KYOWA HAKKO USA

Inspired by Nature.
Improved by Science.

Clinical Review:
An abbreviated look at the science supporting
the memory, brain energy and focus benefits
of Cognizin citicoline

www.cognizin.com
www.kyowa-usa.com

KYOWA HAKKO USA

Inspired by Nature. Improved by Science.

Cognizin is a branded form of pure, stable citicolinean organic molecule

produced endogenously and found in every living cell. This molecule is needed
to build cell membranes throughout the body, but its cognitive health benefits
have been studied repeatedly. This paper introduces some of the more important
studies pertaining to citicolines ability to support cognitive health in three areas:
1 Healthy memory function*
2 Brain metabolism and energy*
3 Focus and attention*

Citicoline

Citicoline is an important building block that is synthesized into two types of

compounds vital to healthy brain function:
Phospholipids
Phospholipids are essential constituents of cell membranesincluding
phosphotidylcholine, phosphatidylserine and phosphatidyl-ethanolamine. Because
cell membranes have a very high turnover rate, these phospholipids must be
continuously synthesized to ensure adequate function of cells.
Neurotransmitters
Neurotransmitters, including acetylcholine, dopamine and noradrenaline, all play a
role in healthy brain function, including the formation of new memories, focus and
attention.
The scientific name for citicoline is cytidine 5-diphosphocholine

Chemistry

may be of use in mitigating changes in the brain relating to phosphotidylcholine

decline.5

Healthy memory function

As a choline donor, citicoline has been shown to increase levels of several

neurotransmitters, including acetylcholine, that affect memory and overall
cognitive function. A meta-analysis of double-blind, randomized human trials
on the effects of citicoline on cognitive performance concluded that citicoline
modestly improves memory.11 In addition, Cognizin citicoline has been shown
to support the activity of nerves that respond to acetylcholine, helping to
raise activity levels in the brains learning and memory circuits.
Citicoline immediate and short-term memory function
A 4-week study conducted on 24 older adults (with memory deficits and without
dementia) measured memory performance. Results indicated that supplementation
with citicoline significantly improved immediate and short-term memory on free
recall tasks, suggesting that citicoline supplementation has beneficial effects on the
underlying cognitive processes of memory retrieval and storage.3
Citicoline supports memory performance in elderly subjects 3
Memory retrieval and storage

Introducing Cognizin citicoline

8.5

8
7

6.5

5.17

5
4

Word Recall

Placebo

Structural formula

Immediate Object Recall Delayed Object Recall

(mean) (P < 0.005)

(mean) (P < 0.005)

Citicoline (1000mg)

Citicoline improves verbal memory in aging adults

A randomized, double-blind, cross-over study on 47 female and 48 male aging
(50-85 years of age) subjects tested the effect of citicoline supplementation
(1000mg) on verbal memory. Memory scores were correlated with plasma
choline concentrations. Results positively correlate citicoline supplementation with
improved verbal memory.12

Natural aging and decrease of phosphatidylcholine

The synthesis of citicoline into phosphotidylcholine supports healthy

aging, as phosphotidylcholine levels in the brain tend to decline with age4
(phosphotidylcholine makes up approximately 30% of brain tissue). In a human
clinical trial, older subjects who received 500mg citicoline for six weeks showed
a 7.3% increase in phosphorus metabolites over the placebo group.
The researchers concluded that the increase in phosphodiesters seen in the
study indicated that phospholipid synthesis and resulting cell membrane turnover
were stimulated by oral citicoline supplementation, suggesting that oral citicoline

w w w.cognizin.com

5.5

3.95
(mean) (P < 0.005)

Molecular formula: C14H26N4O11P2

6.7

w w w.kyowa-usa.com

Brain metabolism and energy

The brain makes up only two percent of a persons body weight, yet it consumes
roughly 20 percent of the bodys energy when at rest.6 Citicoline helps keep the
brains metabolic activity at healthy levels.
Animal studies on brain metabolism
Cognizin citicoline has been shown to support the health of mitochondrial
functioning in animal brains, which resulted in higher levels of ATP in brain cells.7, 8

KYOWA HAKKO USA

Inspired by Nature. Improved by Science.

The Anterior Cingulate

Cortex (ACC) is the
area of the brain
activated with Cognizin

5.50

2.70
0.90

2.68

1.47

CPT-II M=Omission Errors (mean)

250mg

CPT-II M=Commission Errors

500mg

Researchers suggested that the observed improvement in performance might

be related to increased dopaminergic uptake. Previous investigations have shown
that citicoline increases dopamine and dopamine receptor densities as well as
aiding in the protection of neurons related to dopamine.

Cellular Synthesis

Metabolite Level

Metabolite Level

6.70

Placebo

26%

Baseline

7
6
5
4
3
2
1
0

Data from measurement at end of treatment period

General brain health benefits

Cognizin citicoline cellular synthesis and brain energy 9

0.08
0.075
0.07
0.065
0.06
0.055
0.05
0.045
0.04
0.035

Improved attentional performance following citicoline supplementation10

Number of errors

Cognizin cellular synthesis and brain energy

A study on the effects of Cognizin citicoline on brain cellular metabolism in humans
was conducted. The study quantified the effects of citicoline on high-energy
phosphate metabolites and constituents of cellular membrane synthesis in the
frontal lobe of 16 healthy men and women. The data show that citicoline improves
frontal lobe bioenergetics and alters phospholipid cell membrane turnover.7

0.08
0.075
0.07
0.065
0.06
0.055
0.05
0.045
0.04
0.035

13.6%

What structure/function claims can Cognizin

products make?

