Well over a decade ago, resveratrol made its introduction
into the dietary supplement marketplace. Initially, excitement
about resveratrol was based upon the consideration
that intake of it and other polyphenol compounds from
red wine may contribute to the “French paradox”—the unexpectedly
low rate of death from cardiovascular disease in the Mediterranean
population despite the relatively higher intake of saturated
fats.1 Then, excitement increased with the understanding
that resveratrol helped activate the SIRT 1 gene, associated with
longevity.2 Since that time, interest in resveratrol has continued
to expand due to human research demonstrating its effectiveness
for inflammation, immune health/breast cancer prevention,
muscle health, cognitive health, weight loss, blood sugar/
insulin resistance, non-alcoholic fatty liver disease, and more.
These benefits will be the focus of this article.
Before jumping into a discussion about the fascinating human
research, however, let's take a moment to review just what resveratrol
is, in case you're unfamiliar with it. Resveratrol is a type
of natural phenol by several plants in response to injury or attack
by pathogens.3,4 These plants include grapes, peanuts5 and
Japanese Knotweed (Polygonum cuspidatum).6 Resveratrol helps
provide protection to the plants, at least in part, due to its demonstrated
antioxidant properties.7 These antioxidant properties
benefit humans too, as shown in research where resveratrol provided
a direct antioxidant effect against free radicals, and facilitated
an increase in vitamin E8—another powerful antioxidant.
There are two primary isomers (i.e. two forms) of resveratrol,
trans- and cis-. To be clear, trans-resveratrol has been unequivocally
shown to have much greater activity than cis-resveratrol.9 Consequently, when purchasing a resveratrol product,
make sure to check the supplement facts panel to verify that the
product contains trans-resveratrol. If just"resveratrol" is listed,
without the trans-designation, or if cis-resveratrol is listed,
you would be better off choosing a different product that lists
trans-resveratrol. In any case, for ease of reading, I will drop
references to trans- in the rest of this article, although it can be
assumed that any mention of resveratrol will actually refer to
As its first claim to fame, resveratrol has been found to have
activity that may have protective effects on the cardiovascular
system. In both test-tube and animal research, resveratrol has
been shown to inhibit platelet aggregation (i.e. the clumping
together of blood platelets). This has value since excessive or
inappropriate aggregation of platelets can lead to formation
of blood clots and subsequent blockages in blood vessels that
result in insufficient blood flow, heart attack or stroke.10 Resveratrol
can also promote vasodilation (a relaxed and expanded
state of the artery that accommodates increased blood flow) by
enhancing the production of a naturally occurring substance in
the body called nitric oxide.11
More importantly, human clinical research12 has demonstrated
that 100 mg/day of resveratrol significantly reduced arterial
stiffness (a major indicator of atherosclerosis) compared to
placebo, and also lowered systolic blood pressure by 5.5 points
in patients with type 2 diabetes. Another human study,13 which
used a much higher dose (2.3 g) in older adults, found that
resveratrol not only improved vascular function more than placebo,
but also increased the number of mitochondria.those
parts of the cells that help to generate energy for our body!
Another interesting cardiovascular benefit is resveratrol's
effect on Apolipoprotein B (ApoB), a primary component of
many lipoproteins such as LDL (the gbad cholesterolh) that are
involved in atherosclerosis and cardiovascular disease. In human
clinical research14 on overweight or obese individuals with
mild hypertriglyceridemia, 1000 mg/day of resveratrol for one
week followed by 2000 mg/day for two weeks reduced ApoB
production rate by an impressive 22 percent. In addition, flowmediated
dilatation (a measure of arterial circulation and endothelial
function) was increased in human studies15,16,17 where 10
mg to 270 mg/day of resveratrol was given. In one of the studies,18 LDL cholesterol levels were also significantly decreased.
In addition to showing anti-inflammatory effects in in-vitro and
animal studies, resveratrol has also been shown to comprehensively
suppress oxidative and inflammatory stress with as little
as 40 mg/day in normal human subjects.19 This included the
reduction of inflammatory markers such as TNF-alpha, IL-6,
and C-reactive protein, with no changes in the placebo group.
