RESVERATROL

Bhavik Nagda/ 12FET1002

Institute of Chemical Technology, Mumbai

General Information
Belongs to a class of polyphenolic compounds
called stilbenes

Some types of plants produce Resveratrol and

other stilbenes in response to:
stress, injury, fungal infection, and ultraviolet
(UV) radiation

It is a fat soluble compound that occurs in a

trans and a cis configuration

Both cis and trans resveratrol also occur as

glucosides (bound to a glucose molecule)

General Information
Resveratrol is a phytoalexin, a class of antibiotic
compounds produced as a part of a plants
defense system against disease

For example: In response to an invading fungus,

resveratrol is synthesized from p-coumaroyl CoA
and malonly CoA

Since fungal infections are more common in

cooler climates, grapes grown in cooler climates
have a higher concentration of resveratrol

Food Sources
Found in grapes, wine, grape juice, and berries of Vaccinum
species including blueberries, bilberries, and cranberries

In grapes, resveratrol is found only in the skins

The amount of resveratrol in grape skins varies with the
grape cultivar, its geographic origin, and exposure to fungal
infection

Also, the amount of fermentation time a wine spends in

contact with grape skins is an important determinant of its
resveratrol content

White and rose wines generally contain less resveratrol than

red wines, which is because the skins are removed earlier
during their production, lessening the amount that is
extracted

Total R.C. in Grape Juice &

Wine
Beverage

Total
resveratrol
(mg/liter)

White wines
(Spanish)
Rose wines
(Spanish)
Red wines
(Spanish)
Red wines
(global)
Red grape juice

0.05-1.80

Total
resveratrol in a
5 ounce glass
(mg)
0.01-0.27

0.43-3.52

0.06-.53

1.92-12.59

0.29-1.89

1.98-7.13

0.30-1.07

1.14-8.69

0.17-1.30

R.C. in Select Foods

Food

Serving

Total
resveratrol
(mg)

Peanuts
(raw)

1 c (146 g)

0.01-0.26

Peanuts
(boiled)

1 c (180 g)

0.32-1.28

Peanut
butter

1 c (258 g)

0.04-0.13

Red grapes

1 c (160 g)

0.24-1.25

Metabolism &
Bioavailibility
Although trans-resveratrol appear to be wellabsorbed by humans when taken orally, its
bioavailability is relatively low due to its rapid
metabolism and elimination

Information

about
the
bioavailability
resveratrol in humans is important

of

This is because much of the basic research on

resveratrol has been conducted in cultured cells
exposed to unmetabolized resveratrol at
concentrations that are often 10-100 times
greater than peak concentrations observed in
human plasma after oral consumption

The French Paradox

The French Paradox was the observation that mortality from
coronary heart disease is relatively low in France despite
relatively high levels of dietary saturated fat and cigarette
smoking

This led to the idea that the regular consumption of red wine
might provide additional protection from cardiovascular disease

Red wine contains resveratrol and even higher levels of

flavonoids

These polyphenolic compounds have antioxidant, antiinflammatory, and other potentially anti-atherogenic effects in
the test tube and in some animal models of atherosclerosis

Although moderate alcohol consumption has been consistently

associated with 20-30% reductions in coronary heart disease
risk, it is not yet clear whether red wine polyphenols confer any
additional risk reduction

Benefits Cardiovascular
Resveratrol has been found to exert a number of
potentially
including:

cardio

protective

effects

in

vitro

Inhibition of platelet aggregation

Promotion of vasodilation by enhancing the production of NO
Inhibition of inflammatory enzymes

But,

concentrations of resveratrol required to

produce these effects are often higher than those
that have been measured in human plasma after
oral consumption of resveratrol

 Although its presence in red wine has stimulated

much interest in the area of cardiovascular
disease prevention, currently there is no
convincing evidence that resveratrol has cardio
protective effects in humans

