatments in 9 months. She rated
an improvement of 50%."

PubMed

1000

18

56

18

72
(3p)

16

780
7200

7
9

540

10

"The result showed that both HILT and LLLT significantly improved the recovery of
patients with Bell's palsy. Moreover, HILT was the most effective treatment
modality compared to LLLT and massage with exercises."

PubMed

"LLLT exhibited satisfactory results on facial nerve regeneration, being therefore a

useful technique to stimulate axonal regeneration process."

PubMed

"These findings demonstrate that 633 nm laser light upregulates CGRP mRNA
and support the theory that laser irradiation increases the rate of regeneration,
target reinnervation, and neuronal survival of the axotomized neuron."

PubMed

"The most effective laser parameters for the low power treatment included daily
irradiation with a helium-neon (HeNe) or argon pumped tunable dye laser a
wavelength of 633 nm, with a power of 8.5 mW for 90 minutes (45.9 J, 162.4
J/cm2)."

PubMed

"These data indicate that transcutaneous low power irradiation with the lasers and
parameters involved in this study increased the rate of regeneration of rat facial
nerve following crush injury."

633
+
660
+
850

Human
Observationa
l

"Our results indicate that R/NIR-LT is an effective antioxidant therapy, and indicate
that effective wavelengths and ranges of intensities of treatment can be adapted
for a variety of CNS injuries and conditions, depending upon the transmission
properties of the tissue to be treated."

"These 2 patients seemed to respond to a different degree to the MIRE therapy.

As 71% of patients with Bell's palsy recover uneventfully without any treatment,
the present study describes the course of care but cannot confirm the
effectiveness of MIRE therapy in the management of Bell's palsy."

Nerves

n. facialis

Results: positive / unclear/modest / negative

sec

3.1

3.4

"The result analysis showed significant reduction in Pain using VAS scale (6.47
0.84 to 1.21 0.78 (p<0.001), MNSI (5.52 1.26 to 2.71 0.97 (reduction in
Vibration perception threshold (32.68 6.08 to 24.84 4.29 (<0.001) and a
significant increase in the temperature from baseline to post intervention (30.01
2.11 to 31.75 1.03 (p<0. 001)."

PubMed

Comment: Parameters were poorly reported. The article had interesting results but
wasn't very well written...
Comment: The first authors surname might be "Kumar" instead of "Cg".

Nerves

Diabetic
neuropathy

Bashiri H

Iran
(Kermanshah)

2013

Acta Med Iran

Evaluation of low level laser therapy in reducing diabetic

polyneuropathy related pain and sensorimotor disorders.

(780?)

Human
RCT

2.5

"Laser therapy resulted in improved neuropathy outcomes in diabetic patients who

received it relative to the group that received sham therapy, evaluating before and
after LLLT assessments."

PubMed

Comment: A poorly written paper.

Nerves

Diabetic
neuropathy

Yamany & Sayed Egypt

(Giza)

2012

J Adv Res

Effect of low level laser therapy on neurovascular function of

diabetic peripheral neuropathy

850

Human
RCT/SB

5.7

900

"Pain was significantly decreased (p 0.05) and electrophysiological parameters

and foot skin microcirculation were significantly improved (p 0.05) in the laser
group, while no significant change was obtained in the control group.

ScienceDir
ect

Low level laser therapy within the applied parameters and technique could be an
effective therapeutic modality in reducing pain and improving neurovascular
function in patients with diabetic polyneuropathy."
Comment: The parameters were poorly reported. The other parts of paper seem
fine.

Nerves

Diabetic
neuropathy

Nawfar & Yacob

Malaysia
(Kota Bharu)

2011

Singapore Med J

Effects of monochromatic infrared energy therapy on diabetic feet

with peripheral sensory neuropathy: a randomised controlled trial.

Human
RCT/SB

Nerves

Diabetic
neuropathy

Khamseh

Iran
(Tehran)

2011

Lasers Med Sci

Diabetic distal symmetric polyneuropathy: effect of low-intensity

laser therapy.

Human

Nerves

Diabetic
neuropathy

Swislocki

USA
(Martinez, CA)

2010

J Pain Symptom
Manage

A randomized clinical trial of the effectiveness of photon

stimulation on pain, sensation, and quality of life in patients with
diabetic peripheral neuropathy.

Human
RCT

MIRE treatment with

"Anodyne" LED pad
device

890

808
905

10

1
cm2

12

"No improvement of neuropathy was observed following MIRE treatment in the

neuropathic feet of diabetic patients."

PubMed

10

"At the end of the study, the subjects showed a significant increase in neural
potential amplitudes (p < 0.05). This study clearly demonstrated a significant
positive effect of LILT on improvement of nerve conduction velocity on diabetic
distal symmetric polyneuropathy (DSP)."

PubMed

Comment: The parameters were insufficiently reported.

LED phototherapy
LED cluster

870

1800

420

"No differences, over time, in any pain intensity scores (i.e., pain intensity
immediately post-treatment, average pain, worst pain) or pain relief scores were
found between the placebo and treatment groups."

PubMed

"Four treatments with photon stimulation resulted in significant improvements in

some pain qualities, sensation, and QOL outcomes in a sample of patients with a
significant amount of pain and disability from their diabetes. A longer duration
study is needed to further refine the photon stimulation treatment protocol in these
chronically ill patients and to evaluate the sustainability of its effects."
Comment: Parameters were quite shortly reported. These studies on diabetic
neuropathy weren't done by "photobiomodulation" researchers.

Nerves

Diabetic
neuropathy

Lavery

USA
(Temple, TX)

2008

Diabetes Care

"Anodyne MIRE therapy was no more effective than sham therapy in the treatment
of sensory neuropathy in individuals with diabetes."

PubMed

Nerves

Diabetic
neuropathy

Peri Z

Serbia

2007

Srp Arh Celok Lek [Influence of low-intensity laser therapy on spatial perception
threshold and electroneurographic finding in patients with diabetic
polyneuropathy].
[Article in Serbian]

Human

"In this study we registered significant decrease of SPT and increase of NMMCV
after LILT and that indicated a favourable effect of this treatment in analysed
patients with painful DPN. In our opinion these results need further investigation."

PubMed

Nerves

Diabetic
neuropathy

Powell

USA
(Springdale,
AR)

2006

Age Ageing

Reversal of diabetic peripheral neuropathy with phototherapy

(MIRE) decreases falls and the fear of falling and improves
activities of daily living in seniors.

Human
Retrospective

"Incidence of falls and fear of falling decreased within 1 month after reversal of
peripheral neuropathy and remained low after 1 year. Likewise, improved ADL
were evident soon after reversal of peripheral neuropathy and showed further
improvement after 1 year. Overall, reversal of peripheral neuropathy in a clinician's
office and subsequent use of MIRE at home was associated with a 78% reduction
in falls, a 79% decrease in balance-related fear of falling and a 72% increase in
ADL (P < 0.0002 for all results)."

PubMed

Nerves

Diabetic
neuropathy

Arnall

USA
(Johnson City,
TN)

2006

Acta Diabetol

The restorative effects of pulsed infrared light therapy on

significant loss of peripheral protective sensation in patients with
long-term type 1 and type 2 diabetes mellitus.

Human

Does anodyne light therapy improve peripheral neuropathy in

diabetes? A double-blind, sham-controlled, randomized trial to
evaluate monochromatic infrared photoenergy.

Human
RCT/DB

MIRE treatment with

"Anodyne" LED pad
device

890

Comment: Parameters were not reported at all.

LED phototherapy
LED cluster

650
880

"PILT improved peripheral protective sensation (PPS) even in patients with longstanding chronic neuropathies whose initial pre-study sensation was not
measurable with a 200-g SWM. PILT significantly improves PPS.

PubMed

While the exact mechanism of action is not understood, infrared light may improve
peripheral neuropathies by improving foot perfusion by stimulating nitric oxide
production."
Comment: Parameters were poorly reported.

Nerves

Diabetic
neuropathy

Clifft

USA
(Memphis, TN)

2005

Diabetes Care

The effect of monochromatic infrared energy on sensation in

patients with diabetic peripheral neuropathy: a double-blind,
placebo-controlled study.

Human
RCT/DB

MIRE treatment with

"Anodyne" LED pad
device

Nerves

Diabetic
neuropathy

Zinman

Canada
(Toronto)

2004

Diabetes Care

Low-intensity laser therapy for painful symptoms of diabetic

sensorimotor polyneuropathy: a controlled trial.

Human
RCT/DB

MIRE treatment with

"Anodyne" LED pad
device

890

"Thirty minutes of active MIRE applied 3 days per week for 4 weeks was no more
effective than placebo MIRE in increasing sensation in subjects with diabetic
peripheral neuropathy. Clinicians should be aware that MIRE may not be an
effective modality for improving sensory impairments in patients with diabetic
neuropathy."

PubMed

Note: A comment to this study was published by Burke, who argued that the
negative result could be due the selected parameters and other methodological
factors.

"Although an encouraging trend was observed with LILT, the study results do not
provide sufficient evidence to recommend this treatment for painful symptoms of
DSP."

PubMed

Jan Tuner's comment: "Unfortunately, this study cannot be evaluated since the
documentation of the actual laser parameters is poor. The only information given
about these essential facts is "The LILT device had a wavelength of 905 nm and
an average power of 0-60 mW. All LILT treatments were for 5 min per site." Which
output was actually used? Pulse repetition rate? Dose? Power density?"

Nerves

Diabetic
neuropathy

Powell

USA
(Springdale,
AR)

Nerves

Diabetic
neuropathy

Leonard

Nerves

Diabetic
neuropathy

Nerves

In vitro

2004

Adv Skin Wound

Care

Reversal of diabetic peripheral neuropathy and new wound

incidence: the role of MIRE.

Human
MIRE treatment with
Retrospective "Anodyne" LED pad
device

USA
2004
(Clearwater, FL)

Diabetes Care

Restoration of sensation, reduced pain, and improved balance in

subjects with diabetic peripheral neuropathy: a double-blind,
randomized, placebo-controlled study with monochromatic nearinfrared treatment.

Human
RCT/DB

Kochman

USA
(Aurora, CO)

2002

J Am Podiatr Med
Assoc

Symptomatic reversal of peripheral neuropathy in patients with

diabetes.

Human

Huang

USA
(Boston, MA)

2014

J Biophotonics

Low-level laser therapy (810 nm) protects primary cortical neurons

against excitotoxicity in vitro.

In vitro

"After reversal of diabetic peripheral neuropathy following treatment with

monochromatic near infrared photo energy, only 1 of 68 patients developed a new
diabetic foot wound, for an incidence of 1.5%. Comparatively, the incidence
previously reported in the Medicare-aged population with diabetes was 7.3%."

PubMed

Comment: Parameters were not reported at all.

MIRE treatment with

"Anodyne" LED pad
device

890

1800

"ATS treatments improve sensation in the feet of subjects with DPN, improve
balance, and reduce pain."

PubMed

"On the basis of Semmes-Weinstein monofilament values, 48 subjects (98%)

exhibited improved sensation after 6 treatments, and all subjects had improved
sensation after 12 treatments. Therefore, MIRE may be a safe, drug-free,
noninvasive treatment for the consistent and predictable improvement of sensation
in diabetic patients with peripheral neuropathy of the feet."

PubMed

Comment: Parameters were not reported.

Primary cortical
neurons

810

Excitotoxicity

In vitro

Burland

France
(Montpellier)

2015

J Biophotonics

Neurite growth acceleration of adult Dorsal Root Ganglion neurons

illuminated by low-level Light Emitting Diode light at 645 nm.

In vitro

LED phototherapy

120

"Although the prevention of cell death was modest but significant, LLLT (3 J/cm(2)
delivered at 25 mW/cm(2) over 2 min) gave highly significant benefits in increasing
ATP, raising mitochondrial membrane potential, reducing intracellular calcium
concentrations, reducing oxidative stress and reducing nitric oxide.

PubMed

The action of LLLT in abrogating excitotoxicity may play a role in explaining its
beneficial effects in diverse central nervous system pathologies."

Glutamate / NMDA /
kainate

Nerves

0.025

645

"Although the axotomized neurons were naturally already in a rapid regeneration

process, an enhancement was found to occur while irradiating with the LED light,
which may be promising for therapy applications."

PubMed

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Nerves

In vitro

Giuliani

Italy
(Bologna)

2009

BMC Complement Low infra red laser light irradiation on cultured neural cells: effects
Altern Med
on mitochondria and cell viability after oxidative stress.

In vitro

670

Nerves

In vitro

Ignatov

Russia
(SaintPetersburg)

2005

Neurosci Behav
Physiol

In vitro

Category

Effects of helium-neon laser irradiation and local anesthetics on

potassium channels in pond snail neurons.

Biphasic dose
response (?)

633

Anesthetics-induced
NMJ injury
(bupivacaine)

904

0.003

50

4.8

Nerves

Neuromuscular
junction

Pissulin

Brazil
(Presidente
Prudente)

2016
epub

J Photochem
Photobiol B

GaAs laser therapy reestablishes the morphology of the NMJ and

nAChRs after injury due to bupivacaine

Rat

Nerves

Neuromuscular
junction

Nicolau

Brazil

2004

Lasers Surg Med

Effect of low power 655 nm diode laser irradiation on the

neuromuscular junctions of the mouse diaphragm.

Mouse

Nerves

Neuronal
growth

Rochkind

Israel
(Tel Aviv)

2009

Lasers Surg Med

Increase of neuronal sprouting and migration using 780 nm laser

phototherapy as procedure for cell therapy.

In vitro

Biphasic dose
response

780

10
30
50
110
160
200
250

Nerves

Oral

Miloro

USA
(Omaha, NE)

2002

Oral Surg Oral

Low-level laser effect on neural regeneration in Gore-Tex tubes.
Med Oral Pathol
Oral Radiol Endod

Rabbit

Inferior alveolar nerve

820830

70

Nerves

PNS

Ziago

Brazil
2017
(Ribeiro Preto) epub

Lasers Med Sci

Analysis of the variation in low-level laser energy density on the

crushed sciatic nerves of rats: a morphological, quantitative, and
morphometric study.

Rat

Dose response

780

40

4
10
50

0.04
cm2

Synergistic effects of low-level laser and mesenchymal stem cells

on functional recovery in rats with crushed sciatic nerves.

Rat

660

30

0.2
cm2

Nerves

PNS

Yang & Huang

Taiwan
(Taichung)

2016

J Tissue Eng
Regen Med

0.035
cm2

48

655
60
240
420

Biphasic dose
response

Results: positive / unclear/modest / negative

Link

Additional info

sec

0.45 *
10^-3

360

240

10

"These data suggest that red light radiation protects the viability of cell culture in
case of oxidative stress, as indicated by MMP measurement and MTT assay. It
also stimulates neurite outgrowth, and this effect could also have positive
implications for axonal protection."

PubMed

"Combined application of laser irradiation at a dose of 0.7 x 10(-3) J increased the

blocking effect of 10 microM bupivacaine on the slow potassium current, while an
irradiation dose of 0.7 x 10(-4) J weakened the effect of bupivacaine."

PubMed

"These results demonstrate that LLLT at the dose used in this study reduced
structural alterations in the NMJ and molecular changes in nAChRs triggered by
bupivacaine, providing important data supporting the use of LLLT in therapeutic
protocols for injuries triggered by local anesthetics."

ScienceDir
ect

This study showed that LLLT (655 nm) in these doses has no detectable
physiological effect on the motor end-plate neurotransmitter release in mice.

PubMed

"780 nm laser phototherapy of embryonic rat brain cultures embedded in

hyaluronic acid-laminin gel and attached to positively charged cylindrical MCs,
stimulated migration and fiber sprouting of neuronal cells aggregates, developed
large size neurons with dense branched interconnected network of neuronal fibers
and, therefore, can be considered as potential procedure for cell therapy of
neuronal injury or disease."

PubMed

"Histomorphometric evaluation revealed increased axonal density in the laser

treated group as compared with the control."

PubMed

"Groups L0, L4, L10, and L50 exhibited diminished values of all the quantitative
and morphometric parameters in comparison to the control group. The
morphological, quantitative, and morphometric data revealed improvement after
injury in groups L4, L10, and L50 (irradiated groups) compared to the injured-only
group (L0); the best results, in general, were observed for the L10 group after 15
days of nerve injury."

PubMed

"The MSCLLLT group showed a greater recovery in SFI, VA and AA, with
significant difference from MSC, LLLT and control groups (p < 0.05). Moreover,
markedly enhanced electrophysiological function and expression of S100
immunoreactivity, as well as fewer inflammatory cells and less vacuole formation
were also demonstrated after nerve crush injury in the MSCLLLT group when
compared with the groups receiving a single treatment (p < 0.05).

PubMed

MSC transplantation combined with LLLT could achieve better results in functional
recovery than a conventional treatment of MSC or LLLT alone. LLLT has a
synergistic effect in providing greater functional recovery with MSC transplantation
after nerve crush injury."

Nerves

PNS

MandelbaumLivnat

Israel
(Tel Aviv)

2016

Photomed Laser
Surg

Photobiomodulation Triple Treatment in Peripheral Nerve Injury:

Nerve and Muscle Response.

"In the present study, the effectiveness of triple treatment laser phototherapy,
namely, applied simultaneously at three areas: injured area of the peripheral
nerve, corresponding segments of the spinal cord, and corresponding denervated
muscle (triple treatment), was evaluated for the treatment of incomplete PNI in rats
with the ultimate goal of achieving improved limb function."

Rat

PubMed

"The present study and our previous investigations showed that the laser
phototherapy increases biochemical activity and improves morphological recovery
in muscle and, thus, could have direct therapeutic applications on muscle,
especially during progressive atrophy resulting from PNI."

Nerves

PNS

de Oliveira

Brazil
(So Paulo)

2015

Lasers Med Sci

Benefits of laser phototherapy on nerve repair.

Review

Parameters

"According to the findings of the literature, laser therapy accelerates and improves the regeneration of the affected nerve tissues, but there are many
conflicting results about laser therapy. This can be attributed to several variables such as wavelength, radiation dose, and type of radiation. All the early
in vivo studies assessed in this research were effective in restoring sensitivity.

PubMed

Although these results indicate a potential benefit of the use of lasers on nerve repair, further double-blind controlled clinical trials should be conducted in
order to standardize protocols for clinical application."

Nerves

PNS

Buchaim

Brazil
(Bauru)

Injury

Effect of low-level laser therapy (LLLT) on peripheral nerve

regeneration using fibrin glue derived from snake venom.

Rat

830

30

Nerves

PNS

Dias

Brazil
2015
(Ribeiro Preto)

J Neurol Sci

Morphometric and high resolution scanning electron microscopy

analysis of low-level laser therapy and latex protein (Hevea
brasiliensis) administration following a crush injury of the sciatic
nerve in rats.

Rat

780

30

Nerves

PNS

Takhtfooladi

Iran

2015

Lasers Med Sci

Effect of low-level laser therapy (685 nm, 3 J/cm(2)) on functional

recovery of the sciatic nerve in rats following crushing lesion.

Rat

685

15

Nerves

PNS

Takhtfooladi &
Sharifi

Iran

2015

Lasers Med Sci

A comparative study of red and blue light-emitting diodes and lowlevel laser in regeneration of the transected sciatic nerve after an
end to end neurorrhaphy in rabbits.

Rabbit

Nerve injury

680

10

LLLT vs LED

650

2.4

450

2.4

2015

Nerve regeneration

0.116
cm2

16
/point

16

"The present study demonstrated that the fibrin glue makes axonal regeneration
feasible and is an efficient method to recover injured peripheral nerves, and the
use of low-level laser therapy enhances nerve regeneration."

PubMed

15

0.04
cm2
spot

60

"LLLT and F1 resulted in structural nerve improvements after 4 or 8 weeks of

injury."
"In general only F1 protein was more effective compared to LLLT and LLLT + F1"

PubMed

0.028
cm2

21

"The SFI and SSI results were significant when comparing two groups on the 14th
and 21st postoperative days (p < 0.05). There were intra-group differences
detected in laser group in different periods (p < 0.05). Low-level laser irradiation,
with the parameters used in the present study, accelerated and improved sciatic
nerve function in rats after crushing injury."

PubMed

10

4
mm2
1.5
cm2
1.5
cm2

600

14

In LLLT group (680nm), increase in Schwann cells, large myelinic axons and
neurons was noted, compared to other groups.

PubMed

600

14

600

14

3.8
cm2

67
179
336

20

Sural nerve
0.75

1.8

0.12
total

Nerves

PNS

Wang

Taiwan
(Kaohsiung)

2014

PLoS One

Low-level laser irradiation improves functional recovery and nerve

regeneration in sciatic nerve crush rat injury model.

Rat

Nerve injury

808

170

0.045

3
8
15

(810)
980

1000

0.01

10^-6
5

Sciatic nerve

Red LED (650nm) treatment wasn't beneficial in this study.

"Taken together, these results suggest that 808-nm LLLT at a low energy density
(3 J/cm(2) and 8 J/cm(2)) is capable of enhancing sciatic nerve regeneration
following a crush injury."

PubMed

"In vitro, 980 nm wavelength light at 10 mW/cm(2) significantly improved neurite

elongation at energy densities between 2 and 200 mJ/cm(2) ."

PubMed

Biphasic dose
response

Nerves

PNS

Anders

USA
(Bethesda, MD)

2014

Lasers Surg Med

In vitro and in vivo optimization of infrared laser treatment for

injured peripheral nerves.

In vitro &
Rabbit

Nerve injury

"In vivo penetration of the infrared light measured in anesthetized rabbits showed
that on average, 2.45% of the light applied to the skin reached the depth of the
peroneal nerve."
"The in vivo pilot study data revealed that the 4W parameters inhibited nerve
regeneration while the 2W parameters significantly improved axonal regrowth."
"For the final set of experiments, the irradiated group performed significantly better
in the toe spread reflex test compared to the control group from week 7 postinjury, and the average length of motor endplates returned to uninjured levels."
Star: An exceptionally thorough study, with a huge amount of interesting data!

Nerves

PNS

Al-Shenqiti &
Oldham

Saudi Arabia
(Medina)

2014

Expert Rev
Neurother

The use of phototherapy in peripheral nerve regeneration: an

updated critical review.

"Twenty five studies were critically reviewed and showed considerable variability in irradiation parameters, techniques, approaches, length of irradiation
courses, experimental injury tools and procedures. Many studies that have investigated the use of phototherapy in nerve regeneration produce positive
results.

Review

PubMed

However, the majority of these studies suffered from a number of shortcomings: no evidence of blinding and/or randomizing procedures, lack of
specification of irradiation parameters, unspecified and/or inadequate tests in their experimental injury procedures, inappropriate irradiation parameters
and/or poor experimental conditions."
"Although the mechanism by which phototherapy exerts its effect is not completely understood, the emerging utility and effectiveness of phototherapy in
peripheral nerve injury is exciting, and we anticipate further advancement and application of this modality in the near future."

Nerves

PNS

Shen

Taiwan
(Taichung)

2013

J Biomed Mater
Res A

Effects of large-area irradiated laser phototherapy on peripheral

nerve regeneration across a large gap in a biomaterial conduit.

Rat

660

50

Nerves

PNS

Shen

Taiwan
(Taichung)

2013

J Biomed Mater
Res A

Neural regeneration in a novel nerve conduit across a large gap of

the transected sciatic nerve in rats with low-level laser
phototherapy.

Rat

660

50

Nerves

PNS

Alcntara

Brazil
(So Carlos)

2013

Lasers Surg Med

Effect of low-level laser therapy (LLLT) on acute neural recovery

and inflammation-related gene expression after crush injury in rat
sciatic nerve.

Rat

Sciatic nerve

660

"Histomorphometric assessments revealed that the EGT/laser group had

undergone more rapid nerve regeneration than the EGT/sham group. The lasertreated group also presented greater neural tissue area as well as larger axon
diameter and thicker myelin sheath than the tube group without the laser
treatment, indicating improved nerve regeneration. Thus, these assessments
demonstrate that LLL therapy can accelerate the repair of a transected peripheral
nerve in rats after being bridged with EGT conduit."
120

0.04

10

60

"Histomorphometric assessments showed that the EGT/LS group had undergone

more rapid nerve regeneration than the EGT group. Therefore, motor function,
electrophysiological reaction, muscular reinnervation, and histomorphometric
assessments demonstrate that LLL therapy can accelerate the repair of a 15-mm
transected peripheral nerve in rats after being bridged with the EGT nerve
conduit."

PubMed

"The current study showed that LLLT increased MMPs activity, mainly MMP-9,
and TNF- protein level during the acute phase of nerve injury, modulating
inflammation.

PubMed

Based on these results, it is recommended that LLLT should be started as soon as

possible after peripheral nerve injury."

Nerves

PNS

Cidral-Filho

Brazil
(Florianpolis)

2013

Eur J Pain

Light-emitting diode therapy induces analgesia and decreases

spinal cord and sciatic nerve tumour necrosis factor- levels after
sciatic nerve crush in mice.

Nerves

PNS

Telemeco &
Schrank

USA
(Winchester,
VA)

2013

J Lasers Med Sci

The Effect of Light Therapy on Superficial Radial Nerve Conduction Human

Using a Clustered Array of Infrared Super luminous Diodes and
RCT/SB
Red Light Emitting Diodes.

950

Mouse

Nerve conduction
LED phototherapy
LED cluster

2,5

15

880
+
660

Nerves

PNS

Sousa

Brazil
2013
(Ribeiro Preto)

Acta Ortop Bras

Lack of effectiveness of laser therapy applied to the nerve course

and the correspondent medullary roots.

Rat

Fibular nerve

830

Nerves

PNS

Sene

Brazil
2013
(Ribeiro Preto)

Acta Ortop Bras

Effects of laser therapy in peripheral nerve regeneration.

Rat

Fibular nerve
(common)

830

Nerves

PNS

Rochkind S

Israel
(Tel Aviv)

Photomed Laser
Surg

Phototherapy in peripheral nerve injury for muscle preservation

and nerve regeneration.

Guest
Editorial

2013

0.08

30

30

1.2
/p

10.34

0.116
cm2

14

5
10
20

0.02
cm2

21

"Compared with the SNC group, LEDT reduced mechanical hypersensitivity but
not cold hypersensitivity which is induced by SNC, decreased spinal cord and
sciatic nerve levels of tumour necrosis factor alpha (TNF-) but did not alter
interleukin (IL)-1 and IL-10 levels, and finally, failed to accelerate motor functional
recovery and morphological nerve regeneration."

PubMed

"Light irradiation using a cluster probe containing infrared super luminous and red
light emitting diodes does not impact the neurophysiological properties of the
superficial radial nerve."

PubMed

"According to the statistical analysis there was no significant difference among

groups and the authors conclude that low intensity laser irradiation has little or no
influence on nerve regeneration and functional recovery."

PubMed

"The low power AsGaAl laser irradiation did not accelerate nerve recovery with
any of the doses used."

PubMed

"The extensive review articles, which were published in Muscle and Nerve and Neurosurgical Focus revealed that most of experimental studies showed
phototherapy to promote the recovery of the severely injured peripheral nerve. These reviews make it possible to suggest that a time for broader clinical
trials has arrived. The significance of the experimental and clinical studies is the provision of new laser technology for treatment of severe nerve injury."

PubMed

The parameters were slightly different in the LLLT vs LED groups. Cytochrome oxidase action spectrum could also explain why 680nm was more beneficial than 650nm.

Comment

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More info:

---> Facebook group! (840+ members)

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Nerves

PNS

Rochkind

Israel
(Tel Aviv)

2013

BOOK: Int Rev

Neurobiol

Phototherapy and nerve injury: focus on muscle response.

Review
+ new data

Nerves

PNS

Marcolino

Brazil
2013
(Ribeiro Preto)

J Hand Microsurg

Assessment of functional recovery of sciatic nerve in rats

submitted to low-level laser therapy with different fluences. An
experimental study: laser in functional recovery in rats.

Rat

Nerves

PNS

Gomes

Brazil
(Blumenau)

Photomed Laser
Surg

The brain-derived neurotrophic factor, nerve growth factor,

neurotrophin-3, and induced nitric oxide synthase expressions
after low-level laser therapy in an axonotmesis experimental
model.

Rat

Category

2012

nm

mW

W/cm2

J/cm2

830

Axonotmesis

30

633

1.16
4.64
9.28
0.0005
(?)
or
0.5 (?)

10
40
80

0.116
cm2

39
155
309

10

0.10
cm2
spot

20

21

1
cm2
total

Nerves

PNS

Hsieh

Taiwan
(Taichung)

2012

J Comp Neurol

Low-level laser therapy alleviates neuropathic pain and promotes

function recovery in rats with chronic constriction injury: possible
involvements in hypoxia-inducible factor 1 (HIF-1).

Rat

Chronic constructive
injury (CCI)

660

0.2
cm2

Allodynia
Inflammation

Nerves

PNS

Santos

Brazil
(Diamantina)

2012

Lasers Med Sci

Functional and morphometric differences between the early and

delayed use of phototherapy in crushed median nerves of rats.

Results: positive / unclear/modest / negative

PubMed

"It was possible to observe that the LLLT at fluency of 40 J/cm(2) and 80 J/cm(2)
had a positive influence on the acceleration of the functional nerve recovery."

PubMed

"Comparisons between groups showed that HeNe laser increased the mRNA
expression of both BDNF and NGF factors after 14 days of LLLT, with peak
expression at the 21st day. Increase in NT-3 mRNA expression was not observed.
In addition, HeNe laser produced iNOS expression reduction, which played an
important role in the inflammatory process."

PubMed

"Low-level laser therapy significantly improved paw withdrawal threshold and the
sciatic, tibial, and peroneal functional indices after CCI. The therapy also
significantly reduced the overexpressions of HIF-1, TNF-, and IL-1, and
increased the amounts of VEGF, NGF, and S100 proteins.

PubMed

In conclusion, a low-level laser could modulate HIF-1 activity. Moreover, it may

also be used as a novel and clinically applicable therapeutic approach for the
improvement of tissue hypoxia/ischemia and inflammation in nerve entrapment
neuropathy, as well as for the promotion of nerve regeneration. These findings
might lead to a sufficient morphological and functional recovery of the peripheral
nerve."
904

Rat

Link

sec

"Preservation of biochemical processes in muscles is a major challenge in patients with severe peripheral nerve injury. In this chapter, we address the
effects of laser irradiation and biochemical transformation in muscle, using in vitro and in vivo experimental models. The authors attempt to explain the
possible mechanism of laser phototherapy applied on skeletal muscle on the basis of literature review and new results."

40

7.2

0.2
cm2

180

10

"In the early group, the first laser treatment started immediately after surgery, and
in the delayed group, after 7 days."

PubMed

"The untreated, early, and delayed groups presented a 50, 57, and 81% degree of
functional recovery, respectively, at 21 days after injury, with a significant
difference between the untreated and delayed groups.
The results suggest that the nerves irradiated with low-power laser exhibit
myelinated fibers of greater diameter and a better recovery of function."

Nerves

PNS

Yazdani

Iran
(Tehran)

2012

J Photochem
Photobiol B

Effects of low level laser therapy on proliferation and neurotrophic

factor gene expression of human schwann cells in vitro.

In vitro

Schwann cells

810

50

1
4

Nerves

PNS

Serafim

Brazil
(Londrina)

2012

Lasers Med Sci

Effects of 940 nm light-emitting diode (led) on sciatic nerve

regeneration in rats.

Rat

Nerve injury

940

9.5

Nerves

PNS

Chow R

Australia
(Sydney)

2011

Photomed Laser
Surg

Phototherapy and the peripheral nervous system.

Editorial

Nerves

PNS

Cmara

Brazil
(Belm)

2011

Acta Cir Bras

Histological analysis of low-intensity laser therapy effects in

peripheral nerve regeneration in Wistar rats.

Rat

Nerves

PNS

Shen

Taiwan
(Taichung)

2011

Injury

Large-area irradiated low-level laser effect in a biodegradable nerve Rat

guide conduit on neural regeneration of peripheral nerve injury in
rats.

1
cm2

420

10

LED phototherapy

"Our results demonstrate that low level laser therapy stimulate human schwann
cell proliferation and NGF gene expression in vitro."

PubMed

"The morphological analysis of the nerve indicated that phototherapy can reduce
the migration of mononuclear cells to damaged tissue, which reduces areas of
edema and fiber degeneration. A 940 nm LED phototherapy source seems to
favor the early functional recovery of the injured sciatic nerve."

PubMed

"Effects of laser irradiation on the peripheral nervous system (PNS) underlie the potential for phototherapy to be acknowledged as a mainstream therapy
for the future. Pain and inflammation are among the most important manifestations of PNS function and the spectrum of diseases with these symptoms
and signs, from osteoarthritis to diabetic neuropathy, which can be modified by phototherapy, is vast [...]"

LLLT cluster

PubMed

904

26.3

0.0413

0.63
cm2

192

21

"The irradiation with low intensity laser (904nm) influenced positively the
regeneration of the sciatic nerve in Wistar rats after being injured by crush
(axonotmesis), becoming the nerve recovery more rapid and efficient."

PubMed

660

50
(?)
or
1000
(?)

0.0032

3.84

314
cm2

300

21

"Eight weeks after implantation, walking track analysis showed a significantly

higher sciatic function index (SFI) score (P<0.05) and better toe spreading
development in the laser-treated group than in the sham-irradiated control group.

PubMed

For electrophysiological measurement, both the mean peak amplitude and nerve
conduction velocity of compound muscle action potentials (CMAPs) were higher in
the laser-treated group than in the sham-irradiated group. The two groups were
found to be significantly different during the experimental period (P<0.005).
Histomorphometric assessments revealed that the qualitative observation and
quantitative analysis of the regenerated nerve tissue in the laser-treated group
were superior to those of the sham-irradiated group.
Thus, the motor functional, electrophysiologic and histomorphometric
assessments demonstrate that LLL therapy can accelerate neural repair of the
corresponding transected peripheral nerve after bridging the GGT nerve guide
conduit in rats."

Nerves

PNS

Gigo-Benato

Brazil
(So Carlos)

Nerves

PNS

Barbosa

Brazil
2010
(Ribeiro Preto)

2010

Lasers Surg Med

Effects of 660 and 780 nm low-level laser therapy on

neuromuscular recovery after crush injury in rat sciatic nerve.

Rat

Biphasic dose
response

660
780

Lasers Med Sci

Comparative effects of wavelengths of low-power laser in

regeneration of sciatic nerve in rats following crushing lesion.

Rat

Wavelength
comparison

660
830

10
60
120
30
30

10
10

0.06
0.116

20
38.66

21

cm2

"Six hundred sixty nanometer LLLT either using 10 or 60 J/cm restored muscle
fiber, myelin and nerve fiber CSA compared to the normal group (N)."

PubMed

"Differences in SFI were found between group 660 nm and the other ones at the
14th day. One can observe that laser application at 660 nm with the parameters
and methods utilised was effective in promoting early functional recovery, as
indicated by the SFI, over the period evaluated."

PubMed

Comment: 830nm was not effective in this study. In the 660nm group, the SFI
benefit was not very large.

Nerves

PNS

Zhang

China
(Shenyang)

2010

Synapse

Effects of 660-nm gallium-aluminum-arsenide low-energy laser on

nerve regeneration after acellular nerve allograft in rats.

660

Rat

24
(?)

1800

20

"Compared with the ARSN group, laser therapy significantly increased nerve
conduction velocity, restoration rate of tibialis anterior wet muscle weight,
myelinated nerve number, and CGRP protein and mRNA expression of the L(4)
spinal cord at the injury site."

PubMed

Comment: Irradiation parameters were insufficiently reported.

LED phototherapy

660

"Nerve regeneration was promoted in the LED group. Antioxidation of the chamber
fluid significantly decreased from 3 days to 7 days in the control group. In the LED
group, antioxidation levels did not decrease until 7 days."

PubMed

"The utilization of low-power galliumaluminumarsenide laser (660 nm) showed

positive results with regard to functional recovery in the sciatic nerve of rats
following crushing lesion."

PubMed

Nerves

PNS

Ishiguro

Japan
(Kanazawa)

2010

J Orthop Sci

Effect of near-infrared light-emitting diodes on nerve regeneration.

Nerves

PNS

Belchior

Brazil
(Campo
Grande)

2009

Lasers Med Sci

Influence of laser (660 nm) on functional recovery of the sciatic

nerve in rats following crushing lesion.

Nerves

PNS

Rochkind

Israel
(Tel Aviv)

2009

Neurosurg Focus

Phototherapy in peripheral nerve regeneration: From basic science Review

to clinical study.

"Laser activation of nerve cells, their growth, and axonal sprouting can be considered as potential treatment of neuronal injury. Animal and clinical
studies show the promoting action of phototherapy on peripheral nerve regeneration, making it possible to suggest that the time for broader clinical trials
has arrived."

PubMed

Nerves

PNS

Rochkind

Israel
(Tel Aviv)

2009

BOOK: Int Rev

Neurobiol

Phototherapy in peripheral nerve injury: effects on muscle

preservation and nerve regeneration.

Review

"Animal and clinical studies show the promoting action of phototherapy on peripheral nerve regeneration, which makes it possible to suggest that the
time for broader clinical trials has come."

PubMed

Nerves

PNS

dos Reis

Brazil
(Campo
Grande)

2009

Lasers Med Sci

Effect of laser therapy (660 nm) on recovery of the sciatic nerve in

rats after injury through neurotmesis followed by epineural
anastomosis.

Rat

660

26.3

Nerves

PNS

Rochkind

Israel
(Tel Aviv)

2007

Photomed Laser
Surg

Laser phototherapy (780 nm), a new modality in treatment of longterm incomplete peripheral nerve injury: a randomized doubleblind placebo-controlled study.

Human
RCT/DB

780

250

Nerves

PNS

Mohammed

Iraq
(Baghdad)

2007

Photomed Laser
Surg

Promotion of regenerative processes in injured peripheral nerve

induced by low-level laser therapy.

Rabbit

901

10

Nerves

PNS

Gigo-Benato

Italy
(Orbassano)

2005

Muscle Nerve

Phototherapy for enhancing peripheral nerve repair: a review of the Review

literature.

"The present article reviews literature on one possible rehabilitation approach for enhancing nerve recovery, namely phototherapy. The number of
experimental studies that have reported on the promoting action of phototherapy on peripheral nerve regeneration, together with the few known side
effects related to the use of this type of physical therapy, make it possible to suggest that the time for broader clinical trials has come."

PubMed

Nerves

PNS

Anders

USA
(Bethesda, MD)

2004

Neurol Res

Phototherapy promotes regeneration and functional recovery of

injured peripheral nerve.

"Numerous attempts have been made to enhance and/or accelerate the recovery of injured peripheral nerves. One of the methods studied is the use of
phototherapy (low power laser or light irradiation) to enhance recovery of the injured peripheral nerve."

PubMed

Nerves

PNS

Gigo-Benato

Italy
(Orbassano)

2004

Lasers Med Sci

Low-power laser biostimulation enhances nerve repair after end-to- Rat

side neurorrhaphy: a double-blind randomized study in the rat
median nerve model.

660

Rat

Review

26.3

20

0.63
cm2

0.63
cm2
(spot)

16
cm2

20

"The use of AlGaAs laser (660 nm) provided significant changes to the
morphometrically assessed area of the myelin sheath, but it did not culminate in
positive results for functional recovery in the sciatic nerve of the rats after injury
through neurotmesis."

PubMed

5h
(??)

21

"The analysis of motor function during the 6-month follow-up period compared to
baseline showed statistically significant improvement (p = 0.0001) in the lasertreated group compared to the placebo group. No statistically significant difference
was found in sensory function. Electrophysiological analysis also showed
statistically significant improvement in recruitment of voluntary muscle activity in
the laser-irradiated group (p = 0.006), compared to the placebo group."

PubMed

600

11

"This experiment affirms the beneficial effect of LLLT on nerve regeneration, since
LLLT produced a significant amount of structural and cellular change. The results
of the present study suggest that laser therapy may be a viable approach for nerve
regeneration, which may be of clinical relevance in scheduled surgery or
microsurgery."

PubMed

808

"Results showed that laser biostimulation induces:

905

(1) a statistically significant faster recovery of the lesioned function;

808+
905

(2) a statistically significant faster recovery of muscle mass;

PubMed

(3) a statistically significant faster myelination of the regenerated nerve fibers.

From comparison of the three different types of laser emissions, it turned out that
the best functional outcome was obtained by means of pulsed-continuouscombined laser biostimulation."

Nerves

PNS

Shin

Korea
(Seoul)

2003

Neurosci Lett

Growth-associated protein-43 is elevated in the injured rat sciatic

nerve after low power laser irradiation.

Rat

650

Nerves

PNS

Bagis

Turkey
(Adana)

2003

Lasers Med Sci

No effect of GA-AS (904 nm) laser irradiation on the intact skin of

the injured rat sciatic nerve.

Rat

904

Nerves

PNS

Shamir

Israel
(Tel Aviv)

2001

J Reconstr
Microsurg

Double-blind randomized study evaluating regeneration of the rat

transected sciatic nerve after suturing and postoperative lowpower laser treatment.

Rat

Nerve injury
n. ischiadicus

780

0.31
2.48
19

0.28
cm2

300

"This immunocytochemical study using GAP-43 antibody study shows for the first
time that LPLI has an effect on the early stages of the nerve recovery process
following sciatic nerve injury."

PubMed

900

"No statistically significant difference (p > 0.05) was found regarding the
amplitude, area, duration and conduction velocity of CMAP for each applied dose
(0.31, 2.48 and 19 J/cm2) on the irradiated (right) side and the control (left) side,
or between irradiated groups. Twenty-one days after injury there were no
qualitative differences in the morphological pattern of the regenerated nerve fibres
in either irradiated (0.31, 2.48 and 19 J/cm2) or control nerves when evaluated by
light microscopy. This study showed that low-energy GaAs irradiation did not have
any effect on the injured rat sciatic nerve."

PubMed

1800

21

"Positive somatosensory evoked responses were found in 69.2 percent of the

irradiated rats (p = 0.019), compared to 18.2 percent of the non-irradiated rats.
Immunohistochemical staining in the laser-treated group showed an increased
total number of axons (p = 0.026), and better quality of the regeneration process,
due to an increased number of large-diameter axons (p = 0.021), compared to the
non-irradiated control group."

PubMed

Additional info

Comment

Reply

 Category
Nerves

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

PNS

Rochkind

Israel
(Tel Aviv)

2001

Lasers Surg Med

Effects of laser irradiation on the spinal cord for the regeneration

of crushed peripheral nerve in rats.

Rat

633

16

830

70

Nerve injury

Results: positive / unclear/modest / negative

21

"The electrophysiologic activity of the injured nerves (compound muscle action

potentials--CMAPs) was found to be approximately 90% of the normal precrush
value and remained so for up to a long period of time. In the control nonirradiated
group, electrophysiologic activity dropped to 20% of the normal precrush value at
day 21 and showed the first signs of slow recovery 30 days after surgery. The two
groups were found to be significantly different during follow-up period (P < 0.001)."

Link

sec

180

n. ischiadicus

PubMed

Comment: Parameters were insufficiently reported.

Nerves

Nerves

PNS

PNS

Khullar

Rochkind

Norway
(Oslo)

1995

Israel
(Tel Aviv)

1989

Eur J Oral Sci

Neurosurgery

The effects of low level laser treatment on recovery of nerve

conduction and motor function after compression injury in the rat
sciatic nerve.

Rat

0.55

48

(or
820?)

Stimulatory effect of He-Ne low dose laser on injured sciatic nerves Rat
of rats.

Nerve injury

633

0.13
cm2

85

28

17

n. ischiadicus

Nerves

PNS

Rochkind

Israel
(Tel Aviv)

1987

Lasers Surg Med

Response of peripheral nerve to He-Ne laser: experimental studies. Rat

Nerves

PNS

Rochkind

Israel
(Tel Aviv)

1978

Morphogen
Regen

Stimulation effect of laser energy on the regeneration of

traumatically injured peripheral nerves. (Morphogen Regen 1978;
83:25-27)

Nerves

Spinal cord

Veronez

Brazil
(So Paulo)

2016

Lasers Med Sci

Effects of different fluences of low-level laser therapy in an

experimental model of spinal cord injury in rats.

633

808

Rat

30

1.07

500
750
1000

0.028
cm2

141
212
282

"At 21 d post-injury, the laser-treated group had a significantly lower median SFI
than the sham laser-treated group, indicating that the real laser treatment had
improved functional recovery in the nerve. However, no differences were found
between the evoked cAP parameters that were measured in the laser-treated and
sham laser-treated groups. Histological examination reiterated the lack of
difference between the two groups. Consequently, the effects of LLL on recovery
must have occurred more peripherally to the point measured."

PubMed

"The action potential of the injured sciatic nerves that were laser-irradiated
increased to values close to that of a noninjured nerve. The studies include followup for 1 year after the injury. This electrophysiological manifestation of the effect of
laser treatment on injured nerves was accompanied by a diminution of the size of
the scar tissue from these nerves. Yet to be resolved is whether these two
phenomena (i.e., electrophysiological and morphological responses) coincide or
whether they relate to each other."

PubMed

"Action potential (AP) in the healthy nerve increased by 33% following a single
transcutaneous irradiation. Similar irradiation in crushed nerves caused AP to
increase significantly over the AP of nonirradiated crushed nerve. Morphological
observations revealed that a laser-irradiated injured nerve had diminished scar
tissue as compared to an injured but not an irradiated nerve."

PubMed

"Functional evaluation and tactile sensitivity were improved after LLLT, at the
higher fluence. Additionally, LLLT, at 750 and 1000 J/cm2, reduces the lesion
volume and modulates the inflammatory process with decrease of CD-68 protein
expression.

PubMed

These results suggest that LLLT at higher doses was effective in promoting
functional recovery and modulating inflammatory process in the spinal cord of rats
after SCI."

Nerves

Spinal cord

Hu

Australia
(Canberra)

2016

J
Neuroinflammatio
n

Red LED photobiomodulation reduces pain hypersensitivity and

improves sensorimotor function following mild T10 hemicontusion
spinal cord injury.

Rat

Microglia

670

0.35

63

75
mm2

1800

"We demonstrate that red light penetrates through the entire rat spinal cord and
significantly reduces signs of hypersensitivity following a mild T10 hemicontusion
spinal cord injury.

LED phototherapy

PubMed

This is accompanied with improved dorsal column pathway functional integrity and
locomotor recovery. The functional improvements were preceded by a significant
reduction of dying (TUNEL(+)) cells and activated microglia/macrophages (ED1
(+)) in the spinal cord.
The remaining activated microglia/macrophages were predominantly of the antiinflammatory/wound-healing subpopulation (Arginase1(+)ED1(+)) which were
expressed early, and up to sevenfold greater than that found in sham-treated
animals."
"These findings demonstrate that a simple yet inexpensive treatment regime of red
light reduces the development of hypersensitivity along with sensorimotor
improvements following spinal cord injury and may therefore offer new hope for a
currently treatment-resistant pain condition."

Nerves

Spinal cord

Chen

Taiwan
(Kaohsiung)

2014

PLoS One

Effect of low level laser therapy on chronic compression of the

dorsal root ganglion.

Rat

Chronic compression
of dorsal root
ganglion

808

190

0.38

72
(skin)

0.5
cm2

207
/p

8
(ganglio
n)

"Our data indicate that LLLT significantly decreased the tolerable sensitivity to pain
and heat stimuli in the CCD groups. The expression levels of the pro-inflammatory
cytokines TNF- and IL-1 were increased following CCD, and we found that
these increases could be reduced by the application of LLLT. Furthermore, the
expression of GAP-43 was enhanced by LLLT.

PubMed

In conclusion, LLLT was able to enhance neural regeneration in rats following

CCD and improve rat ambulatory behavior. The therapeutic effects of LLLT on the
DRG during CCD may be exerted through suppression of the inflammatory
response and induction of neuronal repair genes.
These results suggest potential clinical applications for LLLT in the treatment of
compression-induced neuronal disorders."

Nerves

Spinal cord

Paula

Brazil
(So Jos dos
Campos)

2014

Lasers Surg Med

Low-intensity laser therapy effect on the recovery of traumatic

spinal cord injury.

780

Rat

44

0.224

6.16

0.196
cm2

(5p)

140

21

(5p)
or
153?

Nerves

Spinal cord

Ando

Japan
(Yokohama)

2013

J Biomed Opt

Low-level laser therapy for spinal cord injury in rats: effects of

polarization.

808

Rat

25

0.008

9.6

d=
20 mm

1200

"The results showed faster motor evolution in rats with spinal contusion treated
with LILT, maintenance of the effectiveness of the urinary system, and
preservation of nerve tissue in the lesion area, with a notorious inflammation
control and increased number of nerve cells and connections.

PubMed

In conclusion, positive effects on spinal cord recovery after moderate traumatic

spinal cord injury were shown after LILT."
6
(?)

"Regardless of the polarization direction, functional scores of SCI rats that were
treated with the 808-nm laser irradiation were significantly higher than those of
SCI alone group (Group 1) from day 5 after injury. The locomotive function of SCI
rats irradiated parallel to the spinal column (Group 3) was significantly improved
from day 10 after injury, compared to SCI rats treated with the linear polarization
perpendicular to the spinal column (Group 2).

PubMed

There were no significant differences in ATP contents in the injured tissue among
the three groups.
We speculate that the higher efficacy with parallel irradiation is attributable to the
deeper light penetration into tissue with anisotropic scattering."

Nerves

Spinal cord

Wu

USA
(Bethesda, MD)

2012

Lasers Med Sci

Comparison of the effects of pulsed and continuous wave light on

axonal regeneration in a rat model of spinal cord injury.

Rat

808

35
(CW)

0.5

Nerves

Spinal cord

Wu

USA
(Bethesda, MD)

2009

Lasers Surg Med

810 nm Wavelength light: an effective therapy for transected or

contused rat spinal cord.

Rat

810

150

0.53

450

1500

d=
3 mm

3000

14

"In conclusion, CW and pulsed laser light support axonal regeneration and
functional recovery after SCI. Pulsed laser light has the potential to support axonal
regrowth to spinal cord segments located farther from the lesion site. Therefore,
the use of pulsed light is a promising noninvasive therapy for SCI."

PubMed

1.589

0.3
cm2

2997

14

"The average length of axonal re-growth in the rats in the light treatment (LT)
groups with the hemisection (6.89+/-0.96 mm) and contusion (7.04+/-0.76 mm)
injuries was significantly longer than the comparable untreated control groups
(3.66+/-0.26 mm, hemisection; 2.89+/-0.84 mm, contusion).

PubMed

spot

The total axon number in the LT groups was significantly higher compared to the
untreated groups for both injury models (P<0.05).
For the hemisection model, the LT group had a statistically significant lower angle
of rotation (P<0.05) compared to the controls.
For contusion model, there was a statistically significant functional recovery (P<0.
05) in the LT group compared to untreated control."
"Light therapy applied non-invasively promotes axonal regeneration and functional
recovery in acute SCI caused by different types of trauma. These results suggest
that light is a promising therapy for human SCI."

Nerves

Spinal cord

Byrnes

USA
(Bethesda, MD)

2005

Lasers Surg Med

810

Light promotes regeneration and functional recovery and alters the Rat
immune response after spinal cord injury.

150

0.53

450

1.589

0.3
cm2

2997

14

spot

"PBM, with 6% power penetration to the spinal cord depth, significantly increased
axonal number and distance of regrowth (P < 0.001).

PubMed

PBM also returned aspects of function to baseline levels and significantly

suppressed immune cell activation and cytokine/chemokine expression."
"Our results demonstrate that light, delivered transcutaneously, improves recovery
after injury and suggests that light will be a useful treatment for human SCI."
Star: Parameters were well reported and results were interesting.

Nerves

Spinal cord

Rochkind

Israel
(Tel Aviv)

2002

Neurol Res

Transplantation of embryonal spinal cord nerve cells cultured on

biodegradable microcarriers followed by low power laser
irradiation for the treatment of traumatic paraplegia in rats.

780

Rat

250

1800

14

"Eleven of the 15 (73%) showed different degrees of active leg movements and
gait performance, compared to 4 (44%) of the 9 rats with implantation alone. In a
control group of seven rats with spinal cord transection and no transplantation or
laser, six (86%) remained completely paralyzed.

PubMed

Three months after transection, implantation and laser irradiation, SSEPs were
elicited in 69% of rats (p = 0.0237) compared to 37.5% in the nonirradiated group.
The control group had no SSEPs response.
Intensive axonal sprouting occurred in the group with implantation and laser. In the
control group, the transected area contained proliferating fibroblasts and blood
capillaries only."
Comment: Parameters were insufficiently reported.

Nerves

Systemic
effects

Rochkind

Israel
(Tel Aviv)

1989

Lasers Surg Med

Systemic effects of low-power laser irradiation on the peripheral

and central nervous system, cutaneous wounds, and burns.

Rat

Systemic effect

"HeNe laser irradiation applied to a crushed injured sciatic nerve in the right leg in
a bilaterally inflicted crush injury, significantly increased the compound action
potential in the left nonirradiated leg as well."

PubMed

"The bilateral retrograde degeneration of the motor neurons of the spinal cord
expected after the bilateral crush injury of the peripheral nerves was greatly
reduced in the laser treated group."

Nerves

Belkin &
Schwartz

Israel
(Ramat Gan)

1994

Neurosurg Rev

Evidence for the existence of low-energy laser bioeffects on the

nervous system.

Review

"The reported effects of low-energy laser irradiation on the nervous system are manifested in alterations in cellular and extracellular biochemical
constituents and reactions, as well as in changes in cell division rates. These bioeffects were observed in both in vivo and in vitro experiments. Other
observed phenomena relate to the function of the nervous system and consist mainly of induced alteration in electrical conduction, stimulation
thresholds, and behavioral effects.
Clinical aspects of low-energy laser bioeffects relate mainly to pain mitigation and postponement of the posttraumatic neural degeneration processes.
Many of the reported observations were obtained by experiments apparently conducted according to less than rigorous scientific criteria, and some could
not be duplicated. On the whole, however, there is little doubt that low-energy laser irradiation exerts some effects on the nervous system under specific
conditions of irradiation and tissue exposure via a mechanism which is probably photochemical in nature."

PubMed

Additional info

Comment

Reply

 Category

Subcategory

Nerves

Oncology

Human
research

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Rochkind &
Ouaknine

Israel
(Tel Aviv)

1992

Neurol Res

New trend in neuroscience: low-power laser effect on peripheral

and central nervous system (basic science, preclinical and clinical
studies).

Review

Low-Level Laser Therapy May Have Cancer Fighting Role.

Guest
Editorial

Hode L

Sweden
(Lidingo)

2016

Photomed Laser
Surg

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

sec

"The present review summarizes findings in our continuing study of the use of low-power laser irradiation (LPLI) in the treatment of severely injured
peripheral (PNS) and central nervous systems (CNS). The radiation method was proposed by Rochkind and has been modified over the last 13 years."

PubMed

"In a previous experimental work, we showed that direct laser treatment on nerve tissue promotes restoration of the electrophysiological activity of the
severely injured peripheral nerve, prevents degenerative changes in neurons of the spinal cord and induces proliferation of astrocytes and
oligodendrocytes. This suggested a higher metabolism in neurons and improved ability for myelin production under the influence of laser treatment. The
tethering of the spinal cord causes mechanical damage to neuronal cell membranes leading to metabolic disturbances in the neurons. For this reason,
we believe that using LPLI may improve neuronal metabolism, prevent neuronal degeneration and promote improved spinal cord function and repair. The
possible mechanism of LPLI is investigated."
"Since to our knowledge no double-blind placebo-controlled studies have been performed, we plan to carry out one. We want to study the effect of LLLT
in combination with chemotherapy in patients with metastatic HER-2 negative breast cancer. We will take repeated tumor biopsies and do imaging tests
as well as taking blood samples before, during, and after treating the patients. We will also analyze molecular changes in the tumor cells and their
microenvironment, as well as any immunological changes reflected in the tumor and the blood induced by the addition of LLLT

PubMed

Apart from clinical efficacy, we will also study safety and tolerability of the combined treatment."
"However, this is easier said than done. We started planning a double-blind study with 100 patients and estimated the cost to be around USD $5 million.
We talked to a major cancer foundation and they said: Show us a large pilot study and we might consider supporting the project. So, now we plan to do
a cohort study with less MRI and fewer blood samples that we hope to be able to finance, one way or another."

Oncology

Human
research

Mikhailov

Russia
(Moscow)

2000

Proc. SPIE 4166

Results of treatment of patients with second- to third-stage breast

cancer by combination of low-level laser therapy (LLLT) and
surgery: ten-year experience

Human

Oncology

Supportive care

Robijns

Belgium
(Hasselt)

2016
epub

Lasers Med Sci

The use of low-level light therapy in supportive care for patients

with breast cancer: review of the literature.

Review

890

"86.9% (76.19% in control group) of patients with stage II breast cancer survived
10 years after LLLT treatment. For patients with stage III breast cancer treated by
LLLT the rate was 83.3% (68.4% in control group)."

"For this review, all existing literature concerning the use of LLLT for breast cancer was used to provide evidence in the following domains: oral mucositis
(OM), radiodermatitis (RD), lymphedema, chemotherapy-induced peripheral neuropathy (CIPN), and osteonecrosis of the jaw (ONJ).