Similarly, in postmenopausal women with osteoarthritis pain,
75 mg of resveratrol twice daily significantly reduced pain and
improved total well-being.20
Ulcerative colitis (UC), a chronic inflammatory bowel disease,
has also responded to treatment with resveratrol. In one
study21 with 56 UC patients, those receiving 500 mg/day of resveratrol
had significant symptom improvement, reduced malondialdehyde
(a highly reactive oxidative stress compound), and
increased superoxide dismutase (SOD), and total antioxidant
capacity. In another human study22 with 50 UC patients, 500
mg/day of resveratrol also reduced the activity of inflammatory
compounds, including TNF-α, hs-CRP, and activity of NF-κB.
Furthermore, in a study23 of firefighters, supplementation
with 100 mg/day resveratrol for 90 days, plasma biomarkers of
inflammation were reduced after a physical fitness test, including
IL-6 and TNF-α. This adds further credence to resveratrol's
Immune Health/Breast Cancer Prevention
resveratrol's effect on immune health can be as fundamental
as increasing certain circulating immune cells, or as profound
at reducing the risk of breast cancer. For example, human research24
was conducted to assess the effects of repeated doses
of resveratrol (1000 mg/day for 28 days) on circulating immune
cells in healthy individuals. The results were that resveratrol was
safe and well tolerated and was associated with significant increases
in the numbers of circulating gamma delta T cells (functioning
as a first line of defense and a bridge between innate
and adaptive responses) and regulatory T cells—demonstrating
that resveratrol has clear biological effects on human circulating
With regard to breast cancer prevention, resveratrol may
help in a couple of ways. First, resveratrol has been shown to
have a dose-dependent effect on reducing the formation of
mammary tumors in-vitro as a result of down-regulating DNA
methyltransferases. To see if it had a similar effect in humans,
a study25 was conducted in which 39 adult women at increased
breast cancer risk received a placebo, 5 or 50 mg of resveratrol
twice daily for 12 weeks. Results were that there was indeed decrease
in methylation of the tumor suppressor gene with increasing
levels of resveratrol (P = .047).
In another study26 of 34 overweight, postmenopausal women
(BMI ≥ 25 kg/m2), the clinical effect of resveratrol on systemic
sex steroid hormones were investigated, since high estrogen
levels may contribute to breast cancer. The subjects received 1
g of resveratrol daily for 12 weeks. The results were that resveratrol
supplementation led to an average of 73 percent increase in
urinary 2-hydroxyestrone (the "good estrogen") levels leading to
a favorable change in estrogen ratios that are less conducive to
the development of breast cancer. This research demonstrated
that among overweight and obese postmenopausal women, a
daily 1 g dose of resveratrol has favorable effects on estrogen
In a 12-week study,27 older men and women (aged 65.80 years)
exercised and took either a placebo or 500 mg/day of resveratrol
to determine if resveratrol would have additive effects to
those of exercise. Results showed that exercise added to resveratrol
treatment increased the number of mitochondria, and
improved muscle fatigue resistance more than placebo and
exercise treatments. In addition, subjects treated with resveratrol
had an increase in muscular torque and power after training,
whereas exercise did not increase these parameters in the
placebo-treated older subjects. Furthermore, exercise combined
with resveratrol significantly improved muscle fiber. Together,
these data suggest that resveratrol combined with exercise
might provide a better approach for reversing sarcopenia than
Research suggests that resveratrol may have cognitive health
benefits in people with and without dementia. For example, the
ongoing dysfunction of small blood vessels in patients with
type 2 diabetes mellitus (T2DM) may impair the ability of cerebral
vessels to supply blood to various brain regions, thereby
increasing risks of dementia. To determine if resveratrol could
benefit cerebral circulation, a study28 was conducted in which
36 dementia-free, non-insulin dependent T2DM older adults
(49–78 years old) consumed single doses of resveratrol (0, 75,
150, and 300 mg) at weekly intervals. Results were that 75–300
mg of resveratrol enhanced vasodilator responsiveness in cerebral
In another study,29 80 post-menopausal women aged 45–85
years received resveratrol or placebo for 14 weeks to examine
the effect on cognitive performance and other parameters. Results
were that compared to placebo, significant improvements
