Professional Documents
Culture Documents
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Key Words: Nutraceutical, cardiovascular diseases, coronary heart diseases, prebiotics, omega-3 fatty acids, functional foods.
INTRODUCTION
Sugar alcohols
Minerals
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Ramaa et al.
however the role of isoflavones of soy in reducing cholesterol is still unclear due to conflicting reports. The relatively
short duration and small sample size of many of the human
studies in this field likely contribute to the inconsistent results. Soy and its associated isoflavones reduce LDL oxidation and improve vascular reactivity [24].
Based on the review of more than 50 recent trials, Hermansen et.al. reported that consumption of new soy products
containing high fixed levels of isoflavones, cotyledon soy
fibre and soy phospholipids (Abaco and Abalon) significantly reduced the LDL: HDL. On an average Abaco and
Abalon reduced the LDL: HDL ratio by 20%, LDL cholesterol by 15%, total cholesterol by 10% and triglycerides by
6% and increased HDL cholesterol by 5% [25].
Sanders et.al. conducted randomized cross over trials in
22 young, healthy normolipidemic subjects (5 men and 17
women) who consumed diets providing 56 or 2 mg isoflavones per day for 17 days each with a 25 day wash out period between treatment. They reported that as compared to
soy protein from which most of the phytoestrogens (high
isoflavone content) have been extracted, soy protein with
intact phytoestrogens increases HDL-cholesterol and Apolipoprotein A-1 concentration, but does not influence LDLcholesterol, TGF-beta-1 concentrations and hemostatic risk
factors for coronary heart disease in normolipidemic healthy
subjects [26]. In contrast, in another study in which 41 hyperlipidemic men and postmenopausal women participated,
the conclusion was that substitution of soy foods for animal
products, regardless of isoflavone concentration, reduces the
coronary artery disease risk, because of both modest reduction in blood lipids and reduction in oxidized LDL, homocysteine and blood pressure [27].
Typically soy foods are divided into two categories: nonfermented and fermented soy products. Traditional nonfermented soy foods include fresh green soybeans, whole dry
soybeans, soy nuts, soy sprouts, whole-fat soy flour, soymilk
and soymilk products, tofu, okara and yuba. Traditional fermented soy foods include tempeh, miso, soy sauces, natto
and fermented tofu and soymilk products [28]. In Asia, the
traditional fermented soy foods are considered to have more
health promoting benefits when consumed in moderate
amounts than the super-processed soy products that are consumed in the West [29, 30]. It has been suggested that the
fermentation process increases availability of isoflavones in
soy [28, 31].
DIETARY FIBRES
Fibres are the endogenous components of plant materials
in the diet, which are resistant to digestion by enzymes produced by humans. Fibres can be broadly classified into soluble and insoluble fibres as per their solubility in the blood
stream. Since all foods contain a mixture of polysaccharides,
only isolated polysaccharides can be simply classified as
soluble or insoluble fibre sources [32]. Fibre is important for
gastrointestinal health as well as cholesterol-lowering benefits [33]. Insoluble fibre reduces rate of colon cancer and
diverticulitis, an inflammatory condition of the colon, while
soluble fibre significantly lowers blood cholesterol, thus reducing the risk of CHD [34-39].
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Table 1.
ANTIOXIDANT VITAMINS
Antioxidant vitamins present in some fixed oils, fruits,
vegetables and fishes are those compounds, which either
prevent the formation of oxygen free radicals or entrap them.
Antioxidants are the magic bullets for a wide range of diseases including cancer and cardiovascular disease. Their
primary function is to counter the damaging effect of free
radicals in our body, thereby reducing LDL-cholesterol oxidation [51]. Although niacin has been first demonstrated to
have an antihyperlipidemic effect, the emergence of HMGCoA inhibitors has reduced its use.
Clinical use of antioxidant vitamin supplementation may
help to prevent CHD. Epidemiologic studies found lower
CHD morbidity and mortality in persons who consume
larger quantities of antioxidants in foods or supplements.
Clinical trials indicate that supplementation with certain nutrients is beneficial in reducing the incidence of CHD events.