SPIE

PubMed

The findings of this review suggest that LLLT is a promising option for the management of breast cancer treatment-related side effects. However, it still
remains important to define appropriate treatment and irradiation parameters for each condition in order to ensure the effectiveness of LLLT."

Oncology

Supportive care

Argenta

USA
(Minneapolis,
MN)

2016

Gynecol Oncol

The effect of photobiomodulation on chemotherapy-induced

peripheral neuropathy: A randomized, sham-controlled clinical
trial.

Human
RCT/DD

Chemotherapyinduced peripheral
neuropathy

800980

Oncology

Tumor cells

Crous &
Abrahamse

South Africa
(Johannesburg)

2016

Photomed Laser
Surg

Low-Intensity Laser Irradiation at 636 nm Induces Increased

Viability and Proliferation in Isolated Lung Cancer Stem Cells.

In vitro

Isolated lung cancer

stem cells

636

LLLT improved the status of patients approximately by 40-50%, while sham

treatment didn't have any effect.

PubMed

Comment: Parameters were extremely poorly reported.

85

5
10
20

"Cellular morphology indicated an increase in cell density caused by cell

proliferation over time. Biostimulatory effects were achieved in lung CSCs when
examining viability and proliferation."

PubMed

"It should, therefore, be noted that a low wavelength of 636 nm at various fluences
induces biostimulation, which may have detrimental effects when using LILI as a
form of regeneration."

Oncology

Tumor cells

Jeong, Andrew

USA
(Boston, MA)

2016

DISSERTATION
(Boston
University)

Safety evaluation of low level light therapy on cancer cells

In vitro

Oncology

Tumor cells

Ramos Silva

Brazil
(So Paulo)

2016

J Biophotonics

Exploring the effects of low-level laser therapy on fibroblasts and

tumor cells following gamma radiation exposure.

In vitro

Gamma radiated
cells

660

Oncology

Tumor cells

Peidaee

Australia
(Melbourne)

2016

Med Biol Eng

Comput

In vitro evaluation of low-intensity light radiation on murine

melanoma (B16F10) cells.

In vitro

Murine melanoma
(B16F10) cells

585
626
810
850
950

Oncology

Tumor cells

Barasch

USA &
Netherlands

2016

Support Care
Cancer

Effects of pre-radiation exposure to LLLT of normal and malignant

cells.

In vitro

Oncology

Tumor cells

Akbarzadeh

Iran
(Tabriz)

2016

Lasers Med Sci

Effects of combination of melatonin and laser irradiation on

ovarian cancer cells and endothelial lineage viability.

In vitro

Oncology

Tumor cells

Samoilova

Russia
(SaintPetersburg)

2015

Photomed Laser
Surg

Regulatory systemic effect of postsurgical polychromatic light

(480-3400 nm) irradiation of breast cancer patients on the
proliferation of tumor and normal cells in vitro.

Human / in
vitro

Oncology

Tumor cells

Knyazev

Russia
(SaintPetersburg)

2015

Photomed Laser
Surg

Downregulation of tumorogenicity and changes in the actin

cytoskeleton of murine hepatoma after irradiation with
polychromatic visible and IR light.

In vitro (-->
transplanted
to mice)

Oncology

Tumor cells

Dastanpour

Iran
(Tehran)

2015

J Lasers Med Sci

The effect of low-level laser therapy on human leukemic cells.

In vitro

810

Oncology

Tumor cells

Sperandio

Brazil
(So Paulo)

2013

J Biophotonics

Low-level laser therapy can produce increased aggressiveness of

dysplastic and oral cancer cell lines by modulation of Akt/mTOR
signaling pathway.

In vitro

660
780

Oncology

Tumor cells

Liu

Taiwan
(Taichung)

2006

Lasers Med Sci

Photoradiation could influence the cytoskeleton organization and

inhibit the survival of human hepatoma cells in vitro.

In vitro

808

Oncology

Tumor cells

Liu

Taiwan
(Taichung)

2004

Res Commun Mol

Pathol Pharmacol

Effects of diode 808 nm GaAlAs low-power laser irradiation on

inhibition of the proliferation of human hepatoma cells in vitro and
their possible mechanism.

In vitro

808

808

0,1
0.5
1
3
10

"The application of LLL at 808 nm with energy densities ranging from 0.1 J/cm2 to
10 J/cm2 under an LED source did not induce cell proliferation or death compared
to control (0 J/cm2) for each cell line in the absence or the presence of each drug,
and no definite trend was observed with increasing energy density.

OpenBU

The study suggests that LLLT at these parameters may be safe to use on cancer
patients, but further studies on different cancer cell lines and animal models with
different parameters (wavelength, energy density, dosage) of LLL are warranted."

LLLT + melatonin
treatment

Polychromatic light

40

"Regarding tumor cells, no influences of LLLT on cell viability are noticed.

Whereas LLLT enhances cell populations in S and G2 /M cell cycle phases for
both cellular lines, a decrease in proliferation and increase in senescence was
verified only for tumor cells."

PubMed

"From irradiation of selected visible and near-infrared wavelengths, no visible

changes were detected in cellular viability of either normal or cancer cells."

PubMed

"LLLT does not confer protection and may even sensitize cancer cells to IR killing"

PubMed

"Combination treatment of both cell lines caused a marked increase in

apoptosis/necrosis rate, reactive oxygen species generation, and heat shock
protein 70 expression compared to incubation of the cells with each agent alone (p
< 0.05)"

PubMed

4803400

"The results suggest an effect at the systemic level where pVIS + pIR light may
stimulate growth of human skin cells and simultaneously downregulate the
proliferation of tumor cells, including BC cells. This argues in favor of the
oncological safety of PT for BC patients postsurgically."

PubMed

4803400

"Polychromatic light of a wide range of doses did not change the viability and
proliferation of cells. After transplantation of cells irradiated with VIS-IR light (4.8
and 9.6 J/cm(2)) and VIS light (38.4 J/cm(2)) the tumor volume was lower in the
treated group than in the control group in vivo. Transplantability of the irradiated
cells also decreased, whereas survival of tumor-bearing mice increased."

PubMed

"Significant increase in cell proliferation was seen only after two exposures at
energy density of 20J/cm2 (P=0.021)."

PubMed

"LLLT significantly modified the expression of proteins related to progression and

invasion in all the cell lines, and could aggravate oral cancer cellular behavior,
increasing the expression of pAkt, pS6 and Cyclin D1 proteins and producing an
aggressive Hsp90 isoform."

PubMed

"Therefore, the net effects by this photoradiation were reduced cell survival."

PubMed

"Two significant findings are raised in this study:

PubMed

633

35

675

80

1.2
3.6
6.0

0.035

30
90
150

0.,04
cm2

30
90
150

0.1
12

1
cm2

3343

13.22

0.32
cm2

60

5
10
20
40

2.05
3.07
6.15

130

0.039
cm2

5.85
7.8

90
120

(1) Diode 808 nm GaAlAs continuous wave laser has an inhibitory effect on the
proliferation of human hepatoma cells line HepG2 and J-5.
(2) The mechanism of inhibition might be due to down-regulation of synemin
expression and alteration of cytokeratin organization that was caused by laser
irradiation."

Oncology

Tumor cells

Kreisler

Germany
(Mainz)

2003

Lasers Med Sci

Low-level 809 nm GaAlAs laser irradiation increases the

proliferation rate of human laryngeal carcinoma cells in vitro.

In vitro

809

Oncology

Tumor cells

Pinheiro

Brazil
(Salvador,
Bahia)

2002

Braz Dent J

Does LLLT stimulate laryngeal carcinoma cells? An in vitro study.

In vitro

635
670

Oncology

0.04
0.48

Tumor cells

Pinheiro

Brazil
(Salvador,
Bahia)

2002

J Clin Laser Med

Surg

Effects of low-level laser therapy on malignant cells: in vitro study.

In vitro

635
670

Oncology

Tumor growth

Rhee

Korea
(Cheonan)

2016

Photomed Laser
Surg

Low-Level Laser Therapy Promoted Aggressive Proliferation and

Mouse
Angiogenesis Through Decreasing of Transforming Growth Factor1 and Increasing of Akt/Hypoxia Inducible Factor-1 in Anaplastic
Thyroid Cancer.

650

0.1

0.04
4.8

Oncology

Tumor growth

Ottaviani

Italy
(Trieste)

2016

EBioMedicine

Laser Therapy Inhibits Tumor Growth in Mice by Promoting

Immune Surveillance and Vessel Normalization.

660
800
970

0.05
0.2
0.2

0.3
0.6

15
30

0.02

150
300

3
6
6

2
cm2
(?)

60
30
30

"The irradiated cells revealed a considerably higher proliferation activity. The

differences were highly significant up to 72 h after irradiation (Mann-Whitney U
test, p < 0.001). A cellular responsiveness of human laryngeal carcinoma cells to
low-level laser irradiation is obvious. The cell line is therefore suitable for basic
research investigations concerning the biological mechanisms of LLLT on cells."

PubMed

"The results showed that 635nm laser light did not significantly stimulate the
proliferation of H.Ep.2 cells at doses of 0.04 J/cm2 to 0.48 J/cm2, However,
670nm laser irradiation led to an increased cell proliferation when compared to
both control and 635nm irradiated cells."

PubMed

"It is concluded, that irradiation with 670-nm laser light applied at doses between
0.04 and 4.810(4) Jm(-2) could significantly increase proliferation of laryngeal
cancer cells."

PubMed

"In conclusion, LLLT led to a decrease in TGF-1 and increase of p-Akt/HIF-1

which resulted to overproliferation and angiogenesis of anaplastic thyroid
carcinoma (ATC). Therefore, we suggest that LLLT can influence cancer
aggressiveness associated with TGF-1 and Akt/HIF-1 cascades in some poorly
differentiated head and neck cancers."

PubMed

Star: Parameters were listed in a table, and a photograph was supplied.

Mouse

In vitro tumor cell

irradiation

"While laser light increased cell metabolism in cultured cells, the in vivo outcome
was reduced tumor progression.

PubMed

This striking, unexpected result, was paralleled by the recruitment of immune cells,
in particular T lymphocytes and dendritic cells, which secreted type I interferons.
Laser light also reduced the number of highly angiogenic macrophages within the
tumor mass and promoted vessel normalization, an emerging strategy to control
tumor progression.
Collectively, these results set photobiomodulation as a safety procedure in
oncological patients and open the way to its innovative use for cancer therapy."
Comment: An interesting paper with many tables. However, parameter reporting
should have been better (eg. beam area in the in vivo part of the study).

Oncology

Tumor growth

MyakishevRempel

USA
2012
(Rochester, NY)

Photomed Laser
Surg

A preliminary study of the safety of red light phototherapy of

tissues harboring cancer.

Mouse

Oncology

Tumor growth

de C Monteiro

Brazil
(Salvador,
Bahia)

2011

Photomed Laser
Surg

Influence of laser phototherapy (660 nm) on the outcome of oral

chemical carcinogenesis on the hamster cheek pouch model:
histological study.

Hamster

Oncology

Tumor growth

Frigo

Brazil
(So Paulo)

2009

BMC Cancer

The effect of low-level laser irradiation (In-Ga-Al-AsP - 660 nm) on

melanoma in vitro and in vivo.

Mouse
In vitro

Oncology

Tumor growth

Ulrich

Germany
(Hamburg)

1996

Book: Laser in der Influence of Laser Light (830nm) on the Growth Kinetics of Rat
Medizin / Laser in Rhabdomyosarcomas
Medicine

Oncology

Tumor growth

Mikhailov

Russia
(Moscow)

1993

Oncology

Tumor growth

Abe

Japan

1993

Keio J Med

Melanoma

"This experiment suggests that LLLT at these parameters may be safe even when
malignant lesions are present. Further studies on the effects of photoirradiation on
neoplasms are warranted."

PubMed

56.4

0.07
cm2

133

14

"It is concluded that LLLT, within the parameters used in the present study,
caused a significant progression of the severity of SCC in the oral cavity of
hamsters."

PubMed

2.5

150
1050

2
mm2

60
420

"This cancer-protective effect was not reproduced in the in vivo experiment where
outcome measures for the 150 J/cm(2) dose group were not significantly different
from controls. For the 1050 J/cm(2) dose group, there were significant increases in
tumor volume, blood vessels and cell abnormalities compared to the other
groups."

PubMed

0.03

15
1500

"The results showed that after single doses of exposure no change of tumor
growth in comparison to untreated controls was observed. During and after the
fractionated exposure with doses of 15 and 1500 J/cm2, respectively, neither an
enhanced tumor growth nor a significant tumor growth delay was obtained."

Springer

0.03
0.3

"Investigations on rats with an implanted tumour-carcinosarcoma of Walker (26

animals), cancer of the mammary glands, RMK-1 (75 animals) and in mice with
spontaneous cancer of the mammary gland (188 animals)-have shown that the
application of a low-level diode laser beam (890 nm) can effect the growth of the
experimental tumour. Minimal doses produce a tumouro-static effect, while other
doses produce different effects. Low level laser irradiation promotes dystrophic
and necrotic changes in tumoural nodes."

J-STAGE

Direct and indirect LLLT inhibited tumor growth. In one model, indirect LLLT also
increased tumor growth.

PubMed

660

30

0.424

660

50

Rat

830

Investigations on the influence of low level diode laser irradiation

of the growth of experimental tumors.

Mouse

890

Role of 830 nm low reactive level laser on the growth of an

implanted glioma in mice.

Mouse

830

60

Additional info

Comment

Reply

 Category

Subcategory

Oncology
Opioid
withdrawal

Morphine

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Journal

Title

Study type Sub-category 2 /

animal model

Lanzafame RJ

USA
2011
(Rochester, NY)

Photomed Laser
Surg

Photobiomodulation and cancer and other musings.

Editorial

Ojaghi

USA
(Chicago, IL)

Lasers Med Sci

Role of low-intensity laser therapy on naloxone-precipitated

morphine withdrawal signs in mice: is nitric oxide a possible
candidate mediator?

Mouse

Year

2014

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

Additional info

Comment

Reply

Comment

Reply

sec

PubMed
830

50

12.5

0.22
cm2

55

"LILT and L-NAME (20, 50, and 100 mg/kg) per se significantly decreased escape
jump count and stool weight in morphine-dependent naloxone-treated mice (p <
0.01). Coadministration of LILT and L-NAME (20, 50, and 100 mg/kg) also
reduced escape jump and stool weight (p < 0.05) but with no synergetic or additive
response.

PubMed

Here, LILT at this fluence may show its maximal effects on NO and therefore no
noticeable effects appeared during coadministration use. Moreover, LILT and LNAME follow the same track of changes in escape jump and stool weight.
Conceivably, it seems that LILT acts partly via NO system, but the exact path is
still obscure and rather intricate. The precise mechanisms need to be clarified."

Opioid
withdrawal

Morphine

Mirzaii-Dizgah

Iran
(Tehran)

2009

Behav Brain Res

Attenuation of morphine withdrawal signs by low level laser

therapy in rats.

830

Rat

50

0.22
cm2

55

"One-way ANOVA showed that the LILT which applied immediately or 15min prior
to naloxone injection significantly decreased total withdrawal score (TWS).

PubMed

These results suggest that LILT prior to naloxone injection attenuates the
expression of withdrawal signs in morphine-dependent rats. Further studies may
elucidate the likely role of LILT in clinical management of opioid withdrawal
syndrome."
Comment: The effect of LLLT was quite modest, but probably still relevant.

Oral

Analgesia

Chan

Australia
(Sydney)

2012

J Dent Res

Pulsed Nd: YAG laser induces pulpal analgesia: a randomized

clinical trial.

Human
RCT

LLLT vs EMLA
anesthetic cream

1064

1100

211312

73107

"The trial confirmed that the pulsed Nd:YAG laser effectively induced pulpal
analgesia, by suppression of intradental nerve responses to electrical and
mechanical stimuli. Such a laser provides an alternative for dental pain
management."

Tooth extraction
before orthodontic
procedures

Oral

Aphthous
stomatitis

Pavli

Serbia (?)

2015

Vojnosanit Pregl

Treatment of recurrent aphthous stomatitis by laser therapy: A

systematic review of the literature.

Systematic
review

Oral

Burning mouth
syndrome

Sugaya

Brazil
(So Paulo)

2016

Braz Oral Res

Low Intensity laser therapy in patients with burning mouth

syndrome: a randomized, placebo-controlled study.

Human
RCT

Oral

Burning mouth
syndrome

Valenzuela &
Lopez-Jornet

Spain
(Murcia)

2016

J Oral Rehabil

Effects of low-level laser therapy on burning mouth syndrome.

Human
RCT

Oral

Burning mouth
syndrome

Arduino

Italy
(Turin)

2016

Lasers Med Sci

A randomized pilot study to assess the safety and the value of low- Human
level laser therapy versus clonazepam in patients with burning
RCT
mouth syndrome.
Comparison

Oral

Burning mouth
syndrome

Spanemberg

Brazil

2015

J Biomed Opt

Efficacy of low-level laser therapy for the treatment of burning

mouth syndrome: a randomized, controlled trial.

Oral

Burning mouth
syndrome

dos Santos Lde

Brazil
(So Paulo)

2015

Photochem
Photobiol

Oral

Burning mouth
syndrome

Pezelj-Ribari

Croatia

2013

Oral

Burning mouth
syndrome

Yang & Huang

Taiwan
(Taichung)

2011

"Even though the assessed literature suggests beneficial outcomes of laser therapy in treatment of RAS, these results should be interpreted with caution.
The issues related to the study designs and different sets of laser irradiation parameters of a limited number of available studies with the same treatment
outcomes prevent us from making definite conclusions."
790

120
(or
20?)

815

1000

980

300

Human
RCT

830

100

Phototherapy on the Treatment of Burning Mouth Syndrome: A

Prospective Analysis of 20 Cases.

Human
Case series

660

40

0.4
/p

Lasers Med Sci

Proinflammatory cytokine levels in saliva in patients with burning

mouth syndrome before and after treatment with low-level laser
therapy.

Human
RCT

685

30

Photomed Laser
Surg

Treatment of burning mouth syndrome with a low-level energy

diode laser.

Human

800

LLLT vs clonazepam

6
/p

6
(?)

4
6

133
200

0.03
cm2
spot
size

50
/p

4
6

10

10

50
10

0.04
cm2

105

1
cm2
(area)

10
/p

PubMed

PubMed

"According to the protocol used in this study, low intensity laser therapy is as
beneficial to patients with BMS as placebo treatment, indicating a great emotional
component of involvement in BMS symptomatology. Nevertheless, there were
positive results in some statistical analyses, thus encouraging further research in
BMS laser therapy with other irradiation parameters."

PubMed

"Overall improvements in VAS scores from baseline to the end of treatment were:
Group I 15.7%; Group II 15.6%; Group III placebo 7.3%."

PubMed

"Comparing the two groups, LLLT appeared to be superior in improving pain

perception, but statistically only at 8 weeks after the end of the protocol proposed
(P = 0.026)."

PubMed

LLLT appeared to be beneficial.

10

1W group = 1 session per week

3W group = 3 sessions per week

"All volunteers reported reduced burning intensity in all sessions when compared
to the previous one and reduction in VAS scores by up to 49% in the last clinical
session when compared to the first session."

PubMed

600

LLLT did not have beneficial effects in this study.

PubMed

70

"The results showed an average reduction in pain of 47.6% (ranging from 9.3% to
91.8%)."

PubMed

Note: A comment on this paper was published by Vukoja (et al).

Oral

Burning mouth
syndrome

dos Santos Lde

Brazil
(Recife)

2011

Photomed Laser
Surg

Effect of low-level laser therapy in the treatment of burning mouth

syndrome: a case series.

Human
Case series

660

Oral

Burning mouth
syndrome

Romeo

Italy
(L'Aquila)

2010

Ann Stomatol
(Roma)

The low level laser therapy in the management of neurological

burning mouth syndrome. A pilot study.

Human
Pilot study

650
+
910
120

30

Oral

Burning mouth
syndrome

Kato

Brazil
(So Paulo)

2010

Photomed Laser
Surg

Low-level laser therapy in burning mouth syndrome patients: a

pilot study.

Human
Pilot study

790

Oral

Caries

Mller

Brazil
(So Paulo)

2007

Arch Oral Biol

Effects of low power red laser on induced-dental caries in rats.

Rat

660

40

0.8
/p

20

10
/p

0.03
cm2

10

"All patients reported improvement in all sessions, with reduction in VAS scores by
up to 58% in the tenth session."

PubMed

"Seventeen patients (68%) had relevant benefits from the treatment with valid
reduction of NRS ratings. In 8 cases the differences of NRS rates were not
relevant being under the limit of reliability established in study design. In no case
there was a worsening of the symptoms."

PubMed

"Burning intensity at the end of the laser therapy was statistically lower than at the
beginning (p < 0.01). Patients reported an 80.4% reduction in the intensity of
symptoms after laser treatment. There was no statistical difference between the
end of the treatment and the 6-week follow-up, except for the tongue site."

PubMed

"The use of laser radiation alone did not promote any additional benefit on the
control of dental caries since LG did not show any differences comparing to CG."

PubMed

[However, laser applied before the fluoride was associated with a little bit better
outcome.]

Oral

Dental implants

Prados-Frutos

Spain

2016

Lasers Med Sci

Lack of clinical evidence on low-level laser therapy (LLLT) on

dental titanium implant: a systematic review.

Systematic
review

Oral

Dental implants

Gokmenoglu

Turkey
(Ordu)

2014

Photomed Laser
Surg

The effect of light-emitting diode photobiomodulation on implant

stability and biochemical markers in peri-implant crevicular fluid.

Human

Currently, there is a lack of human studies.

LED phototherapy

626

185

0.0385

222

46.2

PubMed
4.80
cm2

1200

"In the control group, significant reduction of ISQ values from week 2 to week 12
were demonstrated. In the LED group, baseline ISQ values were maintained
during the study and no significant changes were observed."

PubMed

"LED application to surgical area has a positive effect on the osseointegration

process, and implant stability can be maintained."

Oral

Dental implants

Tang & Arany

USA
(Bethesda, MD)

2013

J Periodontal
Implant Sci

Photobiomodulation and implants: implications for dentistry.

"The use of laser technology with implants has a fascinating breadth of applications, beginning from their precision manufacturing to clinical uses for
surgical site preparation, reducing pain and inflammation, and promoting osseointegration and tissue regeneration. This latter aspect is the focus of this
review, which outlines various studies of implants and laser therapy in animal models. The use of low level light therapy or photobiomodulation has
demonstrated its efficacy in these studies.

Review

PubMed

Besides more research studies to understand its molecular mechanisms, significant efforts are needed to standardize the clinical dosing and delivery
protocols for laser therapy to ensure the maximal efficacy and safety of this potent clinical tool for photobiomodulation."
LLLT appeared to be clearly beneficial for dentin hypersensitivity.

Oral

Dentin
hypersensitivity

Sicilia

Spain

2009

J Clin Periodontol

Immediate efficacy of diode laser application in the treatment of

dentine hypersensitivity in periodontal maintenance patients: a
randomized clinical trial.

Human
RCT

Oral

Dentistry

Pandeshwar

India
(Bangalore)

2016

J Investig Clin
Dent

Photobiomodulation in oral medicine: a review.

Review

"Current literature reports the potential of PBM in various applications in oral medicine. Furthermore, well-documented research confirms its efficacy in
certain conditions, such as oral mucositis, recurrent herpes simplex infection, and burning mouth syndrome. The absence of any reported adverse effects
is an advantage over conventional therapeutic modalities. While PBM has proved to be effective for some specific applications, it is not a panacea."

PubMed

Oral

Dentistry

Nammour S

Belgium
(Liege)

2016

Photomed Laser
Surg

Chronology of the Use of the Laser Beam in Dentistry, and the

State of Postgraduate University Education Programs in this
Domain.

Guest
Editorial

"Worldwide, the total number of universities offering postgraduate programs for laser dentistry is *31 (Fig. 1)"

PubMed

UK
(Chesham)

2014

Dent Mater

Developments in low level light therapy (LLLT) for dentistry.

Review

PubMed

"Further, between 2006 and 2008, seven European universities decided to join their efforts in the European Master Degree in Oral Laser Applications
(EMDOLA) group, to increase the quality of the education program in laser dentistry."
"The universities involved in the EMDOLA program are Liege University (Belgium), Aachen University (Germany), Barcelona University (Spain), Parma
University (Italy), Roma La Sapienza University (Italy), Nice University (France), and Timisoara University (Romania)."

Oral

Dentistry

Carroll

"The initial search returned 2778 results, when filtered this was reduced to 153. 41 were review papers or editorials, 65 clinical and 47 laboratory studies.

PubMed

Of all the publications, 130 reported a positive effect in terms of pain relief, fast healing or other improvement in symptoms or appearance and 23
reported inconclusive or negative outcomes.
Direct application of light as a therapeutic intervention within the oral cavity (rather than photodynamic therapies, which utilize photosensitizing solutions)
has thus far received minimal attention.
Data from the limited studies that have been performed which relate to the oral cavity indicate that LLLT may be a reliable, safe and novel approach to
treating a range of oral and dental disorders and in particular for those which there is an unmet clinical need."

Oral

Dentistry

Ross G

Canada
(Tottenham)

2012

Photomed Laser
Surg

Photobiomodulation in dentistry.

A surprisingly extensive editorial on the use of LLLT/PBM in dentistry.

Guest
Editorial

PubMed

"As a practicing dentist for over 40 years, I have been fortunate to have used laser therapy clinically for my patients for over half that time. The results
seen throughout the years have continued to improve, and I can now treat a number of conditions that would otherwise cause stress both for me and the
patient."
"My use of analgesics and pharmaceutical pain management has decreased by ~90%"
"The reduction in postoperative pain without the use of medications has dramatically changed the way patients view their dental procedures, and makes
dentistry a more pleasant experience. Whereas dentistry has always been closely associated with pain and has even been feared, its reputation is now
changing dramatically, especially in the younger generations that experience this type of 'pain-free dentistry.'"
"In cases where there is postoperative pain from a procedure, it can be managed and eliminated quickly and effectively."
"The number of root canals required has been reduced by ~50%, primarily because the significant inflammation caused by deep cavities that leads to a
root canal treatment can be modulated by laser irradiation. Managing the inflammation at the cavity stage decreases the probability that it will cause
pulpal death and ultimately necessitate a root canal."

Oral

Dentistry

Nammour S

Belgium
(Brussels)

2012

2012 Laser dentistry, current advantages, and limits.

Guest
Editorial

Oral

Denture
stomatitis

Maciel

Brazil

2015

J Prosthodont

Methylene Blue-Mediated Photodynamic Inactivation Followed by

Low-Laser Therapy versus Miconazole Gel in the Treatment of
Denture Stomatitis.

Human
Comparison
trial

Oral

Denture
stomatitis

SimunoviSoski

Croatia

2010

Photomed Laser
Surg

Salivary levels of TNF-alpha and IL-6 in patients with denture

stomatitis before and after laser phototherapy.

Human
RCT

685

Oral

Denture
stomatitis

Maver-Biscanin

Croatia

2005

Photomed Laser
Surg

Effect of low-level laser therapy on Candida albicans growth in

patients with denture stomatitis.

Human

Oral

Denture
stomatitis

Maver-Biscanin

Croatia

2004

Lasers Surg Med

Fungicidal effect of diode laser irradiation in patients with denture

stomatitis.

Oral

Dry mouth
(xerostomia)

Lonar

Croatia

2011

Photomed Laser
Surg

Oral

Dry mouth
(xerostomia)

Vidovi Juras

Croatia

2010

Coll Antropol

PubMed
Miconazole had a better cure rate than PDT (with methylene blue) + LLLT (80% vs
40%).

PubMed

TNF-alpha and IL-6 decreased significantly more in LLLT group.

PubMed

685
830

"Our observations indicate that LLLT might be valuable in the treatment of denture
stomatitis."

PubMed

BTL2000 laser
685 and 830 nm

Human
RCT

685
830

"A fungicidal effect was achieved in the laser treated and antimicotic treated
groups, whereas most subjects in the placebo group were found to have
unchanged conditions"

PubMed

BTL2000 laser
685 and 830 nm

The effect of low-level laser therapy on salivary glands in patients

with xerostomia.

Human
(controlled)

904

10

"Effects of low-level laser therapy on salivary glands are not only stimulating, but
also regenerative to a degree since the glandular response to the same amount of
applied laser energy increased linearly over time."

PubMed

= 904nm
2 minutes
10 treatments

Effects of low-level laser treatment on mouth dryness.

Human

10

"This simple non-invasive method could be used in everyday clinical practice for
the treatment of MD."

PubMed

n= 17
BTL2000 laser
10 sessions

PDT + LLLT

30

d=
2 mm?

600

20

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Oral

Endodontics

Ramalho

Brazil
(So Paulo)

2016

Lasers Med Sci

A randomized placebo-blind study of the effect of low power laser

on pain caused by irreversible pulpitis.

Human
RCT

780

40

4
40

Oral

Endodontics

Moreira

Brazil
(So Paulo)

2016

J Photochem
Photobiol B

In vivo experimental model of orthotopic dental pulp regeneration

under the influence of photobiomodulation therapy.

Rat

660

20

Category

Results: positive / unclear/modest / negative

Link

sec

"The application of 780-nm diode laser irradiation, at 4 and 40 J/cm2, showed no

effect in reducing the pain in SIP in comparison to the placebo group. The fluence
of 4 J/cm2 showed a negative effect in local anesthetics, resulting in significant
increase of complimentary local anesthesia during emergency endodontic
treatment."

PubMed

"LPT should be avoided in teeth with pain due to irreversible pulpitis."

0.028
cm2

"Briefly, this tissue-engineered orthotopic model of dental pulp regeneration

consisted of instrumentation of the dentinal walls with removal of dental pulp
tissue from the mesial root canal of the first molar of rats, followed by treatment of
the root canal walls with an acidic solution to release growth factors and induction
of bleeding into the canal to create a blood clot (i.e., natural scaffold) rich in
endogenous stem cells, prior to the laser PBM therapy application."

PubMed

"No tissue formation was observed in any specimen of the Control group (n = 12).
In three out of the 11 teeth composing the PBM group, the mesial root canal was
filled with an immature connective tissue (Fig. 2).
This tissue was composed of fewer and thinner collagen fibers than the originally
preserved dental pulp of the distal root of the same molar (Fig. 2A and B). A layer
of cells in intimate contact with the dentin wall was observed to exhibit cytoplasmic
extensions into the dentinal tubules (Fig. 2C). Immunohistochemical analysis of
the tissue formed inside the experimental root canal showed an odontoblast-like
cell layer labeled with anti-HSP-25 (Fig. 3A), blood vessels exhibiting SMApositive cells in their walls (Fig. 3B), S-100-positive cells underneath the
odontoblast-like cell layer (Fig. 3C) and a few STRO-1-positive cells in
perivascular niches (Fig. 3D)."
"Most importantly, our results corroborate the hypothesis that PBM therapy may
be an adjunctive therapy that is able to improve dental pulp tissue regeneration."

Oral

Endodontics

Moura

Brazil
(So Paulo)

2016

Braz Oral Res

Low-intensity laser phototherapy enhances the proliferation of

dental pulp stem cells under nutritional deficiency.

In vitro

Dose response

660

10

3
5

0.028
cm2

"These findings indicate that LPT with 5 J/cm2 can enhance the growth of [stem
cells from human exfoliated deciduous teeth] during situations of nutritional
deficiency.

PubMed

Therefore, LPT could be a valuable adjunct treatment in tissue engineering when

using stem cells derived from the dental pulp of primary teeth."

Oral

Oral

Endodontics

Endodontics

de Carvalho

Bramante

Brazil
(Salvador,
Bahia)

Brazil
(Bauru)

2015

2015

Lasers Med Sci

J Endod

Effect of laser ( 660 nm) and LED ( 630 nm) photobiomodulation

on formocresol-induced oral ulcers: a clinical and histological
study on rodents.

Use of a 660-nm Laser to Aid in the Healing of Necrotic Alveolar

Mucosa Caused by Extruded Sodium Hypochlorite: A Case Report.

Rat

LED phototherapy
LED and laser

630
(LED)

150

4.8

0.8
cm2

660
(laser)

40

4.8

4
mm2

"At the end of the experimental period (11 days), there was no difference
regarding to the size of the ulcers between the laser and LED groups, although
there was a difference between the treated and untreated groups (p=0.0019)."

660

Case report

PubMed

Comment: The difference between LLLT and LED groups, compared to the control
group at the end of the study, are huge.
6

"The conventional treatment protocol was combined with low-level laser therapy.
Clinical and radiographic examinations after 7 months revealed complete repair of
the necrotic area with no paresthesia and further indicated the integrity of the
apical region of the tooth where the extrusion of sodium hypochlorite occurred."

PubMed

Comment: The author didn't report dose parameters.

odontoblast-like cells
(MDPC-23).

450
650
840

Oral

Endodontics

Turrioni

Brazil
(Araraquara)

2015

Oper Dent

Transdentinal cell photobiomodulation using different

wavelengths.

In vitro

Oral

Endodontics

Montoro

Brazil
(Araraquara)

2014

Int Endod J

Infrared LED irradiation photobiomodulation of oxidative stress in

human dental pulp cells.

In vitro

855

Oral

Endodontics

Shigetani

Japan
(Nigata)

2011

J Endod

GaAlAs laser irradiation induces active tertiary dentin formation

after pulpal apoptosis and cell proliferation in rat molars.

Rat

810

4
25
2
4
8
15
30
500
1500

180
180

"The infrared LED irradiation at an energy density of 4 J/cm(2) and red LED at an
energy density of 25 J/cm(2) were the most effective parameters for transdentinal
photobiomodulation of cultured odontoblast-like cells."

PubMed

"Biomodulation of oxidative stress of [human dental pulp cells] can be achieved by

irradiation with a single dose of infrared LED. Within the range investigated, 15 J
cm(-2) resulted in the least production of NO."

PubMed

"The output energy determined pulpal healing patterns after GaAlAs laser
irradiation; the higher energy induced the apoptosis in the affected dental pulp
including odontoblasts followed by active cell proliferation in the intense HSP-25immunoreactive areas surrounding the degenerative tissue, resulting in abundant
tertiary dentin formation. Thus, the optimal GaAlAs laser irradiation elicited
intentional tertiary dentin formation in the dental pulp."

PubMed

Comment: Some parameters such as energy density or spot size were not
reported.
Comment: I wonder whether the effect is based on photobiomodulation or heatstress and hormesis.

Oral

Endodontics

Shiba

Japan
(Hiroshima)

2009

J Endod

Neodymium-doped yttrium-aluminium-garnet laser irradiation

abolishes the increase in interleukin-6 levels caused by
peptidoglycan through the p38 mitogen-activated protein kinase
pathway in human pulp cells.

Oral

Endodontics

Payer

Austria
(Graz)

2005

Oral Surg Oral

The clinical effect of LLLT in endodontic surgery: a prospective
Med Oral Pathol
study on 72 cases.
Oral Radiol Endod

"Suppression of the phosphorylated p38 activity by low-power laser irradiation in

HP cells culminates in inhibition of the increase in IL-6 induced by peptidoglycan,
suggesting that low-power laser irradiation regulates intracellular signaling
molecule activities to exert its anti-inflammatory effect."

In vitro

PubMed

Comment: The parameters were strangely reported. Wavelength is unclear,

though Nd:YAG seems to usually be 1064 nm.
680

Human
Observationa
l

75

3-4

"In routine endodontic surgery cases, LLLT does not achieve a significant clinical
benefit. Further, the results indicate a prominent placebo effect of the soft laser
therapy."

PubMed

Comment: Placebo irradiation appeared to be better than control.

Comment: One reason for the lack of result is the fact that the pain levels were
already very low, so there was really nothing to improve.
Comment: Two photographs were supplied.

Oral

Endodontics

Kreisler

Germany
(Mainz)

2004

Int J Oral
Maxillofac Surg

Efficacy of low level laser therapy in reducing postoperative pain

after endodontic surgery-- a randomized double blind clinical
study.

Human
RCT/DB

809

50

150

Oral

Endodontics

Ohbayashi

Japan
(Chiba)

1999

J Endod

Stimulatory effect of laser irradiation on calcified nodule formation

in human dental pulp fibroblasts.

In vitro

830

600

Oral

Graft-versushost disease

Epstein

USA
(Los Angeles,
CA)

2016

Support Care
Cancer

Photobiomodulation therapy in the management of chronic oral

graft-versus-host disease.

Human
Case series

660
(IO)

75

0.03

4.5
/p

1.8

660+
850
(EO)

1400

0.05

84

"The results revealed that the pain level in the laser group was lower than in the
placebo group throughout the 7 day follow-up period. The differences, however,
were significant only on the first postoperative day (Mann-Whitney U-test, p<0.05).
Low level laser therapy can be beneficial for the reduction of postoperative pain.
Its clinical efficiency and applicability with regard to endodontic surgery, however
require further investigation. This is in particular true for the optimal energy dosage
and the number of laser treatments needed after surgery."

PubMed

Comment: The pain levels were low in the control group. Therefore the need for
extra pain reduction via LLLT/PBM might be not that important in this case.

Oral

Mastication

Tullberg

Sweden
(Huddinge)

2003

Oral

Mucoleles

Amaral

Brazil
2012
(Belo Horizonte)

Pain

Effects of low-power laser exposure on masseter muscle pain and

microcirculation.

Human
RCT/DB

Lasers Med Sci

Low level laser effect after micro-marsupialization technique in

treating ranulas and mucoceles: a case series report.

Human
Case series

3.75

600

2.5
cm2

60
/p

8+

"These results suggested that formation of calcified nodules in human dental pulp
cells, as well as in alkaline phosphatase activity, the production of collagen and
osteocalcin were enhanced by laser irradiation."

PubMed

"Oral pain, sensitivity, and dry mouth improved in most patients.

PubMed

These findings suggest PBM therapy may represent an additional approach for
management of oral cGVHD, and suggest that controlled studies should be
conducted to confirm the efficacy and safety of PBM therapy in oral cGVHD and to
determine optimal PBM therapy protocols."

60
28
cm2

"The blood flow did not change significantly in the patients, but increased after
active laser exposure and decreased after placebo exposure in the healthy
individuals. The difference between active laser and placebo was significant. In
conclusion, the results of this study do not support an effect of low-power laser
exposure on masseter muscle microcirculation in patients with chronic orofacial
pain of muscular origin."

PubMed

Comment: The abstract seems difficult to interpret...

660

100

3.53

0.0283
cm2

"All treated oral ranulas and selected mucoceles presented clinical healing. No
evidence of recurrence could be identified during a mean of 11.0-month follow-up
period.

PubMed

The use of InGaAsP diode lasers, within the parameters tested, appears to
present a good alternative treatment to reduce pain and heal oral ranulas and
selected mucoceles associated with micro-marsupialization."

Oral

Nerves

de Oliveira
Martins

Brazil
(So Paulo)

2013

J Neurotrauma

Laser therapy and pain-related behavior after injury of the inferior

alveolar nerve: possible involvement of neurotrophins.

Rat

IAN injury

904

30

~0.1
cm2
(spot)

90

0.5
cm2
(area)

10

"When the animals were subjected to the laser therapy technique, we observed a
recovery of pain threshold to normal levels. These alterations were detected as
early as day 2 and persisted at least until 1 month after surgery (Fig. 1). It is
important to point out that all animals that received laser therapy sessions exhibit
behavioral improvement."

PubMed

"In irradiated animals, there was an enhanced expression of NGF (53%) and a
decreased BDNF expression (40%) after laser therapy."
Comment: If irradiated area is 0.5cm2 with 6J/cm2, then the total radiant energy
should be 3J, not 30J... Calculations gone wrong?

Oral

Oral mucosal
disorders

Spanemberg

Brazil

2016

Altern Ther Health Low-level Laser Therapy: A Review of Its Applications in the
Med
Management of Oral Mucosal Disorders.

Review

Oral

Oral mucosal
necrosis

Epstein

USA
(Los Angeles,
CA)

2016

Support Care
Cancer

Human
Case series

Oral

Oral mucositis

Sonis

USA
(Watertown,
MA)

2016

Oral Oncol

Photobiomodulation therapy: management of mucosal necrosis of

the oropharynx in previously treated head and neck cancer
patients.

Could the biological robustness of low level laser therapy

(Photobiomodulation) impact its use in the management of
mucositis in head and neck cancer patients.

Review

"Very few controlled clinical studies with well-established therapeutic protocols have occurred, except for [oral mucositis], for which LLLT has been widely
researched."

LLLT intraoral
+
LED phototherapy
extraorally
LED cluster (69)

660
(IO)

75

0.03

4.5
/point

1.8

2.5
cm2

60
/point

1400

0.05

84

28
cm2

60

"We report three cases of symptomatic persisting oral ulcerations where the
addition of photobiomodulation therapy resulted in a rapid resolution of the oral
lesions and in patient symptoms."

PubMed
PubMed

+
660&
850
(EO)

"Our investigation identified a substantial number of LLLT-activated pathways that have been strongly associated with negative tumor outcomes
including proliferation, invasion, angiogenesis, metastases and cancer-treatment resistance. In light of these findings, we suggest an investigational
strategy to assure that LLLT's anti-mucositis efficacy is independent of its possible potential to enhance threatening tumor behaviors. Included are
appropriate pre-clinical modeling, short- and long-term follow-up of LLLT-treated patients, and the requirement for consistency of LLLT parameters."

PubMed

Additional info

Comment

Reply

 Category
Oral

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Oral mucositis

Treister

USA
(Boston, MA)

2016

Photomed Laser
Surg

A Feasibility Study Evaluating Extraoral Photobiomodulation

Human
Therapy for Prevention of Mucositis in Pediatric Hematopoietic Cell
Transplantation.

Study type Sub-category 2 /

animal model
THOR Model LX2M
LED phototherapy
LED cluster (69)

nm

mW

W/cm2

J/cm2

660
+
850

340
+
1050

0.05

Results: positive / unclear/modest / negative

Link

Additional info

Comment

Reply

Comment

Reply

sec

"The 10 trained nurses all reported that the device was accessible, maneuverable,
and lightweight, and that training was effective. There was no reported toxicity
attributed to the PBT."

PubMed

"Severe mucositis was found in 40% of the patients (14/35),

PubMed

Extraoral
Pediatric patients

Oral

Oral mucositis

Ferreira

Brazil
(Recife)

2016

Support Care
Cancer

Low-level laser therapy prevents severe oral mucositis in patients

submitted to hematopoietic stem cell transplantation: a
randomized clinical trial.

Human
RCT

Patients undergoing
HSCT

650

100

70

Oral

Oral mucositis

Bezinelli

Brazil
(So Paulo)

2016

Eur J Cancer
Care (Engl)

Quality of life related to oral mucositis of patients undergoing

haematopoietic stem cell transplantation and receiving specialised
oral care with low-level laser therapy: a prospective observational
study.

Human
Patients undergoing
Observationa HSCT
l

660

40

0.24
/p

Cost-effectiveness of low-level laser therapy (LLLT) in head and

neck cancer patients receiving concurrent chemoradiation.

Human
RCT

660

Oral

Oral mucositis

Antunes

Brazil
2016
(Rio de Janeiro)

Oral Oncol

Cost-effectiveness
calculation

0.028
cm2

20s
/p

5+

3 in the intervention group (17.65%) and

11 in the sham group (61.11%) (p = 0.015)."
1200
(?)

"A significant number of patients (46.38%) had grade 1 mucositis (indicating no

ulcers in the oral cavity)."

PubMed

"The study showed that QoL improves over time in these patients undergoing
LLLT therapy for prevention of mucositis."
100

"Our results indicate that morbidity was lower in the Laser Group and that LLLT
was more cost-effective than placebo up to a threshold of at least US$ 5000 per
mucositis case prevented."

PubMed

Jan Tuner has written: "PBM to prevent and reduce the incidence of oral mucositis
has been well documented for 15 years and still not being widely accepted. Now
that there is evidence of a cost saving method we might experience a renewed
interest, because Money Talks."
830

150

685 (I)
830
(E)

35

Patients undergoing
HSCT

660

40

Patients undergoing
HSCT

660

Oral

Oral mucositis

Amadori

Italy (Brescia)

2016

Lasers Med Sci

Low-level laser therapy for treatment of chemotherapy-induced

oral mucositis in childhood: a randomized double-blind controlled
study.

Human
RCT

Pediatric patients

Oral

Oral mucositis

Soto

Brazil
(So Paulo)

2015

Photomed Laser
Surg

Pilot study on the efficacy of combined intraoral and extraoral lowlevel laser therapy for prevention of oral mucositis in pediatric
patients undergoing hematopoietic stem cell transplantation.

Human
RCT

Intraoral + Extraoral

Photomed Laser
Surg

The Impact of Low-Level Laser Therapy on Oral Mucositis and

Quality of Life in Patients Undergoing Hematopoietic Stem Cell
Transplantation Using the Oral Health Impact Profile and the
Functional Assessment of Cancer Therapy-Bone Marrow
Transplantation Questionnaires.

Human
RCT

Lasers Med Sci

Effect of low-level laser therapy on inflammatory mediator release

during chemotherapy-induced oral mucositis: a randomized
preliminary study.

Human
RCT

Pediatric patients
undergoing HSCT

4.5

1
cm2

6.65
(19p)
14.4
(6p)

80

30s
/cm2

10s
/p
30s
/p

4
/wk

4s
/p

7+

"This study reported that there was no difference in the reduction of oral mucositis
between the two groups, but only in the pain amelioration. The slight contrast with
other studies [37] may be partially explained by the wavelengths used. In fact, we
chose a high wavelength (830 nm) in order to verify if, exploiting the spectra
absorption of cytochrome c oxidase, which is about 825 nm, and increasing the
cellular metabolism and the oral mucosa healing process [35, 36], this type of
wavelengths could be an alternative to 632660 nm laser lights."

PubMed

"Clinical mucositis scores were significantly lower in the LLLT group than in the
control group (p = 0.004). Incidence of ulcerative oral mucositis was also
significantly lower in the LLLT group (p = 0.027). Functional limitation associated
with diet/swallowing was less severe in the LLLT group; however, this was not
statistically significant."

PubMed

Star: Nice study setting. A well-written paper.

Oral

Oral

Oral mucositis

Oral mucositis

Silva

Silva

Brazil
(Gois)

2015

Brazil
(Gois)

2015

12.8
(80p)

0.04
cm2

"The laser group presented less severe OM than the control group (p<0.001)."

PubMed

"LLLT did not influence the oral and general health-related QoL of patients
undergoing HSCT, although it was clinically effective in reducing the severity of
chemotherapy-induced OM."
40

12.8
(80p)

0.04
cm2

4s
/p

7+

"The study showed that 72.8 % (8 of 11) of patients treated with laser therapy
were free of ulcers (grades 0 and 1); 27.2 % developed grade 2 mucositis, while
none showed grades 3 or 4 mucositis".

PubMed

"On the other hand, in the control group, 57.1 % (8 out of 14) developed grades 2
and 3 mucositis, and 42.9 % of patients did not develop ulcerative OM."
"its mechanism of action does not seem to be completely linked to the modulation
of pro- or anti-inflammatory cytokines, growth factors or matrix
metalloproteinases."

Oral

Oral mucositis

Oton-Leite

Brazil
(Gois)

2015

Lasers Surg Med

Effect of low-level laser therapy on chemoradiotherapy-induced

oral mucositis and salivary inflammatory mediators in head and
neck cancer patients.

Human
RCT

Patients receiving
chemoradiotherapy

660

25

633

0.024

14.4
(60p)

6.2

0.04
cm2

10
/p

35

1
cm2

125
/p

5
/wk

"LLLT decreased the severity of OM and oral pain in elderly HNC patients. Also,
lesser weight loss, morphine analgesic use and radiation break happened in laser
group."

PubMed

300
720

1
/d

"Specialized oral care, including LLLT, is feasible and affordable for HSCT
pediatric patients, although some adaptation in the patient's oral hygiene routine
must be adopted with help from parents/companions and clinical staff."

PubMed

LLLT increased NF-kB and reduced the severity of oral mucositis.

PubMed

Head&neck cancer

"The laser group showed a reduction in the severity of OM, which coursed with
significantly diminished salivary concentration of EGF and VEGF in the 7th
radiotherapy session and of IL-6 and FGF in the 35th. There was a trend for
reduced levels of IL-1, TNF-, IL-10, TGF-, MMP2/TIMP2, MMP9/TIMP2 in the
laser group compared to the control, however, no statistically significant
differences were found."

PubMed

"These findings demonstrated that LLLT was effective in reducing the severity of
chemoradiotherapy-induced OM and was associated with the reduction of
inflammation and repair."

Oral

Oral mucositis

Gautam

India
(Manipal)

2015

J Photochem
Photobiol B

Low level laser therapy against radiation induced oral mucositis in

elderly head and neck cancer patients-a randomized placebo
controlled trial.

Human
RCT

Elderly patients

Oral

Oral mucositis

Eduardo Fde

Brazil
(So Paulo)

2015

Pediatr Transplant Oral mucositis in pediatric patients undergoing hematopoietic

stem cell transplantation: clinical outcomes in a context of
specialized oral care using low-level laser therapy.

Human
Observationa
l

660

100

Oral

Oral mucositis

Curra

Brazil

2015

J Biomed Opt

Photobiomodulation reduces oral mucositis by modulating NF-kB.

Hamster

660

40

Oral

Oral mucositis

Bensadoun &
Nair

France
(Nice) &
Australia
(Queensland)

2015

Photomed Laser
Surg

Low-Level Laser Therapy in the Management of Mucositis and

Dermatitis Induced by Cancer Therapy.

Letter

Oral

Oral mucositis

Basso

Brazil
(Araraquara)

2015

Photochem
Photobiol

Biomodulation of Inflammatory Cytokines Related to Oral

Mucositis by Low-Level Laser Therapy.

In vitro

Oral

Oral mucositis

Freide Mdo

Brazil
(Salvador,
Bahia))

2014

Clin Oral Investig

LED and laser photobiomodulation in the prevention and treatment

of oral mucositis: experimental study in hamsters.

0.024

36
(12p)

Head&neck cancer
1.92
(8p)

PubMed

Gingival fibroblasts +
LPS
LED phototherapy
LED vs LLLT

780

25

0
0.5
1.5
3

2
cm2

40
120
240

660
(laser)

40

16

4.8

4
mm2

30

670
(LED)

150

4.8

0.5
cm2

16

"For LPS-treated groups, LLLT promoted significant decreases in the expression

of TNF-, IL-6, and IL-8 at 1.5 J cm(-2) and 3 J cm(-2)."

PubMed

"The best results were obtained from the preventive laser and LED
photobiomodulation groups; both treatments were effective in diminishing the OM
lesions."

PubMed

Comment: The laser parameters seem a little bit unlogical. If the radiation time is
30 seconds with the power output of 40mW, then total dose is 1.2J, not 16J.

Oral

Oral mucositis

Fekrazad &
Chiniforush

Iran
(Tehran)

2014

J Lasers Med Sci

Oral mucositis prevention and management by therapeutic laser in

head and neck cancers.

Systematic
review

"The results of most studies showed that photobiomodulation (PBM) reduced the severity of mucositis. Also, it can delay the appearance of severe
mucositis."

PubMed

Oral

Oral mucositis

Oberoi

Canada
(Toronto)

2014

PLoS One

Effect of prophylactic low level laser therapy on oral mucositis: a

systematic review and meta-analysis.

Metaanalysis

The meta-analysis:
- Eighteen RCTs (1144 patients) were included.
- Prophylactic LLLT reduced the overall risk of severe mucositis (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.20 to 0.67; P = 0.001).
- Prophylactic LLLT reduced severe mucositis and pain in patients with cancer and HSCT recipients.
- Future research should identify the optimal characteristics of LLLT and determine feasibility in the clinical setting.

PubMed

Oral

Oral mucositis

Ottaviani

Italy
(Trieste)

2013

Am J Pathol

Effect of class IV laser therapy on chemotherapy-induced oral

mucositis: a clinical and experimental study.

Human
Comparison
trial

"We show that high-power laser therapy is more effective than low-power laser
therapy in improving OM lesion healing, reducing the inflammatory burden, and
preserving tissue integrity."

PubMed

Tunr: "The authors claim to have been using a "standard low power laser
protocol" for comparison. In fact, they have not. The "standard" laser used is a 635
nm diode of 2.5 mW (standard laser pointer), delivering 0.45 J per point and
delivered from a distance of 1 - 3 cm, further reducing the power density and for
some reason pulsed."
Note: Jan Bjordal wrote a comment to this article. The authors have replied to the
comment.

Oral

Oral mucositis

Oton-Leite

Brazil
(Gois)

2013

Spec Care Dentist Effect of low level laser therapy in the reduction of oral
complications in patients with cancer of the head and neck
submitted to radiotherapy.

Human
RCT

Oral

Oral mucositis

Migliorati

USA
(Memphis, TN)

2013

Support Care
Cancer

Systematic review of laser and other light therapy for the

management of oral mucositis in cancer patients.

Systematic
review

Oral

Oral mucositis

Lopez

Brazil
(So Paulo)

2013

Braz Oral Res

Effect of laser phototherapy in the prevention and treatment of

chemo-induced mucositis in hamsters.

Hamster

Patients with
head/neck cancer

Chemo-induced
oral mucositis

685

"Better outcomes were observed in the laser group when compared with the
control in the follow-up sessions, indicating lower degrees of oral mucositis, pain
and higher salivary flow (p < .05)."

PubMed

"A new suggestion was made for low-level laser (wavelength around 632.8 nm) for the prevention of oral mucositis in patients undergoing radiotherapy,
without concomitant chemotherapy, for head and neck cancer. No guideline was possible in other populations and for other light sources due to
insufficient evidence."

PubMed

660

35

40

44
(55p)

1.11

2/30
(?)

39.6
(6p)

0.028
cm2

25
/p

0.036
cm2

1+5
=6

10

Oral mucositis

Gautam

India
(Manipal)

2013

Support Care
Cancer

Effect of low-level laser therapy on patient reported measures of

oral mucositis and quality of life in head and neck cancer patients
receiving chemoradiotherapy--a randomized controlled trial.

Human
RCT/DB

Oral

Oral mucositis

Figueiredo

Brazil
(Salvador, BA)

2013

Rev Assoc Med

Bras (1992)

Laser therapy in the control of oral mucositis: a meta-analysis.

Metaanalysis

Patients with
head/neck cancer
(chemoradiotherapy)

PubMed

"This study showed that positive effects on oral mucositis management were
obtained only when LPT was applied in the therapeutic protocol (from D+5 to
D+15 after chemotherapy)."

Prevention vs therapy

Oral

"The therapeutic group had significantly lower clinical and histological scores than
the other groups at Day 10."

633

0.024

36-40

1
cm2

1500
(?)

"LLLT was effective in improving the patient's subjective experience of OM and

QOL in HNC patients receiving CRT."

"Twelve (studies were included in this systematic review, and the meta-analysis of seven of them showed that LT in patients undergoing oncotherapy is
approximately nine times more effective in the prevention of OM grade > 3 than in patients without laser treatment (OR: 9,5281, confidence interval 95%
1,447-52,0354, p=0,0093."

PubMed

PubMed

"Further studies, with larger sample sizes, are needed for better evaluation of the prophylatic effect of OM grade > 3 by LT."

Oral

Oral mucositis

de Castro

Brazil
(Recife)

2013

Photomed Laser
Surg

Low-level laser in prevention and treatment of oral mucositis in

pediatric patients with acute lymphoblastic leukemia.

Human
(control
group)

Patients with
lymphoblastic
leukemia

660
or
830

100

1/2
/p

35
70

(18p)

0.028
cm2

10/
20
/p

1+

"Prophylactic laser produced a better outcome than when patients did not receive
any preventive intervention"

PubMed

"red laser (660 nm) was better than infrared (830 nm)"

A: prevention of OM
B: treatment of OM
Red vs NIR

Oral

Oral mucositis

Arbabi-Kalati

Iran
(Tehran)

2013

Acta Med Iran

Evaluation of the effect of low level laser on prevention of

chemotherapy-induced mucositis.

Human
RCT/DB

Chemo-induced
oral mucositis

630

30

5
(10p)

"The results showed that low-power laser was able to decrease the effect of
chemotherapy on oral mucositis, xerostomia and pain in a variety of malignancies"
Comment: Results are interesting, but the parameters are poorly reported.

PubMed

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Journal

Title

Study type Sub-category 2 /

animal model

Oral

Oral mucositis

Antunes

Brazil
2013
(Rio de Janeiro)

Radiother Oncol

Phase III trial of low-level laser therapy to prevent oral mucositis in

head and neck cancer patients treated with concurrent
chemoradiation.

Human
RCT/DB

Year

Patients with
head/neck cancer
(chemoradiotherapy)

nm

mW

W/cm2

J/cm2

660

100

Results: positive / unclear/modest / negative

5
/wk

"Preventive LLLT in HNSCC patients receiving chemoradiotherapy is an effective

tool for reducing the incidence of grade 3-4 OM. Efficacy data were corroborated
by improvements seen in quality of life."

Link

sec

0.24
cm2

720

PubMed

"At a median follow-up of 18 months (1048 months) differences favoring the LLLT
patients were observed in locoregional disease control, progression-free (P =
0.097) or overall survival (P = 0.147; Fig. 3 and 4 of the Supplementary Data)."
Star: The 18-month follow-up data was supplied.