were observed in the performance of cognitive tasks in the domain
of verbal memory (p = 0.041) and in overall cognitive performance
(p = 0.020). Mood also tended to improve in multiple
measures. These results indicate that regular consumption of a
modest dose of resveratrol can enhance both cerebrovascular
function and cognition in post-menopausal women, potentially
reducing their heightened risk of accelerated cognitive decline
and offering a promising therapeutic treatment for menopauserelated
To test30 whether supplementation of resveratrol (200 mg/
day for 26 weeks) would enhance memory performance in older
adults, 23 healthy overweight older individuals were pairwise
matched to 23 participants that received placebo (total n = 46,
18 females, 50–75 years). Results showed a significant effect of
resveratrol on retention of words over 30 min compared with
placebo (p = 0.038), significant increases in hippocampal functional
connectivity, decreases in glycated hemoglobin (HbA1c)
and body fat, and increases in leptin compared with placebo (all
p < 0.05). This study provides initial evidence that supplementary
resveratrol improves memory performance in association
with improved glucose metabolism in older adults, providing a
basis for helping to maintain brain health during aging.
To determine the effects of oral resveratrol on localized cerebral
blood flow, a study31 was conducted with which 22 healthy
human adults received placebo and two doses (250 and 500
mg) of resveratrol in counterbalanced order on separate days.
After a 45-min resting absorption period, the participants performed
a selection of cognitive tasks. Resveratrol administration
resulted in dose-dependent increases in cerebral blood
flow during task performance, and enhanced oxygen extraction.
These results showed that single doses of orally administered
resveratrol can modulate cerebral blood flow variables.
Finally, a clinical study32 was conducted to determine if up
to 1 g of resveratrol twice daily could benefit Alzheimer's disease
(AD) patients. The results demonstrated that resveratrol
decreased CSF MMP9 (a biomarker for confirmed AD), modulates
neuro-inflammation, and induces adaptive immunity—
suggesting that resveratrol may be a viable target for treatment
or prevention of neurodegenerative disorders.
One of the reasons that resveratrol has received widespread interest
is because of its ability to mimic effects of calorie restriction.
To gain more insight into this effect on adipose tissue,
a study33 was conducted in which healthy obese subjects were
supplemented with 150 mg/day of resveratrol or placebo for 30
days. Results showed that resveratrol significantly decreased
the size of adipocytes (fat cells), with a shift toward reducing the
proportion of large and very-large adipocytes and an increase in
small adipocytes. Furthermore, lysosomal/phagosomal pathway
and transcription factor EB were up-regulated reflecting an
alternative pathway of lipid breakdown by autophagy.
Similarly,34 T2DM patients received 3 g resveratrol or placebo
daily for 12 weeks. Results were that there was a significant
increase in both SIRT1 expression and resting metabolic rate
compared with the placebo group. In patients with T2DM, treatment
with resveratrol helped regulate energy expenditure, suggesting
that resveratrol may have beneficial exercise-mimetic
Again,35 healthy, obese subjects were treated with placebo
and 150 mg/day resveratrol for 30 days. The results were that
resveratrol increased SIRT1 and improved the muscle's use of
fatty acids as an energy fuel, demonstrating that 30 days of resveratrol
supplementation induces metabolic changes in obese
humans, mimicking the effects of calorie restriction. Given
these results, one might think that resveratrol may aid in weight
loss—and indeed this has been shown to be the case in clinical
Orlistat is an over-the-counter drug (also known as Alli®)
designed to treat obesity by reducing the absorption of fats
from the human diet. A study36 was conducted to evaluate the
efficacy of combining orlistat with resveratrol in 84 obese subjects
over a 6-month period. The subjects consumed a diet with
500 fewer calories than their usual diet for two weeks, and were
randomly assigned to four groups, placebo, resveratrol, orlistat,
or the O-R combination, and they consumed the energyreduced
diet for 6-months. Results were significant weight loss
of 15 lbs in the O-R group compared with 7.7 lbs in the placebo
group. Significant decreases in BMI, waist circumference, fat
mass, triglycerides, leptin, and leptin/adiponectin ratio were
observed with the O-R combination, indicating that it was the
most effective weight loss treatment.