Supplementation with antioxidant vitamins E and C has
benefits in CHD prevention; however, supplementation with
-carotene may have deleterious effects and is not recommended [51]. Adams et.al. suggested that patients with CHD
would probably benefit from taking vitamin E in a dosage of
400 IU per day and vitamin C in a dosage of 500 to 1,000
mg per day. Clinicians may also want to consider vitamin
supplementation for CHD prevention in high-risk patients
[52].
In the Heart Outcomes Prevention Evaluation Study
(HOPE) in which 9279 patients belonging to the high-risk
category for CHD events participated. In a 2x2 factorial design, patients were randomly assigned to receive ramipril or
placebo and vitamin E (400 IU per day) or placebo. They
were followed up for 3.5yrs. Vitamin E supplementation was
without any benefit [53, 54].
Many epidemiologic studies have linked diets high in
antioxidants with reduced CHD risk (Tables 1 [54-57] and 2
[58-62]). Randomized, controlled trials of antioxidant vitamin supplementation are summarized in Table 3 [63-69].
Supplementary vitamin E in a dosage of greater than 100 IU
per day was associated with reduced lesion progression.
Clinical trials strongly supports that vitamin E in dosages
greater than 100 IU per day reduces CHD events. CHD relative risk reductions of 31 to 65 percent were found with vitamin E supplementation [52] Patients receiving warfarin
Observational Study on the Relationship between Antioxidant Vitamins and Coronary Heart Disease (CHD)
Study
Population
Observations
WHO/MONICA
16 European regions
Verlangieri, et al.
United States
Inverse association between fruit and vegetable consumption and CHD mortality
Riemersma, et al.
Luoma, et al.
Northern Finland
WHO = World Health Organization; MONICA = Multinational Monitoring of Trends and Determinants in Cardiovascular Disease.
Table 2.
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Prospective Cohort Studies on the Relationship between Antioxidant Vitamins and Coronary Heart Disease
Vitamin E
Vitamin C
-carotene
Men
Women
NHANES
+(Smokers only)
EPESE
Study
NHANES = National Health and Nutrition Examination Survey I; EPESE = Established Populations for Epidemiologic Studies of the Elderly; + = Significant inverse relationship
benefit observed between vitamin and coronary heart disease; 0 = no significant relationship observed; X = vitamin not studied.
Table 3.
Randomized Controlled Trials on the Relationship between Antioxidants and Coronary Heart Disease (CHD)
Vitamin
Study
Dosage
Outcome
Primary prevention
ATBC
50 mg per day
Secondary prevention
ATBC subset
50 mg per day
+ (Alone)
- (with -carotene)
CHAOS
CLAS
+ (Dose dependent)
Primary prevention
Secondary prevention
CLAS
Primary prevention
ATBC
20 mg per day
15 mg per day
Vitamin E
Vitamin C
-carotene
Secondary prevention
CARET
ATBC subset
20 mg per day
ATBC = Alpha-Tocopherol Beta-Carotene Cancer Prevention Study; CHAOS = Cambridge Heart Antioxidant Study; CLAS = Cholesterol Lowering Atherosclerosis Study; CARET
= Beta-Carotene and Retinol Efficacy Trial; + = Significant positive effect of vitamin supplementation on CHD; - = Significant negative effect of vitamin supplementation on CHD;
0 = no effect of vitamin supplementation on CHD.
*--A portion of this study (on intake of vitamins C and E) was not randomized.
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smokers [74], patients with hypercholesterolemia and patients with CHD [75]. These findings support the antioxidant
and endothelial effects of vitamin C.
Lycopene is a carotenoid, which is the main active constituent in tomatoes, and has been a recent focus in cardiovascular health research. Findings suggest that dietary lycopenes or other phytochemicals consumed as oil based tomato
products confer cardiovascular benefits [22]. Natural tomato
lycopene rather than synthetic lycopene has been found to
confer heart health benefits.
Antioxidant vitamins have also been proved beneficial in
countering endothelial dysfunction, which is an early step in
the development of artherosclerosis [76]. Folate lowers elevated homocysteine level, but evidence suggesting routine
use as supplement does not exist. The role of beta-carotene in
CHD is also dubious and may have deleterious effects [51].
Pantothenic acid lowered LDL-cholesterol by 13.5% and
increased HDL-cholesterol by 10% in a study of 11 patients
[77].