Oral

Oral mucositis

Oton-Leite

Brazil
(Gois)

2012

Head Neck

Effect of intraoral low-level laser therapy on quality of life of

patients with head and neck cancer undergoing radiotherapy.

685

Human
RCT

35

6
?

"Laser therapy reduces the impact of radiotherapy on the QOL of patients with
head and neck cancer."

PubMed

Comment: The parameters were poorly reported.

Human
RCT & DB?

LED phototherapy

670

Patients with
head/neck cancer
(chemoradiotherapy)

660

0.05

Oral

Oral mucositis

Hodgson

USA
2012
(Milwaukee, WI)

Support Care
Cancer

Amelioration of oral mucositis pain by NASA near-infrared lightemitting diodes in bone marrow transplant patients.

Oral

Oral mucositis

Gouva de Lima

Brazil
(So Paulo)

2012

Int J Radiat Oncol

Biol Phys

Oral mucositis prevention by low-level laser therapy in head-andHuman

neck cancer patients undergoing concurrent chemoradiotherapy: a RCT/DB
phase III randomized study.

Oral

Oral mucositis

Gautam

India
(Manipal)

2012

Radiother Oncol

Low level laser therapy for concurrent chemoradiotherapy induced

oral mucositis in head and neck cancer patients - a triple blinded
randomized controlled trial.

Human
RCT/DB

Oral

Oral mucositis

Bensadoun &
Nair

France
(Nice) &
Australia
(Queensland)

2012

Photomed Laser
Surg

Efficacy of low-level laser therapy (LLLT) in oral mucositis: what

have we learned from randomized studies and meta-analyses?

Letter

Oral

Oral mucositis

Bensadoun &
Nair

France
(Nice) &
Australia
(Queensland)

2012

Curr Opin Oncol

Low-level laser therapy in the prevention and treatment of cancer

Review
therapy-induced mucositis: 2012 state of the art based on literature Metareview and meta-analysis.
analysis

Oral

Oral mucositis

Silva

Brazil
(Gois)

2011

Photomed Laser
Surg

The prevention of induced oral mucositis with low-level laser

therapy in bone marrow transplantation patients: a randomized
clinical trial.

Human
RCT

HSCT patients

660

40

Oral

Oral mucositis

Cauwels &
Martens

Belgium
(Ghent)

2011

Eur Arch Paediatr

Dent

Low level laser therapy in oral mucositis: a pilot study.

Human
Pilot study

Pediatric patients

830

150

Oral

Oral mucositis

Carvalho

Brazil
(So Paulo)

2011

Oral Oncol

Evaluation of low-level laser therapy in the prevention and

treatment of radiation-induced mucositis: a double-blind
randomized study in head and neck cancer patients.

Human
RCT/DB

Dose response

660

15
5

Oral

Oral mucositis

Bjordal

Norway
(Bergen)

2011

Support Care
Cancer

A systematic review with meta-analysis of the effect of low-level

laser therapy (LLLT) in cancer therapy-induced oral mucositis.

Metaanalysis

Oral

Oral mucositis

Ramalho

Brazil
(So Paulo)

2011

Int Wound J

Use of laser phototherapy on a delayed wound healing of oral

mucosa previously submitted to radiotherapy: case report.

Human
Case report

660

40

Oral

Oral mucositis

Lino

Brazil
(Salvador,
Bahia)

2011

Braz Dent J

Laser phototherapy as a treatment for radiotherapy-induced oral

mucositis.

Human
Case report

660
+
780

40

Oral

Oral mucositis

Zanin

Brazil
(So Paulo)

2010

Photomed Laser
Surg

Use of 660-nm diode laser in the prevention and treatment of

human oral mucositis induced by radiotherapy and chemotherapy.

Human

660

30

10

633

2.5

0.024

36-40

80

4
mm2

1
cm2

14

"Phototherapy demonstrated a significant reduction in patient-reported pain as

measured by the WHO criteria in this patient population included in this study.
Improvement trends were noted in most other assessment measurements."

PubMed

5
/wk

"LLL therapy was not effective in reducing severe oral mucositis, although a
marginal benefit could not be excluded. It reduced RT interruptions in these headand-neck cancer patients, which might translate into improved CRT efficacy."

PubMed

"LLLT decreased the incidence of CCRT induced severe OM and its associated
pain, dysphagia and opioid analgesics use."

PubMed

1500
(?)

PubMed

"There is moderate-to-strong evidence in favor of LLLT at optimal doses as a well tolerated, relatively inexpensive intervention for
cancer therapy-induced oral mucositis. It is envisaged that LLLT will soon become part of routine oral supportive care in cancer."

12.8

3.8
1.3

0.04
cm2

320

4
mm2

35
100

830

15

660

50

Human
Dose comparison
Observationa No control group
l

660

40

808

1000

660

35
100

Lopes

Brazil
(So Paulo)

2010

Lasers Surg Med

Effects of low-level laser therapy on collagen expression and

neutrophil infiltrate in 5-fluorouracil-induced oral mucositis in
hamsters.

Hamster

Oral

Oral mucositis

Lima

Brazil
(So Paulo)

2010

Braz Dent J

Efficacy of low-level laser therapy and aluminum hydroxide in

patients with chemotherapy and radiotherapy-induced oral
mucositis.

Human
(not RCT)

Oral

Oral mucositis

Chor

Brazil
2010
(Rio de Janeiro)

Eur J Haematol

Low-power laser to prevent oral mucositis in autologous

hematopoietic stem cell transplantation.

Letter

Laser phototherapy as topical prophylaxis against head and neck

cancer radiotherapy-induced oral mucositis: comparison between
low and high/low power lasers.

PubMed

"Low-level laser therapy during radiotherapy was found to be effective in

controlling the intensity of mucositis and pain."

PubMed

LLLT vs aluminum
hydroxide

PubMed

10

"The wound healed completely after ten sessions. This treatment proved to be
conservative and effective, inducing healing of a chronic wound in a tissue
previously submitted to radiotherapy.2

PubMed

4
mm2

12

"Treatment results indicate that the use of LPT on oral mucositis was effective and
allowed the patient to carry on the RT without interruption.

PubMed

"Patients in group L usually did not present with OM or pain, but all patients in
group C presented with OM ranging from Level I to III associated with pain."

PubMed

70

660

Oral mucositis

PubMed

"Immediately after beaming the OM, pain relief was noticed. Depending on the
severity of OM, on average, 2.5 treatments per lesion in a period of 1 week were
sufficient to heal a mucositis lesion."

0.04
cm2
spot

2
/p

d=
2 mm

(?)

Oral

"In the LLLT group, 57.1% of patients had an OM grade 0, 9.6% had grade 1, and
33.3% had grade 2, whereas in the control group, only 4.8% of patients were free
of OM (grade 0)."

The meta-analysis:
- We found 11 randomised placebo-controlled trials with a total of 415 patients; methodological quality was acceptable at 4.10 (SD 0.74)
on the 5-point Jadad scale.
- There is consistent evidence from small high-quality studies that red and infrared LLLT can partly prevent development of
cancer therapy-induced OM.
- LLLT also significantly reduced pain, severity and duration of symptoms in patients with cancer therapy-induced OM."
2.4

PubMed

Comment: Cool results, but parameters aren't very well reported.

12

"This study supports two mechanisms of action for LLLT in reducing mucositis
severity. The increase in collagen organization in response to the 35 mW laser
indicates that LLLT promotes wound healing. In addition, LLLT also appears to
have an anti-inflammatory effect, as evidenced by the reduction in neutrophil
infiltrate."

PubMed

"The prophylactic use of both treatments proposed in this study seems to reduce
the incidence of severe OM lesions. However, the LLLT was more effective in
delaying the appearance of severe OM."

PubMed

"The cumulative probability to develop oral mucositis was 47% in the laser group
and 69% in the placebo group (P = 0.27)."

PubMed

Comment: Parameters were poorly reported. Control group received LED light...

Oral

Simes

Brazil
(So Paulo)

2009

Lasers Surg Med

0.24
/p

0.036
cm2

1-3
/wk

"All protocols of LPT led to the maintenance of oral mucositis scores in the same
levels until the last RT session. Moreover, LPT three times a week also
maintained the pain levels. However, the patients submitted to the once a week
LPT had significant pain increase; and the association of low/high LPT led to
increased healing time."

PubMed

"Peak severity of mucositis was reduced in the 35 mW laser group as compared to

the 100 mW laser and control groups. This reduced peak clinical severity of
mucositis in the 35 mW laser group was accompanied by a significantly lower level
of COX-2 staining. The 100 mW laser did not have an effect on the severity of
clinical mucositis, but was associated with a decrease in VEGF levels at the later
time-points, as compared to the other groups."

PubMed

"In the laser group, the mean of OM duration was 5.82 days and in the placebo
group was 8.92.4 days (P=0.004)."

PubMed

"In conclusion, laser reduced the frequency and severity of OM, suggesting that
therapeutic laser can be used both as a new form of prevention and treatment of
OM."

PubMed

(73p?)
2.62
2.78

d=
0.6
mm

80
30

Oral

Oral mucositis

Lopes

Brazil
(So Paulo)

2009

Support Care
Cancer

Cyclooxygenase-2 and vascular endothelial growth factor

expression in 5-fluorouracil-induced oral mucositis in hamsters:
evaluation of two low-intensity laser protocols.

Hamster

Oral

Oral mucositis

Kuhn

Brazil (Porto
Alegre)

2009

J Pediatr Hematol
Oncol

Low-level infrared laser therapy in chemotherapy-induced oral

mucositis: a randomized placebo-controlled trial in children.

Human
RCT

830

100

Oral

Oral mucositis

Khouri

Brazil
(Ribeiro Preto,
SP)

2009

Braz Dent J

Use of therapeutic laser for prevention and treatment of oral

mucositis.

Human

660
&
780
on
alt.
days

25

6.3

Oral

Oral mucositis

Frana

Brazil
(So Paulo)

2009

J Photochem
Photobiol B

Low-intensity red laser on the prevention and treatment of

induced-oral mucositis in hamsters.

Hamster

660

30

1.2

3
mm2

5
(?)

"The results suggest that laser phototherapy had a positive effect in reducing
mucositis severity, and a more pronounced effect in treating established
mucositis."

PubMed

Oral

Oral mucositis

Eduardo

Brazil
(So Paulo)

2009

Photomed Laser
Surg

Severity of oral mucositis in patients undergoing hematopoietic

cell transplantation and an oral laser phototherapy protocol: a
survey of 30 patients.

Human
Observationa
l/
Case series

660

40

4 or 6

0.036
cm2

1227

"The low grades of OM observed in this survey show the beneficial effects of laser
phototherapy, but randomized clinical trials are necessary to confirm these
findings."

PubMed

40

0.04
cm2

17

"Normal oral function and consequent improvements in the quality of life of this
oncologic patient were observed with LPT."

PubMed

3
/wk

"Our results strongly support the already available literature, suggesting that LEL
is an effective and safe approach to prevent or treat oral mucositis resulting from
cancer chemotherapy."

PubMed

Oral

Oral mucositis

Campos

Oral

Oral mucositis

Genot-Klastersky Belgium
(Brussels)

Oral

Oral mucositis

Oral mucositis

Arora

Brazil
(So Paulo)

India
(Manipal)

Pediatric patients
undergoing
chemo/HSCT

2009

Photomed Laser
Surg

Improvement in quality of life of an oncological patient by laser

phototherapy.

Human
Case report

660

1000

10

2008

Support Care
Cancer

The use of low-energy laser (LEL) for the prevention of

chemotherapy- and/or radiotherapy-induced oral mucositis in
cancer patients: results from two prospective studies.

Human
RCT

red?

50
250
500

IR

100

Human

633

10

1.8

50

2008

Oral Surg Oral

Efficacy of He-Ne Laser in the prevention and treatment of
Med Oral Pathol
radiotherapy-induced oral mucositis in oral cancer patients.
Oral Radiol Endod

Oral

Oral mucositis

Antunes

Brazil
2008
(Rio de Janeiro)

Med Oral Patol

Oral Cir Bucal

The Impact of low power laser in the treatment of conditioninginduced oral mucositis: a report of 11 clinical cases and their
review.

Case series

660

Oral

Oral mucositis

Abramoff

Brazil
(So Paulo)

2008

Photomed Laser
Surg

Low-level laser therapy in the prevention and treatment of

chemotherapy-induced oral mucositis in young patients.

Human
RCT

685

35

Oral

Oral mucositis

Schubert

USA
(Seattle, WA)

2007

Support Care
Cancer

A phase III randomized double-blind placebo-controlled clinical

trial to determine the efficacy of low level laser therapy for the
prevention of oral mucositis in patients undergoing hematopoietic
cell transplantation.

Human
RCT/DB

650
780

40
60

Low-energy laser therapy for prevention of oral mucositis in

hematopoietic stem cell transplantation.

Human
Observationa
l

Oral

Oral mucositis

Jaguar

Brazil
(So Paulo)

2007

Oral Dis

d=
1.2
mm

40

300

Comment: Wavelength was not reported.

36
(18p)

1800

0.196
cm2

d=
0.6
mm
(?)
2

33

"Laser therapy applied prophylactically during radiotherapy can reduce the

severity of oral mucositis, severity of pain, and functional impairment."

PubMed

312

"Our results have indicated that the use of LPLT in HSCT patients is a powerful
instrument in the treatment of overt OM and is now a standard procedure in this
group of patients in our hospital."

PubMed

"The ease of use of LLLT, high patient acceptance, and the positive results
achieved, make this therapy feasible for the prevention and treatment of OM in
young patients."

PubMed

"The 650 nm wavelength reduced the severity of oral mucositis and pain scores.
Low level laser therapy was well-tolerated and no adverse events were noted."

PubMed

972

713

Comment 1: On the other hand, the 780 nm wavelength appeared to make things
even worse...
Comment 2: The Discussion part seems lengthy. Maybe worth reading.
660

10

2.5

"All patients developed some grade of mucositis. However, the L- group presented
initial mucositis by 4.36 days, whereas the L+ group presented it in 6.12 days (P =
0.01).

PubMed

The maximum mucositis occurred between day +2 and day +6 with healing by day
+25 in the L- group and between day +2 and day +7 with healing by day +14 for
the L+ group (P = 0.84).
Laser therapy also reduced the time of oral pain from 5.64 to 2.45 days (P = 0.04),
and decreased the consumption of morphine (P = 0.07)."
Comment: The parameters were poorly reported.

Oral

Oral mucositis

Cruz

Brazil
(Porto Alegre)

2007

Pediatr Blood
Cancer

Influence of low-energy laser in the prevention of oral mucositis in

children with cancer receiving chemotherapy.

Human
RCT

780

60

"This study showed no evidence of benefit from the prophylactic use of low-energy
laser in children and adolescents with cancer treated with chemotherapy when
optimal dental and oral care was provided."
Comment: The parameters were poorly reported.

PubMed

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Journal

Title

Study type Sub-category 2 /

animal model

Oral

Oral mucositis

Antunes

Brazil
2007
(Rio de Janeiro)

Blood

Low-power laser in the prevention of induced oral mucositis in

bone marrow transplantation patients: a randomized trial.

Human
RCT

Oral

Oral mucositis

Migliorati

USA
2006
(Fort
Lauderdale, FL)

Support Care
Cancer

The role of alternative and natural agents, cryotherapy, and/or laser Review
for management of alimentary mucositis.

Oral

Oral mucositis

Arun Maiya

India
(Manipal)

2006

Indian J Med Res

Effect of low level helium-neon (He-Ne) laser therapy in the

prevention & treatment of radiation induced mucositis in head &
neck cancer patients.

Human
RCT

633

10

1.8

Oral

Oral mucositis

Nes & Posso

Norway
(Drammen)

2005

Int Nurs Rev

Patients with moderate chemotherapy-induced mucositis: pain

therapy using low intensity lasers.

Human

830

250

35

Oral

Oral mucositis

Genot &
Klastersky

Belgium
(Brussels)

2005

Curr Opin Oncol

Low-level laser for prevention and therapy of oral mucositis

induced by chemotherapy or radiotherapy.

Review

Oral

Oral mucositis

Wong & WilderSmith

USA
(Pomona, CA)

2002

Cancer J

Pilot study of laser effects on oral mucositis in patients receiving

chemotherapy.

Human
Pilot study

Category

Year

nm

mW

W/cm2

J/cm2

660

50

Results: positive / unclear/modest / negative

7
(?)

"5.3% of the laser group presented with ulcers of 9.1 cm2 to 18 cm2, whereas
73.6% of the control group presented with ulcers from 9.1 cm2 to 18 cm2 (P = .
003).

Link

Additional info

Comment

sec

0.196
cm2

250

PubMed

Our results indicate that the use of upfront LPLT in patients who have undergone
HSCT is a powerful instrument in reducing the incidence of OM and is now
standard in our center."
"Therefore, although laser therapy seems to be promising in the prevention of oral mucositis and in the control of mucositis-associated pain, the clinical
studies tested small patient populations, the protocols were not standardized, laser devices used were different, laser parameters varied, and mucositis
assessment tools were not uniform, making it almost impossible to implement the existing guidelines. The mechanism of action of laser therapy in the
pathobiology of mucositis remains unknown."

d=
0.6
mm

PubMed

"The low-level He-Ne laser therapy during the radiotherapy treatment was found to
be effective in preventing and treating the mucositis in head and neck cancer
patients."

PubMed

"There was a significant (P = 0.007) 67% decrease in the daily average

experience of pain felt before and after each treatment, confirming that LLLT can
relieve pain among patients who have developed COM."

PubMed

PubMed
"The direct cost by laser therapy is connected to the laser equipment and personnel cost to perform the treatment. The laser used in this study was a Thera Lase with a purchasing
cost in 2002 of US$2500. Each patient requires 30 min of laser treatment by a qualified professional. The cost savings by laser therapy are related to the fact that the COM patients
are able to continue their chemotherapy treatment without interruptions, and a reduction in the use of traditional analgesics."

[See additional info, for information about the device.]

"On the basis of literature data, it is reasonable to conclude that the evidence that low-level laser therapy may be useful in decreasing the severity of
chemotherapy-associated or radiotherapy-associated mucositis is substantial, even though there have been few controlled studies in the field of
prevention."
"Eleven of 15 patients experienced grade 0 mucositis, three patients experienced
grade 1 to 2 mucositis, and one patient experienced grade 3 to 4 mucositis."

PubMed
PubMed

"In this pilot study, laser therapy significantly reduced the incidence and the
severity of mucositis in chemotherapy patients. The laser therapy does not appear
to promote wound healing by affecting the intraoral perfusion, as assessed by
Doppler measurements."

Oral

Oral mucositis

Whelan

USA
2002
(Milwaukee, WI)

J Clin Laser Med

Surg

NASA light-emitting diodes for the prevention of oral mucositis in

pediatric bone marrow transplant patients.

Human

LED phototherapy

670

Oral

Oral mucositis

Whelan

USA
2001
(Milwaukee, WI)

J Clin Laser Med

Surg

Effect of NASA light-emitting diode irradiation on wound healing.

Human

LED phototherapy

670

Oral

Oral mucositis

Bensadoun

France
(Nice)

Support Care
Cancer

Low-energy He/Ne laser in the prevention of radiation-induced

mucositis. A multicenter phase III randomized study in patients
with head and neck cancer.

Human
RCT/DB

"The incidence of UOM was 53%, compared to an expected rate of 70-90%. There
was also a 48% and 39% reduction of treated left and right buccal pain,
respectively, compared to untreated throat pain at about posttransplant day 7 (p <
0.05). There were no significant differences between sides in OMI or pain."

PubMed

"Although more studies are needed, LED therapy appears useful in the prevention
of OM in pediatric BMT patients."

1999

633

60
25

d=
1.2mm
(spot)

"LED produced a 47% reduction in pain of children suffering from oral mucositis."

PubMed

300

35

"Grade 3 mucositis occured with a frequency of 35.2% without LEL and of 7.6%
with LEL (P<0.01). The frequency of "severe pain" (grade 3) was 23.8% without
LEL, falling to 1.9% with LEL (P<0.05). Pain relief was significantly reduced
throughout the treatment period (weeks 2-7). LEL therapy is capable of reducing
the severity and duration of oral mucositis associated with radiation therapy. In
addition, there is a tremendous potential for using LEL in combined treatment
protocols utilizing concomitant chemotherapy and radiotherapy."

PubMed

750

"Helium-Neon laser treatment was well tolerated, feasible in all cases, and
reduced high dose chemoradiotherapy-induced oral mucositis. Optimal laser
treatment schedules still needs to be defined."

PubMed

300+
(?)

"Helium-neon laser treatment was well-tolerated and reduced the severity of

conditioning-induced oral mucositis in BMT patients."

PubMed

"The prevalence of Complete Wound Epithelization was higher in the LLLT group
than in the control group on the 14th day (p < 0.001). The bleeding was lower in
the test group than in the control group during the first 2 days (p 0.001).

PubMed

1
cm2
(treat.
area)

Oral

Oral mucositis

Cowen

France
(Marseilles)

1997

Int J Radiat Oncol

Biol Phys

Low energy Helium-Neon laser in the prevention of oral mucositis

Human
in patients undergoing bone marrow transplant: results of a double RCT/DB
blind randomized trial.

633

60

Oral

Oral mucositis

Barasch

USA
(Farmington)

1995

Cancer

Helium-neon laser effects on conditioning-induced oral mucositis

in bone marrow transplantation patients.

633

25

Oral

Oral mucositis

Ciais

France
(Nice)

1992

Bull Cancer

[Laser therapy in the prevention and treatment of mucositis caused

by anticancer chemotherapy].
[Article in French]

Oral

Oral surgery

Ustaoglu

Turkey
(Trabzon)

2017
epub

Photomed Laser
Surg

Low-Level Laser Therapy in Enhancing Wound Healing and

Preserving Tissue Thickness at Free Gingival Graft Donor Sites: A
Randomized, Controlled Clinical Study.

Human

54

~1.5

1.0

0.8
cm2

Human
RCT

Higher WHI Scores were observed in the test group relative to the control group at
all visits (p 0.001). Color match scores were higher in the test group than in the
control group at the first 3 visits (p < 0.05).
The TT changed from 4.62 0.79 to 4.71 0.82 mm in the LLLT group and from
4.23 0.62 to 4.01 0.68 mm in the control group."
"It can be concluded that LLLT enhances FGG donor site wound healing and
preserves TT at palatinal donor sites."

Oral surgery

Sanz-Moliner

Spain

2013

J Periodontol

The effect of an 810-nm diode laser on postoperative pain and

tissue response after modified Widman flap surgery: a pilot study
in humans.

Human
Pilot study

Oral

Orofacial pain

Amanat

Iran
(Shiraz)

2013

Photomed Laser
Surg

The adjunct therapeutic effect of lasers with medication in the

management of orofacial pain: double blind randomized controlled
trial.

Human
RCT/DB

980

Oral

Orofacial pain

Hansen &
Thore

Denmark
(Copenhagen)

1990

Pain

Low power laser biostimulation of chronic oro-facial pain. A

double-blind placebo controlled cross-over study in 40 patients.

Human
Crossover/D
B

904

Oral

Orthodontics

Meng

China
(Chengdu)

2017

Photomed Laser
Surg

Effect of Low-Level Laser Therapy on Relapse of Rotated Teeth: A

Systematic Review of Human and Animal Study.

Systematic
review

Widman flap

810

Oral

12

12.73

300

10

LLLT seemed to decrease pain and edema.

PubMed

"We found no significant level of efficacy for the GaAs laser in the management of
common orofacial pain. Further studies are suggested to evaluate the efficacy of
other types of lasers with different parameters in the management of orofacial
pains."

PubMed

"No statistically significant difference between the analgesic effect of the laser and
placebo irradiation was found on VAS-scales."

PubMed

Jan Tuner: "It is interesting to note that the authors themselves state the origin of
"burning mouth" as multifactor, psychosomatic or psychogenic. Thus, there would
be no actual injury to the tissue, and laser, like any other modality, would have no
effect. The negative 5-HIAA measurement in the laser group may indeed confirm
the inappropriate inclusion parameters and laser energies in this study."
"Out of 112 studies, two animal experiments and one human study were included."

PubMed

"According to the results of our systematic review, the effect of LLLT on relapse of corrected tooth rotations is related to energy density. Namely, low
energy density seems to promote relapse, while high energy density might alleviate the relapse."
"Since available investigations are limited, more well-designed randomized controlled trials involving humans are needed to get more clinically significant
conclusions."

Oral

Orthodontics

Almallah

Syria
(Damascus)

2016

J Clin Diagn Res

Evaluation of Low Level Laser Therapy on Pain Perception

Following Orthodontic Elastomeric Separation: A Randomized
Controlled Trial.

Human
RCT

Pain

830

100

Oral

Orthodontics

Gonalves

Brazil
(So Paulo)

2016

Lasers Med Sci

Experimental tooth movement and photobiomodulation on bone

remodeling in rats.

Rat

Tooth movement

780

40

10

Oral

Orthodontics

Lee

Korea
(Seoul)

2016

Angle Orthod

Combined effect of photobiomodulation with a matrix

metalloproteinase inhibitor on the rate of relapse in rats.

Rat

Oral

Orthodontics

Yanaguizawa

Brazil
(Campinas)

2016
epub

Photomed Laser
Surg

Effects of Low-Level Laser Therapy in Orthodontic Patients on

Immediate Inflammatory Response After Mini-Implants Insertion: A
Preliminary Report.

Human

Low-level laser therapy effectiveness in accelerating orthodontic

tooth movement: A randomized controlled clinical trial.

Human
RCT

10

"LLLT was successful in reducing post-separation pain when the experimental

side was compared to the placebo side at all assessment times in each group
(p<0.05). There were no statistically significant differences between single and
double irradiation groups in terms of pain reduction (p>0.05)."

PubMed

"PBM applied in one or three sessions increased the population of osteoblasts.

Still, the application of three sessions of PBM increased the density of collagen
fibers and new bone formation compared to the controls. An increase was
observed in the interincisal distance in irradiated groups with three PBM sessions
and the application of force for both 7 or 14 days."

PubMed

"These findings suggest that PBM can contribute positively to the orthodontic
movement."

Oral

Orthodontics

AlSayed Hasan

Syria
(Damascus)

2016
epub

Angle Orthod

780

20

Inflammatory
response

"In the present study, the combined effect of LLLT with doxycycline on both
relapse rate and MMP expression in the PDL was proved to be antagonistic,
although the stimulatory effect of LLLT and inhibitory effect of doxycycline were
separately verified."

PubMed

"PGF around nonirradiated mini-implants showed higher levels of IL-8. Levels of

IL-6 24 h after mini-implant insertion were higher for laser group."

PubMed

"LLLT modulates the initial inflammation after the insertion of mini-implant,

possibly increasing the mini-implant success prognostic and decreasing patient
discomfort."

Tooth movement

830

2
/point

"A statistically significant difference was found between the two groups in the
overall treatment time (P < .001) and the leveling and alignment improvement
percentage at T1 (P = .004) and T2; (P = .001)."

PubMed

"Although the mean rate of canine retraction was higher in the LG (0.013) than the
CG (0.012) and there was definitely a tendency for more canine retraction in the
LLLI, but the results failed to show any significant difference between the mean
rate of canine retraction of both groups (P = 0.068)."

PubMed

8
/tooth

Oral

Orthodontics

Yassaei

Iran
(Yazd &
Mashdad)

2016

Lasers Med Sci

Effects of diode laser (980 nm) on orthodontic tooth movement and Human
interleukin 6 levels in gingival crevicular fluid in female subjects.
RCT/DB
split-mouth

Tooth movement

980

Oral

Orthodontics

Shaughnessy, et
al.

USA&Canada

2016

BMC Oral Health

Intraoral photobiomodulation-induced orthodontic tooth alignment: Human

a preliminary study.
RCT
Pilot study

Tooth alignment

850

Tooth movement

850

100

5.6

56
/tooth
(?)

"A paired t test showed that there was no significant difference in the mean
concentration of IL-6 at various stages of the treatment between the groups during
canine distalization (P > 0.05)."

Oral

Oral

Orthodontics

Orthodontics

Nahas

Ekizer

United Arab
Emirates
(Dubai)

2016

Turkey
(Kayseri)

2016

Lasers Med Sci

Decrowding of lower anterior segment with and without

photobiomodulation: a single center, randomized clinical trial.

Human
RCT

0.090

108

Alignment rate was significantly higher in LLLT group (1.27mm/week versus 0.44
mm/week)

PubMed

1200

~70

"The time between T1 and T2 was significantly reduced by 22 % in the test group
compared to the control group (68.3 vs. 87.8 days, respectively, p < 0.043). The
use of photobiomodulation for 20 min daily at a wavelength of 850 nm might
reduce the time required to resolve lower anterior crowding. This trial and its
protocol were not registered on a publicly accessible registry."

PubMed

1200

21

"Miniscrew stability was similar between control and LPT groups at baseline (T0)
and the 1st month (T1). However, miniscrew stability was significantly increased in
the LPT group in 2nd (T2) and 3rd (T3) months.

PubMed

Extraoral LLLT
Lasers Surg Med

Light emitting diode mediated photobiomodulation therapy

improves orthodontic tooth movement and miniscrew stability: A
randomized controlled clinical trial.

Human
RCT/DB
split-mouth

Tooth movement
Miniscrew stability

618

0.02

Comparison of tooth movement during three different time intervals (T1-T0, T2-T1,
and T3-T2) revealed that statistically significantly increased in every time intervals
after LPT.
No statistically significant change was detected in the IL-1 levels between
groups."
Comment: Parameters were poorly reported.

PubMed

Reply

More info:

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Subcategory

First author

Country

Year

Journal

Title

nm

mW

W/cm2

J/cm2

Oral

Orthodontics

Marini

Italy

2015

Lasers Med Sci

The effect of diode superpulsed low-level laser therapy on

Human
experimental orthodontic pain caused by elastomeric separators: a RCT
randomized controlled clinical trial.

Pain

910

160

Oral

Orthodontics

Ekizer

Turkey
(Kayseri)

2015

Lasers Med Sci

Effect of LED-mediated-photobiomodulation therapy on

orthodontic tooth movement and root resorption in rats.

Rat

Root resorption

618

0.02

Oral

Orthodontics

Domnguez

Spain

2015

Lasers Med Sci

Effects of low-level laser therapy on orthodontics: rate of tooth

movement, pain, and release of RANKL and OPG in GCF.

Human
Volunteers
Controlled

Tooth movement
Pain

670

200

Oral

Orthodontics

Long

China
(Sichuan)

2015

Lasers Med Sci

The effectiveness of low-level laser therapy in accelerating

orthodontic tooth movement: a meta-analysis.

Metaanalysis

Tooth movement

China
(Chengdu)

2015

Efficacy of low-level laser therapy for accelerating tooth movement

during orthodontic treatment: a systematic review and metaanalysis.

Metaanalysis

Tooth movement

Category

Oral

Orthodontics

Ge

Lasers Med Sci

Study type Sub-category 2 /

animal model

Results: positive / unclear/modest / negative

Link

Additional info

Comment

Reply

Editorial
Comment

Another
comment
(Letter to
the Editor)

Comment

Reply

sec

1200

10
(?)

A single LLLT treatment was effective in reducing pain.

PubMed

"The magnitude of movement in the treatment group was higher (1.55 0.33 mm)
compared to the control group (1.06 0.35 mm). Histomorphometric analysis of
root resorption, expressed as a percentage, showed that the average relative root
resorption affecting the maxillary molars on the TM side was 0.098 0.066 in the
LPT group and 0.494 0.224 in the control group."

PubMed

LLLT seemed to have some beneficial effects, but most of the positive effects
weren't statistically significant.

PubMed

"Finally, five studies were included in this meta-analysis."

PubMed

"Weak evidence suggests that low-level laser irradiations at the wavelength of 780 nm, at the fluence of 5 J/cm(2) and/or the output power of 20 mW
could accelerate orthodontic tooth movement within 2 months and 3 months. However, we cannot determine its effectiveness within 1 month due to
potential measurement errors."

Biphasic dose
response

"All nine articles were feasible for the systematic review and meta-analysis, five of which were assessed as moderate risk of bias, while the rest were
assessed as high risk of bias."

PubMed

"he results showed that the LLLT could accelerate orthodontic tooth movement (OTM) in 7 days (mean difference 0.19, 95 % CI [0.02, 0.37], p = 0.03)
and 2 months (mean difference 1.08, 95 % CI [0.16, 2.01], p = 0.02). Moreover, a relatively lower energy density (5 and 8 J/cm(2)) was seemingly more
effective than 20 and 25 J/cm(2) and even higher ones."

Oral

Orthodontics

Li

China
(Wuhan)

2015

Lasers Med Sci

Low-level laser therapy for orthodontic pain: a systematic review.

Metaanalysis

Pain

"However, for the reason of downgrade factors, all the GRADE level of evidences of eight comparisons for three outcomes showed a very low quality.
Therefore, for the methodological shortcomings and risk of bias of RCTs included, insufficient evidence was submitted to judge whether LLLT was
effective in relieving orthodontic pain. Further and more perfect researches should be done in order to recommend LLLT as a routine method for
orthodontic pain."

PubMed

Oral

Orthodontics

Shi

China
(Beijing)

2015

Head Face Med

Does low level laser therapy relieve the pain caused by the
placement of the orthodontic separators?--A meta-analysis.

Metaanalysis

Pain

"Comparing to the placebo group, the LLLT has good analgesic effect at 6 h, 1d, 2d, 3d after placement of separators which is of statistical significance.
While at 2 h, 4d, 5d after the placement, the results tend to support LLLT, but not statistically significant."

PubMed

"Based on current included studies, LLLT can reduce the pain caused by the placement of separators effectively. However, because of the high
heterogeneity, well designed RCTs are required in the future."

Oral

Orthodontics

Nimeri

USA
(Birmingham,
AL)

2014

Clin Cosmet
Investig Dent

The effect of photobiomodulation on root resorption during

orthodontic treatment.

Human

Oral

Orthodontics

Gkantidis

Switzerland
(Bern)

2014

J Dent

Effectiveness of non-conventional methods for accelerated

orthodontic tooth movement: a systematic review and metaanalysis.

Metaanalysis

Tooth movement in orthodontic treatment with low-level laser

therapy: a systematic review of human and animal studies.

Systematic
review

Oral

Orthodontics

Carvalho-Lobato

Spain

2014

Photomed Laser
Surg

850

Tooth movement

0.06

"Our results showed that photobiomodulation did not cause root resorption greater
than the normal range that is commonly detected in orthodontic treatments."

"Higher canine retraction rate was evident with (...) low-intensity laser (WMD=0.42mm/month; 95% CI: 0.26, 0.57, p<0.001) in a period longer than 3
months. The quality of evidence supporting the interventions is moderate for laser therapy (...)."

PubMed

PubMed

"From the qualitative and quantitative synthesis of the studies, it could be concluded that there is some evidence that low laser therapy and corticotomy
are associated with accelerated orthodontic tooth movement, while further investigation is required before routine application."

Tooth movement

The systematic review:

- 11 rat studies
- 5 human studies
- results seemed promising

PubMed

[Also read the Editorial Comment by Carroll JD, mentioning that this review omitted many significant studies.]

Oral

Orthodontics

Torri & Weber

Brazil
(Porto Alegre)

2013

Photomed Laser
Surg

Influence of low-level laser therapy on the rate of orthodontic

movement: a literature review.

Review

Oral

Orthodontics

He

China
(Chengdu)

2013

Lasers Med Sci

Efficacy of low-level laser therapy in the management of

orthodontic pain: a systematic review and meta-analysis.

Metaanalysis

Tooth movement

"Most authors report positive effects of the use of LLLT on speed increase of orthodontic tooth movement when compared with control or placebo
groups. Diode laser, especially gallium aluminum arsenide, used continuously and in direct contact with the irradiated areas, was the most frequent
protocol. Further studies are warranted to determine the best protocols with regard to energy, dose, and intervention schedule."

PubMed

"As a result, four RCTs, two quasi-RCTs, and two CCTs were selected from 152 relevant studies, including 641 patients from six countries.

PubMed

The meta-analysis demonstrated that 24% risk of incidence of pain was reduced by LLLT (RR = 0.76, 95% CI range 0.63-0.92, P = 0.006). In addition,
compared to the control group, LLLT brought forward "the most painful day" (MD = -0.42, 95% CI range -0.74- -0.10, P = 0.009). Furthermore, the LLLT
group also implied a trend of earlier end of pain compared with the control group (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18) and the pseudo-laser
group (MD = -1.04, 95% CI range -4.22-2.15, P = 0.52).
However, because of the methodological shortcomings and risk of bias of included trials, LLLT was proved with limited evidence in delaying pain onset
and reducing pain intensity. In the future, larger and better-designed RCTs will be required to provide clearer recommendations."

Oral

Orthodontics

Kau

USA
(Birmingham,
AL)

2013

Prog Orthod

Photobiomodulation accelerates orthodontic alignment in the early

phase of treatment.

Human
Multicenter

Oral

Orthodontics

Arts-Ribas

Spain

2013

Lasers Med Sci

Analgesic effect of a low-level laser therapy (830 nm) in early

orthodontic treatment.

Human
RCT

850

Pain

830

0.06

72
108
216

100

7
mm

120

"Multi-level mixed effect regression analysis was performed on the data, and the
mean rate of change in LII was 0.49 and 1.12 mm/week for the control and test
groups, respectively."

PubMed

LLLT decreased pain, compared to placebo.

PubMed

"An average increase of 30% in the rate of tooth movement was observed with the
low-intensity laser therapy. Pain scores on the experimental sides were
significantly lower compared with the control sides."

PubMed

20s per point (6 points)

(diame
ter)

Oral

Orthodontics

Doshi-Mehta &
Bhad-Patil

India
(Nagpur)

2012

Am J Orthod
Dentofacial
Orthop

Efficacy of low-intensity laser therapy in reducing treatment time

and orthodontic pain: a clinical investigation.

810

Human

0.7
0.25

4
mm2

Comment: An extremely low dose was used according to this paper. In my

opinion, that low dose is unlikely to have biological effects.
Note: A comment to this paper was published.

Oral

Orthodontics

Uysal

Turkey
(Kayseri)

2012

Eur J Orthod

Resonance frequency analysis of orthodontic miniscrews

subjected to light-emitting diode photobiomodulation therapy.

Rabbit

Oral

Orthodontics

Altan

Turkey
(Sivas)

2012

Lasers Med Sci

Metrical and histological investigation of the effects of low-level

laser therapy on orthodontic tooth movement.

Rat

Orthodontic
miniscrews to rabbit
tibia

618

820

100

3.18
3.18

54
15

1717
477

d=
2 mm
(?)

540
150

"Within the limits of this in vivo study, the present RFA findings suggest that LPT
might have a favourable effect on healing and attachment of titanium orthodontic
miniscrews."

PubMed

"No statistical difference was found for the amount of tooth movement in between
the control and study groups (p > 0.05).

PubMed

The number of osteoclasts, osteoblasts, inflammatory cells, capillary

vascularization, and new bone formation were found to be increased significantly
in group II (p < 0.05). Immunohistochemical staining findings showed that RANKL
immunoreactivity was stronger in group II than in the other groups."
Group III (the lower-dose LLLT group) didn't seem to have any important benefits.

Oral

Orthodontics

Sousa

Brazil
(So Paulo)

2011

Photomed Laser
Surg

Influence of low-level laser on the speed of orthodontic movement.

Oral

Orthodontics

Gama

Brazil
(Salvador,
Bahia)

2010

Photomed Laser
Surg

Tooth movement after infrared laser phototherapy: clinical study in Rat

rodents.

Human

Tooth movement

Oral

Orthodontics

Youssef

Syria
(Damascus)

2008

Lasers Med Sci

The effect of low-level laser therapy during orthodontic movement:

a preliminary study.

Human

Tooth movement
Pain

Oral

Orthodontics

Limpanichkul

Thailand
(Songkhla)

2006

Orthod Craniofac
Res

Effects of low-level laser therapy on the rate of orthodontic tooth

movement.

Human

Tooth movement

780

20

10

790

809

"The diode laser used within the protocol guidelines increased the speed of tooth
movement. This might reduce orthodontic treatment time."

PubMed

"The results showed no statistically significant difference, p = 0.079 (T0-T7), p =

0.597 (T7-T13), and p = 0.550 (T13-T19) between the laser and control groups on
the amount of tooth movement in the different times evaluated. It may be
concluded that laser phototherapy, with the parameters in the present study, did
not significantly increase the amount of tooth displacement during induced
orthodontic movement in rodents."

PubMed

"The velocity of canine movement was significantly greater in the lased group than
in the control group. The pain intensity was also at lower level in the lased group
than in the control group throughout the retraction period."

PubMed

"There was no significant difference of means of the canine distal movement

between the LLLT side and the placebo side for any time periods (p-value =
0.77)."

PubMed

100

25

"The energy density of LLLT (GaAlAs) at the surface level in this study (25 J/cm
(2)) was probably too low to express either stimulatory effect or inhibitory effect on
the rate of orthodontic tooth movement."

Oral

Orthodontics

Cruz

Brazil
(So Paulo)

2004

Lasers Surg Med

Effects of low-intensity laser therapy on the orthodontic movement

velocity of human teeth: a preliminary study.

Human

780

20

Oral

Osteonecrosis

Martins

Brazil
(So Paulo)

2012

Oral Oncol

Association of laser phototherapy with PRP improves healing of

bisphosphonate-related osteonecrosis of the jaws in cancer
patients: a preliminary study.

Human

660

40

Oral

Osteonecrosis

Vescovi

Italy
(Parma)

2012

Photomed Laser
Surg

Early surgical laser-assisted management of bisphosphonaterelated osteonecrosis of the jaws (BRONJ): a retrospective
analysis of 101 treated sites with long-term follow-up.

Human
Retrospective

1064

1250

Tooth movement

5
0.24
(/p ?)

10
0.042
cm2

4
/mo

6
(/p ?)

"Our findings suggest that LILT does accelerate human teeth movement and could
therefore considerably shorten the whole treatment duration."

PubMed

"These results suggest that the association of pharmacological therapy and

surgical therapy with PRP plus LPT significantly improves BRONJ healing in
oncologic patients. Although prospective studies with larger sample sizes are still
needed, this preliminary study may be used to inform a better-designed future
study."

PubMed

"Clinical improvement was achieved in 3 out of 12 (25%) BRONJ sites in G1. Sites
if G2 with an improvement were 18 out of 27 (66%). (...) For sites in G4, a clinical
improvement was recorded in 40 out of 45 cases (89%)."

PubMed

G1 = medical therapy
G2 = LLLT
G3 = medical + surgical + LLLT

Oral

Osteonecrosis

da Guarda

Brazil
(Salvador,
Bahia)

2012

Photomed Laser
Surg

Laser GaAlAs (860 nm) photobiomodulation for the treatment of

bisphosphonate-induced osteonecrosis of the jaw.

Case report

Oral

Osteonecrosis

Romeo

Italy
(Rome)

2011

Photomed Laser
Surg

Observation of pain control in patients with bisphosphonateinduced osteonecrosis using low level laser therapy: preliminary
results.

Human

Oral

Osteonecrosis

Scoletta

Italy
(Turin)

2010

Photomed Laser
Surg

Effect of low-level laser irradiation on bisphosphonate-induced

osteonecrosis of the jaws: preliminary results of a prospective
study.

Human

860

Pain

70

4.2

4
mm2

650
+
904
904

900

28.4

d=
0.8
cm
(?)

"Reduction in painful symptoms was reported after the second irradiation session,
and tissue healing was complete at the end of the third week following oral
curettage. The patient was followed up for 12 months and exhibited good oral
health and quality of life."

PubMed

"This pilot study suggests that LLLT may be a valid technique to support the
treatment of BRONJ-related pain, even though the low number of cases in this
study does not permit any conclusive consideration."

PubMed

"Four weeks after LLLT, a statistically significant difference was observed for
reported pain (p = 0.0001), clinical size (p = 0.0034), edema (p = 0.0005), and
presence of pus and fistulas (p = 0.0078 and p = 0.03, respectively)."

PubMed

"Of course, this needs to be addressed further in larger and randomly controlled
studies in different clinical settings."

Oral

Pericoronitis

Sezer

Turkey
(Gaziantep)

2012

Photomed Laser
Surg

Effects of low-level laser therapy as an adjunct to standard therapy

in acute pericoronitis, and its impact on oral health-related quality
of life.

Human
RCT

660
808
1064

8
8
8

"The results demonstrate that both the 1064-nm Nd:YAG and the 808-nm diode
lasers were effective in improving trismus and OHRQoL in acute pericoronitis.
Taking into account the limitations of this study, we conclude that the 1064-nm Nd:
YAG laser has biostimulatory effects and improves OHRQoL, making it suitable for
LLLT."
Note: In this study, 660nm didnt have a beneficial effect.

PubMed

Comment

 Category
Oral

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Periodontium

Pansani

Brazil
(Araraquara)

2017

Lasers Med Sci

Effects of low-level laser therapy and epidermal growth factor on

the activities of gingival fibroblasts obtained from young or elderly
individuals.

In vitro

780

25

Results: positive / unclear/modest / negative

Link

Additional info

sec

"Y and E fibroblasts irradiated with laser or exposed to EGF showed increased
viability and collagen synthesis.

PubMed

Enhanced cell migration was observed for Y fibroblasts after both treatments,
whereas only the LLLT stimulated migration of E cells.
VEGF synthesis was higher for Y and E cells exposed to EGF, while this synthesis
was reduced when E fibroblasts were irradiated. Increased gene expression of
VEGF was observed only for Y and E fibroblasts treated with LLLT."
"Regardless of a patient's age, the LLLT and EGF applications can biostimulate
gingival fibroblast functions involved in tissue repair."

Oral

Periodontium

Alzoman & Diab

Saudi Arabia
(Riyadh)

2016

Int J Dent Hyg

Effect of gallium aluminium arsenide diode laser therapy on

Porphyromonas gingivalis in chronic periodontitis: a randomized
controlled trial.

685

Human
RCT

1.6

20
/tooth

"There were statistically significant improvements in GI, PD, CAL and GBI for the
SRP + DL group compared to SRP group but no significant difference in PI
between the groups."

PubMed

"Additionally, the percentage of P. gingivalis-positive sites in the SRP + DL group

decreased from 80% (12/15) to 20% (3/15) after laser irradiation (P < 0.05). No
significant changes were noted in the SRP group."

Oral

Oral

Periodontium

Periodontium

Kumaresan

DemirturkGocgun

India
(Chennai)

Turkey
(Istanbul)

2016

2016
epub

Eur J Dent

Photomed Laser
Surg

Gingival crevicular fluid periostin levels in chronic periodontitis

patients following nonsurgical periodontal treatment with low-level
laser therapy.

Human
Controlled

Role of Low-Level Laser Therapy as an Adjunct to Initial

Periodontal Treatment in Type 2 Diabetic Patients: A Split-Mouth,
Randomized, Controlled Clinical Trial.

Human
split-mouth

The role of low-level laser in periodontal surgeries.

Review

"Comparison of mean periostin levels between both the treatment groups showed
a significant increase in LLLT group than RSD at the 3rd month (P < 0.05)."

PubMed

"Within the limitations of the present study, LLLT application was found to have
additional benefits over RSD with respect to clinical periodontal parameters and
GCF periostin levels. Moreover, periostin may be used as a possible biomarker to
evaluate the outcome following NSPT."

Diabetes + chronic
periodontitis

808

1.25
/point

4.46

5
/point

5
/tooth

"Test sites showed significant improvement in PI and BOP in deep pockets at the
1-month follow-up period (p < 0.001 and <0.001, respectively), whereas no
difference was found between the control and the test sites in other periodontal
parameters."

PubMed

"LLLT during periodontal treatment offered minimal short-term additional benefit in

deep pocket healing in patients with type 2 DM."

Oral

Periodontium

Sobouti

Iran
(Mazandaran)

2015

J Lasers Med Sci

"The present study has sought to review the cellular impacts of low-level lasers and its role on reducing pain and inflammation following soft tissue
surgical treatments."

PubMed

"It seems that numerous future studies with adequate samples and various parameters have to be conducted, so more comprehensive conclusions of
the low-level laser effect following periodontal surgery would be obtained."

Oral

Periodontium

Qadri

Sweden
(Huddinge)

2015

Photomed Laser
Surg

Role of diode lasers (800-980 nm) as adjuncts to scaling and root

planing in the treatment of chronic periodontitis: a systematic
review.

"Ten clinical studies were included. In all studies, patients were systemically healthy, and cigarette smokers were included in two studies. In five studies,
SRP plus diode laser application was more effective in the treatment of CP than SRP, and three studies showed no difference. In two studies, there was
a moderate reduction in periodontal inflammation using SRP plus diode laser.

Systematic
review

PubMed

The diameter of optic fiber, laser wavelengths, power, pulse repetition rate, and duration of laser exposure ranged between 300 m and 2 mm, 810-980
nm, 0.8-2.5 W, 10-60 Hz, and 10-100 ms, respectively."

Oral

Periodontium

Chang

Taiwan (Taipei)

2015

Lasers Med Sci

Controlling periodontal bone levels with multiple LED irradiations.

Rat

LED phototherapy

660

0.014

10

"By day 7, PBL was significantly reduced (p < 0.05), with significantly reduced
inflammation (p < 0.05) and gingival hyperplasia (p < 0.001), in the animals
receiving three irradiations per week. At day 14, the reduction in gingival
hyperplasia was still significant (p < 0.05), and collagen matrix deposition and
realignment appeared to be accelerated in the animals receiving three irradiations
per week, despite a lack of significant difference in PBL. The treatment regimen
receiving three LED light irradiations per week apparently extended the effects in
reducing PBL and inflammation to 7 days."

PubMed

LLLT provided minimal additional benefits to normal periodontal treatment.

PubMed

"Reduction of inflammation, accelerated collagen deposition and realignment was

noted following irradiation with LED light at densities of 10 and 15 J/cm2, and
temporary reduction of periodontal bone loss, as well as bundle bone apposition,
was noted at day 3 in rats treated with 10 J/cm2 light."

PubMed

Multiple sessions of LLLT reduced pro-inflammatory mediators and RANKL/OPG

ratio.

PubMed

"SRP combined with LLLT improved radiographic bone density and short-term
PPD reduction in patients with chronic periodontitis, but did not significantly affect
either the gingival crevicular fluid of IL-1 or the gingival or plaque index."

PubMed

"LPS treatment of gingival fibroblasts led to the increased release of the proinflammatory-related cytokines interleukin-6 (IL-6) and IL-8, whereas LED
irradiation inhibited their release. Analysis of MAPK signal transduction revealed a
considerable decrease in p38 phosphorylation in response to 635-nm radiation
either in the presence or absence of LPS. In addition, 635-nm LED irradiation
significantly promoted JNK phosphorylation in the presence of LPS. LED
irradiation can inhibit activation of pro-inflammatory cytokines, mediate the MAPK
signaling pathway, and may be clinically useful as an anti-inflammatory tool."

PubMed

"The current literature suggests that LPT is effective in modulating different periodontal disease aspects in vitro, in animals, and in simple clinical models.
Further development of this therapy is now dependent on new clinical trials with more complex study designs."

PubMed

2-3
/wk

Oral

Periodontium

Duki

Croatia

2013

J Periodontol

Clinical effectiveness of diode laser therapy as an adjunct to nonsurgical periodontal treatment: a randomized clinical study.

Human
split-mouth
study

Periodontitis

980

Oral

Periodontium

Chang

Singapore

2013

J Periodontal Res

Irradiation by light-emitting diode light as an adjunct to facilitate

healing of experimental periodontitis in vivo.

Rat

Experimental
periodontitis

660

5
10
15

LED phototherapy

Oral

Periodontium

Calderin

Spain

2013

Lasers Med Sci

Short-term clinical and osteoimmunological effects of scaling and

root planing complemented by simple or repeated laser
phototherapy in chronic periodontitis.

Human

Oral

Periodontium

Makhlouf

Egypt
(Cairo)

2012

Photomed Laser
Surg

Effect of adjunctive low level laser therapy (LLLT) on nonsurgical

treatment of chronic periodontitis.

Human
Split-mouth
DB

Oral

Periodontium

Choi

Korea
(Gwangju)

2012

Lasers Med Sci

Inflammatory cytokines are suppressed by light-emitting diode

irradiation of P. gingivalis LPS-treated human gingival fibroblasts:
inflammatory cytokine changes by LED irradiation.

In vitro

Laser phototherapy in the treatment of periodontal disease. A

review.

Review

Oral

Periodontium

de Paula
Eduardo

Brazil
(So Paulo)

2010

Lasers Med Sci

Periodontitis

Inflammation

670

200

830

100

635

60
/tooth

3
/point

10

0.005

3600
= 1h

LED phototherapy

"The optimal laser parameters and the irradiation protocols are not fully described in the literature. The main factors hindering their precise definition are
the lack of standardization in the reporting of laser parameters and the great variety of research methodologies used. However, considering the high
number of positive reports currently available in the literature, new in vitro investigations should no longer seek to confirm the effectiveness of LPT, but to
determine its precise mechanism and to identify the ideal set of parameters and protocols for different clinical situations.
Although LPT seems to enhance clinical outcomes in periodontology, it is only reasonable to perform it in a decontaminated and calculus-free
periodontium. This means that conventional periodontal treatment should not be discarded. LPT must be considered an adjuvant therapy, which may
have additional benefit for a previously well-treated periodontal tissue."

Oral

Periodontium

Pejcic

Serbia (Nis)

2010

Photomed Laser
Surg

The effects of low level laser irradiation on gingival inflammation.

Human

670

0.100
0.150

Oral

Periodontium

Angelov

USA (CA)

2009

Gen Dent

Periodontal treatment with a low-level diode laser: clinical findings. Human

RCT

630670

Oral

Periodontium

Qadri

Sweden
(Huddinge)

2007

Lasers Med Sci

The importance of coherence length in laser phototherapy of

gingival inflammation: a pilot study.

Human
Pilot study

633

650

d=
3 mm

0.54
/point

120

10

"A general conclusion can be drawn that low level laser irradiation (semiconductor,
670 nm) can be used as a successful physical adjuvant method of treatment,
which, together with traditional periodontal therapy, leads to better and longerlasting therapeutic results."

PubMed

5
10

"These findings suggest that a low-level diode laser can have a beneficial effect
for treating inflammatory chronic advanced periodontitis."

PubMed

180
/point

"At the follow up examination, all clinical parameters had improved significantly in
both groups. A more pronounced decrease of clinical inflammation was observed
after HeNe treatment."

PubMed

"The clinical variables i.e. probing pocket depth, plaque and gingival indices were
reduced more on the laser side than on the placebo one (p<0.01)."

PubMed

"This study concludes that helium-neon diode lasers, at the previously mentioned
energy level, increase the rate of gingival wound healing in 69 percent of patients,
without any side effects."

PubMed

"The results showed no significant differences in the gingival index, healing index
and pain reduction when the soft laser treatment was compared to the placebo
operation. These results suggest that soft laser (As-Ga and He-Ne) treatments
may not be a useful adjunct after certain periodontal surgical procedures."

PubMed

Oral

Periodontium

Qadri

Sweden
(Huddinge)

2005

J Clin Periodontol

The short-term effects of low-level lasers as adjunct therapy in the

treatment of periodontal inflammation.

Human
Split-face

635
+
830

10

0.05

0.9

4.5

90

70

0.35

1.75

8.75

25

Oral

Periodontium

Neiburger EJ

1999

J Mass Dent Soc

Rapid healing of gingival incisions by the helium-neon diode laser.

Human

670

1.4

Oral

Periodontium

Masse

Canada
(Qubec)

1993

Int Dent J

Effectiveness of soft laser treatment in periodontal surgery.

Human
placebo
controlled

Oral

Root resorption

Higashi

Brazil
(Londrina)

2016

Lasers Med Sci

Three consecutive days of application of LED therapy is necessary

to inhibit experimentally induced root resorption in rats: a
microtomographic study.

Rat

940

Oral

Safety

Chan

Australia
(Sydney)

2014

Laser Ther

Low-power pulsed Nd:YAG laser irradiation for pre-emptive

anaesthesia: A morphological and histological study.

Human

1064

1100

Oral

Salivary glands

de Jesus

Brazil
(Salvador,
Bahia)

2015

Lasers Med Sci

Influence of laser photobiomodulation (GaAlAs) on salivary flow

rate and histomorphometry of the submandibular glands of
hypothyroid rats.

Rat

660

40

780

40

780

70

660

90

30

0.06

Comment: Tuner&Hode (1998) mention that in this study, the dose was 0.06
J/cm2.

Hypothyroid rats

39

0.260

1
2
3
0.28
cm2

"In conclusion, three daily LED therapy doses are required to inhibit root resorption
after appliance of orthodontic forces."

PubMed

"Low-power pulsed Nd:YAG laser dose, as used in the clinical trial to induce
anaesthesia, does not cause morphological damage to the mineralized tooth
structure. Both Laser and EMLA groups showed minor superficial pulpal change
following cavity preparation which was not statistically significant. Laser and
Control groups minus preparation had no pulpal changes."

PubMed

"No significant difference was found in the salivary flow of rats that received laser
photobiomodulation compared with their control groups. Histological analysis
revealed a decrease in the parenchyma of the salivary glands of hypothyroid rats,
but the laser was not able to reverse this process.