Cellular Energy

6 weeks * Significant change from baseline

PE: Phosphoethanolamine
Data represent mean SD metabolite ratios relative to the total 31P siganl at each visit.

The following claims are provided for informational purposes and should be
reviewed by your legal counsel prior to use in marketing materials, including
product labels.
Supports memory function and healthy cognition* 5, 13, 14, 15,
Provides the compound needed for the synthesis of phosphatidylcholine, a
major constituent of brain tissue* 1, 2, 5, 14, 15
Enhances communication between neurons to support visual function* 11, 12

Focus and attention

Adequate energy reserves serves a critical role in healthy brain function across
the lifespan.
Cognizin improves attentional performance
A double-blind, randomized, placebo-controlled study conducted on 60 healthy,
middle-aged women found that citicoline supplementation was associated
with improved attentional focus and inhibition. After 28 days of supplementation,
the women were evaluated using the Continuous Performance Test II (CPT-II),
a measure that quantified both attentional errors of commission and omission.
The subjects were divided into three groups: 250mg daily dose, 500mg daily
dose and placebo. Both the 250mg and 500mg groups showed significantly
better ability to produce correct responses, likely due to both improved focus
and inhibition of other stimuli.10

w w w.cognizin.com

The biochemical support provided by citicoline suggests general benefits relating

to the cognitive functioning of aging adults. A review of citicoline supplementation
with elderly subjects resulted in improvements in a wide range of cognitive
and behavioral measures, including memory, attention, behavior, reaction time,
relational life, independence and cooperation.13

w w w.kyowa-usa.com

Helps protect neural structures from accumulating free-radical damage* 15

Supports brain performance by enhancing metabolism and healthy brain
activity* 9, 11, 16
Assists in sustaining healthy mitochondria in the brain, the energy factories
inside brain cells* 9, 11, 16
Supports healthy brain metabolism by nourishing and maintaining brain
cell phospholipids* 5, 14, 15
Helps maintain normal levels of acetyl- choline, a chemical that helps
regulate memory and cognitive function* 11, 12
Supports the activity of nerve cells that respond to acetylcholine* 15
Helps maintain brain cell membranes in a healthy condition* 13

KYOWA HAKKO USA

Inspired by Nature. Improved by Science.

Cognizin is easy to use

Manufacturers and formulators will love the more practical benefits of Cognizin.
This ingredient is:
Pure. Cognizin contains no food additives, artificial flavors or
preservatives.
Stable. Cognizin is stable in liquids and to high heat.
Water-soluble. Water-soluble Cognizin is easy to use in beverages and
liquids.
Neutral in taste. Cognizins neutral and slightly acidic taste compliments
numerous product flavors.
GRAS. Cognizin achieved self-affirmed GRAS status and is considered
safe for food and beverage applications.
Vegetarian. No animal origin material is used in Cognizin.
Allergen-free. Cognizin is considered allergen-free.
Kosher. Cognizin is a certified Kosher ingredient.
Patented. Cognizin is produced by a patented fermentation process.

Cognizin productapplications
Cognizin is suitable for use in:
Dietary supplements
Beverages and beverage bases
Breakfast cereals
Chewing gum
Dairy product analogs
Frozen dairy desserts
Hard and soft candies
Milk and milk products
Processed fruits and fruit juices

w w w.cognizin.com

w w w.kyowa-usa.com

References

Wurtman RJ et al. Biochem Pharmacol. 2000; 60(7): 98992.

Rao AM et al. J Neurosci Res. 1999; 58(5): 697705.
3
Alvarez XA et al. Meth Find Exp Clin Pharmacol. 1997; 19(3): 20110.
4
Cohen, Bruce M., et al. Decreased brain choline uptake in older adults: an in
vivo proton magnetic resonance spectroscopy study. Jama 274.11 (1995):
902-907.
5
Babb SM et al. Psychopharmacology, 2002; 161(3): 24854.
6
Drubach, Daniel. The Brain Explained. New Jersey: Prentice-Hall, 2000.
7
Hurtado O et al. Neurobiol Dis. 2005; 18: 33645.
8
Kakihana M et al. Jpn Pharmacol Ther. 1985; 13(9): 24153.
9
Silveri MM et al. NMR Biomed. 2008; 21(10): 106675.
10
McGlade E et al. Food and Nutr. Sciences. 2012; 3(6): 769773.
doi: 10.4236/fns.2012.36103.
11
Fiorvanti M, Yanagi M. The Cochrane Library, Oxford, England. 2006; Issue 4.
12
Spiers PA et al. Arch of Neuro. 1996; 53(5): 4418.
13
Secades JJ, Lorenzo JL. Meth Find Exp Clin Pharmacol.
2006; 27(Suppl B): 156.
14
Lopez-Coviella I et al. J Neurochem. 1995; 65(2):889-94.
15
Conant R, Schauss AG. Alt Med Rev. 2004; 9:1, 17-31.
16
Watanabe S et al. Folia Psychiatr Neurol Jpn. 1975; 29(1):67-76.
1
2

KYOWA HAKKO USA

Inspired by Nature. Improved by Science.

KYOWA HAKKO USA, INC.

600 Third Ave. 19th Floor
New York, NY 10016
Tel: 212.319.5353
Fax: 212.421.1283
info@kyowa-usa.com
www.kyowa-usa.com
www.cognizin.com

w w w.cognizin.com

w w w.kyowa-usa.com

Cognizin is a trademark of KYOWA HAKKO BIO CO., LTD.

Copyright 2014 KYOWA HAKKO BIO CO., LTD. All Rights Reserved.

*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.

This information is being provided to you for

educational and informational purposes only.
This information is not intended to be used as
marketing materials to consumers.