Other antioxidants that may provide protection against
CHD include selenium, bioflavonoids and ubiquinone.
Selenium levels are inversely associated with CHD mortality
[78], conflicting results were reported in other studies [79].
Ubiquinone, a reduced form of coenzyme Q10, decreases
LDL oxidation, but no event reduction data are available.
Ubiquinone may reduce symptoms and improve ejection
fractions in patients with heart failure [80-82].
PLANT STEROLS
Plant sterols also known as phytosterols are found naturally in a range of plant sources such as vegetable oils, nuts,
grains, seeds, wood pulp and leaves. Typical diets commonly
include sitosterol, campesterol and stigmasterol along with
smaller amounts of plant stanols (saturated plant sterols) like
sitostanol. Being structurally similar to cholesterol, they
compete with ingested cholesterol for absorption through the
small intestine. This reduction in absorption of cholesterol
increases hepatic uptake of LDL and reduces blood LDL
levels, although there are compensatory mechanisms that
increase the rate of endogenous cholesterol synthesis which
limit the magnitude of the effect [83].
Plant sterols have been shown in studies to reduce LDL
cholesterol by 8-15%. Plant sterols are derived from natural
grains including soy, corn and sunflower. Studies have demonstrated the efficacy of plant sterols in reducing the risk of
CHD [84]. However long term use might lead to a decrease
in plasma carotenes, vitamin-E and lycopene. AHA has recommended restricted use to adults only requiring treatment
for hypercholesterolemia or needing secondary prevention of
CHD [85]. Various studies suggested that the consumption
of about 2-3gm per day of plant sterols/stanols reduce LDLcholesterol levels between 9%-20% although there is considerable variation amongst individuals [86]. Little effect on
HDL-Cholesterol or triglyceride levels has been reported.
Plant stanol ester margarines have also been shown to be
effective adjunct to hypercholesterolaemia treatment using
statins and fibrates [86, 87].
Foods that may qualify for the health claim based on
plant sterol ester content include spreads and salad dressings.
Ramaa et al.
Among the foods that may qualify for claims based on plant
stanol ester content are spreads, salad dressings, snack bars,
and dietary supplements in softgel form. U.S.FDA authorized new coronary heart disease health claim that 1.3gm per
day of plant sterol esters or 3.4gm per day of plant stanol
esters in the diet are needed to show a significant cholesterol
lowering effect. In order to qualify for this health claim, a
food must contain at least 0.65gm of plant sterol esters per
serving or at least 1.7gm of plant stanol esters per serving.
The claim must specify that the daily dietary intake of plant
sterol esters or plant stanol esters should be consumed in two
servings eaten at different times of the day with other foods
[88]. This interim final rule was based on U.S.FDA's conclusion that plant sterol esters and plant stanol esters reduces the
risk of CHD by lowering blood cholesterol levels.
FLAVONOIDS
The flavonoids, which occur both in free state and as
glycosides, are the largest group of naturally occurring phenols. Polyphenolic compounds, which suggested playing a
dominant role in the prevention of heart disease, include the
isoflavones, flavonoid glycosides, catechins, and anthocyanins [89]. These effects have been attributed to the influence of flavonoids on arachidonic acid metabolism [3, 89].
Flavonoids are antioxidants found in tea (green and
black), wine, fruits and vegetables. These antioxidants
reduces platelet activation, but studies do not yet support an
associated reduction in CHD [90, 91]. An epidemiologic
study found inverse correlation between dietary flavonoid
intake and CHD [91]. Flavonols and flavones are subgroups
of flavonoids. As they have antioxidant properties, intake of
these dietary compounds is associated with a lower risk of
fatal and nonfatal CHD [92].
In a study conducted on 15 patients with coronary artery
disease, consumption of red wine or purple grape juice offered increased protection against LDL-Cholesterol oxidation and also improved endothelial function. Hence it was
suggested that moderate amounts of red wine and purple
grape juice be included among 5-7 daily servings of fruits
and vegetables per day as recommended by AHA to reduce
the risk of cardiovascular disease [93]. A reduced incidence
of CHD and other vascular diseases is well related to a high
dietary intake of flavonoids from fresh fruit and vegetables
[94, 95].