PubMed

Hypothyroid rats irradiated or not with laser showed acini and acinar cells with
significantly smaller areas than euthyroid groups. The laser photobiomodulation
protocol used was not able to change salivary flow or reverse the acinar atrophy
process in the submandibular glands of hypothyroid rats."

Oral

Salivary glands

Ibuki

Brazil
(So Paulo)

2013

Lasers Med Sci

Laser irradiation affects enzymatic antioxidant system of

streptozotocin-induced diabetic rats.

Rat

Diabetes

5.76
23.04

5
20

Antioxidant system

64
256

"SOD and CAT activities, as well as [total antioxidant value] were higher in SMG of
irradiated diabetic rats. However, in [submandibular salivary gland] of non-diabetic
rats, laser irradiation decreased [total antioxidant] values and led to an increase in
the CAT activity. In addition, there was a decrease in the activity of CAT in [parotid
gland] of diabetic and non-diabetic animals after laser irradiation."

PubMed

Oral

Stem cells

Marques

Brazil
(So Paulo)

2016

Photomed Laser
Surg

Photobiomodulation of Dental Derived Mesenchymal Stem Cells: A

Systematic Review.

Systematic
review

"PBM therapy has no deleterious effects on ddMSCs. Although no other clear conclusion was obtained because of the scarce number of publications,
the results of these studies are pointing to an important tendency of PBM therapy to improve ddMSCs' viability and proliferation."

PubMed

Oral

Stem cells

BorzabadiFarahani A

Italy/UK

2016

J Photochem
Photobiol B

Effect of low-level laser irradiation on proliferation of human dental

mesenchymal stem cells; a systemic review.

Systematic
review

"There is limited evidence that in-vitro LLLI (660/810/980nm, with energy densities of 0.1-3J/cm(2)) increases the proliferation of DMSCs. Considering
the limited evidence and their method heterogeneity it is difficult to reach a firm conclusion.

PubMed

Further research is necessary to identify the optimal characteristics of the LLLI setting (wave length, energy density, power output, frequency/duration of
irradiations, distance between the cells and the laser spot/probe) to increase proliferation of DMSCs, and assess its impact on replicative senescence, as
well as determine feasibility of the use in the clinical setting."

Oral

Surgery

Doeuk

France
(Crteil)

2015

Br J Oral
Maxillofac Surg

Current indications for low level laser treatment in maxillofacial

surgery: a review.

Review

Oral

Tooth
replantation

de Carvalho

Brazil
(Salvador,
Bahia)

2016

Dent Traumatol

Evaluation of laser phototherapy ( 780 nm) after dental

replantation in rats.

Rat

- We found 45 papers that we screened independently.

- The resulting full texts were scrutinised by two authors who awarded a maximum of 5 points using the Jadad scale for assessing the quality of RCT,
and extracted the data according to sample size, variables of LLLT, the authors' conclusions, and the significance of the result.
- LLLT seems to be effective for the treatment of oral mucositis after treatment for head and neck cancer.
- However, it cannot yet be considered a valid treatment for disorders of the TMJ.
- It seems to improve gingival healing, and myofacial and dental pain."
780

70

21

"The use of laser phototherapy on the root surface and at the entrance of the
alveolus prior to replantation had a positive biomodulative effect on alveolar repair
after tooth replantation in rats."

PubMed

PubMed

"was applied into the sulcus"

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Reply

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Category

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Oral

Tooth
replantation

Matos Fde

Brazil
(Aracaju)

2016

Dent Traumatol

Effect of laser photobiomodulation on the periodontal repair

process of replanted teeth.

Rat

660
808

Oral

Tooth
replantation

Carvalho

Brazil
(Salvador,
Bahia)

2016

Dent Traumatol

Effects of diode laser irradiation and fibroblast growth factor on

periodontal healing of replanted teeth after extended extra-oral dry
time.

Rat

810

Oral

Tooth
replantation

Vilela

Brazil
(So Paulo)

2012

Lasers Med Sci

Histomorphometric analysis of inflammatory response and

necrosis in re-implanted central incisor of rats treated with lowlevel laser therapy.

Rat

685

Oral

Tooth
replantation

Carvalho Edos

Brazil
(Taubat)

2012

Dent Traumatol

Root surface treatment using diode laser in delayed tooth

Rat
replantation: radiographic and histomorphometric analyses in rats.

810

Teeth

Arany

USA
2014
(Cambridge and
Boston, MA)

Sci Transl Med

Photoactivation of endogenous latent transforming growth factor1 directs dental stem cell differentiation for regeneration.

Oral

Oral

Tissue
engineering

Theocharidou

Greece
(Thessaloniki)

2016

Lasers Med Sci

Odontogenic differentiation and biomineralization potential of

dental pulp stem cells inside Mg-based bioceramic scaffolds under
low-level laser treatment.

Oral

TMJ

Cavalcanti

Brazil
(So Paulo)

2016
epub

Photomed Laser
Surg

Comparative Study of the Physiotherapeutic and Drug Protocol

and Low-Level Laser Irradiation in the Treatment of Pain
Associated With Temporomandibular Dysfunction.

Oral

TMJ

Machado

Brazil
2016
(Ribeiro Preto)

Lasers Med Sci

Effects of oral motor exercises and laser therapy on chronic

temporomandibular disorders: a randomized study with follow-up.

Mouse

In vitro

nm

mW

W/cm2

J/cm2

Dentin regeneration
Mechanisms
Stem cells

810

Pulp stem cells

Bioceramic scaffolds

660

30

2.5

4
(4p)

50

0.02
cm2

1000

30

0.01

Results: positive / unclear/modest / negative

Link

Additional info

sec

1000

300

"The LPBM protocol at 808 nm and 660 nm as well as whole milk and soy milk
favored the periodontal repair process of replanted teeth in rats."

PubMed

"DL, with or without FGF, reduced the occurrence of external root resorption and
ankylosis. Periodontal healing was favored and some fiber reinsertion occurred
only when FGF was used."

PubMed

"These results showed that the laser groups developed less root resorption areas
than the control group in all experimental periods. Additionally, histological
analysis revealed less inflammatory cells and necrotic areas in laser groups."

PubMed

"Root surface treatments with high-powered diode laser irradiation prior to delayed
replantation reduced the occurrence of external root resorption compared to no
treatment or sodium fluoride treatment at up to 60 days."

PubMed

"Further, an in vivo pulp capping model in rat teeth demonstrated significant

increase in dentin regeneration after LPL treatment. "

PubMed

"These findings indicate a pivotal role for TGF- in mediating LPL-induced dental
tissue regeneration. More broadly, this work outlines a mechanistic basis for
harnessing resident stem cells with a light-activated endogenous cue for clinical
regenerative applications."
max
140

2
4

780

780

Human
RCT/SB

60

"LLLI treatment proved to be beneficial for odontogenic differentiation and

biomineralization of DPSCs inside the bioceramic scaffolds, making this
therapeutic modality promising for targeted dentin engineering."

PubMed

35

20

12

"Based on obtained data, we concluded that, compared to PDP, LLL treatment is

effective to control pain associated with TMD."

PubMed

60

40

12
(?)

"However, LLLT alone was not sufficient for TMD rehabilitation"

PubMed

Seems that LLLT alone didn't outdo placebo treatment.

Comment: Parameters were limitedly reported.

Oral

TMJ

Chen

China
(Chengdu)

2015

J Oral Rehabil

Efficacy of low-level laser therapy in the treatment of TMDs: a

meta-analysis of 14 randomised controlled trials.

Metaanalysis

Oral

TMJ

Leal de Godoy

Brazil
(So Paulo)

2015

J Oral Maxillofac
Surg

Effect of low-level laser therapy on adolescents with

temporomandibular disorder: a blind randomized controlled pilot
study.

Human
RCT

"This study indicates that using LLLT has limited efficacy in reducing pain in patients with TMDs. However, LLLT can significantly improve the functional
outcomes of patients with TMDs."

Insufficient dosage

780

50

1.67

33.5

20

PubMed

"No statistically significant differences were found regarding pain, mandibular

range of motion, or the distribution of occlusal contacts after treatment with lowlevel laser therapy."
Tuner: "The energy used here is 1 J per point (50 mW x 20 s = 1000 mJ = 1 J).
For a muscle, this is far from the therapeutic window and a failure is to be
expected. We found 6 J per point effective, but not necessarily optimal(Ahrari et al.
2013), even higher energies are sometimes clincally needed for reasonable
results. Muscles are thick and contain a lot of hemoglobin, a major absorber of the
light. Irradiation with or without pressure also changes to energy at target. The
laser parameters here are well described but inadequate."

Oral

TMJ

Fornaini

Italy

2015

Laser Ther

The "at-home LLLT" in temporo-mandibular disorders pain control: Human

a pilot study.
Pilot study

808

250
(?)

4.5
cm2

Oral

TMJ

Peimani &
Sardary

Iran
(Rafsanjan)

2014

J Dent (Tehran)

Effect of low-level laser on healing of temporomandibular joint

osteoarthritis in rats.

Rat

880

100

d=
0.8
mm

600

14

Oral

TMJ

Salmos-Brito

Brazil
(Recife)

2013

Lasers Med Sci

Evaluation of low-level laser therapy in patients with acute and

chronic temporomandibular disorders.

Human

830

40

d=
6 mm

60
/side

Oral

TMJ

Herranz-Aparicio

Spain

2013

Med Oral Patol

Oral Cir Bucal

The use of low level laser therapy in the treatment of

temporomandibular joint disorders. Review of the literature

Oral

TMJ

Maia

Brazil
(Aracaju)

2012

J Appl Oral Sci

Effect of low-level laser therapy on pain levels in patients with

temporomandibular disorders: a systematic review.

LLLT was more effective than placebo.

PubMed

"After three days of treatment the grade of cartilage defects, number of

inflammatory cells, angiogenesis, number of cell layers and arthritis in rats in the
case group were not significantly different compared with controls (P>0.05).

PubMed

After seven days, the grade of cartilage defects, number of inflammatory cells,
number of cell layers, and arthritis in the case group improved compared to
controls (P<0.05); angiogenesis in both groups was similar."
8
(?)

12

"In summary, considering the non-invasive and harmless characteristics of this

modality, and the significant improvement obtained in both groups (acute and
chronic TMD) in subjective parameters (e.g., pain), as well as, in objective
functional parameters (e.g., maximal mouth opening), LLLT may promote some
anti-inflammatory effect and pain relief in painful and dysfunctional
temporomandibular muscles."

PubMed

Systematic
review

Currently there is a scientific evidence level B in favor of using LLLT for treatment of TMDs. The great majority of the studies concluded that the results
should be taken with caution due to the methodological limitations.

PubMed

Systematic
review

"After a careful review, 14 studies fit the criteria for inclusion, of which, 12 used a placebo group.

PubMed

As for the protocol for laser application, the energy density used ranged from 0.9 to 105 J/cm, while the power density ranged from 9.8 to 500 mW. The
number of sessions varied from 1 to 20 and the frequency of applications ranged from daily for 10 days to 1 time per week for 4 weeks.
A reduction in pain levels was reported in 13 studies, with 9 of these occurring only in the experimental group, and 4 studies reporting pain relief for both
the experimental group and for the placebo."
"Most papers showed that LLLT seemed to be effective in reducing pain from TMD. However, the heterogeneity of the standardization regarding the
parameters of laser calls for caution in interpretation of these results. Thus, it is necessary to conduct further research in order to obtain a consensus
regarding the best application protocol for pain relief in patients with TMD."

Oral

TMJ

Dostalov

Czech

2012

Photomed Laser
Surg

Effectiveness of physiotherapy and GaAlAs laser in the

management of temporomandibular joint disorders.

Human
noncontrolled

Oral

TMJ

Petrucci

Italy
(L'Aquila)

2011

J Orofac Pain

Effectiveness of low-level laser therapy in temporomandibular

disorders: a systematic review and meta-analysis.

Metaanalysis

830

280

LLLT appeared to reduce pain a lot, and improve mouth opening.

PubMed

Comment: Interesting results.

"The literature search identified 323 papers without overlap between selected databases, but after the two-phase study selection, only six randomized
clinical trials (RCT) were included in the systematic review."

PubMed

"The pooled effect of LLLT on pain, measured through a visual analog scale with a mean difference of 7.77 mm (95% confidence interval [CI]: -2.49 to
18.02), was not statistically significant from placebo."
"Change from baseline to endpoint of secondary outcomes was 4.04 mm (95% CI 3.06 to 5.02) for mandibular maximum vertical opening; 1.64 mm (95%
CI 0.10 to 3.17) for right lateral excursion and 1.90 mm (95% CI: -4.08 to 7.88) for left lateral excursion."

Oral

TMJ

Carvalho

Brazil
(Salvador,
Bahia)

2010

Lasers Med Sci

Wavelength effect in temporomandibular joint pain: a clinical

experience.

Human
Retrospective

660
780
790
830

Oral

TMJ

Kucuk

Turkey
(Istanbul)

2010

J Orofac Pain

The anti-inflammatory effect of low-level laser therapy on

experimentally induced inflammation of rabbit temporomandibular
joint retrodiscal tissues.

Rabbit

815

14.2

250

12

48

"At the end of the 12 sessions the patients were again examined, and they scored
their pain using the VAS. The results were statistically analyzed and showed that
64% of the patients were asymptomatic or had improved after treatment and that
the association of both wavelengths was statistically significant (P = 0.02) in the
asymptomatic group. It was concluded that the association of red and infrared (IR)
laser light was effective in pain reduction on TMJ disorders of several origins."

PubMed

"Under the conditions used in this study, quantitative scintigraphic measurements

of TMJ inflammation of the treated TMJ group decreased but did not differ
significantly from those of the control TMJ group."

PubMed

Jan Tuner: "It is suggested that the lack of effect in the Kucuk paper is due to
gross over dosage and subsequent inhibition."

Oral

TMJ

Emshoff

Austria
(Innsbruck)

2008

Oral Surg Oral

Low-level laser therapy for treatment of temporomandibular joint
Med Oral Pathol
pain: a double-blind and placebo-controlled trial.
Oral Radiol Endod

633

30

Oral

TMJ

Fikckov

Czech

2007

Photomed Laser
Surg

Effectiveness of low-level laser therapy in temporomandibular joint Human

disorders: a placebo-controlled study.
RCT

830

40

Oral

TMJ

Fikckov

Czech

2006

Photomed Laser
Surg

Arthralgia of the temporomandibular joint and low-level laser

therapy.

Human
noncontrolled

830

400

Oral

Tooth extraction

Pedreira

Brazil
(Salvador,
Bahia)

2016

Minerva Stomatol

Thermographic and clinical evaluation of 808-nm laser

photobiomodulation effects after third molar extraction.

Human

Oral

Tooth extraction

Sierra

Brazil
(So Paulo)

2016

Lasers Surg Med

Choosing between intraoral or extraoral, red or infrared laser

irradiation after impacted third molar extraction.

Human

Oral

Tooth extraction

Ribeiro

Brazil
(So Paulo)

2016

Oral Surg

The effect of the low-level laser therapy on healing and pain after
tooth extraction: a systematic review

Systematic
review

Oral

Tooth extraction

Pol

Italy
(Novara)

2016

J Craniofac Surg

Efficacy of Anti-Inflammatory and Analgesic of Superpulsed Low

Level Laser Therapy After Impacted Mandibular Third Molars
Extractions.

Human

Oral

Tooth extraction

Hamad

Iraq
(Kurdistan)

2016

J Maxillofac Oral
Surg

Effect of Diode Laser on Healing of Tooth Extraction Socket: An

Experimental Study in Rabbits.

Rabbit

Oral

Tooth extraction

Eshghpour

Iran
(Mashhad)

2016

J Oral Maxillofac
Surg

Is Low-Level Laser Therapy Effective in the Management of Pain

and Swelling After Mandibular Third Molar Surgery?

Human
RCT/DB

Human
RCT/DB

Wisdom tooth

1624

"The study suggests that LLLT is not better than placebo at reducing TMJ pain
during function."

PubMed

LLLT was effective for the pain related to TMD.

PubMed

LLLT reduced pain and inflammation (according to tissue temperature).

PubMed

808

"A slight improvement was observed for swelling, pain and trismus in patients who
received laser irradiation, although the differences were not statistically significant
(P>0.05). Laser therapy had a significant influence on the local circulation in the
area near the temporomandibular joint, as determined by infrared thermography
(P<0.05)."

PubMed

660
808

"The intra-group analyses showed that 808 nm laser applied extra-orally favored
reductions in postoperative facial swelling and trismus, although the inter-group
comparisons revealed no statistically significant differences."

PubMed

15

10

"A decrease in pain level after tooth extraction was reported after low-level laser therapy; however, there is no evidence regarding the effect on tissue
healing. Adequately powered and randomised controlled trials are required to address this issue."

900

Wisdom tooth

660

200

Combined
wavelengths

+
810

200

Oral

Tooth extraction

Eroglu & Keskin

Tunc

Turkey
(Van)

2016

Photomed Laser
Surg

Effectiveness of Single Session of Low-Level Laser Therapy with a

940 nm Wavelength Diode Laser on Pain, Swelling, and Trismus
After Impacted Third Molar Surgery.

Human

Wisdom tooth

940

Oral

Tooth extraction

Elbay

Turkey
(Kocaeli)

2016

Photomed Laser
Surg

Efficacy of Low-Level Laser Therapy in the Management of

Postoperative Pain in Children After Primary Teeth Extraction: A
Randomized Clinical Trial.

Human
RCT/DB

Primary teeth

810

300

Oral

Tooth extraction

Alan

Turkey
(Malatya)

2016

Head Face Med

Evaluation of the effects of the low-level laser therapy on swelling,

pain, and trismus after removal of impacted lower third molar.

Wisdom tooth

810

300

"Results indicate that in the treated site SLLLT determines a reduction in pain and
swelling statistically significant compared with the control site (P < 0.05). The
authors found that the effectiveness of laser therapy is in the first 5 days after
surgery, showing a significant reduction of pain and swelling in the treated site
than the control site."

PubMed

"Diode laser application to tooth extraction socket has a positive effect on bone
formation."

PubMed

"Pain level was significantly lower in the laser than in the placebo side at all time
points during the experiment (P < .05). Swelling was significantly lower in the laser
than in the placebo group on days 2, 4, and 7 after surgery (P < .05)."

PubMed

"There was no statistically significant difference in pain, swelling, or trismus

between the sides (Mann-Whitney U test p > 0.05). However, according to the
clinical outcomes, swelling and trismus were less in the laser-treated side than in
the placebo side."

PubMed

180

"Within the limitations of this study, LLLT application following primary molar
extraction was not found to affect postoperative pain in children."

PubMed

40

"Although there were decreasing trismus, swelling, and pain level, with this LLLT,
there was significant difference only in the 7th day pain level in the laser group
compared with the control group."

PubMed

300
24
(4p)
+
24
(4p)

1
+
3
4

12

3
cm2

(Not in
Pubmed
yet)

B-Cure Laser was used.

Comment

Reply

 Category
Oral

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Tooth extraction

Sierra

Brazil
(Bauru)

2015

Br J Oral
Maxillofac Surg

Effect of low-intensity laser treatment on pain after extraction of

impacted mandibular third molars: a randomised, controlled,
clinical trial.

Human
RCT

652
808

100
100

3.537
3.537

12
12

106
106

Bone healing after low-level laser application in extraction sockets

grafted with allograft material and covered with a resorbable
collagen dressing: a pilot histological evaluation.

Human
RCT

Wisdom tooth
intraoral vs extraoral

Results: positive / unclear/modest / negative

1
1

"We conclude that a single session of low intensity laser had no significant effect
on the amount of pain under the conditions investigated."

Link

Additional info

Comment

sec

d=
0.094
cm

120
120

PubMed

Note: Even control group had very low pain levels to begin with, which might
explain the lack of success in this study.
Comment: Parameters are very nicely reported in a table.

Oral

Tooth extraction

Monea

Romania
(Trgu Mure)

2015

BMC Oral Health

618
(?)

0.02

1200

21

"The histological results of the site treated with LLLT for 21 days, harvested at 60
days after grafting showed abundant new bone formation without any sign of
inflammation. The same results were obtained in the control group not before 120
days post-surgery."

PubMed

"It can be concluded that LLLT photobiomodulation can reduce the healing time
after grafting the extraction socket."
Comment: Parameters were poorly reported... Even wavelength was left
unmentioned, but the device name (OsseoPulse) was mentioned.

Oral

Tooth extraction

Abdel-Alim

Saudi Arabia
(Jeddah)

2015

Photomed Laser
Surg

A Comparative Study of the Effectiveness of Immediate Versus

Delayed Photobiomodulation Therapy in Reducing the Severity of
Postoperative Inflammatory Complications.

Human

Immediate LLLT vs
delayed LLLT (1 day
after operation)

830

Oral

Tooth extraction

Merigo

Italy

2015

Laser Ther

Efficacy of LLLT in swelling and pain control after the extraction of

lower impacted third molars.

Human
RCT

Wisdom tooth

910
650

Oral

Tooth extraction

He

China
(Guangzhou)

2015

Lasers Med Sci

A systematic review and meta-analysis on the efficacy of low-level

laser therapy in the management of complication after mandibular
third molar surgery.

Metaanalysis

4000

171
(?)

2.8
cm2

120

"Eighty patients with horizontally impacted mandibular third molars with no inferior
alveolar canal approximation were recruited for this study. They were divided into
two groups. The immediate group received PBM therapy immediately after surgery
and on the 3rd day postoperatively. Subjects in the delayed group received PBM
therapy on the 2nd and 4th days postoperatively. All subjects received 2 min of
treatment using a 4 W laser beam, during which 171 J were delivered via a 2.8 cm
(2) spot size."

PubMed

"Clinical and statistical results showed a significant reduction in pain, trismus, and
swelling in the immediate PBM therapy group compared with the delayed PBM
therapy group."
A strangely written paper, but they claim that LLLT was beneficial.

Studies:
- Six RCTs in which involves 193 participants are included in the meta-analysis.
- Among them, three RCTs exhibit a moderate risk of bias, while the other three show a high bias risk.

PubMed
PubMed

Results:
- Compared with placebo laser/control group, pain is significantly reduced with LLLT on the first day (mean difference [MD] = -2.63, P = 0.005).
- The superiority of LLLT in pain control persists on the second day (MD = -2.34, P = 0.04) and the third day (MD = -3.40, P < 0.00001).
- Moreover, LLLT reduces an average of 4.94 mm (MD = 4.94, P = 0.004) of trismus compared with placebo laser irradiation in the first 3 days.
- In the first 3 days after surgery, extraoral irradiation (MD = -0.69, P = 0.03) and intraoral combined with extraoral irradiation (MD = -0.65, P = 0.01)
reduced facial swelling significantly.
- On the seventh day, the intraoral combined with extraoral irradiation group (MD = -0.32, P = 0.02) still showed benefit in relieving facial swelling.
Discussion:
- However, because of the heterogeneity of intervention and outcomes assessment and risk of bias of included trials, the efficacy is proved with limited
evidence.
- In the future, well-designed RCTs with larger sample size will be required to provide clearer recommendations.
"The pain level and the number of analgesics tablets taken were lower in the
ozonated and LLLT applied groups than in the control group. This study showed
that ozone and low power laser therapies had a positive effect on the patients'
quality of life. Trismus in the LLLT group was significantly less than in the
ozonated and control groups (p = 0.033). Ozone application showed no superiority
in regards of postoperative swelling; however, LLLT group had significantly lower
postoperative swelling."

Oral

Tooth extraction

Kazancioglu

Turkey
(Istanbul)

2014

Lasers Med Sci

Comparison of the influence of ozone and laser therapies on pain,

swelling, and trismus following impacted third-molar surgery.

Human
RCT

Wisdom tooth

Oral

Tooth extraction

Oliveira Sierra

Brazil
(So Paulo)

2013

Trials

Effect of low-level laser therapy on the post-surgical inflammatory

process after third molar removal: study protocol for a doubleblind randomized controlled trial.

Study
protocol

Wisdom tooth

Oral

Tooth extraction

Ferrante

Italy

2013

Lasers Med Sci

Effect of low-level laser therapy after extraction of impacted lower

third molars.

Human
RCT
(no placebo)

Wisdom tooth

Oral

Tooth extraction

Batinjan

Croatia

2013

J Lasers Med Sci

Assessing Health-Related Quality of Life with Antimicrobial

Photodynamic Therapy (APDT) and Low Level Laser Therapy
(LLLT) after Third Molar Removal.

Human

Wisdom tooth

Oral

Tooth extraction

Lpez-Ramrez

Spain
(Barcelona)

2012

Lasers Med Sci

Efficacy of low-level laser therapy in the management of pain,

facial swelling, and postoperative trismus after a lower third molar
extraction. A preliminary study.

Human
RCT/DB

Oral

Tooth extraction

BrignardelloPetersen

Canada
(Toronto)

2012

J Oral Maxillofac
Surg

Is adjuvant laser therapy effective for preventing pain, swelling,

and trismus after surgical removal of impacted mandibular third
molars? A systematic review and meta-analysis.

Metaanalysis

Oral

Tooth extraction

Park & Kang

Korea
(Seoul)

2012

Lasers Med Sci

Effect of 980-nm GaAlAs diode laser irradiation on healing of

extraction sockets in streptozotocin-induced diabetic rats: a pilot
study.

Rat

Diabetic rats

980

Oral

Tooth extraction

Aras &
Gngrm

Turkey
(Gaziantep)

2010

Lasers Med Sci

Placebo-controlled randomized clinical trial of the effect two

different low-level laser therapies (LLLT)--intraoral and extraoral-on trismus and facial swelling following surgical extraction of the
lower third molar.

Human
RCT

Wisdom tooth

808

100

Oral

Tooth extraction

AmarillasEscobar

Mexico
(San Luis
Potos)

2010

J Oral Maxillofac
Surg

Use of therapeutic laser after surgical removal of impacted lower

third molars.

Human
RCT/DB

Wisdom tooth

810

100

PubMed

Comment

Note: There seemed to be no placebo group. A comment was published, noting

that this might affect the results.

980

300

54

180

"The present study aims to provide a randomized, controlled, double-blind trial to

compare four different LLLT parameters in relation to the outcomes of pain,
swelling and muscle spasm following surgery for the extraction of impacted third
molars and evaluate the effects os surgery on patients' quality os life (QOL)."

PubMed

There was much less pain and swelling in LLLT group.

PubMed

PDT+LLLT seemed to have some mild beneficial effects.

PubMed

"The application of a low-level laser with the parameters used in this study did not
show beneficial affects in reducing pain, swelling, and trismus after removal of
impacted lower third molars."

PubMed

PDT + LLLT
Wisdom tooth

810

400

12.8

d=
0.7 cm
(??)

32

"There was no benefit of LLEI on pain or swelling and a moderate benefit on trismus after removal of IMTMs. It is necessary to standardize the
intervention and outcomes assessment and to conduct adequately powered, well-designed trials to evaluate the efficacy of LLEI."

12

PubMed

13.95

60

"Histological observations and gene expression analyses revealed that groups 2

(normal rats with LLLT) and 4 (diabetic rats with LLLT) showed faster initial
healing and more new alveolar bone formation than group 1 (normal rats without
LLLT) and group 3 (diabetic rats without LLLT), respectively."

PubMed

120

"This study demonstrates that extraoral LLLT is more effective than intraoral LLLT
for the reduction of postoperative trismus and swelling after extraction of the lower
third molar."

PubMed

"The experimental group exhibited a lower intensity of postoperative pain,

swelling, and trismus than the control group, without significant statistical
differences."

PubMed

Intraoral+Extraoral

Comment: Parameters were poorly reported.

Oral

Tooth extraction

Markovi &
Todorovi

Serbia
(Belgrade)

2007

Int J Oral
Maxillofac Surg.

Effectiveness of dexamethasone and low-power laser in minimizing Human

oedema after third molar surgery: a clinical trial.

Wisdom tooth

637

50

"LPL irradiation with local use of dexamethasone (group 2) resulted in a

statistically significant reduction of postoperative oedema in comparison to the
other groups. No adverse effects of the procedure or medication were observed."

PubMed

Comment: A good photograph of the LLLT treatment was supplied.

Comment: Parameters were quite poorly reported.

Oral

Tooth extraction

Markovi &
Todorovi

Serbia
(Belgrade)

2006

Oral Surg Oral

Postoperative analgesia after lower third molar surgery:
Med Oral Pathol
contribution of the use of long-acting local anesthetics, low-power
Oral Radiol Endod laser, and diclofenac.

Human
LLLT+diclo

Oral

Tooth extraction

Freitas

Brazil
(Porto Alegre)

2001

Braz Dent J

Assessment of anti-inflammatory effect of 830nm laser light using

C-reactive protein levels.

Human

Wisdom tooth
Postoperative
analgesia

Oral

Tooth extraction

Braams

Netherlands

1994

Ned Tijdschr
Tandheelkd

[Treatment with soft laser. The effect on complaints after the

removal of wisdom teeth in the mandible].
[Article in Dutch]

Human

Wisdom tooth

Oral

Tooth extraction

Rynesdal

Norway
(Oslo)

1993

Int J Oral
Maxillofac Surg

The effect of soft-laser application on postoperative pain and

swelling. A double-blind, crossover study.

Human
Crossover,
DB

Wisdom tooth

Oral

Tooth extraction

Fernando

UK
(Cardiff)

1993

Br J Oral
Maxillofac Surg

A randomised double blind comparative study of low level laser

therapy following surgical extraction of lower third molar teeth.

Human
RCT/DB

Oral

Tooth extraction

Carrillo

Spain
(Madrid)

1990

Int Dent J

A randomized double-blind clinical trial on the effectiveness of

helium-neon laser in the prevention of pain, swelling and trismus
after removal of impacted third molars.

Human
RCT/DB

Oral

Ulcers

Cabras

Italy
(Turin)

2016

Case Rep Dent

Laser Photobiomodulation for a Complex Patient with Severe

Hydroxyurea-Induced Oral Ulcerations.

Human
Case report

810

Oral

Uncategorized
(dental)

Ramalho

Brazil
(So Paulo)

2014

Case Rep Dent

Lasers in esthetic dentistry: soft tissue photobiomodulation, hard

tissue decontamination, and ceramics conditioning.

Human
Case report

660

Oral

Wound healing:
palatal wounds

Keskiner

Turkey
(Samsun)

2016

Photomed Laser
Surg

Effect of Photobiomodulation on Transforming Growth Factor-1,

Platelet-Derived Growth Factor-BB, and Interleukin-8 Release in
Palatal Wounds After Free Gingival Graft Harvesting: A
Randomized Clinical Study.

Human
RCT

1064

Oral

Wound healing

Wagner

Brazil
(Porto Alegre)

2016

Lasers Med Sci

Photobiomodulation regulates cytokine release and new blood

vessel formation during oral wound healing in rats.

Rat

660

830

40

830

40

830

40

4.8

132

Wisdom tooth

"In the second part of the study, low-power laser irradiation significantly reduced
postoperative pain intensity in patients premedicated with diclofenac, compared
with the controls."

PubMed

"CRP values were more symmetric and better distributed for the irradiated group
(0.320 mg/dl) than for the control (0.862.mg/dl) 48 h after surgery, however there
was no statistically significant difference. After 72 h, both groups had statistically
similar CRP levels (0.272 and 0.608 mg/dl), because of the normal tendency of
decreasing CRP levels."

PubMed

"The results of this study show that therapeutic low level laser treatment could not
statistically reduce the postoperative pain, swelling, trismus and function
impairment after extraction of lower third molars."

PubMed

"No statistically significant differences were observed in comparison of the

experimental side with the placebo side."

PubMed

"The results showed that there was no evidence of a difference in pain and
swelling on the third day after operation between laser and placebo sides. There
was no difference between the two sides when they were assessed for healing 7
days after surgery."

PubMed

"The effect of helium-neon (He-Ne) laser on the prevention of pain, swelling and
trismus following the removal of an impacted third molar was studied in 100
patients randomly allocated to receive He-Ne laser, ibuprofen or placebo in a
prospective double-blind parallel clinical trial.

PubMed

Trismus was significantly reduced in the He-Ne laser and ibuprofen treatment
groups. Pain was significantly less in the ibuprofen group with regard to He-Ne
laser and placebo groups. Swelling was the same in the three treatment groups."
50

40

0.32
1.6
(2p)

Oral

Wound healing

Khan & Arany

USA
(Bethesda, MD)

2015

Adv Wound Care

(New Rochelle)

Biophysical Approaches for Oral Wound Healing: Emphasis on

Photobiomodulation.

Other

Editorial

Abrahamse H

South Africa
(Johannesburg)

2016

Photomed Laser
Surg

Photobiomodulation: An Accepted Therapeutic Modality?

Review

Mechanisms
Editorial

4
20

1.3
cm2

0.04
cm2

160

"In this case report laser photobiomodulation has achieved pain control and has
contributed to the healing of oral ulcers without any adverse effect; this has
permitted a reduction in the dose of systemic corticosteroids and the suspension
of the use of the topic ones, due to the long-term stability of oral health, even after
the interruption of LLLT sessions."

PubMed

"Three different laser wavelengths were applied throughout the treatment with
different purposes: Nd:YAG laser (1,064 nm) for dentin decontamination, diode
(660 nm) for soft tissue biomodulation, and Er:YAG laser (2,940 nm) for inner
ceramic surface conditioning. Lasers were successfully applied in the present
case report as coadjutant in the treatment."

PubMed

4
(?)

"Observed increases in PWF TGF-1, PDGF-BB, and IL-8 levels suggest that
PBM may accelerate wound healing by stimulating production of selected
mediators."

PubMed

14

"PBM increased the tissue levels of IL-1 at the early stage of oral wound healing
(p < 0.01) and increased the tissue levels of TNF- during all stages of oral wound
healing (p < 0.05). PBM at a dose of 4 J/cm(2) produced more significant results
regarding cytokine modulation and was associated with higher MVD at day 5.
Collectively, these findings indicate that cytokine modulation and increased
angiogenesis are among the basic mechanisms whereby PBM improves oral
wound repair."

PubMed

"Photobiomodulation is increasingly popular for wound care and specifically suitable for oral wound care. While some of its mechanisms are well worked
out, others are being actively explored."

PubMed
PubMed

This paper seems to be somewhat poorly written.

Reply

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Subcategory

First author

Country

Journal

Title

Other

Editorial

Lanzafame RJ

USA
2015
(Rochester, NY)

Photomed Laser
Surg

Janusian peregrinations and progress.

Editorial

Other

Editorial

Brugnera Junior
& Bagnato

Brazil
(So Paulo)

2015

Photomed Laser
Surg

Biophotonics and the life sciences.

Guest Editorial

The authors list some of the benefits of LLLT and photodynamic therapy (PDT).

PubMed

Other

Editorial

Bjordal JM

Norway
(Bergen)

2015

Photomed Laser
Surg

Evidence-Based Medicine Turned Upside Down.

Guest Editorial

The author critisizes Cochrane Collaboration. An excerpt:

PubMed

Category

Year

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

sec

"[L]et us consider photobiomodulation (PBM), its visibility in the scientific literature, and its acceptance in the mainstream. Readers of this journal
generally understand the merits and limits of applying light in clinical and research scenarios. However, that is often not the case in the mainstream
scientific and clinical communities, despite the publication of thousands of publications on the topic. Proponent believers would argue that there is a
preponderance of literature that demonstrates the scientific validity of the PBM effect and supports its use.

PubMed

Nonbelievers on the other hand, are either unaware of the literature or question its validity. This lack of knowledge or lack of acceptance has some
interesting effects. Some of the so-called believers have asserted that the reason for this is either because PBM articles are not being published in, or
alternatively should only be published in high quality or high powered journals rather than in journals such as Photomedicine and Laser Surgery,
which are familiar with the discipline."

"Another issue possibly indicating a decline in transparency is their current procedure for exclusion of trials if only average pain scores, and not
dichotomous data of success, are reported. In their topical NSAID review, seven trials were excluded for not reporting dichotomous data. For low-level
laser therapy (LLLT) trials, it has been more common to report mean pain scores rather than dichotomized outcomes. Consequently, our research group
has reported both continuous and dichotomized outcome measures, to give the fullest picture of the evidence from available LLLT data. Omitting
continuous data, which consist of more than half of the evidence, is in my opinion, scientifically unacceptable, whereas integrating both outcome
measures will make the review conclusion more robust.
The question then is, why are continuous data omitted from meta-analyses. The most obvious reason is that it makes the results look better than they
are."
Also, Osteoarthritis Research Society International (OARSI), is being critisized:
"LLLT was left out of the new OARSI guidelines because it was infrequently recommended by other guidelines.
That could be considered acceptable if the LLLT evidence was presented by OARSI at the top tier of the level of evidence, the quality of studies, and the
effect size, but in 2014, it all changed when OARSI left the evidence mostly untouched, omitted LLLT completely, and founded their guidelines largely on
expert consensus. After a quarter of a century with EBM, it is sad to witness how OARSI has effectively turned the evidence pyramid upside down. I
should also add that 9 out of 17 members of the OARSI guideline board declare conflicts of interest with Big Pharma"
The conclusion is good:
"Consequently, I prefer to seek advice directly from the data in high quality trials in osteoarthritis, rather than relying on biased expert opinions. I feel that
I owe my patients the option of a safer nonpharmacological treatment alternative for their osteoarthritic pain."

Guest Editorial

"In 2008, my collaborators and I published an article in IEEE Journal of Selected Topics in Quantum Electronics in which we reported that P2Y receptors,
which are also endogenous receptors belonging to the G-protein-coupled superfamily, were involved in light-mediated neurite outgrowth. In this study, we
used 810 nm wavelength light and hypothesized that neurite outgrowth was caused by increases in adenosine triphosphate (ATP) acting as a signaling
molecule through the P2Y receptors. These findings suggest that G-protein coupled membrane receptors, which are ubiquitous and represent the largest
superfamily of proteins in the body, may play a critical role in the response of cells to light."

Other

Editorial

Anders JJ

USA
(Bethesda, MD)

2015

Photomed Laser
Surg

The International Year of Light: Celebrate and Educate.

Other

Editorial

Trelles MA

Spain
(Tarragona)

2014

Photomed Laser
Surg

Scientific rigor and strategic vision are the key points for going
forward in photomedicine.

Other

Editorial

Robinson NG

USA
(Fort Collins,
CO)

2014

Photomed Laser
Surg

Laser acupuncture: keep it scientific.

Guest Editorial

Other

Editorial

Liu & Kang

China
(Guangzhou)

2014

Photomed Laser
Surg

Functional photobiomodulation.

Guest Editorial

Other

Editorial

Lanzafame RJ

USA
2014
(Rochester, NY)

Photomed Laser
Surg

One man's light: mechanistic convergence of photobiomodulation

and biological effects.

Editorial

Other

Editorial

Choy DS

USA
(New York, NY)

2014

Photomed Laser
Surg

History of lasers in medicine.

Editorial

The author, inventor of the first laser knife (1962), tells interesting facts about lasers.

PubMed

Other

Editorial

Karu TI

Russia
(Troitsk)

2013

Photomed Laser
Surg

Is it time to consider photobiomodulation as a drug equivalent?

Guest Editorial

"The goal of the present Editorial is to highlight some important recent developments in clinical applications and in studies of cellular and molecular
mechanisms behind the clinical findings."

PubMed

PubMed

"The IYL 2015 is a time for celebrating light. It is also a time to celebrate the role of light in medicine. On a personal note, I am celebrating the pre-clinical
and clinical experiments that have resulted in the significant increase in interest in photobiomodulation"

Guest
Editorial

An excerpt: "There are no other choices than scientific rigor, personal enthusiasm, and strategic vision, to go forward in photomedicine. Without these,
chances would be missed to use light therapeutically to generate health and well-being in individuals"

PubMed

"Laser acupuncture is a rapidly developing discipline with a growing research basis. This wedding between laser and acupuncture, as in most marriages,
is for better or worse;usually with some of both. Like laser therapy, acupuncture can be approached scientifically; that is, one can describe its
mechanisms of action with contemporary biomedical terminology[...]"

PubMed

PubMed
PubMed

Taru goes on to mention about LLLT/PBM research/usage related to wounds/ulcers, pain management, nervous system injuries, Parkinson's disease,
stem cell stimulation, myocardial infarction, vitiligo, oral mucositis, depression/anxiety and gene expression.

Other

Editorial

Lanzafame RJ

USA
2013
(Rochester, NY)

Photomed Laser
Surg

Photobiomodulation: an enlightened path emerges.

Editorial

Other

Editorial

Lanzafame RJ

USA
2012
(Rochester, NY)

Photomed Laser
Surg

Minding the mind in photobiomodulation: it matters!

Editorial

Other

Editorial

Lanzafame RJ

Brazil
(So Paulo)

2011

Photomed Laser
Surg

Photobiomodulation, tissue effects and bystanders.

Editorial

Other

Editorial

Hamblin MR

2010

Lasers Surg Med

Introduction to experimental and clinical studies using low-level

laser (light) therapy (LLLT).

Editorial

Other

Hypothesis

Mathewson I

Australia
(Brisbane)

2015

Med Hypotheses

Did human hairlessness allow natural photobiomodulation 2

million years ago and enable photobiomodulation therapy today?
This can explain the rapid expansion of our genus's brain.

Pancreas

Regeneration

Huang

China
(Guangzhou)

2015

J Cell Biochem

Photoactivation of Akt1/GSK3 Isoform-Specific Signaling Axis

Promotes Pancreatic -Cell Regeneration.

Pancreas

Function

Irani

Iran
(Tehran)

2009

Transplant Proc

Effect of low-level laser irradiation on in vitro function of

pancreatic islets.

In vitro

Pain

Acute

Bjordal

Norway
(Bergen)

2006

Photomed Laser
Surg

Low-level laser therapy in acute pain: a systematic review of

possible mechanisms of action and clinical effects in randomized
placebo-controlled trials.

Systematic
review

Low-level laser therapy alleviates mechanical and cold allodynia

induced by oxaliplatin administration in rats.

Rat

Nocebo

Dose response

"Our path forward is best paved with careful research and methodical testing of parameters and treatment paradigms, coupled with honest evaluation of
the results, both positive and negative. This balanced approach requires our constant vigilance and patience. The enlightened path becomes brighter as
we proceed forward and continue to build responsibly on our collective efforts."

PubMed

"It would be a good idea to consider the potential influence of nocebo effects and nocebo responses in the clinical and investigational applications of light
in so-called low-level laser therapy (LLLT). There are numerous positive outcomes reported in the literature, as well as others that either demonstrated
no effect or an effect that was indistinguishable from the control or placebo. We would be foolish to presume that all of the negative reports were caused
by nocebo effects or responses. However, we should always be circumspect and vigilant as we describe the anticipated effects, outcomes, and
responses to a particular treatment, light-based or not. It would be unethical not to provide accurate information to the patient or to withhold information
from the patient during the informed consent process."

PubMed

PubMed
In this article, Hamblin describes various LLLT/PBM studies that had been recently published.

PubMed

"Assuming significant quantities of ATP are synthesised and brain energy and genetic expression changes occur as expected, this should be related to
the fact that these early Homo people are envisaged as being active in dappled savannah sunlight for most of the 12 daylight hours. For the hairless
ones, the extra ATP and the cerebral advantages would greatly improve their hunting abilities, giving them a big competitive advantage and allowing
them to add more animal protein to their diet. When a few related individuals became hairless, these more adept, more energetic early humans, with
much improved hunting skills, would find themselves in great demand as mates for the hairy ones."

PubMed

633

"In the present study, we showed that LPLI promoted -cell replication and cell
cycle progression through activation of Akt1/GSK3 isoform-specific signaling
axis. Inhibition of PI3-K/Akt or GSK3 with specific inhibitors dramatically reduced
or increased LPLI-induced -cell replication, revealing Akt/GSK3 signaling axis
was involved in -cell replication and survival upon LPLI treatment."

PubMed

"These findings suggest that low-level laser irradiations improved islet cell function
before transplantation."

PubMed

- Nine randomized placebo-controlled trials (n = 609) were of acceptable methodological quality, and irradiated three or more points and/or more than 2.5
cm(2) at site of injury or surgical incision, with a total energy of 5.0-19.5 Joules.

PubMed

630
810

0.01

0.2
0.4
0.8
1.2

40
50

1
3
5

- Results in these nine trials were significantly in favor of photoradiation groups over placebo groups in 15 out of 18 outcome comparisons.
- Poor and heterogeneous data presentation hampered statistical pooling of continuous data.
- Photoradiation can modulate inflammatory processes in a dose-dependent manner and can be titrated to significantly reduce acute inflammatory pain in
clinical settings.

Pain

Allodynia

Hsieh

Taiwan
(Taichung)

2016

Support Care
Cancer

Pain

Analgesia

Meireles

Brazil
(Cascavel)

2012

Rev Dor

Role of endogenous opioids in 820 nm low power laser analgesia

in the knees of Wistar rats

Rat

Pain

Analgesia

Hagiwara

Japan
(Yufu)

2008

Anesth Analg

Pre-Irradiation of blood by gallium aluminum arsenide (830 nm)

low-level laser enhances peripheral endogenous opioid analgesia
in rats.

Rat

Pain

Analgesia

Hagiwara

Japan
(Yufu)

2007

Lasers Surg Med

GaAlAs (830 nm) low-level laser enhances peripheral endogenous

opioid analgesia in rats.

Rat

Pain

Back pain

Holanda

Brazil
(So Paulo)

2016

Lasers Surg Med

Photobiomodulation of the dorsal root ganglion for the treatment of Human

low back pain: A pilot study.
Comparison
trial

780

820

Endogenous opioids

50

62.5
(?)

30

7.5

0.2
cm2
spot

30
/point

"LLLT relieved both cold and mechanical allodynia induced by oxaliplatin in rats.
Oxaliplatin-related increases in protein levels of NGF and TRPM8 in DRG and SP
in the dorsal horn were also reduced after LLLT."
"The findings of this study support LLLT as a potential treatment for oxaliplatininduced neuropathy. Moreover, our findings suggest that SP, TRPM8, and NGF
proteins in the superficial dorsal horn and DRG may be involved in an antiallodynic
effect for LLLT."

0.1160
cm2

"Our study has observed that low power 820 nm laser analgesic effect has
suffered significant interference and was antagonized by naloxone. To justify such
effect, it is inferred that the group receiving naloxone and low power laser
association has maintained pain in intra-group comparison for the third evaluation
moment. It is then believed that laser might have induced endogenous opioids
production and release by blood cells15, thus explaining our results."

SciELO

"These findings suggest that that LLLT pretreatment of blood induces analgesia in
rats by enhancing peripheral endogenous opioid production, in addition to
previously reported mechanisms."

PubMed

"LLLT produced an analgesic effect in inflamed peripheral tissue which was

transiently antagonized by naloxone. Beta-endorphin precursor mRNA expression
increased with LLLT, both in vivo and in vitro."

PubMed

"All patients in the local anesthetic and laser treatment groups reported a pain
reduction of at least 50% immediately post-procedure and 10 out of 11 patients in
the radiofrequency group reported a pain reduction of at least 50%. At 1 month
post-treatment, the laser treatment group had the greatest number of patients who
reported more than 50% pain relief based on PRS (7 out of 10 patients) while only
2 out of 7 patients and 3 out of 11 patients in the lidocaine and radiofrequency
treatment groups respectively reported more than a 50% pain relief."

PubMed

830

Systemic effects
Endogenous opioids

830

200.7

Systemic effects
LLLT vs lidocaine

808

100

35

8.4

2800

PubMed

0.8
cm2
total
area

0.003
cm2

84

PBM of dorsal root

ganglion (DRG)
Photon Lase III
DCM, Brazil

"Laser irradiation caused an immediate decrease in low back pain post-procedure

similar to pain reduction caused by lidocaine injection."

Pain

Back pain

Glazov

Australia

2016

Acupunct Med

Low-level laser therapy for chronic non-specific low back pain: a

meta-analysis of randomised controlled trials.

Metaanalysis

Pain

Back pain

Huang

China
(Chengdu)

2015

Arthritis Res Ther

The effectiveness of low-level laser therapy for nonspecific chronic Metalow back pain: a systematic review and meta-analysis.
analysis

Pain

Back pain

Vallone

Italy
(Genoa)

2014

Photomed Laser
Surg

Effect of diode laser in the treatment of patients with nonspecific

chronic low back pain: a randomized controlled trial.

Human
RCT

Pain

Back pain

Glazov

Australia
(Crawley)

2014

Acupunct Med

Low-dose laser acupuncture for non-specific chronic low back

pain: a double-blind randomised controlled trial.

Human
RCT/DB

"We demonstrated moderate quality of evidence (GRADE) to support a clinically important benefit in LLLT for CNLBP in the short term, which was only
seen following higher laser dose interventions and in participants with a shorter duration of back pain. Rigorously blinded trials using appropriate laser
dosage would provide greater certainty around this conclusion."

PubMed

"Our findings indicate that LLLT is an effective method for relieving pain in NSCLBP patients. However, there is still a lack of evidence supporting its
effect on function."

PubMed

980

20000

840

20

1200
/p

37.5

32
cm2

"At the end of the 3 week period, the Laser+EX group showed a significantly
greater decrease in pain than did the EX group. There was a significant difference
between the two groups, with average VAS scores of 3.96 (Laser+EX group)
and 2.23 (EX group)."

PubMed

Comment: One of the rare studies with a large spot size!

Laser acupuncture

0.1

0.2
0.8

"The analysis showed no difference between sham and the laser groups at 6
weeks for pain or disability."

PubMed

12

"HILT combined with exercise appears to be more effective in patients with CLBP
than either HLLT alone or placebo laser with exercise."

PubMed

/p

Pain

Back pain

Alayat

Egypt
(Cairo)

2014

Lasers Med Sci

Long-term effect of high-intensity laser therapy in the treatment of

patients with chronic low back pain: a randomized blinded
placebo-controlled trial.

Human
RCT/DB (?)

1064

3000

0.2
cm2
(spot)

900

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Back pain

Lin

Taiwan
(Taipei)

2012

Evid Based
Complement
Alternat Med

Evaluation of the effect of laser acupuncture and cupping with

ryodoraku and visual analog scale on low back pain.

Human
RCT/DB

Laser acupuncture

Serbia
(Belgrade)

2010

Photomed Laser
Surg

Acute low back pain with radiculopathy: a double-blind,

randomized, placebo-controlled study.

Human
RCT/DB

Radiculopathy

Pain

Pain

Back pain

Konstantinovic

nm

mW

W/cm2

J/cm2

808

40

Results: positive / unclear/modest / negative

Link

Additional info

Comment

Reply

PubMed

Comment

Reply

PubMed

Comment

sec

~15

0,8
cm2

600

No difference between active laser and placebo.

PubMed

Note: The anatomical site of irradiation was leg, not back...

904

100

0.02

12

d=
1 cm

600

15

"Statistically significant differences were found in all outcomes measured (p <

0.001), but were larger in [LLLT group] than in [nimesulide group] (p < 0.0005) and
[nimesulide + sham-LLLT group] (p < 0.0005).

PubMed

The results in [nimesulide + sham-LLLT group] were better than in [nimesulide

group] (p < 0.0005)."

Pain

Back pain

Ay

Turkey
(Ankara)

2010

Clin Rheumatol

Is low-level laser therapy effective in acute or chronic low back

pain?

Human
RCT/DB

Pain

Back pain

Glazov

Australia
(Perth)

2009

Acupunct Med

Laser acupuncture for chronic non-specific low back pain: a

controlled clinical trial.

Human
RCT/DB

Pain

Back pain

Yousefi-Nooraie

Iran
(Tehran)

2008

Cochrane
Database Syst
Rev

Low level laser therapy for nonspecific low-back pain.

Metaanalysis

Pain

Back pain

Djavid

Iran

2007

Aust J Physiother

In chronic low back pain, low level laser therapy combined with
exercise is more beneficial than exercise alone in the long term: a
randomised trial.

Human
RCT/DB (?)

Pain

Back pain

Gur

Turkey
(Diyarbakir)

2003

Lasers Surg Med

Efficacy of low power laser therapy and exercise on pain and

functions in chronic low back pain.

Human

Pain

Back pain

Basford

USA
(Rochester,
MN)

1999

Arch Phys Med

Rehabil

Laser therapy: a randomized, controlled trial of the effects of lowintensity Nd:YAG laser irradiation on musculoskeletal back pain.

Human
RCT/DB

Pain

Back pain

Klein & Eek

USA
1990
(Santa Barbara,
CA)

Arch Phys Med

Rehabil

Low-energy laser treatment and exercise for chronic low back pain:
double-blind controlled trial.

Pain

Hyperalgesia

Martins

Brazil
(Palhoa)

Neuroscience

Light-emitting diode therapy reduces persistent inflammatory pain: Mouse

Role of interleukin 10 and antioxidant enzymes.

Laser acupuncture

850

100

830

10

40

0.07
cm2

480960

0.2
/p

15

"no significant differences were detected between four treatment groups with
respect to all outcome parameters (p > 0.05)"

PubMed

510

"This study did not show a specific effect for LA using infrared laser at 0.2 Joules
per point for chronic low back pain."

PubMed

Based on the heterogeneity of the populations, interventions and comparison groups, we conclude that there are insufficient data to draw firm
conclusions on the clinical effect of LLLT for low-back pain.

(no control group)

810

50

904
(?)

4.2

27

0.221
cm2

~
1200

1
cm2

1800

20

1060

0.1

PubMed

"in the laser therapy plus exercise group pain had reduced by 1.8 cm (95% CI 0.1
to 3.3, p = 0.03), lumbar range of movement increased by 0.9 cm (95% CI 0.2 to
1.8, p < 0.01) on the Schober Test and by 15 deg (95% CI 5 to 25, p < 0.01) of
active flexion, and disability reduced by 9.4 points (95% CI 2.7 to 16.0, p = 0.03)
more than in the exercise group at 12 weeks."

PubMed

"Low power laser therapy seemed to be an effective method in reducing pain and
functional disability in the therapy of chronic LBP."

PubMed

"Treatment with low-intensity 1.06 microm laser irradiation produced a moderate

reduction in pain and improvement in function in patients with musculoskeletal low
back pain. Benefits, however, were limited and decreased with time."

PubMed

"There were significant improvements in objective parameters in both the laser

and placebo groups, but no relative advantage accrued to either group. Under the
conditions of this study, low-energy laser stimulation plus exercise did not provide
a significant advantage over exercise alone."

PubMed

Note: According to Tuner&Hode 1998, the power density was 0.1 J/cm2 instead of
the stated 1.3 J/cm2.

2016

Chronic inflammatory
hyperalgesia induced
by Complete
Freund's Adjuvant
(CFA)

950

0.08

1
2
4

1
cm2

13
25
50

"LEDT inhibited mechanical and thermal hyperalgesia induced by CFA injection.

LEDT significantly prevented TBARS increase in both acute and chronic phases
post-CFA injection; whereas protein carbonyl levels were reduced only in the
acute phase.

LED phototherapy

LEDT induced an increase in both SOD and CAT activity, with effects observable
in the acute but not in the chronic. And finally, pre-administration of naloxone or
fucoidin prevented LEDT analgesic effect."

Dose response

Pain

Hyperalgesia

Nadur-Andrade

Brazil
(So Paulo)

2016

PLoS Negl Trop

Dis

Analgesic Effect of Photobiomodulation on Bothrops Moojeni

Venom-Induced Hyperalgesia: A Mechanism Dependent on
Neuronal Inhibition, Cytokines and Kinin Receptors Modulation.

Mouse

Pain

Hyperalgesia

Nadur-Andrade

Brazil
(So Paulo)

2014

Photochem
Photobiol

Analgesic Effect of Light-Emitting Diode (LED) Therapy at

Wavelengths of 635 and 945 nm on Bothrops moojeni VenomInduced Hyperalgesia.

Mouse

Pain

Mechanisms

Chow & Armati

Australia
(Sydney)

2016

Photomed Laser
Surg

Photobiomodulation: Implications for Anesthesia and Pain Relief.

Review

Hyperalgesia induced
by snake poison

PubMed

LEDT did not reduce paw edema, neither influenced the levels of TNF- and IL1; although it increased the levels of IL-10.

(area)

685

30

2.2

635
945

110
120

3.76
3.8

0.2
cm2

15

1/2
?

41
38

"These data demonstrate that LLLT interferes with mechanisms involved in

nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The
use of photobiomodulation in reducing local pain induced by Bothropic venoms
should be considered as a novel therapeutic tool for the treatment of local
symptoms induced after bothropic snakebites."

PubMed

"Both 635 nm and 945 nm LED inhibited mechanical allodynia and hyperalgesia of
mice alone or in combination with antivenom treatment, even when the symptoms
were already present."

PubMed

"Evidence shows that PBM can inhibit nerve function in vivo, in situ, ex vivo, and in culture. Animal studies using noxious stimuli indicate nociceptorspecific inhibition with other studies providing direct evidence of local conduction block, leading to inhibited translation of pain centrally."

PubMed

"Evidence of PBM-disrupted neuronal physiology affecting axonal flow, cytoskeleton organization, and decreased ATP is also presented. PBM changes
are reversible with no side effects or nerve damage."
Comment: It is interesting that they are reporting decreased ATP instead of increased.