Especially in the amounts present in 1-2 glasses

of red wine

Anti-Cancer
Resveratrol has been found to inhibit the proliferation of a
variety of human cancer cell lines, including those from breast,
prostate, stomach, colon, pancreatic and thyroid cancers when
added to cells cultured outside the body

In animal models, there has been marked inhibition in the

development of esophageal, intestinal, and breast cancer with
oral administration of resveratrol

In mice, genetically predisposed to colon cancer, effects

from oral resveratrol administration have been mixed

It is currently not known whether or not high intakes of

resveratrol can help prevent cancer in humans

Studies suggest that even very high dietary intakes of

resveratrol may not result in tissue levels that are high enough
to demonstrate the protective effects that resveratrol has shown
in cell culture studies

Biological Activity
Resveratrol is said to prevent
cardiovascular disease by:

1. Inhibition of Vascular Cell

Adhesion Molecule
Expression

2. Inhibition of Vascular
Smooth Cell Proliferation

3. Stimulation of Endothelial
Nitric Oxide Synthase
Activity

4. Inhibition of Platelet
Aggregation

Resveratrol is said to
prevent cancer due to:

1. Effects on
biotransformation enzymes

2. Preservation of Normal Cell

Cycle Regulation

3. Inhibition of Proliferation
and Induction of Apoptosis

4. Inhibition of Tumor Invasion

and Angiogenesis

5. Anti-Inflammatory Effects

Longetivity
Caloric restriction has been proven to extend the lifespan of a
number of species, including mammals

In yeast, a caloric restriction stimulates the activity of an enzyme

referred to as Sir2

Administering resveratrol to yeast increased Sir2 activity in the

absence of caloric restriction and extended the replicative lifespan
of yeast by 70%

Although resveratrol did increase the activity of the homologous

human enzyme (Sirt1) in the test tube, whether or not resveratrol
can extend the human lifespan is currently unknown

And again, the resveratrol concentrations that were necessary to

increase Sirt1 activity in the test tube were considerably higher
than any concentration previously measured in human plasma

Toxicity
Resveratrol is not known to be toxic or cause adverse effects
in humans, but there have been only a few controlled clinical
trials to date. A recent trial that evaluated the safety of oral
resveratrol in ten subjects found a single dose up to 5 grams
resulted in no serious adverse effects

Pregnancy and Lactation: The safety of resveratrolcontaining supplements during pregnancy and lactation has
not been established

Estrogen-sensitive Cancers: Until more is known about the

estrogenic activity of resveratrol in humans, women with a
history of estrogen-sensitive cancers, such as breast, ovarian,
and uterine cancers, should avoid resveratrol supplements

Drug Interaction Potential

Resveratrol

has
been
found to inhibit human
platelet aggregation in
vitro. Theoretically, high
intakes
of resveratrol (e.g., from
supplements) could increa
se the risk of bleeding wh
en taken with
anticoagulant drugs, such
as warfarin (Coumadin);
antiplatelet drugs, such
as clopidogrel (Plavix) a
nd dipyridamole (Persanti

Resveratrol

has
been
reported to inhibit the
activity of cytochrome
P450
3A4
(CYP3A4
in vitro .
Although this interaction
has not been reported in h
umans, high intakes of res
veratrol (e.g., from suppl
ements) could theoreticall
y increase the bioavailabi

Manufactured in India by

Aarkios Health
Private Limited
Cost:Rs 3000/Qty : 60 capsules

Zenith Nutritions,
Mumbai
Cost:Rs 2430/Qty :120capsules

Current Scenario
We conclude that recommending consumption of resveratrol to
patients is premature because

1. Little is known about the absorption and clearance of resveratrol,

the identities of its metabolic products, or its effects on the liver

2. The research on resveratrol has focused on its short-term effects

and has been dominated by in vitro studies on non-human
models

3. Its role as a potentiator of breast carcinomas may significantly

limit its use, even for its proven benefits

4. Its main dietary source is red wine, which is not only extremely
variable, but possibly harmful to be recommending increased
intakes of red wine to the population at this point