Anderson et al. suggested that isoflavones associated
with soy protein might be responsible for their cardioprotective effect. In support of this suggestion, the results of a dietary trial in monkeys fed semipurified atherogenic diets
showed that the presence of large amounts of isoflavones
was associated with a favourable lipid profile, including a
lower concentration of lipoprotein A [96, 97]. The beneficial
effects observed in the epidemiologic studies, confirmed that
flavonoids represent an important part of a daily "health" diet
[98].
PREBIOTICS
A prebiotic is defined as a nondigestible food ingredient
that beneficially affects the host by selectively stimulating
the growth and/or activity of one or a limited number of
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dophilus, Bifidobacteria bifidum, and Lactobacillus bulgaricus bacteria lower cholesterol in a significant fashion when
its level is too high [109-113].
The hypocholesterolemic effects of probiotics are the
subjects of controversy. Studies published in the 1970s and
1980s consistently reported 517% reductions in serum cholesterol concentrations after 2 to 4 weeks of daily consumption of fermented milk products, but these data have been
challenged by the results of more recent studies, almost all of
which did not report any significant effect. As discussed recently by Jackson et al., the major limitations of these earlier
studies were as follows: 1) the excessive volumes (0.58.4 L)
of yogurt consumed daily in most of the positive studies, 2)
failure to assess or control for the background diet and exercise patterns of the subjects studied, 3) failure to randomize
groups for confounding factors, 4) lack of run-in periods
during which the volunteers adapted to the diet, 5) lack of
multiple baseline measurements, and 6) changes in control
groups. Jackson et al. concluded that experimental evidence
does not support a hypocholesterolemic effect for probiotics
when consumed in easily achievable quantities [112].
If cholesterol problem is linked to a high fat diet, putting
beneficial bacteria back into the intestine as supplements
offers a natural way to help balance out lipid and fat levels.
A research report from Denmark published in the European
Journal of Clinical Nutrition noted that lactobacillus bacteria
significantly lowered blood pressure in men and women 18
to 55 years of age after eight weeks of supplementation
[111]. Those in the control group who did not receive the
selected strains of lactobacillus bacteria did not experience a
drop in their high blood pressure. Thus, there is significant
evidence that specific kinds of lactobacillus bacteria and
bifidobacteria can lower the three major risk factors for CHD
and stroke: excessive cholesterol, high blood pressure, and
high triglyceride levels. But one has to be careful with the
strain selection of the beneficial bacteria supplement used to
get the best results. Not all strains of L. acidophilus, B. bifidum, and L. bulgaricus bacteria available on the market
work to lower cholesterol [113-115].
CONCLUSION
CVDs are not the consequence of a single isolated risk
factor but the result of a merging of several complex processes that commence early in life. These include behavioral,
environmental, and socio-economic as well as genetic risk
factors. The focus of the pharmaceutical industry should now
be towards maintenance of optimal heart health rather than
treatment of people with cardiovascular disease. There are
multiple ways to address heart health, either use supplements
that directly affect heart health or use those that help to reduce weight, improve general activity and achieve long term
heart goals.
Some functional foods have intrinsic heart health promoting constituents; others have such constituents added,
while third category includes those in which ingredients
harming heart health are exchanged. These foods include
garlic, polyunsaturated fatty acids from plant and marine
sources; soy products; dietary fibres in oats; psyllium husk
and flaxseed; peptides from milk proteins; antioxidant vitamin containing foods; certain grapes and many others.
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Regular consumption may serve to reduce the risk of cardiovascular disease by several potential mechanisms such as
enhancing electrical stability of heart cells, reducing LDL
oxidation, scavenging free radicals, lowering blood lipids,
reducing blood pressure, inhibiting platelet aggregation and
decreasing plaque formation. As physicians increase their
awareness regarding natural products to promote cardiovascular health, they may include them in their treatment alternatives.
[22]
ACKNOWLEDGEMENT
[28]
[29]
[23]
[24]
[25]
[26]
[27]
[30]
[31]
ABBREVIATIONS
[32]
CVDs
Cardiovascular diseases
[33]
CHD
AHA
EPA
Eicosapentaenoic acid
DHA
Docosahaexanoic acid
HDL
[36]
LDL
[37]
ACE
[38]
HMG-CoA =
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