Pain

Mechanisms

Chow

Australia
(Sydney)

2007

J Peripher Nerv
Syst

830 nm laser irradiation induces varicosity formation, reduces

mitochondrial membrane potential and blocks fast axonal flow in
small and medium diameter rat dorsal root ganglion neurons:
implications for the analgesic effects of 830 nm laser.

In vitro

Analgesia

830

"Photoacceptors in the mitochondrial membrane absorb laser and mediate the

transduction of laser energy into electrochemical changes, initiating a secondary
cascade of intracellular events. In neurons, this results in a decrease in MMP with
a concurrent decrease in available ATP required for nerve function, including
maintenance of microtubules and molecular motors, dyneins and kinesins,
responsible for fast axonal flow. Laser-induced neural blockade is a consequence
of such changes and provide a mechanism for a neural basis of laser-induced pain
relief."

PubMed

Tuner commented: "By using high energies, the pain transmission in nerves is temporarily slowed down [4]. This is a useful option in many situations of acute pain. But on the other
hand, the inflammatory background of the pain is also inhibited and the actual healing is slower."

"The repeated application of laser in a clinical setting modulates nociception and

reduces pain. The application of laser therapy for chronic pain may provide a nondrug alternative for the management of chronic pain."
[See additional info]

Pain

Mechanisms

Bjordal

Norway
(Bergen)

2006

Photomed Laser
Surg

Low-level laser therapy in acute pain: a systematic review of

possible mechanisms of action and clinical effects in randomized
placebo-controlled trials.

"There is strong evidence from 19 out of 22 controlled laboratory studies that photoradiation can modulate inflammatory pain by reducing levels of
biochemical markers (PGE(2), mRNA Cox 2, IL-1beta, TNFalpha), neutrophil cell influx, oxidative stress, and formation of edema and hemorrhage in a
dose-dependent manner (median dose 7.5 J/cm(2), range 0.3-19 J/cm(2))."

Systematic
review

PubMed

"Four comparisons with non-steroidal anti-inflammatory drugs (NSAIDs) in animal studies found optimal doses of photoradiation and NSAIDs to be
equally effective."
"Seven randomized placebo-controlled trials found no significant results after irradiating only a single point on the skin overlying the site of injury, or after
using a total energy dose below 5 Joules."
"Nine randomized placebo-controlled trials (n = 609) were of acceptable methodological quality, and irradiated three or more points and/or more than 2.5
cm(2) at site of injury or surgical incision, with a total energy of 5.0-19.5 Joules. Results in these nine trials were significantly in favor of photoradiation
groups over placebo groups in 15 out of 18 outcome comparisons."
"Poor and heterogeneous data presentation hampered statistical pooling of continuous data. Categorical data of subjective improvement were
homogeneous (Q-value = 7.1) and could be calculated from four trials (n = 379) giving a significant relative risk for improvement of 2.7 (95% confidence
interval [CI], 1.8-3.9) in a fixed effects model."

Pain

Pain

Pain

Myofascial

Myofascial

Myofascial

Hsieh

Manca

Simunovic Z

Taiwan
(Taichung)

Italy

Switzerland

2015

2014

1996

Lasers Med Sci

Fluence-dependent effects of low-level laser therapy in myofascial

trigger spots on modulation of biochemicals associated with pain
in a rabbit model.

"LLLT irradiation with fluences of 4.5 and 27 J/cm(2) at [myofascial trigger points]
can significantly reduce SP level in [dorsal root ganglion].

Rabbit

Physiother Res Int Ultrasound and laser as stand-alone therapies for myofascial
trigger points: a randomized, double-blind, placebo-controlled
study.

Human
RCT

Pain (trigger points)

J Clin Laser Med

Surg

Low level laser therapy with trigger points technique: a clinical

study on 243 patients.

Human
Biphasic dose
Retrospective response

904

30

4
cm2

600

LLLT+ultrasound was not better than placebo. LLLT and placebo were better than
control (no treatment).

633
820830
904

Myofascial

Airaksinen

Finland

1989

Acupunct
Electrother Res

Effects of the infrared laser therapy at treated and non-treated

trigger points

Human
RCT,
crossover

Pain

Neck

Wong

Canada

2016

Spine J

Are manual therapies, passive physical modalities, or acupuncture

effective for the management of patients with whiplash-associated
disorders or neck pain and associated disorders? An update of the
Bone and Joint Decade Task Force on Neck Pain and Its
Associated Disorders by the OPTIMa collaboration.

Systematic
review

Is low-level laser therapy in relieving neck pain effective?

Systematic review and meta-analysis.

Metaanalysis

Neck

Kadhim-Saleh

Canada
(Ottawa)

2013

Rheumatol Int

PubMed

Note: In the PubMed Commons, there is some discussion between Jan Tunr and
the study author Andrea Manca.

Pain

Pain

PubMed

LLLT with lower fluence of 4.5 J/cm(2) exerted lower levels of TNF- and COX-2
expression in laser-treated muscle, but LLLT with higher fluence of 27 J/cm(2)
elevated the levels of [-endorphin] in serum, [dorsal root ganglion], and muscle."

Trigger point pain

"Results measured according to VAS/VRS/PTM: in acute pain, diminished more

than 70%; in chronic pain more than 60%. Clinical effectiveness (success or
failure) depends on the correctly applied energy dose--over/underdosage
produces opposite, negative effects on cellular metabolism. We did not observe
any negative effects on the human body and the use of analgesic drugs could be
reduced or completely excluded. LLLT suggests that the laser beam can be used
as monotherapy or as a supplementary treatment to other therapeutic procedures
for pain treatment."

PubMed

"Our research study results suggest that infrared laser had an effect at the trigger
points and that the treatment significantly increased the pain threshold."

IngentaCo
nnect

(1) According to the abstract, evidence on LLLT seems negative: "LLLT does not offer benefits"
(2) Because of this conclusion, Roberta Chow published a Letter to the Editor, noting that the full text of the article suggests that there is "consistent
evidence" for LLLT in neck pain and associated disorders.
(3) In their response, Wong et al mention that the abstract summarizes only the "new evidence", while the totality of data supports LLLT.
"This systematic review provides inconclusive evidence because of significant between-study heterogeneity and potential risk of bias. The benefit seen in
the use of LLLT, although statistically significant, does not constitute the threshold of minimally important clinical difference."
In their critique of this paper, Bjordal et al mention that in this meta-analysis, one important paper was excluded for erroneous reasons, and that there
were also other false statements and methodological shortcomings in the paper.
In a PubMed Commons comment, James Carroll (THOR Photomedicine Ltd) also critisizes the review in a similar manner as Bjordal et al.

Pain

Neck

Swedish Council
on Health
Technology
Assessment
(SBU)

Sweden

2014

Swedish Council
on Health
Technology
Assessment
(SBU)

Laser Treatment of Neck Pain [Internet].

Systematic
review

"In cases of chronic neck pain, low effect laser therapy can provide relief from pain for 26 months after the completion of treatment. The studies have
not especially focused on side effects, but no serious complications or side effects have been reported. There are no cost-effectiveness studies
comparing low level laser to other treatments. Several well-executed studies are necessary to determine with certainty the effects of treatment with low
level laser compared to placebo and other methods, above all in cases of acute pain, and with regard to function and working capacity, and to long-term
effects."

PubMed

Pain

Neck

Gross

Canada
(Hamilton)

2013

Open Orthop J

Low Level Laser Therapy (LLLT) for Neck Pain: A Systematic

Review and Meta-Regression.

Systematic
review

"Of 17 trials, 10 demonstrated high risk of bias.

PubMed

For chronic neck pain, there was moderate quality evidence (2 trials, 109 participants) supporting LLLT over placebo to improve pain/disability/QoL/GPE
up to intermediate-term (IT).
For acute radiculopathy, cervical osteoarthritis or acute neck pain, low quality evidence suggested LLLT improves ST pain/function/QoL over a placebo.
For chronic myofascial neck pain (5 trials, 188 participants), evidence was conflicting; a meta-regression of heterogeneous trials suggests super-pulsed
LLLT increases the chance of a successful pain outcome."

Pain

Neck

Konstantinovic

Serbia
(Belgrade)

2010

Pain Med

Low-level laser therapy for acute neck pain with radiculopathy: a

double-blind placebo-controlled randomized study.

Human
RCT/DB

905

0.012

120

15

"LLLT gave more effective short-term relief of arm pain and increased range of
neck extension in patients with acute neck pain with radiculopathy in comparison
to the placebo procedure."

PubMed

 Category
Pain

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Neck

Chow

Australia

2009

Lancet

Efficacy of low-level laser therapy in the management of neck pain: Metaa systematic review and meta-analysis of randomised placebo or
analysis
active-treatment controlled trials.

Study type Sub-category 2 /

animal model
Chronic neck pain

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

Additional info

Comment

Reply

Editorial

Comment
ary

sec

The meta-analysis:

PubMed

"Patients in 11 trials reporting changes in visual analogue scale had pain intensity reduced by 19.86 mm (10.04-29.68)."
"We show that LLLT reduces pain immediately after treatment in acute neck pain and up to 22 weeks after completion of treatment in patients with
chronic neck pain."

Pain

Neck

Chow

Australia
(Sydney)

2006

Pain

830

The effect of 300 mW, 830 nm laser on chronic neck pain: a double- Human
blind, randomized, placebo-controlled study.
RCT/DB

300

14

"Low-level laser therapy (LLLT), at the parameters used in this study, was
efficacious in providing pain relief for patients with chronic neck pain over a period
of 3 months."

PubMed

Editorial notes: "Although patients were randomly assigned to the laser group and
placebo group, there was a substantial imbalance of baseline pain scores between
the groups (i.e. a difference of 1.9 on a 10-points scale)."

Pain

Neck

Chow & Barnsley Australia

(Sydney)

2005

Lasers Surg Med

Holanda

Brazil
(So Paulo)

2017
epub

Lasers Surg Med

Germany
(Landstuhl)

2016
epub

Pain Med

Systematic review of the literature of low-level laser therapy (LLLT)

in the management of neck pain.

Systematic
review

The mechanistic basis for photobiomodulation therapy of

neuropathic pain by near infrared laser light.

Rat
+ in vitro

"Significant positive effects were reported in four of five trials in which infrared wavelengths (lambda = 780, 810-830, 904, 1,064 nm) were used.

PubMed

Heterogeneity in outcome measures, results reporting, doses, and laser parameters precluded formal meta-analysis. Effect sizes could be calculated for
only two of the studies."
"This review provides limited evidence from one RCT for the use of infrared laser for the treatment of acute neck pain (n = 71) and chronic neck pain
from four RCTs (n = 202). Larger studies are required to confirm the positive findings and determine the most effective laser parameters, sites and
modes of application."

Pain

Pain

Neuropathic

Neuropathic

Kobiela Ketz

Characterization of Macrophage/Microglial Activation and Effect of

Photobiomodulation in the Spared Nerve Injury Model of
Neuropathic Pain.

Spared nerve injury

surgery (SNI)

808

Irradiation of affected
hind paw + dorsal
root ganglia + spinal
cord regions

980

10000

0.270

120

heat hyperalgesia, cold allodynia, mechanical hyperalgesia

PubMed

"Of clinical relevance is the duration of the effect. As demonstrated, even after 21
days, the laser treated group showed less sensitivity to the heat stimulus
compared to control group. For cold allodynia and mechanical hyperalgesia, the
duration of the effect was 5 days"
1000
+
4500
+
1500

0.043
+
0.043
+
0.043

20
+
85.5
+
28.5

20
+
19
+
19

11
(?)

"Injured groups demonstrated mechanical hypersensitivity 1-30 days postoperatively. Photobiomodulation-treated animals began to recover after two
treatments; at day 26, mechanical sensitivity reached baseline."

PubMed

"Peripheral nerve injury caused region-specific macrophages/microglia activation

along spinothalamic and dorsal-column medial lemniscus pathways. A proinflammatory microglial marker was expressed in the spinal cord of injured rats
compared to photobiomodulation-treated and sham group."

Microglia (M2
activation by LLLT)

"Photobiomodulation-treated dorsal root ganglion macrophages expressed antiinflammatory markers."

"Photobiomodulation effectively reduced mechanical hypersensitivity, potentially
through modulating macrophage/microglial activation to an anti-inflammatory
phenotype."
Comment: The 'sham group' refers to sham surgery, not sham treatment.

Pain

Neuropathic

Oliveira

Brazil
(So Paulo)

2016
epub

Photochem
Photobiol Sci

Low Level Laser Therapy alters satellite glial cell expression and
reverses nociceptive behavior in rats with neuropathic pain

Rat

Chronic constriction
injury

904

54
(9p)

0.1
cm2
spot

162
(9p)

10

IL-1, CX3CL1, gliosis of DRG, hyperalgesia

RSC

"These data provide evidence that LLLT reverses CCI-induced behavioral

hypersensitivity, reduces glial cell activation in the DRG and decrease proinflammatory cytokines; we suggest that this involvement of glial cells can be one
potential mechanism in such effect."

0.9
cm2
area

Pain

Neuropathic

Janzadeh

Iran
(Tehran)

2016

Lasers Med Sci

Photobiomodulation therapy reduces apoptotic factors and

increases glutathione levels in a neuropathic pain model.

Rat

Chronic constriction
injury

660

100

0.354

0.238
cm2

11

14

"CCI decreased the pain threshold, 2-week photobiomodulation therapy

significantly increased mechanical and thermal threshold, decreased P2X3
expression (p < 0.001), and increased bcl2 expression (p < 0.01), but it was not
effective on the Bax expression. We speculated that although photobiomodulation
therapy increased ROS generation, it increased antioxidants such as GSH."

PubMed

Pain

Neuropathic

Masoumipoor

Iran
(Tehran)

2014

Lasers Med Sci

Effects of 660- and 980-nm low-level laser therapy on neuropathic

pain relief following chronic constriction injury in rat sciatic nerve.

Rat

Chronic constriction
injury

660
980

100
70

0.354
0.248

4
4

0.238
cm2

11.3
16.13

14

"CCI decreased the pain threshold, whereas both wavelengths of LLLT for 2
weeks increased mechanical and thermal threshold significantly."

PubMed

"Based on our findings, the laser with a 660-nm wavelength had better therapeutic
effects than the laser with a 980-nm wavelength, so the former one may be used
for clinical application in neuropathic cases; however, it needs more future
studies."

Pain

Nociception

Chow

Australia
(Sydney)

2011

Photomed Laser
Surg

Inhibitory effects of laser irradiation on peripheral mammalian

nerves and relevance to analgesic effects: a systematic review.

"We identified 44 studies suitable for inclusion. In 13 of 18 human studies, pulsed or continuous wave visible and continuous wave infrared (IR) LI slowed
conduction velocity (CV) and/or reduced the amplitude of compound action potentials (CAPs). In 26 animal experiments, IR LI suppressed electrically
and noxiously evoked action potentials including pro-inflammatory mediators. Disruption of microtubule arrays and fast axonal flow may underpin neural
inhibition."

Systematic
review

PubMed

"This review has identified a range of laser-induced inhibitory effects in diverse peripheral nerve models, which may reduce acute pain by direct inhibition
of peripheral nociceptors. In chronic pain, spinal cord changes induced by LI may result in long-term depression of pain. Incomplete reporting of
parameters limited aggregation of data."

Pain

Pain

Nociception

Postoperative

Laakso & Cabot

Cidral-Filho

Australia
(Gold Coast)
Brazil
(Florianpolis)

2005

2014

Photomed Laser
Surg
Lasers Med Sci

Nociceptive scores and endorphin-containing cells reduced by

low-level laser therapy (LLLT) in inflamed paws of Wistar rat.

Rat

Light-emitting diode therapy induces analgesia in a mouse model

of postoperative pain through activation of peripheral opioid
receptors and the L-arginine/nitric oxide pathway.

Mouse

Dose response (?)

780

Dose response

950

0.08

Biphasic dose
response
LED phototherapy

Pain

Review

Cotler

USA
(Houston, TX)

2015

MOJ Orthop
Rheumatol

The Use of Low Level Laser Therapy (LLLT) For Musculoskeletal

Pain.

Review

Pain

Sciatica

Bertolini

Brazil
(Cascavel)

2011

Arq
Neuropsiquiatr

Low-level laser therapy, at 830 nm, for pain reduction in

experimental model of rats with sciatica.

Rat

Pain

Shoulder

Kibar

Turkey
(Ankara)

2016

Pain Med

Pain

Shoulder

Yavuz

Turkey
(Ankara)

2014

Pain

Shoulder

Montes-Molina

Spain

Pain

Shoulder

Dogan

Turkey
(Ankara)

Pain

Shoulder

Stergioulas A

Greece
(Sparta)

"A dose of 1 J/cm(2) had no statistically significant effect on antinociceptive

responses. A dose of 2.5 J/cm(2) demonstrated a statistically significant effect on
paw pressure threshold ( p < 0.029) compared to controls. There was no
difference in paw thermal threshold responses and paw volumes at either dose."

PubMed

1
3
5
7
9
11
13

"In conclusion, our results demonstrate, for the first time, that LEDT (950 nm, 80
mW/cm2) induced a doseresponse analgesic effect in the model of PI in mice. At
the energy density of 9 J/cm2, LEDT presented the most significant results
through (1) activation of peripheral opioid receptors which involve, at least in part,
the recruitment of opioid-containing leukocytes to the PI site and (2) activation of
the l-arginine/NO pathway."

PubMed

"The purpose of this paper is to review the use of LLLT for pain, the biochemical mechanisms of action, the dose response curves, and how LLLT may
be employed by orthopedic surgeons to improve outcomes and reduce adverse events."

Biphasic dose
response (?)

830

Laser Acupuncture Treatment Improves Pain and Functional Status Human

in Patients with Subacromial Impingement Syndrome: A
RCT/DB
Randomized, Double-Blind, Sham-Controlled Study.

Subacromial
impingement
syndrome

850

J Back
Musculoskelet
Rehabil

Low-level laser therapy versus ultrasound therapy in the treatment

of subacromial impingement syndrome: a randomized clinical trial.

Human
Randomized
Comparison
trial

Subacromial
impingement
syndrome

2012

Physiotherapy

Interferential laser therapy in the treatment of shoulder pain and

disability from musculoskeletal pathologies: a randomised
comparative study.

Human
Comparison
trial

2010

Clinics (Sao
Paulo)

The effectiveness of low laser therapy in subacromial impingement Human

syndrome: a randomized placebo controlled double-blind
RCT/DB
prospective study.

2008

Photomed Laser
Surg

Low-power laser treatment in patients with frozen shoulder:

preliminary results.

Human
RCT/SB

1
2.5

Subacromial
impingement
syndrome

4
8

100

850

810

60

14.4
(8p)

3.6

0.5
cm2

240

12

PubMed

"Low-level laser was effective in reducing the painful condition."

PubMed

"All parameters of pain and functional status in the treatment group were
significantly better than those in the control group at week 3."

PubMed

"The results suggest that efficacy of both treatments were comparable to each
other in regarding reducing pain severity and functional disability in patients with
subacromial impingement syndrome. Based on our findings, we conclude that lowlevel laser therapy may be considered as an effective alternative to ultrasound
based therapy in patients with subacromial impingement syndrome especially
ultrasound based therapy is contraindicated."

PubMed

Interferential LLLT wasn't better than normal LLLT.

PubMed

"The Low level laser therapy seems to have no superiority over placebo laser
therapy in reducing pain severity, range of motion and functional disability."

PubMed

"Relative to the placebo group, the active laser group had:

PubMed

(1) a significant decrease in overall, night, and activity pain scores at the end of 4
wk and 8 wk of treatment, and at the end of 8 wk additional follow-up (16 wk postrandomization);
(2) a significant decrease in shoulder pain and disability index (SPADI) scores and
Croft shoulder disability questionnaire scores at those same intervals;
(3) a significant decrease in disability of arm, shoulder, and hand questionnaire
(DASH) scores at the end of 8 wk of treatment, and at 16 wk posttreatment; and
(4) a significant decrease in health-assessment questionnaire (HAQ) scores at the
end of 4 wk and 8 wk of treatment.
There was some improvement in range of motion, but this did not reach statistical
significance."

Pain

Surgical

Alvarange

Brazil
(So Paulo)

2016
epub

Lasers Surg Med

Effect of low-level laser therapy on pain and perineal healing after

episiotomy: A triple-blind randomized controlled trial.

Human
RCT/DB (TB)

780

20

1.8

0.04
cm2
(spot)

90

Pain

Surgical

Santos Jde

Brazil
(So Paulo)

2012

J Clin Nurs

Low-level laser therapy for pain relief after episiotomy: a doubleblind randomised clinical trial.

Human
RCT/DB

Pain

Surgical

Santos Jde

Brazil
(So Paulo)

2012

Midwifery

A randomised clinical trial of the effect of low-level laser therapy

for perineal pain and healing after episiotomy: a pilot study.

Human
RCT/DB
Pilot study

Pain

Trigeminal
neuralgia

Falaki

Iran
(Mashdad)

2014

J Dent Res Dent

Clin Dent
Prospects

The Effect of Low-level Laser Therapy on Trigeminal Neuralgia: A

Review of Literature.

Review

660

15

0.45

3.8

0.04
cm2

"The use of LLLT does not provide any benefit for treating postpartum perineal
trauma using these specific protocol and parameters."

PubMed

"Further research may be necessary to define an appropriate irradiation protocol

to treat post-partum perineal pain."

(9 pts)

"The effect of laser in perineal pain relief was not demonstrated in this study. The
dosage may not have been sufficient to provide relief from perineal pain after
episiotomy during a vaginal birth."

PubMed

"This pilot study showed that LLLT did not accelerate episiotomy healing. Although
there was a reduction in perineal pain mean scores in the experimental group, we
cannot conclude that the laser relieved perineal pain. This study led to the
suggestion of a new research proposal involving another irradiation protocol to
evaluate LLLT's effect on perineal pain relief."

PubMed

Comment: Quite a low dose was used.

"However, in most studies laser therapy was associated with significant reduction in the intensity and frequency of pain compared with other treatment
strategies, a few studies revealed that between laser and placebo group there was not any significant difference according to the analgesic effect. Lowlevel laser therapy could be considered in treatment of trigeminal neuralgia without any side effects."
Comment: This review wasn't very critical/extensive.

PubMed

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Trigeminal
neuralgia

Aghamohammad Iran
i
(Tabriz)

Pain

Year

Journal

Title

Study type Sub-category 2 /

animal model

2012

Neurosurg Q

Gasserian Ganglion Block With or Without Low-intensity Laser

Therapy in Trigeminal Neuralgia: A Comparative Study

Human
RCT
Comparison
trial

nm

mW

W/cm2

890

J/cm2

Results: positive / unclear/modest / negative

Link

sec

3-10
/point

"The severity of pain was significantly lower in group A, from day 7 until the end of
the study period (month 6). The number of carbamazepine tablets taken was also
significantly lower in group A compared with group B from the initial months until
the end of the study period (month 6). The period of a pain-free state was
significantly higher in group A than in group B (P<0.00l).""

LWW

Comment: LLLT was very clearly superior in this study.

Comment: Parameters were poorly reported. According to the paper, they used
"Mustang 026 Russia, and the probe type was LO3"". The following paper ( http:
//proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=887067 ) seems to
have some data on these Russian lasers, but it seems impossible to retrieve the
relevant parameters.
Comment: This journal isn't indexed in PubMed, and its' ranking is surprisingly
poor: "Neurosciences 250/251"

Pain

Robinson NG

USA
(Fort Collins,
CO)

2016

Photomed Laser
Surg

Photomedicine, Not Opioids, for Chronic Pain.

Guest
Editorial

Pain

Zarkovi

Yugoslavia
(Zagreb)

1989

Lasers Surg Med

Effect of semiconductor GaAs laser irradiation on pain perception

in mice.

Mouse

"Whereas opioids lead to addiction, photomedicine leads to healing. Photobiomodulation repairs tissue, relaxes muscles, reduces inflammation and
edema, and restores circulation as well as nerve function to more normal levels. No opioid can match the reparative value of light. It is time for
photomedicine practitioners to educate the public and the medical profession about this valuable, cost-effective, and well-received treatment option."
905

0.0004

50

"Laser treatment induced further shortening of latencies, suggesting its stimulatory

influence on pain perception."

PubMed

PubMed

Note: There is no reason to believe that this ultra-low dose of 0.41 mJ/cm2 would
have had any biological effects.

Parameters

Coherence

Hode L

Sweden
(Stockholm)

2005

Photomed Laser
Surg

The importance of the coherency.

"The coherence of the laser light is an important optical parameter. It is not lost when the light enters tissue, but the length of coherence is reduced.
Laser speckles are formed within the entire illuminated volume"

Letter to the
Editor

PubMed

"Whenever compared, coherent light has so far demonstrated better results than non-coherent light."
"The superiority of coherent light is shown to be relevant only for bulk tissue. The pain-relieving and healing effect in superficial wounds may be good
also for both coherent and non-coherent polarized light."
Comment: In order to argue for laser light (vs uncoherent light), Hode refers to several studies. Some of them are not very valid for these comparisons.
For example, there was a study that compared 4J/cm2 dose of visible polarized broadband light to 4J/cm2 dose of 830nm laser light. There are several
differences between these light setups, and the coherence is only one of them. However, some of the other studies seem valid.
"All too often the laser phototherapy literature is written as if a laser is magical. Lasers can seem magical if their unique properties of micro-dot focusing,
high intensity, possibility of ultrashort pulses, coherent radiation, and monochromaticity are all made use of. If the first four properties are not useful in a
particular application, as is the case for laser phototherapy, then a laser is just an expensive light bulb, whose emitted radiation follows (except for
coherence) all of the same laws of physics and chemistry that the same wavelength of radiation from a conventional (non-coherent) light source follows"

Parameters

Coherence

Smith KC

USA
(Stanford, CA)

2005

Photomed Laser
Surg

Laser (and LED) therapy is phototherapy.

Letter to the
Editor

Parameters

Editorial

Tunr & Jenkins

Sweden & USA

2016

Photomed Laser
Surg

Parameter Reproducibility in Photobiomodulation.

Guest
Editorial

"PBM has been used for >50 years, and no serious side effects have been reported. In a decade when side effects of pharmaceuticals are alarming and
antibiotic resistance is a threat, this treatment modality appears to be much needed in the medical armamentarium, but first the scientific strength needs
to be increased, and this can only occur if the basic use and reporting of light parameters are improved."

PubMed

Parameters

Editorial

Bayat M

Iran
(Tehran)

2014

Photomed Laser
Surg

The necessity for increased attention to pulsed low-level laser

therapy.

Guest
Editorial

The author argues for superiority of pulsing in some circumstances. He mentions several studies to support his argument.

PubMed

Parameters

Editorial

Bjordal JM

Norway
(Bergen)

2012

Photomed Laser
Surg

Low level laser therapy (LLLT) and World Association for Laser
Therapy (WALT) dosage recommendations.

Guest
Editorial

"In the near future, we think that we will also be able to identify therapeutic windows in nerve repair and peripheral nerve analgesia. The limited available
evidence suggests already that this therapeutic window will have a somewhat higher dose range and, possibly, a higher power density than the WALT
musculoskeletal dosage recommendations.

PubMed

PubMed

"More and more papers are appearing in the therapy literature using non-coherent light sources such as LEDs. In general, they are less expensive than
lasers, and as discussed above, in phototherapy it is the wavelength of the light that is important, not the coherence or lack of same."

Only the future will show if we reach our ambitious goals of providing clinicians with the best recommendations. However, we sincerely believe that these
are currently the best guidelines to be found for optimal administration of LLLT for musculoskeletal pain."

Parameters

Editorial

Enwemeka CS

USA
2011
(Milwaukee, WI)

Photomed Laser
Surg

The relevance of accurate comprehensive treatment parameters in

photobiomodulation.

"Correct measurement and reporting of dose remains a major problem in photobiomodulation literature; making it difficult to adequately interpret or
reproduce and replicate published reports."

Editorial

PubMed

"In this issue of the Journal, Jenkins and Carroll present tabulations of treatment parameters and equipment-related parameters that could significantly
enhance reproducibility of research reports, if complied with by research investigators and others."

Parameters

Original
research

Giacci

Australia

2015

J Vis Exp

Method for the assessment of effects of a range of wavelengths

and intensities of red/near-infrared light therapy on oxidative
stress in vitro.

670
810

In vitro

"Non-coherent Xenon light was filtered through narrow-band interference filters to

deliver varying wavelengths (center wavelengths of 440, 550, 670 and 810 nm)
and fluences (8.5x10(-3) to 3.8x10(-1) J/cm2) of light to cultured cells."

PubMed

"While the fluences of R/NIR-LT used in the current study did not exert an effect
on ROS generated by the cultured cells, the method of light delivery is applicable
to other systems including isolated mitochondria or more physiologically relevant
organotypic slice culture models, and could be used to assess effects on a range
of outcome measures of oxidative metabolism."

Parameters

Recommendati
on

Jenkins & Carroll

Australia
(Oakbank, SA)

2011

Photomed Laser
Surg

How to report low-level laser therapy (LLLT)/photomedicine dose

and beam parameters in clinical and laboratory studies.

Recommend
ation

The eight most important beam parameters to report:

- wavelength
- power
- irradiation time
- beam area at the skin or culture surface (this is not necessarily the same as the aperture size)
- pulse parameters
- anatomical location
- number of treatments
- interval between treatments

PubMed

Parameters

Review

Hadis

UK
(Birmingham)

2016

Lasers Med Sci

The dark art of light measurement: accurate radiometry for lowlevel light therapy.

Review

For all papers reviewed, missing information for specific light parameters included
- wavelength (3%)
- light source type (8%)
- power (41%)
- pulse frequency (52%)
- beam area (40%)
- irradiance (43%)
- exposure time (16%)
- radiant energy (74%) and
- fluence (

PubMed

"Frequent use of incorrect terminology was also observed within the reviewed literature."
"A poor understanding of photophysics is evident as a significant number of papers neglected to report or misreported important radiometric data. These
errors affect repeatability and reliability of studies shared between scientists, manufacturers and clinicians and could degrade efficacy of patient
treatments."

Parameters

Review

Hashmi

USA
(Boston, MA)

2010

Lasers Surg Med

Effect of pulsing in low-level light therapy.

Review

Pulsing

"There is some evidence that pulsed light does have effects that are different from those of continuous wave light. However further work is needed to
define these effects for different disease conditions and pulse structures."

PubMed

Hamblin mentions in (Lasers Surg Med 2010;42:447-9): "They reviewed the literature containing 33 studies of pulsed LLLT and found that out of nine
studies that directly compared pulsed with CW light, six found a direct benefit for pulsing. They provided some mechanistic hypotheses for why pulsing
could be superior to CW including increased penetration depth and kinetics of ion channels."

Parameters

Review

Tunr & Hode

Sweden
(Stockholm)

1998

J Clin Laser Med

Surg

It's all in the parameters: a critical analysis of some well-known

negative studies on low-level laser therapy.

Review

Negative results

"A study of 1,200 papers on LLLT has resulted in 85 positive and 35 negative double-blind studies. The negative studies have been scrutinized carefully
in an effort to pinpoint possible reasons for the failures."

PubMed

"In the following, the majority are double-blind studies, but some non-blinded and animal studies have been included to give typical examples of pitfalls."

Hart & Fitzgerald

Penetration

Australia
(Perth)

2016

Discov Med

A new perspective on delivery of red-near-infrared light therapy for

disorders of the brain.

Review

Brain

"Calculations of the average irradiance of light delivered by sunlight demonstrate that sunlight can provide doses of light equivalent to -- and in some
cases greater than -- those used in therapeutic trials."

PubMed

"For targets deep within the brain, it is unlikely that sufficient doses of light can be delivered trans-cranially; therapeutic light must be supplied via optical
fibers or implanted light sources."

Penetration

Chen

China
(Shanghai)

2016

Neural Regen Res Low-power laser therapy for carpal tunnel syndrome: effective
optical power.

Penetration

Anders & Wu

USA
(Bethesda, MD)

2016

Photomed Laser
Surg

Human

PubMed
810
904

Comparison of Light Penetration of Continuous Wave 810 nm and

Superpulsed 904 nm Wavelength Light in Anesthetized Rats.

"The percentages of light transmission (fluence rate) through muscle and skin
were 7.42% (810 nm wavelength) and 4.01% (904 nm wavelength) and through
skin were 24.63% (810 nm wavelength) and 19.94% (904 nm wavelength).

PubMed

These data prove that transmission of CW 810 nm wavelength light through

muscle and skin and skin alone is greater than transmission of superpulsed 904
nm wavelength light."

Penetration

Tedford

USA
(Poulsbo, WA)

2015

Lasers Surg Med

Quantitative analysis of transcranial and intraparenchymal light

penetration in human cadaver brain tissue.

Human
cadaver

660
808
940

"The 808 nm wavelength light demonstrated superior CNS tissue penetration."

PubMed

Penetration

Pitzschke

Switzerland

2015

Phys Med Biol

Red and NIR light dosimetry in the human deep brain.

Human
cadaver

671
808

"Our study demonstrates that it is possible to illuminate deep brain tissues

transcranially, transsphenoidally and via different application routes. This opens
therapeutic options for sufferers of PD or other cerebral diseases necessitating
light therapy."

PubMed

Penetration

Henderson &
Morries

USA
(Lakewood,
CO)

2015

Neuropsychiatr
Dis Treat

Near-infrared photonic energy penetration: can infrared

phototherapy effectively reach the human brain?

Review

Hudson

USA (CT)

2013

Photomed Laser
Surg

Penetration of laser light at 808 and 980 nm in bovine tissue

samples.

Brain

"Our recent tissue studies demonstrate no penetration of low level NIR energy through 2 mm of skin or 3 cm of skull and brain."

PubMed

"However, at 10-15 W, 0.45%-2.90% of 810 nm light penetrated 3 cm of tissue. A 15 W 810 nm device (continuous or non-pulsed) NIR delivered 2.9% of
the surface power density."
"Approximately 1.22% of the energy of 980 nm light at 10-15 W penetrated to 3 cm."

Penetration

808
980

"For 808 nm, 1 mW/cm(2) was achieved at 3.4 cm, but for 980 nm, 1 mW/cm(2)
was achieved at only 2.2 cm depth of tissue."

PubMed

"It was determined that 808 nm of light penetrates as much as 54% deeper than
980 nm light in bovine tissue."

Penetration

Joensen

Norway
(Bergen)

2012

Photomed Laser
Surg

Skin penetration time-profiles for continuous 810 nm and

Superpulsed 904 nm lasers in a rat model.

Penetration

Neupane

Nepal

2010

Photodiagnosis
Photodyn Ther

Effect of light emitting diodes in the photodynamic therapy of

rheumatoid arthritis.

Penetration

Esnouf

UK
(London)

2007

Acupunct
Electrother Res

Depth of penetration of an 850nm wavelength low level laser in

human skin.

Human skin
samples

850

100

Penetration

Ryan & Smith

UK
(Hatfield)

2007

Ir Vet J

An investigation into the depth of penetration of low level laser

therapy through the equine tendon in vivo.

Equine
tendon

810

500

Turrioni

Brazil

2013

Am J Dent

LED light attenuation through human dentin: a first step toward

pulp photobiomodulation after cavity preparation.

Human
dentin
samples

450
630
850

Penetration

Teeth

d=
0.28
mm

Red, white, yellow and infra-red (IR) LEDs were tested to measure the optical
penetration for soft tissue and their scattering.

PubMed

"The intensity of laser radiation reduced by 66% after being transmitted through a
0.784mm sample of human abdominal tissue. In this study most laser radiation
was absorbed within the first 1mm of skin."

PubMed

"These results suggest that, when applying laser to a subcutaneous structure in

the horse, the area should be clipped and cleaned beforehand."

PubMed

"In terms of minimum (0.2 mm) and maximum (1.0 mm) dentin thicknesses, the
percentage of light attenuation varied from 49.3% to 69.9% for blue light, 42.9% to
58.5% for red light and 39.3% to 46.8% for infrared."

PubMed

Additional info

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Penetration

Thermal effects

Grandintti Vdos

Brazil
(So Paulo)

2015

Lasers Med Sci

The thermal impact of phototherapy with concurrent super-pulsed

lasers and red and infrared LEDs on human skin.

905
+
875
+
640

Penetration

Thermal effects

Joensen

Norway
(Bergen)

2011

Photomed Laser
Surg

The thermal effects of therapeutic lasers with 810 and 904 nm

wavelengths on human skin.

810

200

6.37

0.0314
cm2

904

60

1.67

0.0364
cm2

Category

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

Additional info

sec

"No significant skin temperature increases were observed among the different skin
color groups (p > 0.05), age groups (p > 0.05), or gender groups (p > 0.05). Our
results indicate that the concurrent use of super-pulsed lasers and pulsed red and
infrared LEDs can be utilized in patients with all types of skin pigmentation without
concern over safety or excessive tissue heating."

PubMed

"The thermal effects of LLLT at doses recommended by WALT-guidelines for

musculoskeletal and inflammatory conditions are negligible (<1.5C) in light,
medium, and dark skin. However, higher LLLT doses delivered with a strong 3B
laser (200 mW) are capable of increasing skin temperature significantly and these
photothermal effects may exceed the thermal pain threshold for humans with dark
skin color."

PubMed

Comment: The power density is very high in this study.

Brondon

USA
(Rochester,
MN)

2007

Photomed Laser
Surg

Melanin density affects photobiomodulation outcomes in cell

culture.

Penetration

Bashkatov

Russia
(Saratov)

2005

J Phys D Appl
Phys

Optical properties of human skin, subcutaneous and mucous

tissues in the wavelength range from 400 to 2000 nm

Penetration

Muller & Wilson

1986

Phys Med Biol

An update on the penetration depth of 630 nm light in normal and

malignant human brain tissue in vivo.

2007

Photomed Laser
Surg

Low-level laser therapy (GaAs lambda = 904 nm) reduces

inflammatory cell migration in mice with lipopolysaccharideinduced peritonitis.

Mouse

Penetration

Melanin

670

In vitro

"The Proliferation Index (PI) as measured by CyQuant assay was not statistically
different amongst the groups in either cell line. MTT assay results demonstrated a
significant dose response effect (p < or = 0.05) in both cell lines with activity
inversely proportional to melanin concentration."

PubMed

"These results demonstrate that cutaneous melanin content should be taken into
consideration in photobiomodulation paradigms. Further studies to quantify these
effects are warranted."

Peritoneum

Peritonitis

Correa

Brazil
(So Paulo)

904

3
7.5
15

"The optical properties of human skin, subcutaneous adipose tissue and human
mucosa were measured in the wavelength range 4002000 nm."

IOPscienc
e

"The 3-J/cm(2) exposure group showed the best results at 24 hours, with
reductions of 77% in neutrophil and 49% in leukocyte counts."

PubMed

"Low-level laser therapy (904 nm) can reduce inflammatory cell migration in mice
with LPS-induced peritonitis in a dose-dependent manner."
Note: The single dose was given in three parts, within 3h.

Plastic
surgery

Hersant

France
(Creteil)

2015

Photomed Laser
Surg

Current indications of low-level laser therapy in plastic surgery: a

review.

Systematic
review

Polychromatic
light

lker

Turkey

2016

Lasers Med Sci

Polychromatic light-induced osteogenic activity in 2D and 3D

cultures

In vitro

Systematic review:
- Thirteen studies on animals showed that LLLT had efficacy in the improvement of flap survival.
- LLLT seemed to improve chronic burn scars in humans, and acute wound healing in animals.
- LLLT cannot be considered as a valid therapeutic option for venous ulcers
- Alopecia: published studies did not show that LLLT had efficacy for this indication
- Skin aging: only two studies are reported showing that LLLT globally improved aging of skin
"We decided to use a specially designed plasma arc light source providing
wavelengths between 590 and 1500 nm"

PubMed

Springer

"Light source used in this study induces formation of bone tissue and so, this light
source is proposed as an appropriate system for in vitro bone tissue engineering
applications"

Poor science

Wellington J

USA
(Indianapolis,
IN)

2014

Neuromodulation

Noninvasive and alternative management of chronic low back pain

(efficacy and outcomes).

Poor science

Malm

Sweden

1991

Scand J Plast
Reconstr Surg
Hand Surg

Effect of low power gallium arsenide laser on healing of venous

ulcers.

"Studies have been small, and there is insufficient evidence to determine the effectiveness of LLLT on chronic low back pain [38]."

Review

PubMed

Comment: This is a 2014 review, and it cites an outdated 2007 Cochrane review.
904

"One group received standard conservative treatment and gallium arsenide laser,
and the other received the same standard treatment and placebo laser treatment.
There were no differences in results between the two groups."

PubMed

Hode and Tuner:

"First of all, the treatment time was said to be 10 minutes per patient regardless of wound size. Wound size in the laser group was in the range 4-52 cm2 (average 12 cm2 ). With an
average output power of 4 mW and a treatment time of 600 seconds (10 minutes), an energy of 2.4 joules were emitted from the laser in each session. If the whole wound area was
treated, the dose (energy density) for the smallest wounds (4 cm2 ) must have been 0.6 J/cm2 and for the largest wounds (52 cm2 ) the dose was 0.046 J/cm2 . As the stated dose
was 1,96 J/cm2 something seem to be wrong. We contacted the authors about this, but they refused to give any information. Further, according the manufacturer of the laser
equipment (Irradia AB, Sweden), a GaAs laser with as low power as 4 mW has never been produced and a pulse frequency of 3800 Hz is not available with any of their equipment.
Neither has a GaAs laser with a beam divergence of 70 mrad (collimated) been available."

The parameters stated in the report are: "A GaAs laser (Irradia) was used. The
wavelength was 904 nm, average output 4 mW, peak power 10 W, pulse
frequency 3800 Hz and duration 180 ns, and divergence 70 mrad. Energy density
was 1.96 J/cm2 . The placebo laser was of the same brand but the invisible GaAs
laser light had been removed so that nobody in the study could tell the difference
between the two."
According to Hode&Tuner: [Read additional info]

Lundeberg

Poor science

Sweden

1988

Acupunct
Electrother Res

Effect of low power laser irradiation on nociceptive cells in Hirudo

medicinalis.

Leech

Nociception

633
904

1.56
0.07

60
300
600

"The results show that low power laser irradiation does not: affect the membrane
potential or the excitability of the nociceptive neurons, affect the mechanical
pressure required to activate the nociceptors or their action potentials."

PubMed

As mentioned by Hode&Tuner: "In this study, Lars Hode did not take part but is
listed as a co-author. He was asked before it started if he wanted to take part and
he said yes. About half a year later he found out that it was published!"

Lundeberg

Poor science

Sweden

1987

Acta Physiol
Scand

A comparative study of the pain-relieving effect of laser treatment

and acupuncture.

Human

Pain relief

633
904

1.56
0.07

"Our results indicate that the analgesic effects reported in humans with similar
modes of low power laser might be due to placebo."

PubMed

Thomas Lundeberg, the Dean of research of Karolinska Institute has written as follows:
"Following a number of allegations made 2002 2004, I carried out an investigation of Dr Thomas Lundeberg and his group. The result of this investigation was a clear indication of
scientific fraud and malpractice. We therefore asked the Swedish Research Councils expert group on scientific malpractice to make an independent investigation which, due to the
complexity of the case, was completed on May 31st this year.

According to Hode&Tuner, "the study was published without the knowledge of

Lars Hode". This is interesting, since Hode's name is in the author list.
Regarding the researcher: [See additional info]

The conclusion of this investigation was that scientific malpractice was demonstrated with numerous examples of plagiarism within scientific publications and patent applications.
Furthermore, the documentation of the research carried out and its description was so poor, and in many cases lacking, that it was impossible to determine if and when experiments
were carried out or by whom. The conclusion of the Rector is that we completely lack confidence in Thomas Lundeberg as a scientist.
Thomas Lundeberg resigned from his position as professor at Karolinska Institutet in October 2003. He has not been associated with Karolinska Institutet since that time and has no
affiliation with the university today. He resigned his position following confrontation concerning a manuscript that was used for a patent application and that was plagiarised from a
published paper from another group and that contained manipulated data that could not be verified with documented primary data. All connections with Karolinska Institutet were
severed following that incident."
Read more: http://www.laser.nu/lllt/pdf/Scientific_fraud_in_lasers.pdf

Poor science

Lundeberg

Sweden

1987

Scand J Rehabil
Med

Effect of laser versus placebo in tennis elbow.

Human

Tennis Elbow

633

1.56

< 0.1
/joint

904

0.07

<
0.005
/joint

PubMed

Protozoa

Paramecium

Amaroli

Italy
(Genoa)

2016

Photochem
Photobiol

Photobiomodulation by Infrared Diode-Laser: Effects on

Intracellular Calcium Concentration and Nitric Oxide Production of
Paramecium.

Protozoa

Calcium release by
980nm

808
980

"Lastly, the 980nm and 64J/cm2 or 96J/cm2 were the only parameters to induce a
release of stored calcium."

PubMed

Protozoa

Paramecium

Amaroli

Italy
(Genoa)

2016

Lasers Med Sci

808-nm laser therapy with a flat-top handpiece photobiomodulates

mitochondria activities of Paramecium primaurelia (Protozoa).

Protozoa

Penetration

808

"Our results suggest that thanks to flat-top handpiece we used, high fluences by
high-powered laser have to be reconsidered as an effective and non-invasive
therapy. Possible associated benefits of deeper tissue penetration would increase
treatment effectiveness and reduced irradiation time."

PubMed

808nm LLLT increased oxygen consumption of protozoa by 40%.

PubMed

"The 808 nm infrared diode laser light, at the irradiation parameters used in our
work, results in a precocious fission rate in P. primaurelia cells, probably through
an increase in metabolic activity, secondary to an energy transfer."

PubMed

"(1) the 808 nm laser stimulates the P. primaurelia without a thermal effect,

PubMed

Protozoa

Paramecium

Amaroli

Italy
(Genoa)

2015

Altern Lab Anim

The protozoan, Paramecium primaurelia, as a non-sentient model

to test laser light irradiation: The effects of an 808nm infrared laser
diode on cellular respiration.

Protozoa

808

Protozoa

Paramecium

Amaroli

Italy
(Genoa)

2015

Photomed Laser
Surg

Paramecium: a promising non-animal bioassay to study the effect

of 808 nm infrared diode laser photobiomodulation.

Protozoa

808

Protozoa

Paramecium

Amaroli

Italy
(Genoa)

2015

Photochem
Photobiol

Effect of 808 nm Diode Laser on Swimming Behavior, Food

Vacuole Formation and Endogenous ATP Production of
Paramecium primaurelia (Protozoa).

Protozoa

808

6.4
32
64
96

"The results show that laser treatment is not significantly better than placebo in
treating tennis elbow."

1000

64

d=
1 cm

50

(2) the laser effect is demonstrated by an increase in swimming speed and in food
vacuole formation,
(3) the laser treatment affects endogenous adenosine triphosphate (ATP)
production in a positive way,
(4) the effects of irradiation dose suggest an optimum exposure time of 50 s (64 J
cm(-2) of fluence) to stimulate the Paramecium cells; irradiation of 25 s shows no
effect or only mild effects and irradiation up to 100 s does not increase the effect
observed with 50 s of treatment,
(5) the increment of endogenous ATP concentration highlights the positive
photobiomodulating effect of the 808 nm laser and the optimal irradiation
conditions by the flat-top handpiece."

Purinergic
signalling

Extracellular
ATP

Wang

China
(Shanghai)

2015

Mediators Inflamm Modulation of extracellular ATP content of mast cells and DRG
neurons by irradiation: studies on underlying mechanism of lowlevel-laser therapy.

In vitro

Radiation

Gamma
radiation

Efremova

Czech Republic
(Kladno)

2015

Photomed Laser
Surg

Mouse

Protective effect of 940 nm laser on gamma-irradiated mice.

657

Gamma radiation

940

Biphasic dose
response

5000
5000
5000

0.44
0.44
0.44

3
12
18

7
27
41

"Our results show that irradiation led to elevation of extracellular ATP level in the
human mast cell line HMC-1 in a dose-dependent manner, which was
accompanied by elevation of intracellular ATP content, an indicator for ATP
synthesis, together with [Ca(2+)]i elevation, a trigger signal for exocytotic ATP
release. In contrast to MCs, irradiation attenuated the extracellular ATP content of
neurons, which could be abolished by ARL 67156, a nonspecific ecto-ATPases
inhibitor. "

PubMed

Only the low-dose LLLT seemed to protect against the lethal effect of gamma
radiation:

PubMed

"In Table 4, we summarized the means for survival time for all groups and found
that 50% of mice in the gamma-laser3 group and 9.1% of mice in the gammalaser18 group had survived to the 30th day after gamma irradiation, but only in the
first one was the difference in survival compared with the gamma group significant
(p=0.007 vs. 0.875).
Meanwhile, survival in the gamma-laser3 group was significantly different than in
other gamma-irradiated groups, except the gamma-laser18 group, in which p=0.23
in comparison with the gamma group."

Radiation

Gamma
radiation

Abdul-Aziz &
Tuorkey

Egypt
(Damanhour)

2010

Radiation

Cancer
radiotherapy

Zharinov

Russia
2010
(St. Petersburg)

J Photochem
Photobiol B

Argon laser phototherapy could eliminate the damage effects

induced by the ionizing radiation "gamma radiation" in irradiated
rabbits.

Rabbit

Blue light

488

500

Laser Ther

Late radiation lesions of urinary bladder and rectum in patients

with prostate cancer after external radiation therapy and
phototherapy with low power near infrared laser.

Human

Prostate cancer
patients

890

45

40

10.8

0.25
cm2

20

240

12

"In conclusion, argon laser therapy appears propitious protective effect against the
hazard effects of gamma radiation."

PubMed

"In the control group the radiation damage of urinary bladder and rectum appeared
in 7.6% and 10.7% of patients, while in the main group - in 1.95% and 2.92%,
respectively (p < 0.01).

J-STAGE

Thus, the course of phototherapy with the near infrared low power laser at
performance of radiotherapy decreases incidence of radiation damages of urinary
bladder and rectum in patients with prostate cancer."

Comment

Reply

 Category

Subcategory

Radiation
Respiratory
system

Acute
respiratory
distress
syndrome

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Freitinger
Skalick

Czech

2012

J Photochem
Photobiol B

Indicators of oxidative stress after ionizing and/or non-ionizing

radiation: superoxid dismutase and malondialdehyde.

Mouse

Gamma radiation

830

de Lima

Brazil
(So Jos dos
Campos)

2011

Lasers Med Sci

Low-level laser therapy (LLLT) acts as cAMP-elevating agent in

acute respiratory distress syndrome.

Mouse
+ in vitro

Alveolar
macrophages (for in
vitro experiments)

660

Results: positive / unclear/modest / negative

Link

sec

4.5

LLLT didn't protect from gamma radiation in this study.

PubMed

neutrophil infiltration
TNF- in BALF
LPS-induced alveolar macrophages TNF production
LPS-induced alveolar macrophages TNF- mRNA expression

PubMed

"Taken together, the results obtained in the present manuscript evidenced that
LLLT potentiates the effect of rolipram on ALI by a mechanism that, at least
initially, is not directly linked to generation of cAMP but involves the reduction of
TNF- mRNA expression in AM from mice in an experimental model of LPS
aerosol-induced ALI."
Note: This paper also has a lot of data related to cAMP.

Respiratory
system

Airway smooth
muscle
relaxation

Aimbire

Brazil
(So Jos dos
Campos)

2006

Lasers Surg Med

655

Low level laser therapy partially restores trachea muscle relaxation In vitro
response in rats with tumor necrosis factor alpha-mediated smooth
airway muscle dysfunction.

2.5

31.25

0.22

1.3

0.08
cm2

42

"[LLLT] partially restored TSM relaxation response to isoproterenol. Tension

reduction was 47.0 % (+/-2.85) in the laser-irradiated group compared to 22.0%
(+/-2.21) in the control group (P < 0.01).

PubMed

Accumulation of cAMP was almost normalized after LLLT at 22.3 pmol/mg (+/-2.1)
compared to 17.6 pmol/mg (+/-2.1) in the non-irradiated control group (P < 0.01)."

Respiratory

Allergic asthma

Silva

system

Brazil
(So Paulo)

2014

Respir Physiol
Neurobiol

Low-level laser therapy inhibits bronchoconstriction, Th2

inflammation and airway remodeling in allergic asthma.

660

Mouse

30

0.375

5.4

0.08
cm2

180

"Reduction of [bronchial hyperresponsiveness] post LLLT coincided with lower

RhoA expression in bronchial muscle as well as reduction in eosinophils and
eotaxin. LLLT also diminished ICAM expression and Th2 cytokines as well as
signal transducer and activator of transduction 6 (STAT6) levels in lungs from
challenged mice.

PubMed

Our results demonstrated that LLLT reduced [bronchial hyperresponsiveness] via

RhoA and lessened allergic lung inflammation via STAT6."
Comment: In this study, the authors refer to many russian human studies on LLLT
and airways.

Respiratory
system

Allergic asthma

Wang

China
(Tianjin)

2014

Lasers Med Sci

Effect of low-level laser therapy on allergic asthma in rats.

Rat

LLLT vs budesonide

810

80

d=
4 cm

1200

21

"LLLT could reduce levels of IL-4 and increase IFN- levels in bronchoalveolar
lavage fluid and serum, meanwhile reduce serum IgE levels. Flow cytometry
assay showed that LLLT can regulate the Th1/Th2 imbalance of asthmatic rats.
LLLT had a similar effect to that of budesonide."

PubMed

"These findings suggest that the mechanism of LLLT treatment of asthma is by

adjustment of Th1/Th2 imbalance. Thus, LLLT could take over some of the effects
of budesonide for the treatment of asthma, thereby reducing some of the side
effects of budesonide."

Respiratory
system

Allergic rhinitis

Lee

Korea
(Seoul)

2013

Photochem
Photobiol

A comparative pilot study of symptom improvement before and

after phototherapy in Korean patients with perennial allergic
rhinitis.

Human
Open-label

650

0.195

1.5

0.13
cm2

40

56
(?)

Improvement of nasal obstruction, rhinorrhea, sneezing, itching in 68% of the

patients.

PubMed

"The overall RQLQ scores significantly improved by 45% from the baseline with
the treatment after 4 weeks."
"These results indicate that phototherapy is an effective modality for treating
perennial allergic rhinitis and is another option in the steroid-free management of
immune-mediated mucosal diseases."

Respiratory
system

Allergic rhinitis

Choi

Korea
(Seoul)

Respiratory
system

Allergic rhinitis

Neuman&Finkels Israel
tein
(Petah Tikva)

2013

Evid Based
Complement
Alternat Med

Effects of low level laser therapy on ovalbumin-induced mouse

model of allergic rhinitis.

Mouse

Biphasic dose
response

658

30

1997

Ann Allergy
Asthma Immunol

Narrow-band red light phototherapy in perennial allergic rhinitis

and nasal polyposis.

Human
RCT/DB (?)

Allergic rhinitis
Nasal polyposis

660

0.15

1
2

0.2
cm2

320
640

260

42

"LLLT significantly inhibited total IgE, IL-4, and TARC expression in ovalbumininduced mice at low dose irradiation. The protein expression level of IL-4 in spleen
was inhibited in low dose irradiation significantly. IL-4 expression in EL-4 cells was
inhibited in a dose dependent manner. Histological damages of the epithelium in
the nasal septum were improved by laser irradiation with marked improvement at
low dose irradiation."

PubMed

"These results suggest that LLLT might serve as a new therapeutic tool in the
treatment of AR with more effectiveness at low dose irradiation. To determine the
optimal dose of laser irradiation and action mechanisms of laser therapy, further
studies will be needed."
1

LED phototherapy
BioNase LED light

"Allergic rhinitis, if uncomplicated by polyps or chronic sinusitis, can be effectively

treated by narrow-band red light illumination of the nasal mucosa at 660 nm, with
marked alleviation of clinical symptoms."

PubMed

Comment: If I remember correctly, the sham group results in abstract contradict a

little bit with the results presented in full text (improvement in 3% vs 21%).
Comment: The sham-controlling is suboptimal, since it's bright red light vs no light.

Respiratory
system

Bronchial
hyperresponsiv
eness

Mafra de Lima

Brazil
(So Jos dos
Campos)

2009

Lasers Surg Med

Low level laser therapy (LLLT): attenuation of cholinergic

hyperreactivity, beta(2)-adrenergic hyporesponsiveness and TNFalpha mRNA expression in rat bronchi segments in E. coli
lipopolysaccharide-induced airway inflammation by a NF-kappaB
dependent mechanism.

655

In vitro

2.5

31.25

1.3

0.08
cm2

BSM hyperreactivity to cholinergic agonist

BSM relaxation to isoproterenol
TNF-alpha mRNA expression

PubMed

"An NF-kappaB antagonist (BMS205820) blocked the LLLT effect"

"The results obtained in this work indicate that the LLLT effect on alterations in
responsiveness of airway smooth muscles observed in TNF-alpha-induced
experimental acute lung inflammation seems to be dependent of NF-kappaB
activation."

Bronchial
hyperresponsiv
eness

Aimbire

Respiratory
system

COPD

Respiratory
system

COPD

Respiratory
system

COPD

Respiratory
system

Brazil
(So Jos dos
Campos)

2009

Lasers Med Sci

Effect of low level laser therapy on bronchial hyperresponsiveness.