In another study,37 24 patients with metabolic syndrome received
resveratrol (500 mg) three times per day before meals
for 90 days. Resveratrol administration resulted in significant
differences in total weight (P=0.007), body mass index (BMI)
(P=0.006), fat mass (P=0.001), and waist circumference
(P=0.004). In conclusion, administration of resveratrol significantly
decreased weight, BMI, and fat mass.
Blood Sugar/Insulin Resistance
A study38 was conducted using 480 mg/day of resveratrol or
placebo for four weeks on 43 patients with diabetes who also
had chronic periodontitis (i.e. gum disease). Results were that
serum levels of fasting insulin and insulin resistance were significantly
lower in the resveratrol group compared with control
group. With regard to periodontal disease, there was also a
significant difference in the gum pocket depth between intervention
and control groups with resveratrol. The researchers
recommended that resveratrol supplementation might be beneficial
as adjuvant therapy along with non-surgical periodontal
treatment in insulin resistance and improving periodontal status
among patients with diabetes with periodontal disease.
Another human clinical trial39 was conducted in 32 over-weight, older adults (average age: 73 years). Participants received
placebo, 300 mg/day of resveratrol, or 1000 mg/day of
resveratrol for 90 days. Results were that, compared to placebo,
glucose levels were significantly lower at after treatment among
participants receiving either dose of resveratrol (P<0.05), and
were well tolerated.
In this study,40 62 patients with T2DM received either an
oral hypoglycemic medication, or an oral hypoglycemic medication
along with 250 mg/day of resveratrol. Results were that
supplementation with resveratrol for three months significantly
improved the mean hemoglobin A1c (P<0.05), a measure of
long-term glucose control, systolic blood pressure (P<0.05),
total cholesterol (P<0.05), and total protein (P<0.05) in T2DM.
The researchers concluded that oral supplementation with resveratrol
was effective in improving glycemic control and may
be a potential adjuvant for the treatment and management of
In a pilot study,41 subjects with impaired glucose tolerance
(aged 72 ± 3 years) received 1, 1.5, or 2 g/day of resveratrol for
four weeks. After four weeks of resveratrol supplementation,
results showed that post-meal (P=0.003) and 3-hour glucose
levels (P=0.001) declined. Researchers concluded that, at doses
between 1 and 2 g/day, resveratrol improves insulin sensitivity
and post-meal plasma glucose in subjects with impaired glucose
tolerance. Likewise, in a 4-week study,42 T2DM patients
received 10 mg/day resveratrol or a placebo. Results showed
that, after the fourth week, resveratrol significantly improved
insulin sensitivity, which might be due to a resveratrol-induced
decrease in oxidative stress that leads to a more efficient
Non-Alcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation
of fat in the liver of people who drink little or no alcohol.
Unfortunately, NAFLD is common—with easily one-third of all
American adults being affected43—and often causes no signs
and symptoms, and sometimes no complications. In more
serious cases, however, the fat that accumulates in NAFLD can
cause liver inflammation and scarring.44 In addition, NAFLD
is usually associated with insulin resistance, central obesity,
reduced glucose tolerance, T2DM and high triglyceride levels.
In a clinical study,45 50 NAFLD patients received either a 500
mg/day of resveratrol or a placebo for 12 weeks. Both groups
were advised to follow an energy-balanced diet and physical
activity recommendations. Results were that resveratrol supplementation
reduced alanine aminotransferase (a marker for
NAFLD) and hepatic steatosis (fatty liver) significantly more
than placebo (P<0E05).
In another study,46 60 NAFLD patients received two 150 mg
resveratrol capsules twice daily for three months. Results were
that, compared with the placebo group, resveratrol significantly
decreased aspartate aminotransferase, glucose and low-density
lipoprotein cholesterol (P.0.001) alanine aminotransferase, total
cholesterol (P=0.002), and insulin resistance (P=0.016). The
researchers concluded that resveratrol supplementation might
benefit patients with NAFLD.