Aksenova &
Burduli

Russia
(Vladikavkaz)

2016

Ter Arkh

[Pathogenetic effects of low-intensity laser therapy for chronic

obstructive pulmonary disease].
[Article in Russian]

Human

Peron

Brazil

2015

PLoS One

Human Tubal-Derived Mesenchymal Stromal Cells Associated with

Low Level Laser Therapy Significantly Reduces Cigarette SmokeInduced COPD in C57BL/6 mice.

Mouse

Miranda

Brazil
(So Paulo)

2015

Lasers Med Sci

Phototherapy with combination of super-pulsed laser and lightemitting diodes is beneficial in improvement of muscular
performance (strength and muscular endurance), dyspnea, and
fatigue sensation in patients with chronic obstructive pulmonary
disease.

Human

660

In vitro

31.25

0.105

1.3

0.08
cm2

42

TNF-, inositol phosphate accumulation, (TNF-)-induced contractile response

to carbachol, IP3R mRNA

PubMed

"We conclude that LLLT can reduce Ca2+ sensitization and inositol phosphate
accumulation in rat BSM cells in a TNF--induced bronchial hyper-responsiveness
model."

COPD

"Laser therapy used in the combination treatment of patients with COPD promotes
correction of the typical pathological processes."

PubMed

LLLT augmented the beneficial effect of stromal cell therapy.

PubMed

"Significant differences were also found for MVIC (104.826.0 Nm vs. 87.2
24.0 Nm, p=0.000), sensation of dyspnea (1 [0-4] vs. 3 [0-6], p=0.003), and
fatigue in the lower limbs (2 [0-5] vs. 5 [0.5-9], p=0.002) in favor of phototherapy.

PubMed

Stromal cell therapy

COPD
Muscular
performance

905
+
875
+
640

180

228

(total)

We conclude that the combination of super-pulsed lasers and LEDs administered

to the femoral quadriceps muscle of patients with COPD increased the PT by
20.2% and the TW by 12%.

LED phototherapy
LED cluster

Phototherapy with a combination of super-pulsed lasers and LEDs prior to

exercise also led to decreased sensation of dyspnea and fatigue in the lower limbs
in patients with COPD."
Comment: The parameters are quite complex in this study - read the full text for
further information.

Respiratory
system

COPD

Miranda

Brazil
(So Paulo)

2014

Lasers Med Sci

Acute effects of light emitting diodes therapy (LEDT) in muscle

function during isometric exercise in patients with chronic
obstructive pulmonary disease: preliminary results of a
randomized controlled trial.

Human
RCT

Respiratory
system

COPD

Miranda

Brazil
(So Paulo)

2013

Trials

Effects of light-emitting diodes on muscle fatigue and exercise

tolerance in patients with COPD: study protocol for a randomized
controlled trial.

Study
protocol

Respiratory
system

Diaphragm

Aimbire

Brazil (So
Jos dos
Campos)

2006

Lasers Med Sci

Low-level laser therapy can reduce lipopolysaccharide-induced

contractile force dysfunction and TNF-alpha levels in rat
diaphragm muscle.

Rat

"A single application of LEDT minimizes muscle fatigue and increases isometric
endurance time."

Muscle function

PubMed

PubMed
LPS-induced
diaphragm muscle
weakness

650

maximal tetanic force developed by diaphragm muscle

diaphragm muscle contractile force
TNF- concentration of rat diaphragm

PubMed

"We conclude that LLLT can inhibit the release of TNF- in the rat diaphragm
muscle after LPS injection and thereby reduce the impairment of the contractile
dysfunction in rat diaphragm muscle. Further studies are warranted in this novel
area of research to elucidate the exact mechanism of LLLT action."

Respiratory
system

Respiratory

Lung
hemorrhage

Aimbire

Brazil (So
Jos dos
Campos)

2007

Photomed Laser
Surg

Effect of low-level laser therapy on hemorrhagic lesions induced

by immune complex in rat lungs.

Rat

Hemorrhage

650

2.6

LLLT vs celecoxib vs
dexamethasone

Lung
inflammation

Costa Carvalho

Brazil (So
Jos dos
Campos)

2016

J Biophotonics

system

The chemokines secretion and the oxidative stress are targets of

low-level laser therapy in allergic lung inflammation.

Respiratory
system

Lung
inflammation

Cury

Brazil
(So Paulo)

2016

J Biophotonics

Low level laser therapy reduces acute lung inflammation without

impairing lung function.

Allergic lung
inflammation

660

Intratracheal LPS ->

Lung inflammation

660

30

0.375

112.5

0.08
cm2

300

4
(?)

"LLLT at a dose of 2.6 Joules/cm(2) induces a reduction of HI (hemorrhagic index)

levels and MPO activity in hemorrhagic injury that is not significantly different from
celecoxib. Dexamethasone is slightly more effective than LLLT in reducing HI, but
not MPO activity."

PubMed

"Laser-treated allergic mice presented reduction of both the ICAM-1 and

eosinophil in the lungs. RANTES, CCL8, CCL3 and eotaxins were reduced in
BALF of laser-treated allergic mice. In allergic mice lung LLLT decreased the
CCR1 and CCR3 and restored the oxidative stress balance as well. Laser
decreased the lipidic peroxidation in allergic mice lung as much as increased
SOD, GPx and GR. It shows that LLLT on allergic lung inflammation involves
leukocyte-attractant chemokines and endogenous antioxidant. Based on results,
LLLT may ultimately become a non- invasive option in allergic lung disease
treatment."

PubMed

Comment: The parameters were well reported.

Mouse

10

""Similarly to other authors, we detected a significant increase in the expression of

several pro-inflammatory cytokines (TNF-, IL-1, IL-6), that was inhibited by laser
treatment"
"There was a marked increase in the expression of MCP-1 in the animals exposed
to LPS, which was significantly reduced by laser irradiation. We suggest that this
was one of the mechanisms by which LLLT reduced the number of inflammatory
cells in the lung"
"The LLLT application induced a significant decrease in both inflammatory cells
influx and inflammatory mediators secretion. These effects did not affect lung
mechanical properties, since no change was observed in tissue resistance or
elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs
exposed to LPS without affecting the pulmonary function and recovery."

PubMed

Additional info

Comment

Reply

 Category
Respiratory
system

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Lung
inflammation

Miranda da Silva

Brazil
(So Paulo)

2015

PLoS One

Low Level Laser Therapy Reduces the Development of Lung

Inflammation Induced by Formaldehyde Exposure.

Rat

660

30

0.210

16.2
(9p)
(?)

12.86

Formaldehyde
exposure

Results: positive / unclear/modest / negative

Link

Additional info

sec

0.14
cm2

540
(?)

"The treatment with LLLT reduced the development of neutrophilic lung

inflammation induced by FA, as observed by the reduced number of leukocytes,
mast cells degranulated, and a decreased myeloperoxidase activity in the lung.
Moreover, LLLT also reduced the microvascular lung permeability in the
parenchyma and the intrapulmonary bronchi. Alterations on the profile of
inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-
and the elevated levels of IL-10 in the lung."

PubMed

"Together, our results showed that LLLT abolishes FA-induced neutrophilic lung
inflammation by a reduction of the inflammatory cytokines and mast cell
degranulation. This study may provide important information about the
mechanisms of LLLT in lung inflammation induced by a pollutant."

Dose response

660

Respiratory
system

Lung
inflammation

de Lima

Brazil (So
Jos dos
Campos)

2014

J Lasers Med Sci

Low-level laser therapy attenuates the myeloperoxidase activity

and inflammatory mediator generation in lung inflammation
induced by gut ischemia and reperfusion: a dose-response study.

Mouse

Respiratory
system

Lung
inflammation

Oliveira

Brazil
(So Paulo)

2014

J Photochem
Photobiol B

Low level laser therapy reduces acute lung inflammation in a

model of pulmonary and extrapulmonary LPS-induced ARDS.

Mouse

830

35

Respiratory

Lung
inflammation

de Lima

Brazil (So
Jos dos
Campos)

2013

Photochem
Photobiol

Low-level laser therapy restores the oxidative stress balance in

acute lung injury induced by gut ischemia and reperfusion.

Rat

660

30

Brazil (So
Jos dos
Campos)

2013

1
3
5
7.5

300

240
(3p)

"With exception of 1J/cm(2), LLLT reduced MPO activity as well as IL-1 levels in
the lungs from inflamed mice. LLLT was also markedly effective in reducing both
IL-6 and TNF expression and levels in the lungs from mice submitted to i-I/R in all
laser doses studied. Otherwise, LLLT significantly increased the protein levels of
IL-10 in inflamed mice by i-I/R; however only in the dose of 1J/cm(2)."

PubMed

"We conclude that the LLLT is able to control the neutrophils activation and
proinflammatorycytokines release into the lungs in a model of i-I/R in mice."

system

Respiratory
system

Lung
inflammation

de Lima

0.0384

5.4

6.9

0.08
cm2

180

"LLLT significantly reduced pulmonary and extrapulmonary inflammation in LPSinduced ARDS, as demonstrated by reduced number of total cells (p<0.001) and
neutrophils (p<0.001) in BAL, reduced levels of IL-1beta, IL-6, KC and TNF-alpha
in BAL fluid and in serum (p<0.001), as well as the number of neutrophils in lung
parenchyma (p<0.001). LLLT is effective to reduce pulmonary inflammation in both
pulmonary and extrapulmonary model of LPS-induced ARDS."

PubMed

GSH, HSP70 expression, PPARy expression, lung injury, edema,

neutrophils influx, MPO activity, ICAM-1 mRNA expression, ROS

PubMed

"Results indicate that laser effect in attenuating the acute lung inflammation is
driven to restore the balance between the pro- and antioxidants mediators rising of
PPARy expression and consequently the HSP70 production."

Lasers Med Sci

Suppressive effect of low-level laser therapy on tracheal

hyperresponsiveness and lung inflammation in rat subjected to
intestinal ischemia and reperfusion.

Rat

Tracheal and lung

function after
intestinal I/R

660

30

5.4

0.08
cm2

180

"LLLT (660 nm, 7.5 J/cm(2)) restored the tracheal hyperresponsiveness and
hyporesponsiveness in all the periods after intestinal reperfusion.

PubMed

Although LLLT reduced edema and MPO activity, it did not do so in all the
postreperfusion periods. It was also observed with the ICAM-1 expression.
In addition to reducing both TNF- and iNOS, LLLT increased IL-10 in the lungs of
animals subjected to i-I/R.
The results indicate that LLLT can control the lung's inflammatory response and
the airway reactivity dysfunction by simultaneously reducing both TNF- and
iNOS."

Respiratory
system

Lung
inflammation

de Lima

Brazil (So
Jos dos
Campos)

2011

Lasers Surg Med

Dual Effect of low-level laser therapy (LLLT) on the acute lung

inflammation induced by intestinal ischemia and reperfusion:
Action on anti- and pro-inflammatory cytokines.

Rat

Acute lung
inflammation

660

30

Respiratory
system

Lung
inflammation

Mafra de Lima

Brazil (So
Jos dos
Campos)

2010

J Photochem
Photobiol B

Low intensity laser therapy (LILT) in vivo acts on the neutrophils

recruitment and chemokines/cytokines levels in a model of acute
pulmonary inflammation induced by aerosol of lipopolysaccharide
from Escherichia coli in rat.

Rat

Acute lung
inflammation

650

2.5

Brazil (So
Jos dos
Campos)

2008

5.4

0.031

1.3

0.08
cm2

180

0.08
cm2

42

"The results indicate that the LLLT attenuates the i-I/R-induced acute lung
inflammation which favor the IL-10 production and reduce TNF generation."

PubMed

"LILT inhibited pulmonary edema and endothelial cytoskeleton damage, as well as

neutrophil influx and activation.

PubMed

Similarly, the LILT reduced the TNF- and IL-1, in lung and BALF. LILT
prevented lung ICAM-1 up-regulation. The rise of CINC-1 and MIP-2 protein levels
in both lung and BALF, and the lung mRNA expressions for IL-10, were
unaffected.
Data suggest that the LILT effect is due to the inhibition of ICAM-1 via the
inhibition of TNF- and IL-1."

Respiratory
system

Lung
inflammation

Aimbire

Int
Low-level laser therapy decreases levels of lung neutrophils antiImmunopharmaco apoptotic factors by a NF-kappaB dependent mechanism.
l

660

Mouse

30

7.5

0.785
cm2

Bcl-xL mRNA in lung neutrophils

A1 mRNA in lung neutrophils

PubMed

"LLLT effect on mRNA expression of Bcl-xL and A1 in lung neutrophils was

blocked by pretreatment with BMS 205820. From these results, it is reasonable to
suggest that the anti-inflammatory effect of LLLT can be mediated by NF-B."

Respiratory
system

Lung
inflammation

Aimbire

Brazil (So
Jos dos
Campos)

2008

Inflammation

Low level laser therapy (LLLT) decreases pulmonary microvascular Rat

leakage, neutrophil influx and IL-1beta levels in airway and lung
from rat subjected to LPS-induced inflammation.

Acute lung
inflammation

660

30

Respiratory
system

Lung
inflammation

Aimbire

Brazil (So
Jos dos
Campos)

2006

Photomed Laser
Surg

Low-level laser therapy induces dose-dependent reduction of

TNFalpha levels in acute inflammation.

Lung injury by
ovalbumin+antibody

650

1
2.5
5

Rat

7.5

0.0125
0.0313
0.0625

0.04
0.11
0.22

0.9
2.1
4.2

0.785
cm2

"LLLT attenuated lung permeability. In addition, there was reduced neutrophil

influx, myeloperoxidase activity and both IL-1beta in BAL and IL-1beta mRNA
expression in trachea obtained from animals subjected to LPS-induced
inflammation."

PubMed

"LLLT at a dose of 0.11 Joules reduced the TNF
concentration in bronchoalveolar

lavage fluid to 50.2 (95% CI, 49.451.0), which was significantly lower (p < 0.001)
than the control group and the other LLLT groups of 0.04 and 0.22 Joules,
respectively."

PubMed

80

"Our results demonstrate that LLLT produced anti-inflammatory effects on RTHR,

BAL and lung neutrophils influx in association with inhibition of COX-2-derived
metabolites."

PubMed

5774

"LLLT-660 nm induced an anti-inflammatory effect characterized by inhibition of

either total or differential leukocyte influx, exudation, total protein, NO, IL-6, MCP1, IL-10, and TNF-alpha, in a dose-dependent manner. Under these conditions,
laser treatment with 2.1 J was more effective than 0.9 and 4.2 J."

PubMed

"LLLT administered at 1-3 h after the induction of inflammatory pleurisy

significantly reduces the inflammatory cell migration measured. Under these
conditions and at 2.5 mW, 7.5 J/cm(2) was more effective than 3 J/cm(2) and 15
J/cm(2)."

PubMed

Total symptom score was improved 39% at 2 weeks and 46% at 4 weeks.

PubMed

0.08
cm2

42

0.035
cm2

LLLT vs
chlorpromazine
Biphasic dose
response

Respiratory
system

Lung
inflammation

Aimbire

Brazil (So
Jos dos
Campos)

2005

Lasers Med Sci

Effect of LLLT Ga-Al-As (685 nm) on LPS-induced inflammation of

the airway and lung in the rat.

Rat

Airway inflammation
caused by LPS
injection

685

12

Respiratory
system

Pleurisy

Boschi

Brazil
(Porto Alegre)

2008

Lasers Surg Med

Anti-Inflammatory effects of low-level laser therapy (660 nm) in the

early phase in carrageenan-induced pleurisy in rat.

Rat

Pleurisy

660

20

0.571

2.5

Respiratory
system

Pleurisy

650

2.5

0.031

Biphasic dose
response
Lopes-Martins

Brazil
(So Jos dos
Campos)

2005

Photomed Laser
Surg

Spontaneous effects of low-level laser therapy (650 nm) in acute

inflammatory mouse pleurisy induced by carrageenan.

Mouse

Biphasic dose
response

0.24
0.6
1.2

1
2.5
5

(from
3
treatm
ents?)

Chronic rhinosinusitis

830

Respiratory
system

Rhinosinusitis

Naghdi

Iran
(Tehran)

2013

Physiother Theory A pilot study into the effect of low-level laser therapy in patients
Pract
with chronic rhinosinusitis.

Human

Respiratory
system

Rhinosinusitis

Krespi&Kizhner

USA
(New York)

2011

Lasers Surg Med

Phototherapy for chronic rhinosinusitis.

Human
Randomized

810
940

Respiratory
system

Ezzat

Egypt
(Cairo)

2016

Acta
Otorrinolaringol
Esp

Using low level laser therapy to reduce early postoperative airway

obstruction following modified Hogan's flap.

Human
RCT/DB

970

Respiratory
system

de Lima

Brazil (So
Jos dos
Campos)

2010

Lasers Med Sci

Low-level laser therapy (LLLT) attenuates RhoA mRNA expression

in the rat bronchi smooth muscle exposed to tumor necrosis
factor-alpha.

Rat

660

Sagar

USA
(Miami, FL)

2016

Sci Rep

Coupling of transient near infrared photonic with magnetic

In vitro
nanoparticle for potential dissipation-free biomedical application in
brain.

Engel

USA
(Bethesda, MD)

2016

J Biophotonics

Cell lineage responses to photobiomodulation therapy.

30

"The therapeutic effect was sustained for a mean of 5 months. This pilot study
indicates that LLLT applied for 4 weeks improves symptoms in patients with CRS."
500
500
(?)
2000

35

"NILI of the nasal sinuses with or without PA agents proved to be beneficial

objectively and subjectively in CRS patients who failed medical and surgical
therapies."

PubMed

"The mean of the average oxygen saturation was significantly less in the control
group in the 1st and 2nd day as compared to the laser group. The need for oxygen
and the incidence of OSA in the first 3 days were significantly higher in the control
group as compared to the laser group. The degree of edema showed no
significant difference in the first day but was significantly higher in the control
group in the 2nd and 3rd days. Hence, the need of steroids was significantly
higher in the control group in the first 3 days."

PubMed

Comment: Parameters were poorly reported.

Safety of
LLLT

Safety of
LLLT

Brain cells

In vitro

1.3

808

42

1.5

1/2

120

Fibroblasts
Keratinocytes
Reactive oxygen
species (ROS)

Safety of
LLLT

Moon

South Korea

2016

Lasers Med Sci

Safety assessment of trans-tympanic photobiomodulation.

Rat

830

Safety of
LLLT

Kent

Australia
(Canberra)

2015

J Perinatol

A safety and feasibility study of the use of 670 nm red light in

premature neonates.

Human

670

"We conclude that LLLT administered with this protocol, reduces RhoA mRNA
expression and BSM contraction force in TNF-alpha-induced BSM
hyperreactivity."

PubMed

"We demonstrated that transient NIR irradiation in presence of MNPs is dissipation

free and safe for brain cells. Our results suggest that MNPs-NIR phototargeting
does not have adverse effect on the viability, growth behavior and plasticity of
brain cells. Thus, selected power density of ~1.5 W/cm2 and 2 minute time
window for 808 nm NIR exposure in this report will open a referral point to explore
higher power density laser for brain cells. This opens up a regime that can provide
an exceptional opportunity for the safe use of this novel combinatorial approach
for various biomedical innovations."

PubMed

"We observed keratinocytes have increased sensitivity to laser irradiances (>0.047

W/cm2 , 300 sec, 14.2 J/cm2 ) compared to the fibroblast cells (>0.057 W/cm2 ,
300 sec, 15.1 J/cm2 ) (p < 0.0001). Laser treatments were noted to generate
increased reactive oxygen species (ROS) levels in keratinocytes compared to
fibroblasts that appeared to inversely correlate with higher basal catalase
expression. To validate these observations, melatonin was used to treat
keratinocytes to induce catalase activity (p < 0.0001). Increased melatonininduced catalase levels were noted to significantly improve keratinocyte survival to
phototoxic laser doses."

PubMed

A very high LLLT dose (7560J) was associated with tympanic membrane injury.

PubMed

"There were no skin burns or other documented adverse events. Entry into the
study was readily achieved and treatment was well accepted by parents and
nursing staff."

PubMed

"670 nm red light appears to be a safe and feasible treatment for further research
in respect to [retinopathy of prematurity]"

Safety of
LLLT

McCarthy

USA
(Carlsbad, CA)

2010

Photomed Laser
Surg

Long-term safety of single and multiple infrared transcranial laser

treatments in Sprague-Dawley rats.

Rat

808

Safety of
LLLT

Ilic

USA
(Carlsbad, CA)

2006

Photomed Laser
Surg

Effects of power densities, continuous and pulse frequencies, and

number of sessions of low-level laser therapy on intact rat brain.

Rat

808

70

2.23

268

d=
2 mm

1
3

"Single and multiple applications of transcranial laser therapy with 808-nm CW

laser light at a nominal power density of 10 mW/cm(2) at the surface of the
cerebral cortex appears to be safe in Sprague-Dawley rats 1 year after treatment."

PubMed

"Both the scores from standard neurological tests and the histopathological
examination indicated that there was no long-term difference between lasertreated and control groups up to 70 days post-treatment. The only rats showing an
adverse neurological effect were those in the 750 mW/cm2 (about 100-fold optimal
dose), CW mode group."

PubMed

"Long-term safety tests lasting 30 and 70 days at optimal 10x and 100x doses, as
well as at multiple doses at the same power densities, indicate that the tested
laser energy doses are safe under this treatment regime."

"The animals were irradiated once on the skin over the upper bronchus."

Comment

Reply

 Category

Subcategory

Sinuses

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Ozturan

Turkey
(Istanbul)

2015

Photomed Laser
Surg

Effects of Nd:YAG laser irradiation for minimizing edema and pain

after sinus lift surgery: randomized controlled clinical trial.

Human
RCT

Skin

Acne vulgaris

Lee

Korea
(Daegu)

2016

Ann Dermatol

Efficacy of Red or Infrared Light-Emitting Diodes in a Mouse Model

of Propionibacterium acnes-Induced Inflammation.

Mouse

Skin

Acne vulgaris

Alba

Brazil
(So Paulo)

2016

J Cosmet Laser
Ther

Clinical comparison of salicylic acid peel and LED-Laser

phototherapy to the treatment of acne vulgaris in teenagers.

Human

Skin

Acne vulgaris

Momen & AlNiaimi

UK
(London)

2015

J Cosmet Laser
Ther

Acne vulgaris and light-based therapies.

Review

Skin

Acne vulgaris

Liu

China
(Beijing)

2014

Photodermatol
Photoimmunol
Photomed

Randomized trial of three phototherapy methods for the treatment

of acne vulgaris in Chinese patients.

Human
RCT
(no control)

Skin

Acne vulgaris

Kwon

Korea
(Seoul)

2013

Br J Dermatol

The clinical and histological effect of home-use, combination bluered LED phototherapy for mild-to-moderate acne vulgaris in
Korean patients: a double-blind, randomized controlled trial.

Human
RCT/DB

nm

mW

W/cm2

J/cm2

sec

1064

500

60

Results: positive / unclear/modest / negative

"The results demonstrate that the 1064 nm Nd:YAG laser was effective in
improving OHRQoL and reducing swelling after sinus lift surgery."

LLLT vs LED

Link

Additional info

PubMed
PubMed
PubMed
PubMed

blue+
red

420
+
660

At 1 month, >90% clearance or moderate improvement occurred in 22/50 (44%)

patients in the LED group. There was no control group.

PubMed

"At the final visit at 12 weeks, both inflammatory and noninflammatory acne
lesions had decreased significantly, by 77% and 54%, respectively, in the
treatment group. No significant difference was observed in the control group.

PubMed

In the treatment group, sebum output reduction, attenuated inflammatory cell

infiltrations and a decreased size of the sebaceous gland were found.
The immunostaining intensities for interleukin (IL)-8, IL-1, matrix
metalloproteinase-9, toll-like receptor-2, nuclear factor-B, insulin-like growth
factor-1 receptor and sterol response element binding protein (SREBP)-1 were
reduced concomitantly. Messenger RNA expression of SREBP-1c was also
decreased.
No severe adverse reactions were reported."

Skin

Acne vulgaris

Aziz-Jalali

Iran
(Tehran)

2012

Indian J Dermatol

Comparison of Red and Infrared Low-level Laser Therapy in the

Treatment of Acne Vulgaris.

Human
RCT/SB

Skin

Acne vulgaris

Sadick N

USA
(New York, NY)

2009

J Cosmet Laser
Ther

A study to determine the effect of combination blue (415 nm) and

near-infrared (830 nm) light-emitting diode (LED) therapy for
moderate acne vulgaris.

Human

Skin

Acne vulgaris

Hrfelt

Sweden
(Gteborg)

2009

Acta Derm
Venereol

Single low-dose red light is as efficacious as methylaminolevulinate--photodynamic therapy for treatment of acne:
clinical assessment and fluorescence monitoring.

Human

Red vs NIR

630
890

LED phototherapy
(w/ blue light)

415
+
830

12

"Ten weeks after treatment acne lesion were significantly decreased in the side
treated by 630 nm LLLT (27.712.7 to 6.31.9) (P<0.001), but this decrease was
not significant in the site treated by 890 nm LLLT (26.912.4 to 22.28.5) (P>0.
05)."

PubMed

"The combination therapy for acne produced results which were less effective in
the reduction of inflammatory lesions than those achieved with the previously
reported blue/red combination. Further study with a much larger patient population
is warranted."

PubMed

Red light ("control") was as beneficial as photodynamic therapy. There was no real
control group receiving no treatment.

PubMed

"Seaton et al. (26), suggest that light treatment increases the production of
transforming growth factor (TGF-). which promotes resolution of inflammation.
Thus the improvement on the cheek treated with light only could be explained by
anti-inflammatory properties by influencing cytokine release from macrophages or
other cells (27, 28)."
Overall, the results from trials of light alone were disappointing, but the trials of blue light, blue-red light and infrared radiation were more successful,
particularly those using multiple treatments. Red-blue light was more effective than topical 5% benzoyl peroxide cream in the short term.

Skin

Acne vulgaris

Hamilton

UK
(London)

2009

Br J Dermatol

Laser and other light therapies for the treatment of acne vulgaris:
systematic review.

Systematic
review

Skin

Acne vulgaris

Zane

Italy
(Brescia)

2008

Photodermatol
Photoimmunol
Photomed

Non-invasive diagnostic evaluation of phototherapeutic effects of

red light phototherapy of acne vulgaris.

Human

Skin

Acne vulgaris

Sadick NS

USA
(New York, NY)

2008

J Drugs Dermatol

Handheld LED array device in the treatment of acne vulgaris.

Human

LED phototherapy
(w/ blue light)

415
+
633

Skin

Acne vulgaris

Na & Suh

Korea
(Seoul)

2007

Dermatol Surg

Red light phototherapy alone is effective for acne vulgaris:

randomized, single-blinded clinical trial.

Human
LED phototherapy
Split-face trial

635670

PubMed
PubMed

0.185

900

112

"Lesion counts progressively reduced throughout the 4-week light therapy period
and continued to reduce up to 8 weeks posttherapy, with a final average reduction
of 69% seen 8 weeks after the treatment course (P>.001). This pattern is similar to
previously reported studies."

PubMed

"This study shows that red light phototherapy alone can be a new therapeutic
option for acne vulgaris."

PubMed

Comment: The parameters were poorly reported.

415
+
633

Skin

Acne vulgaris

Lee

Korea
(Seoul)

2007

Lasers Surg Med

Blue and red light combination LED phototherapy for acne vulgaris
in patients with skin phototype IV.

Human

LED phototherapy
(w/ blue light)

Skin

Acne vulgaris

Goldberg &
Russell

USA
(New York, NY)

2006

J Cosmet Laser
Ther

Combination blue (415 nm) and red (633 nm) LED phototherapy in
the treatment of mild to severe acne vulgaris.

Human

LED phototherapy
(w/ blue light)

Skin

Acne vulgaris

Papageorgiou

UK
(London)

2000

Br J Dermatol

Phototherapy with blue (415 nm) and red (660 nm) light in the
treatment of acne vulgaris.

Human

Skin

Aging

Calderhead &
Vasily

Korea & USA

2016

Clin Plast Surg

Low Level Light Therapy with Light-Emitting Diodes for the Aging
Face.

Review

Skin

Burns

Dahmardehei

Iran
(Tehran)

2016

Lasers Med Sci

Effects of low level laser therapy on the prognosis of splitthickness skin graft in type 3 burn of diabetic patients: a case
series.

Human
Case series

Grade 3 burn ulcer

(candidate for
amputation)

650
+
810
+
660
(i.v.)

"Blue and red light combination LED phototherapy is an effective, safe and nonpainful treatment for mild to moderately severe acne vulgaris, particularly for
papulopustular acne lesions."

PubMed
PubMed
PubMed

Comment: This paper contains two useful pictures of absorption spectra of light
(penetration) in the 400-10000 nm wavelength range.
2

"The results of this study showed complete healing in the last 8 weeks for all
patients who were candidates for amputation. In this case series, we present 13
cases of diabetic ulcer with type 3 burn wound, candidate for amputation, who
healed completely using LLLT and STSG. This is the first time that these two
techniques are combined for treatment of burn ulcer in diabetic patients. Using
LLLT with STSG might be a promising treatment for burn victims especially
diabetic patients."

PubMed

Star: The results were interesting, supplied with scary/interesting photographs.

Skin

Cell protection

Mamalis

USA
(Sacramento,
CA)

2016

J Biophotonics

High fluence light emitting diode-generated red light modulates

characteristics associated with skin fibrosis.

In vitro

Skin fibrosis

633

Skin

Cell protection

Chabert

France
(Sophia
Antipolis)

2015

Skin Res Technol

Evaluation of light-emitting diodes (LED) effect on skin biology (in

vitro study).

In vitro

Fibroblasts
Keratinocytes

590
+
630

Wavelength
combination

630
660
830
850

Skin

Cell protection

Tian

Korea
(Goyang)

2012

Dermatol Surg

Antiphotoaging effects of light-emitting diode irradiation on

narrow-band ultraviolet B-exposed cultured human skin cells.

In vitro

Biphasic dose
response

Skin

Dermal
abrasion

Gupta

USA
(Boston, MA)

2014

Lasers Med Sci

Effect of red and near-infrared wavelengths on low-level laser

Mouse
(light) therapy-induced healing of partial-thickness dermal abrasion
in mice.

Wavelengths

635
730
810
980

0.087

"We demonstrate that HF-LED-RL is capable of inhibiting the unifying cellular

processes involved in skin fibrosis including proliferation, migration, and collagen
production in vitro. These findings suggest that HF-LED-RL may represent a
paradigm shifting approach to altering HDF function for treatment of skin fibrosis."

1
2
5
10
20
22.5
22.5
22.5
22.5

0.01
0.01
0.01
0.01

9
9
9
9

4
4
4
4

2.25
cm2

396
396
396
396

7
7
7
7

"Combined, the LED wavelengths could improve in vitro the cell shape, the cell
proliferation, and the level of major proteins involved in the healing process."

PubMed

"The combination of 630/850- or 660/830-nm irradiation led to better direct and

indirect antiphotoaging outcomes than single LED wavelengths in NB-UVBirradiated cultured normal human skin cells."

PubMed

"Wavelengths of 635 and 810 nm were found to be effective in promoting the

healing of dermal abrasions. However, treatment using 730- and 980-nm
wavelengths showed no sign of stimulated healing.

PubMed

Healing was maximally augmented in mice treated with an 810-nm wavelength, as

evidenced by significant wound area reduction (p < 0.05), enhanced collagen
accumulation, and complete re-epithelialization as compared to other wavelengths
and non-illuminated controls."
"The effectiveness of 810-nm wavelength agrees with previous publications and,
together with the partial effectiveness of 635 nm and the ineffectiveness of 730
and 980 nm wavelengths, can be explained by the absorption spectrum of
cytochrome c oxidase, the candidate mitochondrial chromophore in LLLT."

Skin

Fibrosis

Mamalis

USA
(Sacramento,
CA)

2016

Curr Dermatol
Rep

Visible Red Light Emitting Diode Photobiomodulation for Skin

Fibrosis: Key Molecular Pathways.

Review

Mechanisms

"There is a growing body of evidence demonstrating that visible LED light, especially in the red spectrum, is capable of modulating key cellular
characteristic associated with skin fibrosis. We anticipate that as the understanding of LED-RL's biochemical mechanisms and clinical effects continue to
advance, additional therapeutic targets in related pathways may emerge."

PubMed

"We augmented our discussion with additional in vitro data on related pathways. LED phototherapy is an emerging therapeutic modality for treatment of
skin fibrosis."
"We believe that the use of LED-RL, in combination with existing and new therapies, has the potential to alter the current treatment paradigm of skin
fibrosis. There is a current lack of clinical trials investigating the efficacy of LED-RL to treat skin fibrosis. Randomized clinical trials are needed to
demonstrate visible red light's clinical efficacy on different types of skin fibrosis."

Skin

Laser skin
resurfacing
wounds /
erythema

Barolet

Canada

2016

Curr Dermatol
Rep

Accelerating Ablative Fractional Resurfacing Wound Healing

Recovery by Photobiomodulation

Review

Skin

Laser skin
resurfacing
wounds /
erythema

Oh

Korea
(Seoul)

2013

Dermatol Surg

Efficacy of light-emitting diode photomodulation in reducing

erythema after fractional carbon dioxide laser resurfacing: a pilot
study.

Human
Split-face

"A growing body of clinical evidence is showing that PBM, using 6001000 nm light wavelengths, as soon as possible post-procedure and thereafter,
successfully accelerates the acute healing phase via faster wound healing so as to reduce patient downtime."

LED phototherapy

635

0.075

900

(Smartlux, Medmix)

"The postlaser erythema resolved faster on the experimental side than the control
side, with improvements noted according to physician assessment and
chromometer erythema index. Statistically significant improvements between the
two sides were first noted on day 4."

Springer

PubMed

"Treatment using a 635-nm-wavelength LED array decreases the intensity and

duration of post-fractional CO2 laser treatment erythema."
Comment: The differences between the groups are quite modest.

Skin

Laser skin
resurfacing
wounds /
erythema

Alster &
Wanitphakdeede
cha

USA
2009
(Washington, D.
C.)

Dermatol Surg

Improvement of postfractional laser erythema with light-emitting

diode photomodulation.

Human
Split-face

Skin

Peptides

Hochman

Brazil
(So Paulo)

Lasers Med Sci

Low-level laser therapy and light-emitting diode effects in the

secretion of neuropeptides SP and CGRP in rat skin.

Rat

590

4200
(??)

0.1
(??)

35

"The LED-treated facial halves were less erythematous in all 20 patients 24 hours
postoperatively. The six patients who received the highest mean energy densities
during fractional laser treatment continued to exhibit decreased erythema in the
LED-treated areas at 48 hours. At 96 hours post-treatment, no discernible
differences between facial halves were observed in any patient."

PubMed

Comment: The parameters seem contradictory.

Skin

Psoriasis

Ablon G

USA
(Los Angeles,
CA)

2014

2010

Photomed Laser
Surg

Combination 830-nm and 633-nm light-emitting diode phototherapy Human

shows promise in the treatment of recalcitrant psoriasis:
Case series
preliminary findings.

Recalcitrant psoriasis

470
660
(LED)

350
350

660
808
(laser)

100
100

633
+
830

126
+
60

1200

"P was released in Infrared Laser Group (p = 0.01); there was no difference in the
CGRP secretion among groups. Infrared (808 nm) LLLT enhances neuropeptide
[substance P] secretion in healthy rat skin."

PubMed

"Clearance rates at the end of the follow-up period ranged from 60% to 100%.
Satisfaction was universally very high."

PubMed

Device: Softlaser SL30, Beurer GmbH & Co.

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Skin

Rejuvenation

Pereira

Brazil
(Santos)

2016

J Cosmet Laser
Ther

Non-ablative radiofrequency associated or not with Low Level

Human
Laser Therapy on the treatment of facial wrinkles in adult women: a RCT/SB
randomized single-blind clinical trial.

Skin

Rejuvenation

Wunsch &
Matuschka

Germany
(Heidelberg)

2014

Photomed Laser
Surg

A controlled trial to determine the efficacy of red and near-infrared

light treatment in patient satisfaction, reduction of fine lines,
wrinkles, skin roughness, and intradermal collagen density
increase.

Human
RCT
Blinded
evaluation

Polychromatic light

Regulation of skin collagen metabolism in vitro using a pulsed 660

nm LED light source: clinical correlation with a single-blinded
study.

Human
split-face
study

Collagen & wrinkles

Category

Skin

Rejuvenation

Barolet

Canada

2009

J Invest Dermatol

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

658

30

0.24

6.72
(7p)

3.82

Results: positive / unclear/modest / negative

Link

Additional info

sec

0.1257
cm2

"LLLT did not potentiate RF treatment."

PubMed

"The treated subjects experienced significantly improved skin complexion and skin
feeling, profilometrically assessed skin roughness, and ultrasonographically
measured collagen density. The blinded clinical evaluation of photographs
confirmed significant improvement in the intervention groups compared with the
control."

PubMed

"Results yielded a mean percent difference between LED-treated and non-LEDtreated HRS of 31% in levels of type-1 procollagen and of -18% in MMP-1. No
histological changes were observed.

PubMed

(
611650
570850
660

0.05

160

12

Furthermore, profilometry quantification revealed that more than 90% of

individuals showed a reduction in rhytid depth and surface roughness, and, via a
blinded clinical assessment, that 87% experienced a reduction in the Fitzpatrick
wrinkling severity score after 12 LED treatments."
Star: Interesting and quite extensive paper.

Skin

Rejuvenation

Lee

Korea
(Seoul)

2007

J Photochem
Photobiol B

A prospective, randomized, placebo-controlled, double-blinded,

and split-face clinical study on LED phototherapy for skin
rejuvenation: clinical, profilometric, histologic, ultrastructural, and
biochemical evaluations and comparison of three different
treatment settings.

Human
split-face
study

Skin

Review

Barolet

Canada
(Montreal)

2016

J Photochem
Photobiol B

Infrared and skin: Friend or foe.

Review

Skin

Review

Avci

USA
(Boston, MA)

2013

Semin Cutan Med

Surg

Low-level laser (light) therapy (LLLT) in skin: stimulating, healing,

restoring.

Review

Skin rejuvenation
(wrinkles etc)

Mechanisms
LED history
Ablative fractional
resurfacing

Skin

Scars

Park

Korea
(Suwon)

2016

Dermatol Surg

Prevention of Thyroidectomy Scars in Asian Adults With Low-Level Human

Light Therapy.

Skin

Scars

Vranova

Czech

2015

Dermatol Ther

Comparison of quality of facial scars after single low-level laser

therapy and combined low-level with high-level (PDL 595 nm) laser
therapy.

Skin

Vitiligo

Lan

Taiwan
(Kaohsiung)

2009

Br J Dermatol

Low-energy helium-neon laser induces melanocyte proliferation via In vitro

interaction with type IV collagen: visible light as a therapeutic
option for vitiligo.

LED phototherapy

830
633
or
both

0.055
0.105

66
126

1200

"Our study results showed that LED phototherapy is an effective treatment for skin
rejuvenation through objectively measured data and histological and ultrastructural
bodies of evidence of increased collagen and elastic fibers as well as clinical
photographs and double-blinded assessment of the investigators and the
subjects."

PubMed

"This article will focus on key information suggesting that IR-A may be more beneficial than deleterious when the skin is exposed to the appropriate
irradiance/dose of IR-A radiation similar to daily sun exposure received by people in real life.IR-A might even precondition the skin--a process called
photo prevention--from an evolutionary standpoint since exposure to early morning IR-A wavelengths in sunlight may ready the skin for the coming midday deleterious UVR. Consequently IR-A appears to be the solution, not the problem. It does more good than bad for the skin. It is essentially a question
of intensity and how we can learn from the sun."

PubMed

"In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT can reduce UV damage both as a
treatment and as a prophylactic measure. In pigmentary disorders such as vitiligo, LLLT can increase pigmentation by stimulating melanocyte
proliferation and reduce depigmentation by inhibiting autoimmunity. Inflammatory diseases such as psoriasis and acne can also be managed. The
noninvasive nature and almost complete absence of side effects encourage further testing in dermatology."

PubMed

590
+
830

60

660

14

Controlled
trial
633

"The average VSS and GAS scores were lower in the treatment group, whereas
the subjective score was not significantly different."

PubMed

LLLT improved the appearance of facial scars.

PubMed

"In summary, we have demonstrated that the He-Ne laser imparts a growth
stimulatory effect on functional melanocytes via mitochondria-related pathways
and proposed that other minor pathways including DNA damage may also be
inflicted by laser treatment on irradiated cells.

PubMed

More importantly, we have completed the repigmentation scheme of vitiligo

brought about by He-Ne laser light in vitro and provided a solid theoretical basis
regarding how the He-Ne laser induces recovery of vitiligo in vivo."

Skin

Vitiligo

Yu

Taiwan
(Kaohsiung)

2003

J Invest Dermatol

633

Helium-neon laser irradiation stimulates migration and proliferation Human

in melanocytes and induces repigmentation in segmental-type
nonvitiligo.
controlled
+ in vitro

0.03
(?)

0.01
cm2

30

20180

"The results of this in vitro study revealed a significant increase in basic fibroblast
growth factor release from both keratinocytes and fibroblasts and a significant
increase in nerve growth factor release from keratinocytes."

PubMed

"After an average of 16 treatment sessions, initial repigmentation was noticed.

Marked repigmentation (>50%) was observed in 60% of patients with successive
treatments."
Comment: Nicely written paper and interesting results but the dose is surprisingly
low... This paper also is highly cited.

de Jesus

Skin

Brazil
2016
(Ribeirao Preto)

J Biophotonics

An ex vivo study of photobiostimulation in the treatment of skin

pathologies.

Ex vivo

Skin explants

670

0.67

0.07
0.14
0.7

LLLT or LLLT+PDT

".The results indicate that even at the early phase of the treatment (7 days), the
LLLT at low doses 70 mJ cm2 and 140 mJ cm2 promotes the deposition of
new collagen, slightly higher for 70 mJ cm2, and the continuous irradiation with
higher doses (700 mJ cm2) increases the production of type I collagen"

PubMed

Skin

Opel

USA
(Maywood, IL)

2015

J Clin Aesthet
Dermatol

Light-emitting Diodes: A Brief Review and Clinical Experience.

Review +
case series

"The authors clinical experience with a specific yellow light-emitting diode device was mixed, depending on the condition being treated, and was likely
influenced by the device parameters."

PubMed

Skin

Calderhead

Korea

2015

Laser Ther

Adjunctive 830 nm light-emitting diode therapy can improve the

results following aesthetic procedures.

Review

"A growing body of clinical evidence is showing that applying 830 nm LED-LLLT as soon as possible post-procedure, both invasive and noninvasive,
successfully hastens the resolution of sequelae associated with patient downtime in addition to significantly speeding up frank wound healing."

PubMed

Skin

Iyomasa

Brazil
(So Paulo)

2014

Biomed Res Int

Ultrastructure and light microscope analysis of intact skin after a

varying number of low level laser irradiations in mice.

Mouse

Skin

Weiss

USA
(Maryland)

2005

Dermatol Surg

Clinical experience with light-emitting diode (LED)

photomodulation.

Case series

Biphasic dose
response (on
collagen type I)

780

40

0.8

20

0.04
cm2

20

3
7
10

590

"Under these experimental conditions (20 J/cm2), three, six, and 10 laser
applications provided photobiomodulation effect on intact epidermis and dermis of
mice, strain HRS/J, without damage being revealed by electron microscopy.
However, 10 laser applications decreased the type I collagen on the dermis. Thus,
it is clear that more studies are needed to standardize the energy density and
number of applications recommended for therapy of TMD to have a better costbenefit ratio associated with treatment."

PubMed

"LED photomodulation has been used alone for skin rejuvenation in over 300
patients but has been effective in augmentation of results in 600 patients receiving
concomitant nonablative thermal and vascular treatments such as intense pulsed
light, pulsed dye laser, KTP and infrared lasers, radiofrequency energy, and
ablative lasers."

PubMed

"LED photomodulation reverses signs of photoaging using a new nonthermal

mechanism. The anti-inflammatory component of LED in combination with the cell
regulatory component helps improve the outcome of other thermal-based
rejuvenation treatments."

Spinal column Spinal disk

de Carvalho

herniation

Brazil
(So Jos dos
Campos)

2016

Lasers Med Sci

Low intensity laser and LED therapies associated with lateral

decubitus position and flexion exercises of the lower limbs in
patients with lumbar disk herniation: clinical randomized trial.

Human
RCT/SB (?)

904
(laser)

38

0.238

80

0.23

0.16

2080

15

945
(LED)

100

0.100

80
(20p)

0.1

1
cm2

800

15

"We can conclude that in the treatment of L4-L5 and L5-S1 LDH with
radiculopathy, LED, associated with lateral decubitus position and flexion
exercises of the lower limbs, showed better therapeutic performance for radicular
pain, gait claudication, and functional disability."

PubMed

Comment: In this study, LLLT fared as well as placebo (still a great improvement),
but LED seemed to lead to better results.
Comment: The parameters were nicely reported.

Stem cells &

regeneration

Bone marrow
stem cells

Cavalcanti

Brazil
(So Paulo)

2015

Photomed Laser
Surg

Evaluation of the Proliferative Effects Induced by Low-Level Laser

Therapy in Bone Marrow Stem Cell Culture.

In vitro

660

50

112

The parameters used to irradiate DBMSC increased significantly proliferation

without producing high levels of reactive oxygen species (ROS).

PubMed

Stem cells &

regeneration

Myogenesis

Hou

China (Beijing)

2008

Lasers Surg Med

In vitro effects of low-level laser irradiation for bone marrow

mesenchymal stem cells: proliferation, growth factors secretion
and myogenic differentiation.

In vitro

635

60

0
0.5
1.0
2.0
5.0

LLLI stimulates proliferation, increases growth factors secretion and facilitates

myogenic differentiation of BMSCs. Therefore, LLLI may provide a novel approach
for the preconditioning of BMSCs in vitro prior to transplantation.

PubMed

Stem cells &

regeneration

Osteogenesis

Yang

China
(Shenzhen)

2016

Sci Rep

Effects of light-emitting diode irradiation on the osteogenesis of

human umbilical cord mesenchymal stem cells in vitro.

In vitro

620

"In conclusion, low levels of LED light at a wavelength of 620 nm enhance the
proliferation and osteogenic differentiation of hUMSCs during a long culture
period."

PubMed

Stem cells &

regeneration

Osteogenesis

Peng

China
(Wuhan)

2012

Lasers Med Sci

The effect of noncoherent red light irradiation on proliferation and

osteogenic differentiation of bone marrow mesenchymal stem
cells.

In vitro

620

"In conclusion, nonconherent red light can promote proliferation but cannot induce
osteogenic differentiation of MSCs in normal media, while it enhances osteogenic
differentiation and decreases proliferation of MSCs in media with osteogenic
supplements."

PubMed

Stem cells &

regeneration

Osteogenesis

BouvetGerbettaz

France (Nice)

2009

Lasers Surg Med

Effects of low-level laser therapy on proliferation and

differentiation of murine bone marrow cells into osteoblasts and
osteoclasts.

In vitro

808

808nm LLLT didnt alter murine bone progenitor cell proliferation or differentiation.

PubMed

Stem cells &

regeneration

Tenogenic
induction

Gomiero

Italy & Belgium

2016

Vet Res Commun

Tenogenic induction of equine mesenchymal stem cells by means

of growth factors and low-level laser technology.

In vitro

660
905

"In conclusion, the present study might furnish significant suggestions for
developing an efficient approach for tenocyte induction since the external
administration of bFGF2 and TGF3, along with LLLT, influences the
differentiation of PB-MSCs towards the tenogenic fate."

PubMed

Stem cells &

regeneration

Epithelial colony
forming units

Khan & Arany

USA
(Bethesda, MD)

2016

Photomed Laser
Surg

Photobiomodulation Therapy Promotes Expansion of Epithelial

Colony Forming Units.

In vitro

"This study noted a dose-dependent effect of 810 nm laser on increasing eCFUs,

either in terms of size or numbers.

PubMed

Laser vs LED

0.0066
7

1
2
4

150
300
600
3

120

810

Comparisons of different wavelengths and light sources noted better efficacy of

collimated and coherent lasers compared to LEDs and broad-band light."
"PBM therapy promotes expansion of eCFUs that represent progenitors and stem
cell populations capable of contributing to tissue repair and regeneration."

Stem cells &

regeneration

Fekrazad

Iran
(Tehran)

2016

Photomed Laser
Surg

Effect of Photobiomodulation on Mesenchymal Stem Cells.

Systematic
review

"The energy density of the laser was 0.7-9 J/cm2. The power used for visible light was 30-110 mW and that used for infrared light was 50-800 mW.
Nearly all studies showed that low-level laser therapy had a positive effect on cell proliferation. Similar outcomes were found for LED; however, some
studies suggest that the laser alone is not effective, and should be used as an adjunct tool."

PubMed

"This review concluded that doses of 0.7-4 J/cm2 and wavelengths of 600-700 nm are appropriate for light therapy. The results were dependent upon
different parameters; therefore, optimization of parameters used in light therapy to obtain favorable results is required to provide more accurate
comparison."

Stem cells &

regeneration

Fallahnezhad

Iran
(Tehran)

2016

J Biomed Opt

Low-level laser therapy with helium-neon laser improved viability

of osteoporotic bone marrow-derived mesenchymal stem cells
from ovariectomy-induced osteoporotic rats.

In vitro

Stem cells &

regeneration

Ginani

Brazil
(Natal)

2015

Lasers Med Sci

Effect of low-level laser therapy on mesenchymal stem cell

proliferation: a systematic review.

Metaanalysis

633
810

3
50

0.6/
1.2/
2.4

1.91
1.91

"LLLT can enhance the viability and proliferation rate of healthy and especially
osteoporotic autologous BMMSCs that could be very useful in regenerative
medicine for the treatment of OP and fracture of patients who are OP-dependent"

PubMed

cm2
"From 463 references obtained, only 19 papers met the search criteria and were included in this review.
The analysis of the papers showed a concentration of experiments using LLLT on stem cells derived from bone marrow, dental pulp, periodontal
ligament, and adipose tissue.
Several protocols were used to irradiate the cells, with variations on wavelength, power density, radiation time, and state of light polarization.
Most studies demonstrated an increase in the proliferation rate of the irradiated cells. It can be concluded that the laser therapy positively influences the
in vitro proliferation of stem cells studied, being necessary to carry out further experiments on other cell types and to uniform the methodological
designs."

PubMed

LLLI = Low-level laser (light) irradiation

BMSCs = bone marrow-derived mesenchymal stem cells
MSCs = mesenchumal stem cells
CSCs = cardiac stem cells

LLLI = Low-level laser (light) irradiation

BMSCs = bone marrow-derived mesenchymal stem cells
MSCs = mesenchumal stem cells
CSCs = cardiac stem cells

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Stem cells &

regeneration

Mvula &
Abrahamse

South Africa
(Johannesburg)

2016

Photomed Laser
Surg

Differentiation Potential of Adipose-Derived Stem Cells When

Cocultured with Smooth Muscle Cells, and the Role of LowIntensity Laser Irradiation.

Stem cells &

regeneration

Emelyanov &
Kiryanova

Russia
2015
(St. Petersburg)

Photomed Laser
Surg

Photomodulation of proliferation and differentiation of stem cells

by the visible and infrared light.

Systematic
review

Stem cells &

regeneration

Soleimani

Iran (Tehran)

2012

Lasers Med Sci

The effects of low-level laser irradiation on differentiation and

proliferation of human bone marrow mesenchymal stem cells into
neurons and osteoblasts--an in vitro study.

In vitro

Stem cells &

regeneration

Abrahamse H

South Africa
(Johannesburg)

2012

Photomed Laser
Surg

Regenerative medicine, stem cells, and low-level laser therapy:

future directives.

Guest
Editorial

Stem cells &

regeneration

Tuby

2007

Lasers Surg Med

Low-level laser irradiation (LLLI) promotes proliferation of

mesenchymal and cardiac stem cells in culture.

In vitro

StevensJohnson
syndrome

Simes

2011

Photomed Laser
Surg

Laser phototherapy for Stevens-Johnson syndrome: a case report.

Case report

Category

Subcategory

Brazil
(So Paulo)

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

das Neves

Brazil
2016
(Ribeiro Preto) epub

Lasers Med Sci

Laser photobiomodulation (830 and 660 nm) in mast cells, VEGF,

FGF, and CD34 of the musculocutaneous flap in rats submitted to
nicotine.

Results: positive / unclear/modest / negative

"Cell viability and proliferation increased significantly in the cocultured groups that
were exposed to LILI alone, as well as in combination with growth factors. Further,
there was a significant decrease in the expression of stem cell markers with a
concomitant increase in SMC markers."
The systematic review:
- The analysis revealed the importance of cell type when choosing the cell irradiation parameters.
- The influence of wavelength on the SC proliferation rate seemed to be nonsignificant.
- The high values of increased proliferation or differentiation were obtained using high power density, low energy density, and short exposure time.
- SC exposure to light without inducers did not lead to their differentiation
- The maximum differentiation was achieved using irradiation parameters different from the ones needed to achieve the maximum proliferation
of the same cells.
810

2
3
4
6

Link

Additional info

Comment

Reply

The effect of LLLI on differentiation and proliferation of BMSCs is dosedependent. Considering these findings, LLLI could improve current in vitro
methods of differentiating BMSCs prior to transplantation.

PubMed

PubMed

PubMed

PubMed

PubMed

PubMed
1
3

Cardiac stem cells

660

15

0.375

100

3.571

0.15

3.8

0.04
cm2

0.028
cm2

Surgery (flap) TRAM flap

t
sec

660
830

Rat

60

3.9

140

0.028
cm2

10
/p

10

The present study clearly demonstrates the ability of LLLI to promote proliferation
of MSCs and CSCs in vitro.

PubMed

"Because of the lack of progress of the patient, the LPT was selected."

PubMed

"By 6 days after his initial session of LPT, most of the patient's intraoral lesions
had disappeared, and the few that remained were painless; the patient was able to
eat solid food by himself and was removed from the ICU. Ten sessions of LPT
were conducted in the hospital."

2
/p

65

"PBM with a wavelength of 830 nm increased the viability of the TRAM flap, with a
smaller area of necrosis, increased number of mast cells, and higher expression of
VEGF and CD34. PBM increases the viability of musculocutaneous flaps treated
with to nicotine."

PubMed

Note: The photograph quality is low.

Systemic
effects

Johnstone

Australia

2015

Neural Regen Res Targeting the body to protect the brain: inducing neuroprotection
with remotely-applied near infrared light.

Perspective

Alzheimer's disease

Systemic
effects

Lima

Brazil
(Salvador,
Bahia)

2014

Lasers Med Sci

Evaluation of corticosterone and IL-1, IL-6, IL-10 and TNF-

expression after 670-nm laser photobiomodulation in rats.

Rat

Corticosterone
Cytokines

"In practical terms, the indirect protective effects of NIr were an unexpected bonus to the value of direct NIr irradiation, for they overcome the problem of
tissue penetration, currently a major barrier to the clinical application of light-based therapies to brain disorders."
670

980
810

5000

0.031

0.028
cm2

"At 6 h after surgery, a significant increase in corticosterone and a significant

reduction in the levels of IL-1 and IL-6 in tissues of irradiated wounds were
observed when compared to controls (p < 0.05). The levels of TNF- and IL-10
expression were not significantly different between the groups at different time
intervals.

PubMed
PubMed

Thus, this study strongly suggests a systemic and local biomodulation of low-level
laser therapy as indicated by the blood levels of corticosterone and the tissue
expression of IL-1 and IL-6, respectively."

Tendons

Achilles tendon

Tumilty

New Zealand

2016

Lasers Med Sci

Photobiomodulation and eccentric exercise for Achilles

tendinopathy: a randomized controlled trial.

Human
RCT

Tendons

Achilles tendon

Mrdh & Lund

Sweden
(Stockholm)

2016

J Lasers Med Sci

High Power Laser for Treatment of Achilles Tendinosis - a Single

Blind Randomized Placebo Controlled Clinical Study.

Human
RCT

450

90

LLLT seemed to improve the benefits of exercise, but only in the group which had
exercise sessions only twice a week.

PubMed

"The between group difference were significant in four of nine questions regarding
loading activities of the FAOS subscale. Assessed pain thresholds were found
increased in the HPLT group, as compared to the placebo HPLT group. At
individual level, the results varied."

PubMed

"The results indicate that HPLT may provide a future option for treatment of
Achilles tendinosis related pain, but further studies are warranted."
830

40

Collagenase-induced
tendinopathy

830

50

Rat

LED phototherapy

945

32

Rat

Tendon injury

Tendons

Achilles tendon

Da R Guerra

Brazil
(Alfenas)

2016

Lasers Med Sci

Low-level laser therapy modulates pro-inflammatory cytokines

after partial tenotomy.

Rats

Tendons

Achilles tendon

Marques

Brazil
(So Paulo)

2016

Lasers Med Sci

Photobiomodulation therapy on collagen type I and III, vascular

endothelial growth factor, and metalloproteinase in experimentally
induced tendinopathy in aged rats.

Rat

Tendons

Achilles tendon

Helrigle

Brazil
(So Paulo)

2016

Lasers Med Sci

Effects of low-intensity non-coherent light therapy on the

inflammatory process in the calcaneal tendon of ovariectomized
rats.

Tendons

Achilles tendon

Haslerud

Norway
(Bergen)

2016

Photomed Laser
Surg

Low-Level Laser Therapy and Cryotherapy as Mono- and

Adjunctive Therapies for Achilles Tendinopathy in Rats.

0.1160
cm2

16
(CW)
32
(P)

3
/p

107

0.028
cm2

60
/p

3.84

0.032
(?)

1
cm2

120
/p

"Our results showed that the pulsed LLLT seems to exert an anti-inflammatory
effect over injured tendons, with reduction of the release of proinflammatory
cytokines, such as TNF- and the decrease in the i-NOS activity. Thanks to the
pain reduction and the facilitation of movement, there was a stimulation in the
TGF- and IL-1 release.

PubMed

In conclusion, we believe that pulsed LLLT worked effectively as a therapy to

reestablish the tendon integrity after rupture."
1.8

3
/wk

(3p)

"Our findings indicate that PBMT may lead to the improvement and acceleration of
inflammation when compared to tendinopathy aged group."

PubMed

"It was concluded that low-intensity LED treatment using the parameters and
wavelength of 945 nm in the time periods studied reduced the release of IL-6 and
TNF- and increased the release of IL-10, thereby improving the inflammatory
response in OVX rats."

PubMed

"Our results demonstrate that cryotherapy in combination with LLLT can produce
an anti-inflammatory "add-on" effect."

PubMed

"The order of therapy administration seems essential, as superior histology and

biomechanical results were found in the cryotherapy first/LLLT group."

Tendons

Achilles tendon

de Jesus

Brazil
(So Paulo)

2016

Photomed Laser
Surg

Low-Level Laser Therapy (780 nm) on VEGF Modulation at Partially

Injured Achilles Tendon.

Tendon injury

780

70

Tendons

Achilles tendon

Torres-Silva

Brazil
(So Paulo)

2015

Lasers Med Sci

The low level laser therapy (LLLT) operating in 660 nm reduce gene Rat
expression of inflammatory mediators in the experimental model of
collagenase-induced rat tendinitis.

Collagenase-induced
tendinitis

660

100

Tendons

Achilles tendon

Ferreira

Brazil
(So Paulo)

2015

Photomed Laser
Surg

Achilles Tendon Vascularization of Proximal, Medial, and Distal

Portion Before and After Partial Lesion in Rats Treated with
Phototherapy.

Rat

Vascularization

660
830

60

Tendons

Achilles tendon

de Jesus

Brazil
(So Paulo)

2015

Lasers Med Sci

Low-level laser therapy in IL-1, COX-2, and PGE2 modulation in

partially injured Achilles tendon.

Rat

Tendon injury

780

70

Tendons

Achilles tendon

Chang

Taiwan (Taipei)

2015

J Orthop Sports
Phys Ther

Effects of Therapeutic Physical Agents on Achilles Tendon

Microcirculation.

Human

Microcirculation

Tendons

Achilles tendon

Allahverdi

Iran
(Tehran)

2015

Lasers Med Sci

Evaluation of low-level laser therapy, platelet-rich plasma, and their Rabbit

combination on the healing of Achilles tendon in rabbits.

Partial tenotomy

650

30

Tendons

Achilles tendon

Xavier

Brazil
(Diamantina)

2014

Lasers Med Sci

Low-level light-emitting diode therapy increases mRNA

expressions of IL-10 and type I and III collagens on Achilles
tendinitis in rats.

Rat

LED phototherapy

880

22

Tendons

Achilles tendon

Pinfildi

Brazil
(So Paulo)

2014

Photomed Laser
Surg

Mast cell curve-response in partial Achilles tendon rupture after

830 nm phototherapy.

Rat

Tendon rupture by
direct trauma

830

80

Tendons

Achilles tendon

Marcos

Brazil
(So Paulo)

2014

J Mech Behav
Biomed Mater

Biomechanical and biochemical protective effect of low-level laser

therapy for Achilles tendinitis.

Rat

Collagenase-induced
tendinitis

810

100

Rat

1.75

0.7

17.5

0.04
cm2

10

1
3
7

LLLT did not stimulate the expression of VEGF in the treated Achilles tendons.

PubMed

"The laser irradiation (660 nm, 100 mW, 3 J) used in the treatment of the tendinitis
induced by collagenase in Achilles tendon in rats was effective in the reduction of
important pro-inflammatory markers such as IL-6 and TNF-, becoming a
promising tool for the treatment of tendon diseases."

PubMed

"Low-level laser therapy (LLLT) had no effect on the studied parameters."

PubMed

"LLLT decreased Achilles tendon's inflammatory process."

PubMed

"No significant THb and StO2 differences were found after the application of
interferential current or low-level laser."

PubMed

15

"The results for these parameters showed that PRP or LLLT alone has significant
advantages over untreated animals (P < 0.05). Furthermore, it was found that the
combined treatment with PRP and LLLT is even more efficient."

PubMed

1
3

2.14

1.1

40

18.6

17.5

10

1
3
7

5.4
18
1.8

2.8

1.12

40

1
3

1
cm2
0.5
cm2

170

7
14

"LED (880 nm) was effective in increasing mRNA expression of IL-10 and type I
and III collagen. Therefore, LED therapy may have potentially therapeutic effects
on Achilles tendon injuries."

PubMed

0.028
cm2

14

1-3

LLLT was shown to increase the quantity of mastocytes in the assessment periods
compared with the simulation groups.

PubMed

0.028
cm2

10
30

"The treatment by non-steroidal anti-inflammatory drugs such as diclofenac

sodium produces a low protective effect and can affect the short-term biochemical
and biomechanical properties. On the contrary, it is shown that LLLT exhibits the
best results in terms of MMPs reduction and mechanical properties recovery.
Thus, LLLT looks to be a promising and consistent treatment for tendinopathies."

PubMed

PBM vs diclofenac

K30 hand-held probe, AZOR, Technica, Russia, 650 nm

Star: This article contains a lot of data - might be interesting to experts.

Tendons

Achilles tendon

Guerra Fda

Brazil
(So Paulo)

2014

Lasers Med Sci

Pulsed LLLT improves tendon healing in rats: a biochemical,

organizational, and functional evaluation.

Rat

Partial transection of
tendon

830

40

Tendons

Achilles tendon

de Jesus

Brazil
(So Paulo)

2014

Photomed Laser
Surg

Low-level laser therapy on tissue repair of partially injured achilles

tendon in rats.

Rat

Partial tendon injury

780

70

Tendons

Achilles tendon

Casalechi

Brazil
(So Paulo)

2014

Lasers Med Sci

Analysis of the effect of phototherapy in model with traumatic

Achilles tendon injury in rats.

Rat

Injury by contusion

830

50

Tendons

Achilles tendon

Aliodoust

Iran (Tehran)

2014

Lasers Med Sci

Evaluating the effect of low-level laser therapy on healing of

tentomized Achilles tendon in streptozotocin-induced diabetic rats
by light microscopical and gene expression examinations.

Rat

Surgical tenotomy

633

7.2

0.014

Tendons

Achilles tendon

Nouruzian

Iran (Tehran)

2013

Lasers Med Sci

Effect of low-level laser therapy on healing of tenotomized Achilles

tendon in streptozotocin-induced diabetic rats.

Rat

Tenotomy + diabetes

633

7.2

Tendons

Achilles tendon

Barbosa

Brazil
(So Jos dos
Campos)

2013

Lasers Med Sci

Low-level laser therapy combined with platelet-rich plasma on the

healing calcaneal tendon: a histological study in a rat model.

Rat

Tendons

Achilles tendon

Guerra Fda

Brazil
(So Paulo)

2013

Lasers Med Sci

LLLT improves tendon healing through increase of MMP activity

and collagen synthesis.

Rat

Tendons

Achilles tendon

Casalechi

Brazil
(So Paulo)

2013

Lasers Med Sci

Low-level laser therapy in experimental model of collagenaseinduced tendinitis in rats: effects in acute and chronic
inflammatory phases.

Tendons

Achilles tendon

Tumilty

New Zealand

660
830

0.25

4
17.5

1.4

0.35

0.028
cm2

PubMed

1
3
7

"LLLT stimulated collagen I proliferation, improving the injured Achilles tendons'

healing process."

PubMed

120

7
14

"It was concluded that treatment with LIL in the parameters used and the times
studied reduces migration of inflammatory cells and improves the quality of repair
while reducing the functional limitations."

PubMed

5
10
15

"LLLT significantly decreased inflammation in diabetic rats on days 5 (p = 0.03)

and 10 (p = 0.02) compared to the corresponding control diabetic rats. According
to the student's t test, LLLT significantly increased TGF-1 gene expression in
healthy (p = 0.000) and diabetic (p = 0.000) rats compared to their relevant
controls. The He-Ne laser was effective in altering the inflammatory reaction and
increasing TGF-1 gene production."

PubMed

"LLLT at 2.9 J/cm(2) to the tenotomized Achilles tendons in the non-diabetic and
diabetic rats significantly increased the strength and maximum stress of repairing
Achilles tendons in our study."

PubMed

"Results showed that the deposition of collagen type I was higher when treatment
with PRP and LLLT was combined, suggesting a faster regeneration of the
tendon."

PubMed

"Our results indicate that the pulsed LLLT improved the remodeling of the ECM
during the healing process in tendons through activation of MMP-2 and stimulation
of collagen synthesis."

PubMed

"Our results suggest that LLLT with parameters employed in the present study
was able to modulate IL-10, VEGF, MMP1, and MMP13 mRNA gene expression
both in acute than in chronic tendon inflammation. However, further studies are
needed to establish optimal parameters for LLLT."

PubMed

"The clinical effectiveness of adding LLLT to eccentric exercises for the treatment
of Achilles' tendinopathy has not been demonstrated using the parameters in this
study."

PubMed

2.9

2.9
11.5
4.3
0.2

"In conclusion, pulsed LLLT leads to increased organization of collagen bundles

and improved gait recovery."
10

0.0052
cm2

7.0

20
/point
(3p)

2012

Arch Phys Med

Rehabil

Clinical effectiveness of low-level laser therapy as an adjunct to

eccentric exercise for the treatment of Achilles' tendinopathy: a
randomized controlled trial.

830

40

Rat

780

22

0.107

1.54

Human
RCT

810

100

0.1

18
(6p)

Tenotomy

16
32

6
or
13

7.5

0.07
cm2

180

12

(See Comment & Reply. According to Bjordal&Lopes-Martins, the actual dose was
more than 10x smaller than Tumilty et al. reported in their paper.)

Tendons

Achilles tendon

Rowe

UK (London)

2012

Sports Med

Conservative management of midportion Achilles tendinopathy: a

mixed methods study, integrating systematic review and clinical
reasoning.

Systematic
review

Evidence was moderate for LLLT.

PubMed

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

Tendons

Achilles tendon

Ng & Chung

China (Hong
Kong)

2012

Photomed Laser
Surg

Effects of a therapeutic laser and passive stretching program for

treating tendon overuse.

Rat

Achilles overuse

660

8.8

Tendons

Achilles tendon

Marcos

Brazil
(So Paulo)

2012

J Orthop Res

Low-level laser therapy in collagenase-induced Achilles tendinitis

in rats: analyses of biochemical and biomechanical aspects.

Rat

Collagenase-induced
tendinitis

810

100

Category

3.57

J/cm2

0.44

3.4

0.13
cm2

50

1
3

35.71
107.14

0.028
cm2

10
30

214

0.028
cm2

0.38
cm2

Results: positive / unclear/modest / negative

Link

sec

"We conclude that a therapeutic laser and combined laser with passive stretching
might slow down the decrease in Achilles tendon strength but would not be able to
stop the pathological changes of overuse from developing."

PubMed

"Biomechanical properties were preserved in the laser-treated groups when

compared to collagenase and diclofenac groups. We conclude that LLLT was able
to reduce tendon inflammation and to preserve tendon resistance and elasticity."

PubMed

60

1
3

"We conclude that LLLT is an important modulator of inflammatory cytokines

release after injury in Achilles tendon."

PubMed

50

"There was a significant increase in tendon thickness in the active LLLT group
when compared with the placebo group (p < 0.05) and there were no significant
differences between the placebo and uninjured left tendons. There were no
significant differences in UTS between laser-treated, placebo-treated and
uninjured tendons.

PubMed

PBM vs diclofenac

Tendons

Achilles tendon

Laraia

Brazil
(Campo
Grande)

2012

Lasers Med Sci

Effect of low-level laser therapy (660 nm) on acute inflammation

induced by tenotomy of Achilles tendon in rats.

Rat

Tenotomy

660

100

3.57

Tendons

Achilles tendon

Joensen

Norway
(Bergen)

2012

Lasers Med Sci

An experimental study of low-level laser therapy in rat Achilles

tendon injury.

Rat

Blunt trauma

904

60

0.158

Tendons

Achilles tendon

Pires

Brazil
(So Jos dos
Campos)

2011

Lasers Med Sci

Low-level laser therapy (LLLT; 780 nm) acts differently on mRNA

expression of anti- and pro-inflammatory mediators in an
experimental model of collagenase-induced tendinitis in rat.

Rat

Collagenase-induced
tendinitis

780

Laser irradiation of the Achilles tendon at 0.158 W/cm(2) for 50 s (3 J)

administered within the first 30 min after blunt trauma, and repeated after 15 h,
appears to lead to edema of the tendon measured 23 hours after LLLT. "
7.7

2
(?)

"LLLT in both acute and chronic phases decreased IL-6, COX-2, and TGF-
expression after tendinitis, respectively, when compared to tendinitis groups: IL-6,
COX-2, and TGF-.

PubMed

The LLLT not altered IL-1 expression in any time, but reduced the TNF-
expression; however, only at chronic phase. We conclude that LLLT administered
with this protocol reduces one of features of tendinopathies that is mRNA
expression for pro-inflammatory mediators."

Tendons

Achilles tendon

Neves

Brazil
(So Paulo)

2011

Photomed Laser
Surg

Different power settings of LLLT on the repair of the calcaneal

tendon.

Rat

Partial tendon rupture

830

40
60
80
100

Tendons

Achilles tendon

Marcos

Brazil
(So Paulo)

2011

Photochem
Photobiol

Infrared (810 nm) low-level laser therapy in rat achilles tendinitis: a

consistent alternative to drugs.

Rat

Collagenase-induced
tendinitis

810

100

1.4
2.14
2.8
3.5

0.84

30

0.028
cm2

1
3
6

21
14
10.5
8.4

10
30
60

PBM vs diclofenac
Biphasic dose
response
Achilles tendon

Xavier

Brazil
(So Paulo)

2010

Lasers Surg Med

Anti-inflammatory effects of low-level light emitting diode therapy

on Achilles tendinitis in rats.

Rat

880

22

Tendons

Achilles tendon

Wood

Brazil
(So Paulo)

2010

Lasers Surg Med

Collagen changes and realignment induced by low-level laser

therapy and low-intensity ultrasound in the calcaneal tendon.

Rat

830

40

1.4

0.12

Tendons

Achilles tendon

Oliveira

Brazil
(So Paulo)

2009

Lasers Surg Med

Effect of low level laser therapy (830 nm) with different therapy
Rat
regimes on the process of tissue repair in partial lesion calcaneous
tendon.

830

40

1.4

0.12

Tendons

Achilles tendon

Chen

Taiwan
(Kaohsiung)

2009

J Orthop Res

Low-level laser irradiation promotes cell proliferation and mRNA

expression of type I collagen and decorin in porcine Achilles
tendon fibroblasts in vitro.

820
635

40

In vitro

PubMed

"As LLLT seems to act on inflammation through a selective inhibition of the COX-2
isoform in collagenase-induced tendinitis, LLLT may have potential to become a
new and safer nondrug alternative to coxibs."

PubMed

"We found that LLLT dose of 3 J significantly reduced inflammation through less
COX-2-derived gene expression and PGE(2) production, and less edema
formation compared to nonirradiated controls."

Tendons

LED phototherapy

"Low-level laser therapy resulted in significantly greater amounts of type III

collagen (output powers of 60 mW or more) and type I collagen (output power of
80 mW), however, no significant differences between groups were found in the
realignment of collagen fibers."

7.5

0.5
cm2

170

4+
(?)

"Our results showed that LED decreases the inflammatory cells influx and mRNA
expression to IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) in both
phase, and cyclooxygenase-2 (COX-2) just in initial phase (P < 0.05)."

PubMed

0.028
cm2

"Ultrasound, LLLT, and the combined use of LLLT and US resulted in greater
synthesis of type I collagen"

PubMed

0.028
cm2

3
5
7

"Low intensity laser therapy was effective in the improvement of collagen fibers
organization of the calcaneous tendon after undergoing a partial lesion."

PubMed

540
1080
1620

"When compared to the control group, the cell proliferation of irradiated Achilles
tendon fibroblasts in the other three groups increased significantly by 13% +/0.8% (Group 2), 30% +/- 0.4% (Group 3), and 12% +/- 0.6% (Group 4)
respectively. But progressively higher laser intensity did not achieve a
correspondingly higher cell proliferation effect in Achilles tendon fibroblasts.

PubMed

1
2
3

The mRNA expressions of decorin and type I collagen in fibroblasts with LLLI were
significantly higher (p < 0.05). Therefore, suitable dosages of LLLI may result in
more effective tissue healing by promoting type I collagen and decorin synthesis.
However, these positive effects of LLLI on the repair of the Achilles tendon in
humans should be further investigated in clinic."

Tendons

Achilles tendon

Casalechi

Brazil
(So Paulo)

2009

Lasers Med Sci

The effects of low-level light emitting diode on the repair process

of Achilles tendon therapy in rats.

Rat

640

100

Tendons

Achilles tendon

Tumilty

New Zealand

2008

Photomed Laser
Surg

Laser therapy in the treatment of achilles tendinopathy: a pilot

study.

Human
Pilot study

810

100

Tendons

Achilles tendon

Stergioulas

Norway
(Bergen)

2008

Am J Sports Med

Effects of low-level laser therapy and eccentric exercises in the

treatment of recreational athletes with chronic achilles
tendinopathy.

Human
RCT

820

30

Tendons

Achilles tendon

Elwakil TF

Egypt (Cairo)

2007

Lasers Med Sci

An in-vivo experimental evaluation of He-Ne laser photostimulation Rabbit

in healing Achilles tendons.
tendons

Tendons

Achilles tendon

Carrinho

Brazil
(Sao Carlos)

2006

Photomed Laser
Surg

Comparative study using 685-nm and 830-nm lasers in the tissue

repair of tenotomized tendons in the mouse.

Mouse

"All wavelengths and fluences used in this study were efficient at accelerating the
healing process of Achilles tendon post-tenotomy, particularly after the 685-nm
laser irradiation, at 3 J/cm(2). It suggests the existence of wavelength tissue
specificity and dose dependency."

PubMed

Tendons

Achilles tendon

Salate

Brazil
(So Paulo)

2005

Photomed Laser
Surg

Effect of In-Ga-Al-P diode laser irradiation on angiogenesis in

partial ruptures of Achilles tendon in rats.

Rat

660

10
40

2.5
10

10

"LLLT of different intensities seems to promote neovascularization in damaged

Achilles tendons of rats after partial rupture compared to controls."

PubMed

Tendons

Achilles tendon

Fillipin

Brazil (Rio
Grande do Sul)

2005

Lasers Surg Med

Low-level laser therapy (LLLT) prevents oxidative stress and

reduces fibrosis in rat traumatized Achilles tendon.

Rat

904

45

35

"LLLT by Ga-As laser reduces histological abnormalities, collagen concentration,

and oxidative stress in an experimental model of Achilles tendon injury. Reduction
of fibrosis could be mediated by the beneficial effects on the oxidant/antioxidant
balance."

PubMed

Tendons

Achilles tendon

Demir

Turkey
(Kayseri)

2004

Lasers Surg Med

Comparison of the effects of laser, ultrasound, and combined laser

+ ultrasound treatments in experimental tendon healing.

Rat

Traumatized tendons

904

"Although US, L, and combined US + L treatments increased tendon healing

biochemically and biomechanically more than the control groups, no statistically
significant difference was found between them."

PubMed

Tendons

Cells

Chen

Taiwan (Taipei)

2015

Lasers Med Sci

Second messengers mediating the proliferation and collagen

synthesis of tenocytes induced by low-level laser irradiation.

In vitro

Tenocyte function

"The findings suggested that LLLT stimulated ATP production and increased
intracellular calcium concentration. Directly or indirectly via production of TGF-1,
these second messengers mediated the proliferation of tenocytes and synthesis of
collagen."

PubMed

Tendons

Cells

Tsai

Taiwan
(Taoyuan
County)

2014

Lasers Med Sci

Low-level laser irradiation stimulates tenocyte proliferation in

association with increased NO synthesis and upregulation of
PCNA and cyclins.

In vitro

Tenocyte proliferation

"The results revealed that tenocytes proliferation was enhanced dose dependently
by laser. NO secretion was increased after laser treatment. PCNA and cyclins E,
A, and B1 were upregulated by laser. In conclusion, low-level laser irradiation
stimulates tenocyte proliferation in a process that is mediated by upregulation of
NO, PCNA, and cyclins E, A, and B1."

PubMed

Tendons

de Quervain's
tenosynovitis

Sharma

India
(New Delhi)

2015

Indian J Orthop

Outcome of low level lasers versus ultrasonic therapy in de

Quervain's tenosynovitis.

Human
Comparison
trial

"On comparing both the groups, no statistically significant difference was found.
However, looking at the mean values, the grip strength and VAS showed better
improvement in the US Th. group as compared to the laser therapy group."

PubMed

Tendons

Digital flexor
tendons

Iacopetti

Italy
(Padua)

2015

Photomed Laser
Surg

Effect of MLS() laser therapy with different dose regimes for the
treatment of experimentally induced tendinopathy in sheep: pilot
study.

Sheep

"In this study, clinical and histological evaluation demonstrated that a therapeutic
dose <5 J/cm(2) furnished an anti-inflammatory effect, and induced a decrease of
fibroblasts and vessel area. Overall, our results suggest that MLS laser therapy
was effective in improving collagen fiber organization in the deep digital flexor
tendon."

PubMed

20

0.5
cm2

120

7
14
21

18

0.06

5.4

0.5
cm2

633

685
/
830

3
/
10

180

12

"This study demonstrated that LED interfered in the repair process of the tendon
tissue, reducing the number of fibroblasts in the initial periods and improving the
quality of the repair in all periods studied."

PubMed

"This study has demonstrated the feasibility of undertaking a randomized

controlled trial of LLLT for Achilles tendinopathy. Conclusions regarding
effectiveness cannot be made due to the low statistical power of this pilot study."

PubMed

"Low-level laser therapy, with the parameters used in this study, accelerates
clinical recovery from chronic Achilles tendinopathy when added to an EE
regimen. For the LLLT group, the results at 4 weeks were similar to the placebo
LLLT group results after 12 weeks."

PubMed

"The histopathological findings suggest the favorable qualitative pattern of the

newly synthesized collagen of the regenerating tendons after He-Ne laser
photostimulation. The biomechanical results support the same favorable findings
from the functional point of view as denoted by the better biomechanical properties
of the regenerating tendons after He-Ne laser photostimulation with statistical
significance (p <or= 0.01) at most of the biomechanical parameters"

PubMed

Star: Paper was supplied with photographs of Achilles tendon and LLLT.
Comment: Parameters were insufficiently reported.

Tenotomy

MLS laser therapy

Biphasic dose
response (?)

830

3040

4.910
cm2

808
+
905

500
+
54

2.5
5.0

3.14
cm2
+
3.14
cm2

100

"The aggravation of the inflammatory condition, observed during the applications

of MLS laser therapy in the first group, seems to indicate that, for the treatment of
an acute tendinitis with this type of laser emission, the dose of 5 J/cm2 was
excessive for the therapeutic effect. Results from histological examinations
indicate that both treatments induced a statistically significant cell number
decrease, although only in the second group did the values return to normal.
Moreover, the MLS dose of 2.5 J/ cm2 (group 2) caused a significant decrease of
the vessel area"
904

"The results of the study showed a significant improvement in the laser-treated

group only for the parameter of edema reduction (p < 0.01) but the difference
between the two groups was non-significant for pain reduction, hand grip strength,
and functional evaluation performed according to Strickland and Buck-Gramcko
systems using total active motion and fingertip-to distal palmar crease distance
parameters (p > 0.05)."

Tendons

Digital flexor
tendons

Ozkan

Turkey
(Bursa)

2004

J Clin Laser Med

Surg

Investigation of the supplementary effect of GaAs laser therapy on

the rehabilitation of human digital flexor tendons.

Human
RCT/DB

Tendons

Shoulder

Haslerud

Norway
(Bergen)

2015

Physiother Res Int The efficacy of low-level laser therapy for shoulder tendinopathy: a
systematic review and meta-analysis of randomized controlled
trials.

Metaanalysis

Shoulder
tendinopathy

"Seventeen randomized controlled trials (RCTs) met the inclusion criteria, and 13 RCTs were of high and 4 RCTs of moderate methodological quality.

Doyle

USA
(Marion, IN)

2016

J Sport Rehabil

The Effects of Low-Level Laser Therapy on Pain Associated With

Tendinopathy: A Critically Appraised Topic.

Review

Tendinopathy

"Although LLLT significantly decreases pain from baseline, its use may be no better than placebo or traditional treatments such as ultrasound, moist heat
packs, electrical stimulation, or therapeutic exercise to reduce pain associated with tendinopathy. Total accumulated joules across the treatment
sessions may need to be taken into account as a parameter."

PubMed

Weber

Germany
(Darmstadt)

2015

BMC
Musculoskelet
Disord

Efficacy of physical therapy for the treatment of lateral

epicondylitis: a meta-analysis.

Metaanalysis

"Bjordal et al. [7] analyzed 7 studies of LLLT for the treatment of LE. In contrast to Bjordal et al. [7] this meta-analysis identified only 2 LLLT studies which
both, met inclusion criteria and published sufficient data for meta-analysis. This meta-analysis did not include six studies which were included in
Buchbinder et al. [2]. Five studies were excluded due to not reported standard deviations [9, 13, 25, 26, 27], one was not included since the underlying
data is not published [28, 29, 30, 31, 32, 33, 34, 35]."

PubMed

PubMed

Comment: The final results were very good both for placebo and laser. Therefore,
supplementary laser treatment might be not warranted for this condition.

Tendons
Tendons

Tennis elbow

PubMed

Significant and clinically important pain relief was found with weighted mean differences (WMD) over placebo, for LLLT as monotherapy at 20.41 mm
(95% CI: 12.38 to 28.44) and as adjunct to exercise therapy at 16.00 mm (95% CI: 11.88 to 20.12)."

"Due to the small number of studies this meta-analysis offers no interpretation concerning the effectiveness of LLLT in the treatment for LE. Bjordal et al.
[7] concluded that LLLT was safe and effective and that it acted in a dose dependent manner."

Additional info

Comment

Reply

 Category
Tendons

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Tennis elbow

Roberts

Canada
(Castlegar)

2013

Lasers Surg Med

The effectiveness of therapeutic class IV (10 W) laser treatment for

epicondylitis.

Human
RCT/DB

980/
810

10000

0.022

6.6

Results: positive / unclear/modest / negative

"In the laser treated group handgrip strength improved by 17 3%, 52 7%, and
66 6% at 3, 6, and 12 months respectively; function improved by 44 1%, 71
3%, and 82 2%, and pain with resistance to extension of the middle finger was
reduced by 50 6%, 93 4%, and 100 1% at 3, 6 and 12 months, respectively.

Link

Additional info

sec

45
cm2

300

PubMed

In contrast, no changes were seen until 12 months following sham treatment (12
months: strength improved by 13 2%, function improved by 52 3%, pain with
resistance to extension of the middle finger reduced by 76 2%)."
[See additional info]

Tendons

Tennis elbow

Chang

Taiwan
(Miaoli)

2010

Photomed Laser
Surg

Therapeutic effects of low-level laser on lateral epicondylitis from

differential interventions of Chinese-Western medicine: systematic
review.

"We selected ten articles, and in seven of them the irradiation was conducted on tender points or MTrPs in the experimental groups. In two other articles,
the irradiation was conducted on acupuncture points, and the last one was conducted on both kinds of points.

Systematic
review

PubMed

Only three articles provided sufficient data for meta-analysis.

The results revealed that applying LLLT on tender points or MTrPs is an effective means to improve the effect size (ES) of pain release after treatment
(pooled ES: 0.71, 95% CI: 0.82- approximately 0.60) and follow-up (pooled ES: 1.05, 95% CI: 1.16- approximately 0.94). LLLT application was also able
to increase the grip force, ROM, and weight test (p < 0.05)."
Comment: In this systematic review, studies were reviewed according to PEDro.

Tendons

Tennis elbow

Bjordal

Norway
(Bergen)

2008

BMC
Musculoskelet
Disord

A systematic review with procedural assessments and metaanalysis of low level laser therapy in lateral elbow tendinopathy
(tennis elbow).

"18 randomised placebo-controlled trials (RCTs) were identified with 13 RCTs (730 patients) meeting the criteria for meta-analysis. 12 RCTs satisfied half
or more of the methodological criteria. Publication bias was detected by Egger's graphical test, which showed a negative direction of bias."

Metaanalysis

PubMed

"The weighted mean difference (WMD) for pain relief was 10.2 mm [95% CI: 3.0 to 17.5] and the RR for global improvement was 1.36 [1.16 to 1.60]."
"Trials which targeted acupuncture points reported negative results, as did trials with wavelengths 820, 830 and 1064 nm."
"In a subgroup of five trials with 904 nm lasers and one trial with 632 nm wavelength where the lateral elbow tendon insertions were directly irradiated,
WMD for pain relief was 17.2 mm [95% CI: 8.5 to 25.9] and 14.0 mm [95% CI: 7.4 to 20.6] respectively, while RR for global pain improvement was only
reported for 904 nm at 1.53 [95% CI: 1.28 to 1.83]. LLLT doses in this subgroup ranged between 0.5 and 7.2 Joules."
"LLLT administered with optimal doses of 904 nm and possibly 632 nm wavelengths directly to the lateral elbow tendon insertions, seem to offer shortterm pain relief and less disability in LET, both alone and in conjunction with an exercise regimen. This finding contradicts the conclusions of previous
reviews which failed to assess treatment procedures, wavelengths and optimal doses."

Tennis elbow

633
830
904

Simunovic

Switzerland &
Croatia

1998

J Clin Laser Med

Surg

Treatment of medial and lateral epicondylitis--tennis and golfer's

elbow--with low level laser therapy: a multicenter double blind,
placebo-controlled clinical study on 324 patients.

Human
RCT

Tendons

Lopes-Martins
RA

Brazil
(So Paulo)

2014

Photomed Laser
Surg

Tendinitis, an open avenue for low-level laser therapy.

Guest
Editorial

Tendons

Tsai

Taiwan
(Taoyuan
County)

2012

PLoS One

Low-level laser irradiation stimulates tenocyte migration with upregulation of dynamin II expression.

In vitro

Tendons

Tumilty

New Zealand

2010

Photomed Laser
Surg

Low level laser treatment of tendinopathy: a systematic review with Metameta-analysis.

analysis

Tendinopathy:
Achilles and
epicondylitis

Gamma radiation

Tendons

The best result was achieved with combination therapy (trigger points + scanning).
Total relief of the pain with consequently improved functional ability was achieved
in 82% of acute and 66% of chronic cases

"Therefore, we consider that there is an open field for promising research in LLLT as a consistent treatment for tendinopathies."
"In conclusion, low-level laser irradiation stimulates tenocyte migration in a
process that is mediated by up-regulation of dynamin 2, which can be suppressed
by dynasore."

Tenocyte migration

The meta-analysis:
- Twenty-five controlled clinical trials met the inclusion criteria.
- There were conflicting findings from multiple trials: 12 showed positive effects and 13 were inconclusive or showed no effect.
- Dosages used in the 12 positive studies would support the existence of an effective dosage window that closely resembled current
recommended guidelines.
Importance of dosage - In two instances where pooling of data was possible, LLLT showed a positive effect size; in studies of lateral epicondylitis that scored
> or =6 on the PEDro scale, participants' grip strength was 9.59 kg higher than that of the control group; for participants with Achilles
tendinopathy, the effect was 13.6 mm less pain on a 100 mm visual analogue scale."
"Results revealed improvement in thyroid function, liver function and antioxidant
levels, and the blood cells count after LLLT."

PubMed

50

5
10
20

"Although not reaching abnormal values, LLLT applied to the mandible influenced
thyroid function in this model."

PubMed

Systemic effects

830

40

"With the irradiation protocol used in this study, LLLT did not affect thyroid function
in rabbits as assessed by circulating serum triiodothyronine and thyroxine levels."

PubMed

Human
RCT

Autoimmune
hypothyroidism

830

50

"The results showed a significant difference in the mean levothyroxine dose

required to treat the hypothyroidism between the L group (38.59 20.22 g/day)
and the P group (106.88 22.90 g/day, P<0.001). Lower TPOAb (P=0.043) and
greater echogenicity (P<0.001) were also noted in the L group."

PubMed

Assessment of the effects of low-level laser therapy on the thyroid

vascularization of patients with autoimmune hypothyroidism by
color Doppler ultrasound.

Human
RCT

Autoimmune
hypothyroidism

830

50

2
/p

707

LLLT improved thyroid vascularization in the patients.

PubMed

Low-level laser therapy in chronic autoimmune thyroiditis: a pilot

study.

Human
Pilot study

Autoimmune
hypothyroidism

830

50

38208

38-108

The first English paper on treating hypothyroid patients with LLLT. 47% of patients
could discontinue thyroxine medication.

PubMed

Lasers Med Sci

Effect of photobiomodulation on endothelial cell exposed to

Bothrops jararaca venom.

In vitro

660
780

4
5

"PBM at 660 and 780 nm wavelength was able to increase cellular viability and
decrease the release of LDH and the loss of cellular integrity. In addition, the
concentration of pro-inflammatory cytokine IL1- was reduced after PBM by both
wavelengths.

PubMed

2016

PLoS One

Low-Level Laser Therapy (904 nm) Counteracts Motor Deficit of

Mice Hind Limb following Skeletal Muscle Injury Caused by
Snakebite-Mimicking Intramuscular Venom Injection.

Mouse

904

Brazil
(So Paulo)

2016

PLoS One

Photobiomodulation Protects and Promotes Differentiation of

C2C12 Myoblast Cells Exposed to Snake Venom.

In vitro

685
830

Brazil
(So Paulo)

2014

Photochem
Photobiol Sci

Photobiostimulation reduces edema formation induced in mice by

Lys-49 phospholipases A2 isolated from Bothrops moojeni venom.

Mouse

Egypt
(Cairo)

2015

Photochem
Photobiol

Phototherapeutic Effect of Low-Level Laser on Thyroid Gland of

Gamma-Irradiated Rats.

Rat

Weber

Brazil
(Porto Alegre)

2014

Photomed Laser
Surg

Effect of three different protocols of low-level laser therapy on

thyroid hormone production after dental implant placement in an
experimental rabbit model.

Rabbit

Thyroid

Hormones

Fronza

Brazil
(Porto Alegre)

2013

Int J Oral
Maxillofac Surg

Assessment of the systemic effects of low-level laser therapy

(LLLT) on thyroid hormone function in a rabbit model.

Rabbit

Thyroid

Hypothyroidism

Hfling

Brazil
(So Paulo)

2013

Lasers Med Sci

Low-level laser in the treatment of patients with hypothyroidism

induced by chronic autoimmune thyroiditis: a randomized,
placebo-controlled clinical trial.

Thyroid

Hypothyroidism

Hfling

Brazil
(So Paulo)

2012

ISRN Endocrinol

Thyroid

Hypothyroidism

Hfling

Brazil
(So Paulo)

2010

Lasers Surg Med

Toxins

Snake venom

Franco

Brazil
(So Paulo)

2016

Toxins

Snake venom

Vieira

Brazil
(So Paulo)

Toxins

Snake venom

Silva

Toxins

Snake venom

Nadur-Andrade

17.68

2
/p

707

5.73
cm2
area

120

PubMed

12

Morcos

Hormones

0.252

PubMed

830

Hormones

Thyroid

1.4

PubMed

633

Thyroid

0.0021

PubMed

0.2827
mm2

40
/p

10

0.2827
mm2

40
/p

10

10
10

The data reported herein indicates that irradiation with red or near-infrared laser
resulted in protection on endothelial cells after exposure to Bothrops venom and
could be, at least in part, a reasonable explanation by the beneficial effects of
PBM inhibiting the local effects induced by Bothrops venoms, in vivo."

Mouse

Toxins

Snake venom

Dourado

Brazil
(Campinas)

2011

Photochem
Photobiol

Low-level laser therapy promotes vascular endothelial growth

factor receptor-1 expression in endothelial and nonendothelial
cells of mice gastrocnemius exposed to snake venom.

Mouse

Toxins

Snake venom

Doin-Silva

Brazil
(So Paulo)

2009

Photochem
Photobiol Sci

The ability of low level laser therapy to prevent muscle tissue

damage induced by snake venom.

Rat nervemuscle
preparation

Myonecrosis

685

Toxins

Snake venom

Barbosa

Brazil
(So Paulo)

2009

Photomed Laser
Surg

Effect of low-level laser therapy in the myonecrosis induced by

Bothrops jararacussu snake venom.

Mouse

Myonecrosis

685

Toxins

Snake venom

Barbosa

Brazil
(So Paulo)

2008

Toxicon

Effect of low-level laser therapy in the inflammatory response

induced by Bothrops jararacussu snake venom.

Mouse

Edema

685

Toxins

Snake venom

Dourado

Brazil
(So Paulo)

2003

Lasers Surg Med

Effects of the Ga-As laser irradiation on myonecrosis caused by

Bothrops Moojeni snake venom.

Mouse

Myonecrosis

904

Turtles

Skin and shell

ulceration

Kraut

Germany
(Birkenfeld)

2013

Tierarztl Prax
Ausg K Kleintiere
Heimtiere

Laser therapy in a soft-shelled turtle (Pelodiscus sinensis) for the

treatment of skin and shell ulceration. A case report.

Soft-shelled
turtle

LLLT vs LED

Case report
Advertisemen
t

Photomodulation of the osteoclastogenic potential of oral

squamous carcinoma cells.

In vitro

Havel

Germany
(Munich)

2014

Lasers Surg Med

Diode laser-induced tissue effects: in vitro tissue model study and

in vivo evaluation of wound healing following non-contact
application.

Enwemeka

USA
(Old Westbury,
NY)

2004

Photomed Laser
Surg

The efficacy of low-power lasers in tissue repair and pain control: a Metameta-analysis study.
analysis

Uncategorize
d
Uncategorize
d

Tissue repair

PubMed

633
904

Mouse

Effects of photobiostimulation on edema and hemorrhage induced

by Bothrops moojeni venom.

Biolite: A Patented Ultra-Low-Level Laser-Therapy Device for

Treating Musculoskeletal Pain and Associated Impairments.

"At 3 days, LLLT increased angiogenesis (80%:HeNe vs 40%:GaAs), decreased

neutrophils and increased proliferation of regenerating cells. However, after 21
days, myoregeneration observed in the [633nm] group appeared delayed
compared with the V group. As LLLT improved revascularization, the suggestive
delay in myoregeneration could be a dose-response inhibitory effect caused by
multiple irradiations in myogenesis."

2.2

Effects of a low-level semiconductor gallium arsenide laser on

local pathological alterations induced by Bothrops moojeni snake
venom.

Lasers Med Sci

J Biophotonics

PubMed

22

685
635
945

Photochem
Photobiol Sci

2012

J Acupunct
Meridian Stud

PubMed

"In conclusion, both LLL and LED irradiation reduced venom-induced local effects
even though symptoms were already present."

LED phototherapy

2013

2016

"The results indicated that GaAs laser irradiation can help in reducing some local
effects produced by the B. moojeni venom in mice, stimulating phagocytosis,
proliferation of myoblasts and the regeneration of muscle fibers."

2
2

Brazil
(So Paulo)

2015

PubMed

41
38

Nadur-Andrade

Brazil
(So Paulo)

"LLL and LED irradiation significantly reduced the edema formation by both
myotoxins from 1 up to 6 hours after the injection. Both LLL and LEDs were similar
in reducing the edema formation induced by myotoxins. The combined
photobiostimulation with antivenom had the same effect in reducing edema as
treatment with the LLL or LEDs alone."

15

4.0
3.8

Aranha de Sousa Brazil

(Macapa)

Italy

PubMed

2.2

Snake venom

Dias Schalch

"Infrared and red laser at all energy densities were able to considerably decrease
venom-induced cytotoxicity. Laser irradiation induced myoblasts to differentiate
into myotubes and this effect was accompanied by up regulation of MyoD and
specially myogenin. Moreover, LLL was able to reduce the extracellular while
increased the intracellular ATP content after venom exposure."

635
945
(LED)

Snake venom

Gallamini

PubMed

685
(laser)

Toxins

Uncategorize
d

"The venom + laser group kept the values at 3 hours post-Bjssu equal to that at 24
hours before Bjssu injection indicating that the GaAs laser therapy improved
spatially and temporally gait parameters at the critical injury period caused by
Bjssu."

LLLT+LED
LLLT vs LED
LED phototherapy

Toxins

Ultra-low level
laser

29

4.2

29

0.04

29

2
4

"We conclude that HeNe laser irradiation at a dosage of 3.5 J cm(-2) effectively
reduces myonecrosis and the neuromuscular transmission blocking effect caused
by B. jararacussu snake venom."

PubMed

4.2

29

2?

"LLLT significantly reduced myonecrosis by 83.5% at 24 h (p < 0.05) but not at 3

h, and AV therapy alone was ineffective for reducing myonecrosis at 3 and 24 h."

PubMed

4.2

29

"In conclusion, LLLT significantly reduced the edema and leukocyte influx into the
envenomed muscle, suggesting that LLLT should be considered as a potentially
therapeutic approach for the treatment of the local effects of Bothrops species."

PubMed

"Ga-As irradiation significantly decreased the amount of myonecrosis in all the

periods tested (P < 0.05)."

PubMed

"The presented case report describes aetiology including differential diagnoses,

diagnostic procedures and therapy of a soft-shelled turtle (Pelodiscus sinensis)
suffering from a septicaemic ulcerative dermatitis. Central aspect hereby is the
positive curing effect of laser therapy on skin and shell lesions."

PubMed

0.2
cm2

0.0176
cm2

62

5
8

PubMed
"The irradiation of SCC9 cells with PBM with an energy density of 4 J/cm2
decreased the pro-osteoclastogenic potential of those cells. This may represent a
potential useful side effect of PBM therapy. PBM (using recommended parameters
for mucositis treatment) decreases the osteoclastogenic potential of oral
squamous carcinoma cells."
1470

"The positive effect of treatment on specific indices of tissue repair was evident in the treatment effect sizes determined as follows:
collagen formation (d = +2.78),
rate of healing (d = +1.57),
tensile strength (d = +2.13),
time needed for wound closure (d = +0.76),
tensile stress (d = +2.65),
number and rate of degranulation of mast cells (d = +1.87),
and flap survival (d = +1.95).
Further, analysis revealed the positive effects of various wavelengths of laser light on tissue repair, with 632.8 nm having the highest treatment effect (d
= +2.44) and 780 nm the least (d = 0.60). The overall treatment effect for pain control was positive as well (d = +1.11)."

PubMed

PubMed

PubMed

"The total number of perforations within the contours of the gland varied based on the size of the thyroid projection area on the skin, which was determined with the aid of
ultrasound. Thus, the larger the demarcated area, the greater the number of irradiated points."

Comment

Reply

 Category

Subcategory

Urinary
bladder

Vaccination

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Ito

Japan
(Akita)

2011

Low Urin Tract

Symptoms

Pulse Diode Laser Irradiation (830 nm) of Lumbosacral Spinal

Roots Diminished Hyperreflexia-Induced by Acetic Acid or
Prostaglandin E2 Infusion in Rat Urinary Bladder.

Rat

830

1000
(CW)

Kashiwagi

USA
(Charlestown,
MA)

2013

PLoS One

Near-infrared laser adjuvant for influenza vaccine.

and light/laser

1000
0
(P)
1064

0.5 6.0

Results: positive / unclear/modest / negative

Link

Additional info

sec

1.5
cm2

0.2
cm2

up
to
240

"During continuous saline infusion to the urinary bladder, neither continuous (1 W)

nor pulse (10 W) laser irradiation altered the intercontraction interval and nerve
firing during distention of the bladder. Pulse laser, but not continuous laser
irradiation, increased the intercontraction interval with AA or PGE2 infusion and
diminished nerve firing during distention of the bladder with AA or PGE2 infusion."

PubMed

"We show that non-tissue damaging, near-infrared (NIR) laser light given in short
exposures to small areas of skin, without the use of additional chemical or
biological agents, significantly increases immune responses to intradermal
influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine
confers increased protection in a murine influenza lethal challenge model as
compared to unadjuvanted vaccine.

PubMed

We show that NIR laser treatment induces the expression of specific chemokines
in the skin resulting in recruitment and activation of dendritic cells and is safe to
use in both mice and humans.
The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use,
potentially broadly applicable and clinically feasible approach to enhancing
vaccine efficacy as an alternative to chemical and biological adjuvants."
Note: The authors do not refer to LLLT/PBM research. However, I think this type of
method can be categorized as photobiomodulation.

Vestibular

Zhang

system

Australia
(Sydney)

2015

J Vis Exp

670

Near infrared (NIr) light increases expression of a marker of

Mouse
mitochondrial function in the mouse vestibular sensory epithelium.

90

"Figure 2 shows a significant increase in -actin normalized SOD-1 expression of

more than 2-fold in young NIr-treated animals compared to young sham-treated
animals (p < 0.01) and young NIr-blocked animals (p < 0.01). Older NIr-treated
animals also showed more than a 2-fold up-regulation of SOD-1 when compared
with older NIr-blocked animals (p < 0.05)."

PubMed

"Since there are currently no available, affordable, non-invasive methods of

therapy to improve vestibular hair cell function, the application of external NIr
radiation provides a potential strategy to counteract the impact of aging on cellular
metabolism inthe vestibular sensory epithelium."
Star: The article contains a very high-quality video depicting many of the relevant
phases of the study execution. Two photographs are also supplied.
Comment: Parameters weren't reported, though they can be found from other
papers of the same research group.

Pryor & Millis

Veterinary
medicine

USA
(Newark, DE)

2015

Vet Clin North Am

Small Anim Pract

"It is estimated that close to 20% of veterinary hospitals in North America are using a therapeutic laser in their practice. Although lasers have been used
for many years, it has been only in the past 5 or 6 years that use of laser therapy has become so widespread."

Therapeutic laser in veterinary medicine.

PubMed

"Laser therapy is an increasingly studied modality that can be a valuable tool for veterinary practitioners. Mechanisms of action have been studied and
identified for the reduction of pain and inflammation and healing of tissue. Understanding the basics of light penetration into tissue allows evaluation of
the correct dosage to deliver for the appropriate condition, and for a particular patient based on physical properties. New applications are being studied
for some of the most challenging health conditions and this field will continue to grow."
Note: The first author is affiliated with LiteCure.

Voice

Vocal fatigue

Kagan & Heaton

USA
(Boston, MA)

2016

J Voice

The Effectiveness of Low-Level Light Therapy in Attenuating Vocal

Fatigue.

Human

LED phototherapy
LED array

628
828

0.07
0.055

1200

"Red light significantly normalized the combination of PTP, IPSV, and RFF
measures compared to other conditions."

PubMed

"The red setting heats the neck surface to approximately 43.3C, whereas the IR
setting heats the neck surface to 35.5C based on a thermometer"
"Results indicate that red light may be effective in improving acoustic,
aerodynamic, and self-perceptual markers of vocal fatigue. Although these
findings indicate that LLLT is a promising treatment for vocal fatigue, future work is
needed to determine optimal light doses, whether wavelengths are more
efficacious in combination vs isolation, and when the doses should be applied
relative to phonotrauma (before, after, or both) for providing fatigue resistance or
hastening recovery.
LLLT is a simple, potentially efficacious treatment for vocal fatigue that could have
wide clinical relevance to populations with voice disorders or occupations with high
voice use demands."

Water-filtered
infrared-A

Body contouring

Mckel

Germany

2006

Ger Med Sci

Influence of water-filtered infrared-A (wIRA) on reduction of local

fat and body weight by physical exercise.

wIRA improved body composition compared to the control group (quite significant
differences).

PubMed

n = 40

Water-filtered
infrared-A

Fibromyalgia

Brockow

Germany

2007

Clin J Pain

A randomized controlled trial on the effectiveness of mild waterHuman

filtered near infrared whole-body hyperthermia as an adjunct to a
RCT
standard multimodal rehabilitation in the treatment of fibromyalgia.

Heating fibromyalgia patients (-->38.1 celcius) yielded superior results compared

to "multimodal treatment" (MR).

PubMed

n = 139

Water-filtered
infrared-A

Scleroderma

von Felbert

Germany

2011

Dermatology

Irradiation with water-filtered infrared A plus visible light improves

cutaneous scleroderma lesions in a series of cases.

Human

"wIRA(+VIS) therapy led to a marked improvement, persistent even during longterm follow-up, in 7 out of 10 patients with CS."

PubMed

Water-filtered
infrared-A

Venous ulcer

Schumann

Germany

2011

Br J Dermatol

Water-filtered infrared A for the treatment of chronic venous stasis

ulcers of the lower legs at home: a randomized controlled blinded
study.

Human

wIRA appeared to improve healing of chronic venous stasis ulcers.

PubMed

Water-filtered
infrared-A

Venous ulcer

Mercer

Norway

2008

Ger Med Sci

Improvement of wound healing by water-filtered infrared-A (wIRA)

in patients with chronic venous stasis ulcers of the lower legs
including evaluation using infrared thermography.

Human

wIRA seemed to have clear beneficial effects on ulcer healing.

PubMed

Water-filtered
infrared-A

Wound healing

Knzli

Switzerland

2013

Ann Surg

Impact of preoperative local water-filtered infrared A irradiation on

postoperative wound healing: a randomized patient- and observerblinded controlled clinical trial.

Human

wIRA appeared to reduce surgical site infections and post-operative pain.

PubMed

Wavelengths

Blue & Green

Wang

China
(Beijing)

2016

Sci Rep

Photobiomodulation (blue and green light) encourages

osteoblastic-differentiation of human adipose-derived stem cells:
role of intracellular calcium and light-gated ion channels.

In vitro

"The 420 nm and 540 nm wavelengths were more effective in stimulating

osteoblast differentiation compared to 660 nm and 810 nm. Intracellular calcium
was higher after 420 nm and 540 nm, and could be inhibited by capsazepine and
SKF96365, which also inhibited osteogenic differentiation. We hypothesize that
activation of light-gated calcium ion channels by blue and green light could explain
our results."

PubMed

Wavelengths

Blue & Green

Becker

Germany
(Mannheim)

2016

Sci Rep

Gene expression profiling reveals aryl hydrocarbon receptor as a

possible target for photobiomodulation when using blue light.

In vitro

Wavelengths

Far-infrared

Shingyochi

Japan
(Tokyo)

2017

PLoS One

A Low-Level Carbon Dioxide Laser Promotes Fibroblast

Proliferation and Migration through Activation of Akt, ERK, and
JNK.

Human
RCT

Human adiposederived stem cells

420
540

0.023

453

41.4

10600

0.1
0.5
1.0
2.0
5.0

PubMed
"In MTS and cell migration assays, fibroblast proliferation and migration were
promoted after LLLT with a CO2 laser at 1.0 J/cm2. Western blot analysis
revealed that Akt, ERK, and JNK activities were promoted in fibroblasts after LLLT
with a CO2 laser at 1.0 J/cm2. Moreover, inhibition of Akt, ERK, or JNK
significantly blocked fibroblast proliferation and migration."

PubMed

"These findings suggested that LLLT with a CO2 laser would accelerate wound
healing by promoting the proliferation and migration of fibroblasts. Activation of
Akt, ERK, and JNK was essential for CO2 laser-induced proliferation and
migration of fibroblasts."
10600

Wavelengths

Far-infrared

Constantin

Romania
(Bucharest)

2016

Lasers Med Sci

CO2 laser increases the regenerative capacity of human adiposederived stem cells by a mechanism involving the redox state and
enhanced secretion of pro-angiogenic molecules.

Wavelengths

Far-infrared

Lai

Taiwan
(Taipei)

2013

Eur J Vasc
Endovasc Surg

Post-angioplasty far infrared radiation therapy improves 1-year

angioplasty-free hemodialysis access patency of recurrent
obstructive lesions.

Human
Observationa
l

Wavelengths

Far-infrared

Huang

Taiwan
(Taipei)

2012

Cardiovasc
Diabetol

Far infra-red therapy promotes ischemia-induced angiogenesis in

diabetic mice and restores high glucose-suppressed endothelial
progenitor cell functions.

Mouse

Wavelengths

Far-infrared

Yu

Taiwan
(Taipei)

2006

Photodermatol
Photoimmunol
Photomed

Biological effect of far-infrared therapy on increasing skin

microcirculation in rats.

Rat

Wavelengths

Far-infrared

Lee

Korea
(Seoul)

2006

Yonsei Med J

Effects of infrared radiation on skin photo-aging and pigmentation.

Human

Wavelengths

Far-infrared

Toyokawa

Japan
(Osaka)

2003

Exp Biol Med

(Maywood)

Promotive effects of far-infrared ray on full-thickness skin wound

healing in rats.

"CO2 laser has a beneficial effect on stem cells by mechanisms that are not
clearly elucidated. We hypothesize that the effect of fractional CO2 laser on
human adipose-derived stem cells (ADSC) could be due to changes in redox
homeostasis and secretion of factors contributing to cellular proliferation and
angiogenic potential."

PubMed

"In conclusion, the mechanisms underlying the benefic effect of CO2 laser on
ADSC are the activation of the redox pathways which increases cell proliferation
and enhances secretion of angiogenic molecules."

Diabetic mice
Angiogenesis

"The study provides data regarding far infrared (FIR) radiation therapy on
recurrent hemodialysis (HD) access stenosis that has been treated with balloon
angioplasty. The positive results obtained show that FIR radiation therapy
following balloon angioplasty is beneficial in the case of recurrent HD access
stenosis, especially arteriovenous graft stenosis, in terms of improving the
angioplasty-free patency at 1 year. The data may be clinically valid for
management of recurrent HD access stenosis and guidance of FIR radiation
therapy."

PubMed

"Administration of IFR therapy promoted collateral flow recovery and new vessel
formation in STZ-induced diabetic mice, and these beneficial effects may derive
from enhancement of EPC functions and homing process."

PubMed

"In conclusion, FIR therapy exerts a NO-related biological effect to increase skin
microcirculation in rats. This might bring into perspective the clinical application of
FIR to treat ischemic disease by augmenting L-arginine/NO pathway."

PubMed

"These results suggest that infrared radiation may have beneficial effects on skin
texture and wrinkles by increasing collagen and elastin contents from the
stimulated fibroblasts. Therefore, skin treatment with infrared radiation may be an
effective and safe non-ablative remodeling method, and may also be useful in the
treatment of photo-aged skin."

PubMed

"Wound healing was significantly more rapid with than without FIR. Skin blood flow
and skin temperature did not change significantly before or during FIR irradiation.

PubMed

Histological findings revealed greater collagen regeneration and infiltration of

fibroblasts that expressed transforming growth factor-beta1 (TGF-beta1) in
wounds in the FIR group than in the group without FIR. Stimulation of the
secretion of TGF-beta1 or the activation of fibroblasts may be considered as a
possible mechanisms for the promotive effect of FIR on wound healing
independent of skin blood flow and skin temperature."

Wound
healing

Burns

Yadav

India
(Delhi)

2016

J Photochem
Photobiol B

Photobiomodulatory effects of superpulsed 904nm laser therapy

on bioenergetics status in burn wound healing.

Rat

904

0.7

0.0004

0.4

0.23

1.77
cm2

600

"The present study recapitulated the benefits of LLLT in enhancing CCO activity
and ATP synthesis in injured tissue. In addition to this, our results also displayed
the role of cellular redox homeostasis in regulation of energy generation. These
findings indicated that superpulsed 904 nm LLLT favor aerobic regulation of
cellular energy metabolism and a synchronized evasion from the anaerobic
glycolysis in burn wound healing."
Comment: The huge increase in ATP levels is very interesting. Many other
changes were also noted.

PubMed

n = 400

Comment

Reply

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Category

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Burns

Rathnakar

India
(Manipal)

2016

Lasers Med Sci

Photo-biomodulatory response of low-power laser irradiation on

burn tissue repair in mice.

Mouse

Wound
healing

Wavelength
comparison

nm

mW

W/cm2

633
785
830

15

0.0085

J/cm2

1/2/3/4/
6

Results: positive / unclear/modest / negative

Link

sec

"In summary, low-power lasers at wavelength 632.8, 785, and 830 nm have shown
beneficial effects in burn wound healing, compared to untreated controls. Further,
3-J/cm2 fluence of 830 nm exhibited the best response among the other
wavelengths and fluences under study in enhancing wound repair in full thickness
burn injury in mice.