Other Resveratrol Benefits
In addition to the aforementioned applications for resveratrol,
there are additional benefits for this nutraceutical as well. Two
such benefits are related to bone health, and for those who are
In a clinical study,47 66 middle-aged, obese subjects with
metabolic syndrome (average age: 49.3 } 6.3 years) received
oral treatment with 1,000 mg or 150 mg of resveratrol, or a placebo
daily for 16 weeks to assess changes in the bone turnover
marker bone alkaline phosphatase (BAP), and bone mineral density
(BMD). Results were that BAP increased dose dependently
with resveratrol (P<0.001), compared with placebo. Lumbar
spine trabecular volumetric bone mineral density also increased
dose dependently with resveratrol (P=0.036), with a significant
increase of 2.6 percent in the 1,000 mg resveratrol group compared
with placebo (P=0.043). In addition, changes in BAP and
bone mineral density were positively correlated (P=0.027).
Smokers typically experience a state of low-grade systemic
inflammation and oxidant-antioxidant imbalance. To determine
whether resveratrol has beneficial effects on markers of inflammation
and oxidative stress, a study48 was conducted with 50
healthy adult smokers who alternatively were given 500 mg/
day of resveratrol and placebo. Results were that resveratrol
significantly reduced the inflammatory marker C-reactive protein
(CRP), triglyceride concentrations, and increased Total Antioxidant
Status (TAS) values. The researchers concluded that,
because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic
effects, its supplementation might beneficially
affect the increased cardiovascular risk of healthy smokers.
Improving The Bioavailability And Efficacy Of Resveratrol
Now that we've reviewed some of the many benefits associated
with resveratrol supplementation, let's briefly consider ways
to improve the bioavailability and efficacy of this valuable nutraceutical.
First, take resveratrol on an empty stomach. The
reason for this recommendation is a study showing that the
absorption rate of resveratrol following an oral 400 mg singledose
was significantly delayed by the presence of food.49
Second, resveratrol may work better when taken together
with pterostilbene (a related antioxidant) and quercetin (a flavonoid).
In this study,50 the antioxidant activities of resveratrol,
pterostilbene and quercetin, and the effect of their combination
were investigated in human blood cells in-vitro. When used together,
the combination protected the blood cells against destruction
and against depletion of the important antioxidant,
glutathione. Also, the combination of resveratrol with quercetin
or pterostilbene synergistically inhibited oxidative injury of
membrane lipids. These protective effects may partially explain
the health benefit of these bioactive microcomponents when
together in the diet.
The value of supplementation with resveratrol has moved beyond
the "French paradox" and the activation of the SIRT 1
gene, associated with longevity. Human clinical research has
demonstrated efficacy of resveratrol for inflammation, immune
health/breast cancer prevention, muscle health, cognitive
health, weight loss, blood sugar/insulin resistance, non-alcoholic
fatty liver disease, and more.
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- Imamura H, Yamaguchi T, Nagayama D, Saiki A, Shirai K, Tatsuno I. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Int Heart J. 2017 Aug 3;58(4):577–83.
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- Dash S, Xiao C, Morgantini C, Szeto L, Lewis GF. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2895–901.
- Wong RH, Berry NM, Coates AM, Buckley JD, Bryan J, Kunz I, Howe PR. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. J Hypertens. 2013 Sep;31(9):1819–27.
- Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A, Battyany I, Sumegi B, Toth K, Szabados E. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc. 2012;50(3):179–87.
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- Wong RHX, Evans HM, Howe PRC. Resveratrol supplementation reduces pain experience by postmenopausal women. Menopause. 2017 Aug;24(8):916–22.
- Samsamikor M, Daryani NE, Asl PR, Hekmatdoost A. Resveratrol Supplementation and Oxidative/Anti-Oxidative Status in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Arch Med Res.2016 May;47(4):304–9.
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- Wong RH, Nealon RS, Scholey A, Howe PR. Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2016 May;26(5):393–9.
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