1.7
cm2

Dose optimization

PubMed

The treatment promoted proliferation, neovascularization, deposition of collagen,

denser packing of connective tissue, and epithelialization at faster rate to contract
the wound, compared to untreated controls.
Surprisingly, the response observed in the single exposure of 3-J/cm2 treatment of
830 nm was equivalent to the reference standard applied on daily basis."
Star: Nice work with a huge amount of mice (n=170).

Wound
healing

Burns

Brassolatti

Brazil
(So Carlos)

2016

Microsc Res Tech

Comparative effects of two different doses of low-level laser

therapy on wound healing third-degree burns in rats.

Rat

3rd degree burn

660

0.5
1.0

12.5
25

0.04
cm2

"Therefore, our findings suggest that the use of 25 J/cm(2) and 1 J of energy was
more effective in stimulating the cellular processes involved in tissue repair on
third-degree burns in rats by reducing the inflammatory phase, and stimulating
angiogenesis, thus restoring the local microcirculation which is essential for cell
migration."

PubMed

"Low-level red laser exposure contributes to the process of tissue repair of

second-degree burns, but the intervention during proliferative phase is crucial in
the final outcome of the repair process."

PubMed

4
or
7

"The irradiated animals showed a significant reduction in wound area (50%, p <
0.05) on eighth day post-wounding compared with the non-irradiated control
animals (18%, p < 0.05)"

PubMed

Dose optimization
beam

Wound
healing

Burns

Trajano

Brazil
2015
(Rio de Janeiro)

Lasers Med Sci

Low-level red laser improves healing of second-degree burn when

applied during proliferative phase.

Rat

Wound
healing

Burns

Gupta

India
(Delhi)

J Biophotonics

Superpulsed (Ga-As, 904 nm) low-level laser therapy (LLLT)

attenuates inflammatory response and enhances healing of burn
wounds.

Rat

2015

2nd degree burn

660

100

904

0.7

20

0.0004

0.4

0.2

1.77
cm2

600

"Irradiated group exhibited enhanced DNA, total protein, hydroxyproline and

hexosamine contents compared to the control and silver sulfadiazine (reference
care) treated groups.
LLLT exhibited decreased TNF- level and NF-kB, and up-regulated protein levels
of VEGF, FGFR-1, HSP-60, HSP-90, HIF-1 and matrix metalloproteinases-2 and
9 compared to the controls.
In conclusion, LLLT using superpulsed 904 nm laser reduced the inflammatory
response and was able to enhance cellular proliferation, collagen deposition and
wound contraction in the repair process of burn wounds."

Wound
healing

Burns

Firio

Brazil
(Chapec)

2014

Lasers Med Sci

Effect of low-level laser therapy on types I and III collagen and

inflammatory cells in rats with induced third-degree burns.

Rat

3rd degree burn

660

35

Wound
healing

Burns

Chiarotto

Brasil
(Araras)

2014

Lasers Med Sci

Effects of laser irradiation (670-nm InGaP and 830-nm GaAlAs) on

burn of second-degree in rats.

Rat

2nd degree burn

670
830

30
40

0.05
0.05

6.6
8.4

3
4

0.63
cm2

0.36
0.48

4.93
4.48

0.073
0.107

180
240

"Laser irradiation (both 3 and 4 J/cm(2)) resulted in reduction in the inflammatory

process and improved collagen deposition, thereby ameliorating the healing of
third-degree burns."

PubMed

18
18

"Morphometric analysis showed that different lasers 670-nm InGaP and 830-nm
GaAlAs reduced the number of granulocytes and an increase of newly formed
vessels in radiated lesions. The 670-nm InGaP laser therapy was more effective in
increasing the number of fibroblasts.

PubMed

(3p)
12
12

cm2

The different treatments modified the expression of VEGF and TGF-1, when
compared with lesions not irradiated.
The different types of light sources showed similar effects, improved the healing of
second-degree burns and can help for treating this type of injury. Despite the large
number of studies with LLTI application in second-degree burns, there is still
divergence about the best irradiation parameters to be used."

Wound
healing

Burns

Firio

Brazil
(Chapec)

2011

J Cosmet Laser
Ther

Effect of incoherent LED radiation on third-degree burning wounds

in rats.

Rat

3rd degree burn

640

Wound
healing

Burns

Renno

Brazil
(So Paulo)

2011

J Cosmet Laser
Ther

Effect of low-level laser therapy (660 nm) on the healing of seconddegree skin burns in rats.

Rat

2nd degree burn

660

30

8
(?)

"The inflammatory cells as well as the damaged area at the 8th day after burns
were significantly lower for the LED-treated group when compared to control.
Furthermore, the LED phototherapy effect on cellular migration was even more
pronounced at the 16th day."

PubMed

"Our results indicated that the treatment with a LED system was clearly effective in
reducing the number of inflammatory cells and improving the healing process in an
experimental model of third-degree burnings."
"Histopathological analysis revealed a significant decrease in the necrotic area in
the laser-treated group compared to the controls at days 7 and 14 post-injury.

PubMed

COX-2 positive cells were found in a strong pattern in the group submitted to laser
therapy after 7 days. Regarding VEGF immunomarker, a significant VEGF
immunoexpression was detected in the laser-exposed group after 14 days when
compared to the negative control group.
Taken together, our results demonstrate that laser therapy is able to promote skin
repair of burned rats as a result of decreasing necrotic area and an up-regulation
of COX-2 and VEGF immunoexpression."

Wound
healing

Burns

Khoshvaghti

Iran
(Tehran)

2011

Photomed Laser
Surg

Effect of low-level treatment with an 80-Hz pulsed infrared diode

laser on mast-cell numbers and degranulation in a rat model of
third-degree burn.

Rat

Wound
healing

Burns

Ezzati

Iran
(Tehran)

2010

Photomed Laser
Surg

Low-level laser therapy with a pulsed infrared laser accelerates

second-degree burn healing in rat: a clinical and microbiologic
study.

Rat

3rd degree burn

890

0.924

890

70?

2.3
11.7

1
cm2

856

Mast cells
2nd degree burn

"We conclude that LLLT can significantly decrease total numbers of mast cells
during the proliferation and remodeling phases of healing in a rat model of thirddegree burn."

PubMed

"Pulsed LLLT with 11.7 J/cm(2)/890 nm of a deep second-degree burn model in

rat significantly increased the rate of wound closure compared with control burns."

PubMed

Comment: The paper says they used 70-watt output, but it is more likely it was 70
milliwatts.

Wound
healing

Burns

Vasheghani

Iran
(Tehran)

2009

Photomed Laser
Surg

Low-level laser therapy using 80-Hz pulsed infrared diode laser

accelerates third-degree burn healing in rat.

Rat

3rd degree burn

890

Wound
healing

Burns

Ezzati

Iran
(Tehran)

2009

J Rehabil Res
Dev

Low-level laser therapy with pulsed infrared laser accelerates third- Rat
degree burn healing process in rats.

3rd degree burn

890

0.396

70?

2.3
11.7

1
cm2

"LLLT using an 80-Hz pulsed infrared diode laser accelerated third-degree burn
healing in rat." [17.6 vs 19.6 days]

PubMed

"Pulsed LLLT with 11.7 J/cm(2)/890 nm of a third-degree burn in a rat model

significantly increased wound-closure rate compared with control burns."

PubMed

Comment: The paper says they used 70-watt output, but it is more likely it was 70
milliwatts.

Wound
healing

Burns

Oliveira

Brazil
(Salvador,
Bahia)

2008

Photomed Laser
Surg

The use of light photobiomodulation on the treatment of seconddegree burns: a histological study of a rodent model.

Rat

LLLT vs
polychromatic
polarized light

660

35/40

780

35/40

4002000

40

"The analysis of the results demonstrated that the damaged tissue was able to
efficiently absorb and process the light at all tested wavelengths.

PubMed

LPBM at 660 nm showed better results at early stages of wound healing.

However, the use of 780-nm laser light had beneficial effects throughout the
experimental period, with the animals growing newly-formed tissue similar to
normal dermis."
"Despite our findings that the use of both types of light energy improved the
healing of second-degree burns at the early stages, long-term assessment is
needed to verify if this improvement will influence the final results of treatment."

Wound
healing

Burns

Meireles

Brazil
(Salvador,
Bahia)

2008

Photomed Laser
Surg

Effectiveness of laser photobiomodulation at 660 or 780

nanometers on the repair of third-degree burns in diabetic rats.

Rat

3rd degree burn

660
780

35

20
(?)

"The use of 780-nm laser energy was not as effective as 660-nm energy, but it
had positive effects at early stages on the onset and development of inflammation.

Diabetic rats
Wavelength
comparison

Wound
healing

Burns

Meireles

Brazil
(Salvador,
Bahia)

2008

Photomed Laser
Surg

A comparative study of the effects of laser photobiomodulation on

the healing of third-degree burns: a histological study in rats.

Rat

Wound
healing

Incisions

Figurov

Slovakia
(Koice)

2016

Photomed Laser
Surg

Histological Assessment of a Combined Low-Level Laser/LightPig

Emitting Diode Therapy (685 nm/470 nm) for Sutured Skin Incisions (minipig)
in a Porcine Model: A Short Report.

The 660-nm laser at 20 J/cm(2), when used on a daily basis, was more effective
than the 780-nm laser for improving the healing of third-degree burns in the
diabetic rats beginning at the early stages post-burn."

3rd degree burn

660
780

35
35

LED array (4 red + 13

blue)

685
+
470

200
+
208

84

3.36

420

LED phototherapy
Leprosy

Barreto &
Salgado

Brazil
(Marituba)

2010

BMC Infect Dis

Clinic-epidemiological evaluation of ulcers in patients with leprosy

sequelae and the effect of low level laser therapy on wound
healing: a randomized clinical trial.

Human
RCT

660

Wound
healing

Pressure ulcer

Kazemikhoo

Iran
(Tehran)

2015

J Skin Stem Cell

Low-Level Laser Therapy Along With Intravascular Laser in Deep

Pressure Ulcer Resistant to Conventional Therapies

Human
Case report

655
+
980
+
650
(i.v.)

Wound
healing

Pressure ulcer

Taradaj

Poland
(Katowice)

2013

Evid Based
Complement
Alternat Med

Effect of Laser Irradiation at Different Wavelengths (940, 808, and

658 nm) on Pressure Ulcer Healing: Results from a Clinical Study.

Human
Placebocontrolled

658
808
940

Wound
healing

Pressure ulcer

Shojaei

Iran
(Tehran)

2008

Iran J Med Sci

(IJMS)

Low Level Laser Therapy in the Treatment of Pressure Ulcers in

Spinal Cord Handicapped Veterans Living in Tehran

Human

650
+
980

4-6

Wound

Pressure ulcer

Lanzafame

USA
2007
(Rochester, NY)

Lasers Surg Med

Reciprocity of exposure time and irradiance on energy density

Mouse
during photoradiation on wound healing in a murine pressure ulcer
model.

670

healing

"The results showed more deposition of collagen fibers, larger amounts of

granulation tissue, less edema, a more vigorous inflammatory reaction, and
increased revascularization on all laser-treated animals. These features were
more evident at early stages when the 660-nm laser was used, and were more
evident throughout the experimental period for the animals receiving 780-nm laser
therapy."

PubMed

"Combined red and blue PBM accelerated the process of re-epithelization and
formation of cross-linked collagen fibers compared with sham irradiated control
wounds."

PubMed

"Our results demonstrate that the current dose of combined red and blue PBM
improves the healing of sutured skin incisions in minipigs."

Wound
healing

Parameters

PubMed

At the end of the experimental period the primary effect seen was on the amount
and quality of the granulation tissue.

40

0.04
cm2
spot

18

"Statistical analysis of the data determined that there were no significant

differences in the variables analyzed before and after treatment with low level
laser therapy."

PubMed

"The combination of laser therapy with conventional therapy and surgery

increases the process of wound healing remarkably, particularly in resistant wound
cases. In other words, it accelerates the reconstruction of blood vessels and
increases the lesion revascularizations, increases the production and formation of
granulation tissue in the wound, eradicates microbial flora, sterilizes the wound
pathogens, and facilitates graft surgery repairing success. This process not only
leads to a better healing of ulcers, but also prevents recurrent ulcers due to
improvement of perfusion in the treated area."

SSRC

"The laser therapy at a wavelength of 658 nm appeared to be effective at healing

pressure ulcers. The wavelengths of 808 and 940 nm did not have any effect in
our study."

PubMed

"The results demonstrated a statistically significant enhancement of the healing

process by combination of Low Level Laser with conventional treatments of
pressure ulcers."

IJMS

"Specific combinations of parameters were necessaryto achieve accelerated

wound healing despite the delivery ofthe same total daily energy density to all
wounds. Variationof exposure time and irradiance may account for
conflictingresults in the literature. This study appears to confirmearlier in vitro
studies demonstrating that the provisionof multiple treatments per day is more
effective than thetraditional strategy of delivering a single treatment perday.
Further investigations directed at identifying doseresponse curves for specific
tissues and cell lines should beconducted."

PubMed

Comment: This kind of research of different parameters is important. Hopefully

more of similar studies will be conducted.

Additional info

Comment

Reply

 Category
Wound
healing

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

Pressure ulcer

Dehlin

Sweden
(Malm)

2007

Aging Clin Exp

Res

Monochromatic phototherapy: effective treatment for grade II

chronic pressure ulcers in elderly patients.

Human
Controlled

Light probe (110)

nm

mW

W/cm2

J/cm2

Results: positive / unclear/modest / negative

Link

sec

637
+
956

"The mean normalized reduction in pressure ulcer size at week 12 was 0.79 for
the phototherapy group and 0.50 for the placebo group (95% confidence interval
0.01-0.53; p=0.039). No serious side-effects were noted."

PubMed

"Monochromatic pulsating light accelerates healing in grade II pressure ulcers in

elderly patients."
PDF full text: https://www.researchgate.
net/profile/Soelve_Elmstahl/publication/5678172_Monochromatic_phototherapy_E
ffective_treatment_for_grade_II_chronic_pressure_ulcers_in_elderly_patients/links
/004635190e7c37f653000000.pdf

Wound
healing

Wound
healing

Wound
healing

Wound
healing

Wound
healing

Pressure ulcer

Pressure ulcer

Surgical
wounds

Surgical
wounds

Surgical
wounds

Taly

Lucas

Lima

Lima

Ojea

India
(Bangalore)

Netherlands
(Amsterdam)

Brazil
(So Paulo)

Brazil
(So Paulo)

Brazil
(So Paulo)

2004

2003

2017

2016

2016

Arch Phys Med

Rehabil

Lasers Med Sci

Photomed Laser
Surg

Photomed Laser
Surg

Photomed Laser
Surg

Efficacy of multiwavelength light therapy in the treatment of

pressure ulcers in subjects with disorders of the spinal cord: A
randomized double-blind controlled trial.

Human
RCT/DB

Efficacy of low-level laser therapy in the management of stage III

decubitus ulcers: a prospective, observer-blinded multicentre
randomised clinical trial.

Human
RCT/SB
Multicenter

Photobiomodulation (Laser and LED) on Sternotomy Healing in

Hyperglycemic and Normoglycemic Patients Who Underwent
Coronary Bypass Surgery with Internal Mammary Artery Grafts: A
Randomized, Double-Blind Study with Follow-Up.

Human
RCT/DB (?)

Low-Level Laser and Light-Emitting Diode Therapy for Pain Control Human
in Hyperglycemic and Normoglycemic Patients Who Underwent
RCT/DB
Coronary Bypass Surgery with Internal Mammary Artery Grafts: A
Randomized, Double-Blind Study with Follow-Up.
Beneficial Effects of Applying Low-Level Laser Therapy to Surgical
Wounds After Bariatric Surgery.

LLLT cluster (46)

660
+
820
+
870
+
880
+
940
+
950

150
+
15
+
250
+
250
+
125
+
100

904

96

4.5

10
cm2
(?)

60

12
cm2

125

14

"Multiwavelength light therapy from a gallium-aluminum-arsenide laser source did

not influence overall healing pressure ulcers.

PubMed

Limited evidence suggested that it improved healing of stage 3 and 4 pressure

ulcers."

5
/wk

"In this trial we found no evidence that justifies using low-level laser therapy as an
adjuvant to the consensus decubitus ulcer treatment."

PubMed

"LLLT and LED groups had similarly less hyperemia and less incision bleeding or
dehiscence (p 0.005) and the outcomes were also analogous between
hyperglycemic and normoglycemic patients, which indicates no difference
observed in an intragroup analysis (p 0.05)."

PubMed

"LLLT and LED had similar analgesic effects in hyperglycemic and normoglycemic
patients, better than placebo and control groups."

PubMed

"LLLT applied with the described protocol led to a decrease by biochemical

markers and wound temperature compared with the placebo, which indicated that
LLLT was able to control the inflammatory process;

PubMed

6wk
?

LLLT vs LED
LED phototherapy

LLLT vs LED
LED phototherapy

640
(laser)

1.06

660
(LED)

0.24

640
(laser)

1.06

660
(LED)

0.24

808

Human
RCT/SB

100

0.495

2
/p

10

0.20
cm2

20
/p

in addition, seroma and pain were reduced and cicatrization was improved by this
preventive procedure."

Wound
healing

Surgical
wounds

Fernandes

Brazil
(So Paulo)

2016

Lasers Med Sci

660

Low-intensity laser (660 nm) on sternotomy healing in patients who Human

underwent coronary artery bypass graft: a randomized, doubleRCT/DB
blind study.

Wound
healing

Surgical
wounds

Karlekar

India
(New Delhi)

2015

Ann Card Anaesth Assessment of feasibility and efficacy of Class IV laser therapy for
postoperative pain relief in off-pump coronary artery bypass
surgery patients: A pilot study.

Human

LCT-1000
(LiteCure Medical)

980

Wound
healing

Surgical
wounds

de Oliveira

Brazil
(So Paulo)

2014

Lasers Med Sci

The effects of LED emissions on sternotomy incision repair after

myocardial revascularization: a randomized double-blind study
with follow-up.

Human
RCT/DB

LED phototherapy

640

Wound
healing

Surgical
wounds

Dixit

India
(Manipal)

2013

Indian J Palliat
Care

Photobiomodulation of surgical wound dehiscence in a diabetic

individual by low-level laser therapy following median sternotomy.

Human
Case report

Diabetic patient

660
+
950

Wound
healing

Ulcers

Delayed CABG
sternotomy wound
healing

1.06

10000

1500

10

150
cm2

150

1.2

1-2

"The sternotomy incisions in the LLLT group demonstrated less hyperemia,

incisional bleeding, and dehiscence (p 0.005)."

PubMed

"The mean (standard deviation [SD]) VRS of all the 100 patients just before
application of the first dose of laser was 7.31 (0.94) while on MMT; the same fell to
4.0 (1.279) and 3.40 (2.697) at 1 h and 24 h respectively following first dose of
laser. The change of VRS over first 24 h among all the 100 patients was
statistically significant (P = 0.000). Laser was re-applied in 40 patients whose VRS
was 5 (mean [SD] - 6.38 [0.868]) at 24th h. After receiving the 2nd dose of laser
the VRS scores fell significantly (P = 0.000) and became 0 at 54th h. No patients
required 3rd dose of the laser. No patient required rescue analgesic while on laser
therapy."

PubMed

"Three researchers blindly analyzed the incision photographs to determine

hyperemia and wound closure, and they found that the LED group had both less
hyperemia and less incision bleeding or dehiscence. The LED therapy (640 nm)
had an analgesic effect on the sternotomies of patients who underwent CABG,
increasing their incision healing and preventing dehiscence."

PubMed

"After irradiation, proliferation of healthy granulation tissue was observed with

decrease in scores of PUSH for sternal dehiscence and VAS for bilateral
shoulders and sternal dehiscence. We found that LLLT irradiation could be a novel
method of treatment for chronic sternal dehiscence following coronary artery
bypass grafting, as it augments wound healing with an early closure of the wound
deficit."

PubMed

LED phototherapy
LED cluster (34+35)

Sobanko & Alster USA

2008
(Washington, D.
C.)

Dermatol Surg

"The available data suggest that the addition of LLLT in humans does not improve wound healing as thevast majority of comparisons in these studies do
not demonstrate any differences in the relevant outcomes. Of course, it is difficult to entirely ignore the many observations of clinicians over the past 40
years on the subject of LLLT. Additionally, there are in vitro and animal studies that clearly show improvement of factors that, in theory, should facilitate
wound healing in chronic wounds."

Efficacy of low-level laser therapy for chronic cutaneous ulceration Review

in humans: a review and discussion.

PubMed

"Although bench research does not always translate into successful human therapies, the hope of using this modality as an adjunctive measure in the
future should not be ruled out. Once a true pathophysiologic mechanism of the low-level laser in tissue is elucidated and the milieu of the wound healing
model is better understood, it is reasonable to believe that this can beapplied to humans. Of course, research that focuses on the cellular and molecular
mechanisms of LLLT is necessary. Advances in techniques such as cDNA microarray technology and confocal microscopy should further help the cause.
If it is then believed to work inhumans, larger, better-controlled studies must be per-formed to determine the appropriate laser parameters and treatment
protocol, including the number, frequency, and duration of treatment sessions. Until these steps occur, LLLT should not be routinely recommended to
patients."

Wound
healing

Ulcers

Saltmarche AE

Canada
(Mississauga)

2008

Int Wound J

Low level laser therapy for healing acute and chronic wounds - the
extendicare experience.

Human

Wound
healing

Ulcers

Kubota J

Japan
(Tokyo)

2004

J Cosmet Laser
Ther

Defocused diode laser therapy (830 nm) in the treatment of

unresponsive skin ulcers: a preliminary trial.

Human
Controlled
(n=5)

830

Human
RCT/DB

660
+
890

1000

6.3
21

28.7
cm2
(?)

"Staff rated low level laser, easy to learn and use, effective for the majority of their
residents worth the additional time. Staff requested a continuation of low level
laser even after study completion."

PubMed

"In all five patients, the ulcers healed completely between 3 weeks and 7 months
(22.8 +/- 19.3 weeks), without recurrence during a minimum 12-month follow-up."

PubMed

"Defocused 830 nm diode laser therapy was well tolerated, and was very effective
in the treatment of this small number of compromised skin ulcers of different
aetiologies and in a large range of patient ages. Further controlled studies in larger
populations are required. Defocused diode laser therapy nonetheless appears to
be a very useful adjunctive method in the treatment of slow-to-heal and nonhealing skin ulcers."
Comment: The LLLT photo is black-and-white.

Wound
healing

Venous ulcer

Caetano

Brazil
2009
(Ribeiro Preto)

Photomed Laser
Surg

Phototherapy improves healing of chronic venous ulcers.

"Ulcers treated with phototherapy healed significantly faster than controls when
compared at day 30 (p +/- 0.01), day 60 (p +/- 0.05), and day 90 (p +/- 0.001), and
similarly healed faster than the placebo-treated ulcers at days 30 and 90 (p +/0.01), but not at day 60.

PubMed

The beneficial effect of phototherapy was more pronounced when the confounding
effect of small-sized ulcers was removed from the analysis. Medium- and largesized ulcers healed significantly faster with treatment (>or=40% rate of healing per
month) than placebo or control ulcers (p +/- 0.05)."

Wound
healing

Venous ulcer

Franek

Poland
(Katowice)

2002

Med Eng Phys

Does low output laser stimulation enhance the healing of crural

ulceration? Some critical remarks.

Human

Wound
healing

Venous ulcer

Flemming&Cullu
m

UK
(York)

2000

Cochrane
Database Syst
Rev

Laser therapy for venous leg ulcers.

Metaanalysis

Wound
healing

Venous ulcer

Flemming

UK
(York)

1999

J Wound Care

A systematic review of laser therapy for venous leg ulcers.

Systematic
review

810

65

"No significant impact of laser light (lambda=810 nm, P=65 mW, p=4 J/cm2) on
any of the stages of ulceration healing was observed."

"We have found no evidence of any benefit associated with low level laser therapy on venous leg ulcer healing. One small study suggests that a
combination of laser and infrared light may promote the healing of venous ulcers, however more research is needed."

PubMed
PubMed

Note: The review was withdrawn by Cochrane Library in 2014.

"A total of four eligible RCTs were identified. Two compared treatment with laser therapy to sham or placebo laser treatment. One study compared laser
therapy with ultraviolet therapy. The fourth was a three-armed study which compared the effects of laser therapy alone, laser therapy plus infrared light,
and non-coherent unpolarised red light.

PubMed

The comparisons of laser therapy with placebo, and laser therapy with ultraviolet therapy, showed no significant difference between treatments with
regard to ulcer healing rates.
The comparison of laser with red light showed a significant increase in complete healing at nine months for the combination of laser and infrared light
compared to non-coherent unpolarised red light.
We have not found any evidence of the benefit of low-level laser therapy per se on venous leg ulcer healing. It appears that a combination of HeNe laser
and infrared light may promote the healing of venous ulcers, however more research is needed."

Wound
healing

Venous ulcer

Gupta

Canada
(Toronto)

1998

Dermatol Surg

The use of low energy photon therapy (LEPT) in venous leg ulcers:
a double-blind, placebo-controlled study.

660

Human
RCT/DB

60

880

84

60
cm2
+
4
cm2

"Nine patients with 12 venous ulcers were randomized to receive LEPT or placebo
therapy. At the conclusion of the study, the percentage of the initial ulcer area
remaining unhealed in the LEPT and placebo groups was 24.4% and 84.7%,
respectively (P = 0.0008).

PubMed

The decrease in ulcer area (compared to baseline) observed in the LEPT and
placebo groups was 193.0 mm2 and 14.7 mm2, respectively (P = 0.0002)."

Wound
healing

Wound
healing

Venous ulcer

Wounds

Gupta

Yadav & Gupta

Canada
(Toronto)

India
(Delhi)

1997

2016

J Dermatolog
Treat

Photodermatol
Photoimmunol
Photomed

660

The use of low-energy photon therapy in the treatment of leg ulcers Human
a preliminary study
Pilot study

Non-invasive red and near-infrared wavelength-induced

photobiomodulation: promoting impaired cutaneous wound
healing.

Review

Cutaneous wound
healing

60

880

84

60
cm2
+
4
cm2

"Of 15 venous ulcers, 12 (75%) had healed or improved markedly (greater than
75% reduction in pretherapy area of ulcer) by the end of the study. Side-effects
consisted of erythema at the ulcer site in one patient."

"Red and near-infrared light-induced photobiomodulation therapy appears to emerge as a promising drug-free approach for promoting wound healing,
reduction of inflammation, pain and restoration of function owing to penetration power in conjunction with their ability to positively modulate the
biochemical and molecular responses.
This review will describe the physical properties of red and near-infrared light and their interaction with skin, and highlight their efficacy on wound repair
and regeneration.
Near-infrared (800-830 nm) found to be most effective and widely studied wavelength range followed by red (630-680 nm) and 904 nm superpulsed light
exhibiting beneficial photobiomodulatory effects on impaired dermal wound healing."

T&F

PubMed

Additional info

Comment

Reply

 Category
Wound
healing

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Wounds

Solmaz

Turkey
(Istanbul)

2016

Lasers Med Sci

Laser biostimulation of wound healing: bioimpedance

measurements support histology.

Rat

635

Results: positive / unclear/modest / negative

Link

sec

1
3

"Laser irradiations of both energy densities stimulated the wound healing process.
In particular, laser irradiation of lower energy density had more evidence
especially for the first days of healing process. On the 7th day of healing, 3 J/cm2
laser-irradiated tissues had significantly smaller wound areas compared to nonirradiated wounds (p < 0.05). The electrical impedance results supported the idea
of laser biostimulation on healing of cutaneous skin wounds."

PubMed

"Thus, bioimpedance measurements may be considered as a non-invasive

supplementary method for following the healing process of laser-irradiated
tissues."
Comment: On the 10th day, the wound area was smaller in the control group,
compared to the irradiated groups...

Wound

Wounds

Tatmatsu-Rocha

healing

USA (Boston,
MA) & Brazil
(So Paulo)

2016

J Photochem
Photobiol B

904

Low-level laser therapy (904nm) can increase collagen and reduce

oxidative and nitrosative stress in diabetic wounded mouse skin.

40

0.305

2.4

18.3

0.13

60

"The increased production of collagen and decreased oxidative and nitrosative

stress suggests that LLLT may be a viable therapeutic alternative in diabetic
wound healing."

PubMed

Star: The parameters were exceptionally well reported. Worth a look!

Wound
healing

Wounds

Kuffler DP

Puerto Rico

2016

Regen Med

Photobiomodulation in promoting wound healing: a review.

Review

Wound
healing

Wounds

Li

China
(Beijing)

2016

PLoS One

The Histopathological Investigation of Red and Blue Light Emitting

Diode on Treating Skin Wounds in Japanese Big-Ear White Rabbit.

Rabbit

"While data suggest that simultaneous multiple wavelength illumination is more efficacious than single wavelengths, the optimal single and multiple
wavelengths must be better defined to induce more reliable and extensive healing of different wound types. This review focuses on studies in which
specific wavelengths induce wound healing and on their mechanisms of action."
630

0.050

45
90

300
cm2

900
1800

"On days 16 and 17 of irradiation, the healing rates in red (15 min and 30 min) and
blue (15 min and 30 min) groups were 50%, 37.5%, 25% and 37.5%, respectively,
while the healing rate in the control group was 12.5%.

PubMed
PubMed

The percentage healed area in the red light groups was significantly higher than
those in other groups.
Collagen fiber and skin thickness were significantly increased in both red light
groups; expression of EGF, FGF, CD31 and Ki67 in the red light groups was
significantly higher than those in other groups; the expression of FGF in red (30
min) group was not significantly different from that in the blue light and control
groups."
"The effect of blue light on wound healing was poorer than that of red light. Red
light appeared to hasten wound healing by promoting fibrous tissue, epidermal
and endothelial cell proliferation. An increase in the exposure time to 30 min did
not confer any additional benefit in both red and blue light groups. This study
provides a theoretical basis for the potential therapeutic application of LED light in
clinical settings."

Wound

Wounds

Keshri

healing

India
(Delhi)

2016

PLoS One

Photobiomodulation with Pulsed and Continuous Wave NearInfrared Laser (810 nm, Al-Ga-As) Augments Dermal Wound
Healing in Immunosuppressed Rats.

Rat

Immunosuppressed
wound healing

810

70

0.04

28

22.6

1.77
cm2

600

Pulsed vs continuous

"Results clearly delineated that 810 nm PBM at 10 Hz was more effective over
continuous and 100 Hz frequency in accelerating wound healing by attenuating
the pro-inflammatory markers (NF-kB, TNF-), augmenting wound contraction (SM actin), enhancing cellular proliferation, ECM deposition, neovascularization
(HIF-1, VEGF), re-epithelialization along with up-regulated protein expression of
FGFR-1, Fibronectin, HSP-90 and TGF-2 as compared to the non-irradiated
controls.

PubMed

Additionally, 810 nm laser irradiation significantly increased CCO activity and

cellular ATP contents."
Star: Parameters were well reported.

Wound
healing

Wounds

Frana

Brazil
(So Paulo)

2016

Photomed Laser
Surg

Photobiomodulation in Wound Healing: What Are We Not

Considering?

Guest
Editorial

Wound
healing

Wounds

Ranjbar &
Takhtfooladi

Iran
(Tehran)

2016

Acta Cir Bras

The effects of photobiomodulation therapy on Staphylococcus

aureus infected surgical wounds in diabetic rats. A
microbiological, histopathological, and biomechanical study.

Rat

Wound
healing

Wounds

Uzda-E-Silva

Brazil
(Salvador,
Bahia)

2016

Lasers Med Sci

Laser phototherapy improves early stage of cutaneous wound

healing of rats under hyperlipidic diet.

Wound
healing

Wounds

de Medeiros

Brazil
(Natal)

2016

Lasers Med Sci

Wound
healing

Wounds

Arago-Neto

Brazil
(Recife)

2016

Wound
healing

Wounds

Wu

USA
(Bethesda, MD)

2015

"The major issue is why, 45 years after Mesters first description, PBM is still not fully incorporated into the guidelines of wound healing societies, or
recommended as a routine in wound care services. The answers may vary according to the specialty, country, group, or area of interest, but when one
searches for good scientific data in the literature, well-designed clinical trials are, unfortunately, rare."
15

0.028
cm2

Rat

660

40

0.04
cm2

"It can be concluded that the hyperlipidic diet modified the inflammation pattern in
wound healing and that laser light has a positive biomodulative effect on the
healing process only in early stages."

PubMed

Effect of low-level laser therapy on angiogenesis and matrix

metalloproteinase-2 immunoexpression in wound repair.

Rat

660

40

2
4

"LLLT improves wound healing by enhancing neocollagenesis, increasing the

amount of new vessels formed in the tissue (neoangiogenesis), and modulating
MMP-2 expression."

PubMed

Int J Biol
Macromol

Combined therapy using low level laser and chitosan-policaju

hydrogel for wound healing.

Rat

660

100

"These results demonstrated that POLI-CHI contributed to more efficient healing

process and modulation of the inflammation; furthermore, the combined use with
LLLT subtle potentiated this process."

PubMed

Wound Repair
Regen

Organic light emitting diode improves diabetic cutaneous wound

healing in rats.

Rat
+ in vitro

In vitro:
total ATP concentration
metabolic activity (MTS assay)
cell proliferation (CyQuant assay)

PubMed

Infection (staph)

"The result revealed that PBMT resulted in a significant decrease in S. aureus

CFU in the PBMT group in comparison to the control group (P<0.05). The length
of wounds, in the 2nd and 3rd weeks, in the PBMT group were significantly shorter
compared to the control group (P<0.05). PBMT caused a significant increase in
the histological parameters in comparison to the control group (P<0.05). Moreover,
PBMT significantly increased the breaking strength of the surgical scars produced
in the skin of the PBMT group when compared to the control group (P<0.05)."

PubMed

685

Diabetic rats

PubMed

"Photobiomodulation therapy may be useful in the management of wound infection

through a significant bacterial growth inhibition and an acceleration of wound
healing process."

In vitro:
hyperglycemic
diabetic cell culture
LED vs LLLT

Wound
healing

Wounds

Sperandio

Brazil
(Alfenas)

2015

J Biophotonics

Low-level laser irradiation promotes the proliferation and

maturation of keratinocytes during epithelial wound repair.

Rat

Wound
healing

Wounds

Andrade Fdo

Brazil
(Itabuna)

2014

Rev Col Bras Cir

Effects of low-level laser therapy on wound healing.

Review

623
(broad
band)

0.007
0.010

0.2
1.0
5.0

635

0.010

5.0

1
cm2

In vivo:
wound closure
histological score
fibroblast growth factor-2 expression
660

100

3.57

3.3

117.85

0.028
cm2

33

"To the best of our knowledge, this is the first time that the quicker wound healing
promoted by LLLT has been linked to the rapid maturation of KCs, which was
confirmed by the accelerated expression of CK10 (terminal differentiation
biomarker [32]) by these cells. The significantly higher proliferation of in vivo KCs
(p63 expression) was also confirmed in vitro with the improved Cyclin D1
expression for the laser groups. In conclusion, a correlation between the in vitro
and in vivo results was established and may help to elucidate the in vivo laser
mechanisms as well as to support upcoming studies."

"Doses ranging from 3 to 6 J/cm(2) appear to be more effective and doses 10 above J/cm(2) are associated with deleterious effects. The wavelengths
ranging from 632.8 to 1000 nm remain as those that provide more satisfactory results in the wound healing process."

PubMed

PubMed

"Low-level laser can be safely applied to accelerate the resolution of cutaneous wounds, although this fact is closely related to the election of parameters
such as dose, time of exposure and wavelength."

Wound
healing

Wounds

Chaves

Brazil
2014
(Belo Horizonte)

An Bras Dermatol

Effects of low-power light therapy on wound healing: LASER x

LED.

"Sixty-eight studies in vitro and in animals were analyzed. LED and LASER promote similar biological effects, such as decrease of inflammatory cells,
increased fibroblast proliferation, stimulation of angiogenesis, granulation tissue formation and increased synthesis of collagen.

Review

PubMed

The irradiation parameters are also similar between LED and LASER. The biological effects are dependent on irradiation parameters, mainly wavelength
and dose. This review elucidates the importance of defining parameters for the use of light devices."

Wound
healing

Wounds

Wound
healing

Wounds

Nussbaum

Kilik

Dungel

Canada
(Toronto)

2014

Slovakia

2014

Wound
healing

Wounds

Austria
(Vienna)

2014

Wound
healing

Wounds

Gonalves

Wound
healing

Wounds

Oliveira Sampaio Brazil

(Salvador,
Bahia)

Brazil
(Juiz de Fora)

2013

2013

Dadpay

2012

Photonics Lasers
Med

Effects of low intensity laser irradiation during healing of infected

skin wounds in the rat.

Biomed Res Int

Effect of equal daily doses achieved by different power densities of Rat

low-level laser therapy at 635 nm on open skin wound healing in
normal and diabetic rats.

Lasers Surg Med

Rat

Low level light therapy by LED of different wavelength induces

angiogenesis and improves ischemic wound healing.

Rat

Pathol Res Pract

Comparative study of the effects of laser photobiomodulation and

extract of Brassica oleracea on skin wounds in wistar rats: A
histomorphometric study.

Rat

Lasers Med Sci

Effect of laser and LED phototherapies on the healing of cutaneous Rat

wound on healthy and iron-deficient Wistar rats and their impact
on fibroblastic activity during wound healing.

635

1/20

808

1/20

9
(?)

LED phototherapy

Cutaneous wound
Healthy rats
Iron-deficient rats

0.05

629

0.05

0.073

PubMed

Only one 808-nm light protocol enhanced healing; lack of benefit using the
remaining 808-nm light protocols may have been due to stimulatory effects of the
light on S. aureus growth."

Open skin wound

470

"Red light improved healing of wounds.

830

90

60

0.0035
cm2

660
(LLLT)

40

10

0.04
cm2

260

700
(LED)

15

10

1
cm2

670

890

1.08

0.03
0.2

1
cm2

30
200

LLLT decreased the infiltration of polymorphonuclear leukocytes. It also stimulated

neovascularization of the tissue and early formation of collagen fibres.

PubMed

"LED therapy with both wavelengths significantly increased angiogenesis in the

sub-epidermal layer and intramuscularly (panniculus carnosus muscle) which was
associated with significantly improved tissue perfusion 7 days after the ischemic
insult. Accordingly, tissue necrosis was significantly reduced and shrinkage
significantly less pronounced in the LED-treated groups of both wavelengths."

PubMed

"In the present study, LLLT and balsam and Ointment B. oleracea were more
effective at reducing the size of the wounds compared to the control group. LLLT
and B. oleracea application promoted acceleration of wound healing, enhanced
remodeling and repair."

PubMed

"It is concluded that the use of LED light caused a significant positive
biomodulation of fibroblastic proliferation on anemic animals and laser was more
effective on increasing proliferation on non-anemics."

PubMed

"Laser irradiation with 0.03J/cm(2) significantly decreased the maximum load for
wound repair in healthy rats (p=0.015). Laser irradiation with 0.2J/cm(2)
significantly increased the maximum load in wounds from the healthy control (p=0.
021) and diabetic (p<001) groups.

PubMed

LED phototherapy
LED vs LLLT

Wound
healing

Wounds

Wound
healing

Wounds

Wound
healing

Wounds

Iran
(Tehran)

J Photochem
Photobiol B

Effects of pulsed infra-red low level-laser irradiation on open skin

wound healing of healthy and streptozotocin-induced diabetic rats
by biomechanical evaluation.

Rat

Photobiomodulation by helium neon and diode lasers in an

excisional wound model: A single blinded trial.

Rat

Influence of the combination of infrared and red laser light on the

healing of cutaneous wounds infected by Staphylococcus aureus.

Rat

Diabetic rats
Dose response (?)

Laser treatments with a pulsed infrared laser at 0.2J/cm(2) significantly

accelerated wound healing in both healthy and diabetic rats."

Dixit

Santos

India
(Manipal)

2012

Brazil
(Salvador,
Bahia)

2011

Adv Biomed Res

Photomed Laser
Surg

633

540

660
+
950

Infections

660
790
660+
790

"The results indicate that He-Ne laser resulted in more stimulatory effect than
diode lasers. From the histopathological examination, we can conclude that 8
J/cm2 of He-Ne lasers appear to be the threshold dosage for an enhanced
regeneration of tissue and reduced inflammation."

PubMed

"Histological analysis showed that control subjects had a lower amount of blood
vessels when compared with irradiated subjects. Irradiated subjects had more
advanced resolution of inflammation compared with controls. Irradiated subjects
also showed a more intense expression of the collagen matrix. The collagen fibers
were mostly mature and well organized in these subjects at the end of the
experimental time especially when both wavelengths were used."

PubMed

Comment: It seems unclear whether the red laser was 660 or 680 nanometers.

Wound
healing

Wounds

Gonalves

Brazil
(Viosa)

2010

Photomed Laser
Surg

Comparative study of the effects of gallium-aluminum-arsenide

laser photobiomodulation and healing oil on skin wounds in wistar
rats: a histomorphometric study.

Rat

830

30
60

"Results show that the 60 J/cm2 laser was more effective in stimulating
angiogenesis. In addition, the 60 J/cm2 and the 30 J/cm2 laser were both more
effective in promoting collagen maturation in the scar tissue of rats, respectively"

PubMed

Additional info

Comment

Reply

More info:

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Subcategory

First author

Country

Year

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

Wound
healing

Wounds

Chung

New Zealand
(Dunedin)

2010

Photomed Laser
Surg

Laser photobiomodulation of wound healing in diabetic and nondiabetic mice: effects in splinted and unsplinted wounds.

Mouse

Dose response

660

18
80

Wound
healing

Wounds

Marchionni

Brazil
(Salvador,
Bahia)

2010

Photomed Laser
Surg

Influence of laser (670 nm) and dexamethasone on the chronology Rat

of cutaneous repair.

LLLT vs
dexamethasone

670

Wound
healing

Wounds

Santos

Brazil
(Salvador,
Bahia)

2010

Photomed Laser
Surg

Effects of laser photobiomodulation on cutaneous wounds treated

with mitomycin C: a histomorphometric and histological study in a
rodent model.

Rat

Wound
healing

Wounds

Peplow

New Zealand
(Dunedin)

2010

Photomed Laser
Surg

Laser photobiomodulation of wound healing: a review of

experimental studies in mouse and rat animal models.

Review
(animal
models)

Category

J/cm2

Results: positive / unclear/modest / negative

"Healing of splinted wounds was delayed compared to unsplinted wounds, but

laser irradiation (1.6 J/day, 7 days) stimulated healing by re-epithelization and
granulation tissue formation."

Link

sec

0.36
1.6

20

PubMed

Comment: The higher dose was better.

0.031

660
790

"Laser was effective in reducing swelling and polymorphonuclear cells and

accelerated tissue repair, even in the presence of dexamethasone."

PubMed

"LPBM resulted in reduced inflammation and an increase in both fibroblast

proliferation and collagen deposition."

PubMed

"The literature search identified eight studies in mice and 39 in rats. A variety of wound models were investigated, including acute-wound, impairedhealing, and chronic-wound models.

PubMed

Considerable variation was observed in research design, methodology, and irradiation parameters employed, limiting comparison of research findings
between studies. Inadequate reporting of key experimental details, or errors in specification and/or calculation of key irradiation parameters was also
found.
Evidence from the studies reviewed suggested that use of red or infrared wavelength at a range of dosage parameters (median 4.2 J cm(-2)) results in
significant benefits in measured parameters of wound healing.
Interestingly, coherence does not seem essential to the photobiomodulatory effects of 'laser' phototherapy."

Wound
healing

Wounds

Leclre

France

2010

Wound Repair
Regen

A prospective randomized study of 980 nm diode laser-assisted

venous ulcer healing on 34 patients.

Human
Observationa
l

Wound
healing

Wounds

Dall Agnol

Brazil
(So Jos dos
Campos)

2009

Lasers Med Sci

Comparative analysis of coherent light action (laser) versus noncoherent light (light-emitting diode) for tissue repair in diabetic
rats.

Rat

UK
(London)

2009

The light revival: does phototherapy promote wound healing? A

review.

Review

980

15000

90

d=
8 mm

640
(LED)

30

0.5
cm2

100

"980 nm diode laser-assisted venous ulcer healing was easy to perform and very
well tolerated. However, there were no statistically significant differences in
reduction of ulcer size between the two groups, suggesting that this particular
laser regimen does not promote wound healing."

PubMed

Note: This paper isn't actually LLLT, since a very high dose laser was used and it
led to significant heating of the irradiated tissue.

Wound
healing

Wounds

Whinfield &
Aitkenhead

Foot (Edinb)

Diabetic rats
LLLT vs LED
LED phototherapy

660
(laser)

"The coherent and non-coherent lights produced similar effects during a period of
168 h after the lesions had been made.

PubMed

For the group composed of diabetic animals, 72 h after creation of the lesion, it
was observed that the therapy with LEDs had been more efficient than that with
the laser in the reduction of the wounds' diameters."

"The results of numerous in vitro and animal investigations suggest that phototherapy may stimulate cell activity and promote tissue repair. Reports of
human clinical trials are relatively few. There is inconsistency of selected treatment parameters amongst studies testing the effect of phototherapy on
wound healing. Clinical trials using human models do not provide sufficient evidence to establish the usefulness of phototherapy as an effective tool in
wound care regimes."

PubMed

"Phototherapy using low level laser is used in a number of applications in hospitals and clinics all over the world. It is considered to be safe and there are
few contraindications for its use. As an aid to wound repair it has been deemed as an effective treatment, and if this can be proven, phototherapy may
become an attractive treatment option in cases of difficult to heal wounds such as diabetic ulceration. Any such treatment that could potentially lighten
the burden of these troublesome wounds would clearly be of great value. At present, however, not enough is known about the way it works, nor is there
agreement amongst practitioners about optimum treatment parameters. There is an urgent need for good quality clinical research trials to establish its
effectiveness, its indications for use and when and how it should be applied."

Wound
healing

Wounds

Ribeiro

Brazil
(Salvador,
Bahia)

2009

Photomed Laser
Surg

660

Immunohistochemical assessment of myofibroblasts and lymphoid Rat

cells during wound healing in rats subjected to laser
photobiomodulation at 660 nm.

20

"The average number of myofibroblasts was statistically significantly higher in the

irradiated group than in the non-irradiated group on the eighth (p = 0.001) but not
the 14th (p = 0.555) day. B and T cells were significantly more conspicuous in the
irradiated group on both the eighth (p = 0.004 and 0.02, respectively) and 14th
days (p = 0.04 and 0.03, respectively)."

PubMed

"Our results suggest that LLLT facilitates myofibroblastic differentiation during the
early stages of the cicatricial repair process. Furthermore, LLLT also appears to
modulate the inflammatory response by downregulating lymphocytic proliferation
during the wound healing process."

Wound
healing

Wounds

Rodrigo

Brazil
(Porto Alegre)

2009

Photomed Laser
Surg

Analysis of the systemic effect of red and infrared laser therapy on

wound repair.

685
830
or
685
+
830

Rat

35
50

20
20

0.0314
cm2

667
401

35
+
50

10
+
10

(?)

334
+
201

Wound
healing

Wounds

Gonzaga Ribeiro

Brazil
(Aracaju)

2009

Indian J Dent Res

Morphological analysis of second-intention wound healing in rats

submitted to 16 J/cm 2 lambda 660-nm laser irradiation.

Rat

660

Wound
healing

Wounds

Medrado

Brazil
(Salvador,
Bahia)

2008

J Photochem
Photobiol B

Influence of laser photobiomodulation upon connective tissue

remodeling during wound healing.

Rat

670

Wound
healing

Wounds

Reis

Brazil
(Salvador,
Bahia)

2008

Photomed Laser
Surg

Effect of 670-nm laser therapy and dexamethasone on tissue

repair: a histological and ultrastructural study.

Rat

670

Wound
healing

Wounds

Machneva

Russia

2008

Biozifika

[A study of the effect of low-intensity laser radiation of the blue,

Rat
green, and red spectral regions on the healing of experimental skin
wounds in rats].
[Article in Russian]

Wound
healing

Wounds

Corazza

Brazil
(So Carlos)

2007

Photomed Laser
Surg

Photobiomodulation on the angiogenesis of skin wounds in rats

using different light sources.

Rat

"Surgical" wound
Edema
LLLT vs
dexamethasone

Biphasic dose
response

"The combined application of red and infrared lasers resulted in the most evident
systemic effect on the repair of skin wounds produced in rats."

PubMed

"We found that LLLT was able to slightly reduce the intensity of the inflammatory
reaction as well as to enhance substantially the epithelization process at both 8 th
and 14 th days. In addition, it also appeared to stimulate the deposition of collagen
fibers at the final stages of wound healing."

PubMed

"Thus, laser photobiomodulation was able to induce several modifications during

the cutaneous healing process, especially in favoring newly-formed collagen fibers
to be better organized and compactedly disposed."

PubMed

"LLLT alone accelerates post-surgical tissue repair and reduces edema and the
polymorphonuclear infiltrate even in the presence of dexamethasone."

PubMed

0.75
0.75
1.5

"It was shown that irradiation with laser accelerated the healing of wounds in all
cases. The exposure to laser radiations in the red (1.5 J/cm), blue, and green
(0.75 J/cm2) spectral regions shortened the time of wound healing from 22 to 17
and 19 days, respectively."

PubMed

"On days 3, 7, and 14, the proliferation of blood vessels in all irradiated groups
was superior in comparison to those of the control group (p < 0.05). Treatment
with fluence of 5 J/cm(2) was better than the laser group with 20 J/cm(2) on day
21."

PubMed

16

441
532
633

Angiogenesis

4
(?)

660
(LLLT)

40

5
20

0.04
cm2

635
(LED)

90

5
20

0.085
cm2

"Red LLLT and LED demonstrated expressive results in angiogenesis. Light

coherence was shown not to be essential to angiogenesis."

LED phototherapy
LED vs LLLT

Wound
healing

Wounds

Yasukawa

Japan

2007

J Vet Med Sci

The effect of low reactive-level laser therapy (LLLT) with heliumneon laser on operative wound healing in a rat model.

Rat

Surgical wounds

633

Wound
healing

Wounds

Demidova-Rice

USA
(Boston, MA)

2007

Lasers Surg Med

Low-level light stimulates excisional wound healing in mice.

Mouse

Biphasic dose
response

635
670
720
820

Laser vs noncoherent

Wound
healing

Wounds

Posten

USA
(Chicago, IL)

2005

Dermatol Surg

Low-level laser therapy for wound healing: mechanism and

efficacy.

1
2
10
50

LLLT with a He-Ne laser was found to promote the healing of operative wounds in
the present rat model, in which the most favorable application of LLLT was the
17.0 mW setting of 15 seconds a day with a frequency of every other day.

PubMed

"820 nm is the most effective wavelength"

"laser and non-coherent lamp are equivalent"

PubMed

"LLLT stimulates wound contraction in susceptible mouse strains but the

mechanism remains uncertain."

"Some studies, especially those using HeNe lasers, report improvements in surgical wound healing in a rodent model; however, these results have not
been duplicated in animals such as pigs, which have skin that more closely resembles that of humans. In humans, beneficial effects on superficial wound
healing found in small case series have not been replicated in larger studies."

Review

PubMed

"The fundamental question is whether there is sufficient evidence to support the use of LLLT."

Wound
healing

Wounds

Pinheiro

Brazil
(Salvador,
Bahia) (?)

2005

Photomed Laser
Surg

Polarized light (400-2000 nm) and non-ablative laser (685 nm): a

description of the wound healing process using
immunohistochemical analysis.

Rat

Biphasic dose
response

4002000
or
685

Wound
healing

Wounds

Vidinsk

Slovenia

2005

Rozhl Chir

[Effect of laser irradiation of diode laser on healing of surgical

wounds in rats]. [Article in Czech]

Rat

Surgical wounds

670

Wound
healing

Wounds

Byrnes

USA
(Bethesda, MD)

2004

Photomed Laser
Surg

Photobiomodulation improves cutaneous wound healing in an

animal model of type II diabetes.

Sand rat

Wound
healing

Wounds

Woodruff

USA
(Dahlonega,
GA)

2004

Photomed Laser
Surg

The efficacy of laser therapy in wound repair: a meta-analysis of

the literature.

Metaanalysis

Wound
healing

Wounds

Mendez

Brazil
(So Paulo)

2004

J Clin Laser Med

Surg

Dose and wavelength of laser light have influence on the repair of

cutaneous wounds.

Rat

685
or
830
or
685
+
830

Wound
healing

Wounds

Hopkins

USA
(Provo, UT)

2004

J Athl Train

Low-Level Laser Therapy Facilitates Superficial Wound Healing in

Humans: A Triple-Blind, Sham-Controlled Study.

Human
Superficial wounds
RCT/DB (TB)
Laser clusted (46
diodes)

660
+
820
+
870
+
880
+
940
+
950

20
40

"Dose was also shown to have influence on the outcome of the treatment as on
both cases, the use of 20 J/cm2 resulted on better effects on the healing process
resulting on better organization and distribution of collagen fibers and influencing
the numbers of myofibroblast"

PubMed

"The present study indicates that the use of
685-nm laser light or polarized light
with a dose of 20 J/cm2 resulted in increased collagen deposition and better
organization on healing wounds, and that the number of myofibroblasts is
increased when polarized light is used."

632

16

250

LLLT accelerated wound healing.

PubMed

"Significant improvement in wound healing histology and wound closure were

found following treatment with 4 J/cm(2) (16 mW, 250-sec treatments for 4
consecutive days; p < 0.05). The 4 J/cm(2) dosage significantly improved histology
and closure of wounds in the diabetic group in comparison to the non-irradiated
diabetic group."

PubMed

"Twenty-four studies with 31 effect sizes met the stringent inclusion and exclusion criteria. The overall mean effect of laser therapy on wound healing
was highly significant (d = +2.22). Sub-analyses of the data revealed significant positive effects on wound healing in animal experiments (d = +1.97) as
well as human clinical studies (d = +0.54).
The analysis further revealed significant positive effects on specific indices of healing, for example, acceleration of inflammation (d = +4.45);
augmentation of collagen synthesis (d = +1.80); increased tensile strength (d = +2.37), reduced healing time (d = +3.24); and diminution of wound size (d
= +0.55)."
35
35

20/50

PubMed

"Group IV (lambda 830 nm and lambda 685 nm, 20 J/cm(2)) presented better
results at the end of the experimental period. It is concluded that low-level light
therapy (LLLT) can have a positive biomodulatory effect on the repair of
cutaneous wounds."

PubMed

"These data indicate that LLLT is an effective modality to facilitate wound

contraction of partial-thickness wounds."

PubMed

Additional info

Comment

Reply

 Category
Wound
healing

More info:

---> Facebook group! (840+ members)

---> LLLT in high-impact journals (table)

Subcategory

First author

Country

Journal

Title

Study type Sub-category 2 /

animal model

nm

mW

W/cm2

J/cm2

Wounds

Whelan

USA
2002
(Milwaukee, WI)

J Clin Laser Med

Surg

Effect of NASA light-emitting diode irradiation on molecular

changes for wound healing in diabetic mice.

Mouse

670

Year

Diabetic mice

Results: positive / unclear/modest / negative

Link

sec

"Our studies have revealed certain tissue regenerating genes that were
significantly upregulated upon LED treatment when compared to the untreated
sample. Integrins, laminin, gap junction proteins, and kinesin superfamily motor
proteins are some of the genes involved during regeneration process."

LED phototherapy

PubMed

"We believe that the use of NASA light-emitting diodes (LED) for light therapy will
greatly enhance the natural wound healing process, and more quickly return the
patient to a preinjury/illness level of activity."
"This work is supported and managed through the Defense Advanced Research
Projects Agency (DARPA) and NASA Marshall Space Flight Center-SBIR
Program."

Wound
healing

Wounds

Simunovic

Switzerland

2000

J Clin Laser Med

Surg

Wound healing of animal and human body sport and traffic

accident injuries using low-level laser therapy treatment: a
randomized clinical study of seventy-four patients with control
group.

Human

Wound
healing

Wounds

Ghamsari

Japan
(Hokkaido)

1997

Vet Surg

Evaluation of low level laser therapy on primary healing of

experimentally induced full thickness teat wounds in dairy cattle.

Cattle

Wound
healing

Wounds

Longo

Italy
(Florence)

1987

Lasers Surg Med

Effect of diodes-laser silver arsenide-aluminium (Ga-Al-As) 904 nm

on healing of experimental wounds.

Rat

830
633
904

633

Biphasic dose
response

904

8.5

3.64

300
600

"After comparing the healing process between two groups of patients, we obtained
the following results: wound healing was significantly accelerated (25%-35%) in
the group of patients treated with LLLT. Pain relief and functional recovery of
patients treated with LLLT were significantly improved comparing to untreated
patients."

PubMed

"The LLLT affects various aspects of the healing process, including minimizing
inflammation, formation of edema, improvement of skin regeneration and
enhancement of collagen synthesis."

PubMed

LLLT for 5 minutes daily: "promoted healing of experimental wounds in rats from
both a microscopic and histologic point of view"

PubMed

LLLT for 10 minutes daily: "did not affect the experimental wounds"

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