January 16, 2014

Resveratrol Decreases Inflammation

Study evaluates the effects of resveratrol supplementation on inflammatory cytokines in professional male basketball players
At the end of the 6-week intervention, the men in the resveratrol group had a significant decrease in tumor necrosis factor-α and interleukin 6 compared to the placebo control group.


Zahedi HS, Jazayeri S, Ghiasvand R, et al. Effects of polygonum cuspidatum containing resveratrol on inflammation in male professional basketball players. Int J Prev Med. 2013;4(Suppl 1):S1-S4.


Using a randomized, double-blind, placebo-controlled clinical trial, this study examined the effects of trans-resveratrol on the plasma levels of tumor necrosis factor-α and interleukin 6 in male professional basketball players.


The participants were 20 healthy male professional basketball players (age range=17–35 years). The men were randomly assigned to receive either 200 mg/d of Polygonum cuspidatum extract standardized to contain 40 mg of trans-resveratrol (n=10) or a placebo (n=10) for 6 weeks.

Study Parameters Assessed

The blood sample measurements were collected after 2 hours of vigorous endurance exercise performed at baseline and after 6 weeks of supplementation. Nutrient calculations for 3-day dietary records were undertaken before and after the intervention.

Primary Outcome Measures

The serum levels of tumor necrosis factor-α and interleukin 6 were measured by enzyme immunometric assay kits.

Key Findings

No significant group and time differences were found for weight, body mass index, and dietary intake. However, at the end of the 6-week intervention, the men in the resveratrol group had a significant decrease in tumor necrosis factor-α and interleukin 6 compared to the placebo control group.

Practice Implications 

Resveratrol (3,5,4’-trihydroxystilbene) is a polyphenol found in grapes (Vitis vinifera), a variety of berries, peanuts, and medicinal plants, such as Japanese knotweed (Polygonum cuspidatum).1 Another dietary source of resveratrol is red wine, and it is often postulated to be a factor in the French Paradox, a term coined to describe the French population’s low incidence of cardiovascular disease, in spite of its diet high in saturated fats.2 Scientific interest in resveratrol has continually gained momentum since 1997, when it was first found to prevent carcinogenesis in mice.3 Since this time, resveratrol has received research attention for its anti-inflammatory, antitumorigenic, and antioxidant properties, as well as its ability to increase lifespan in lower organisms and improve general health in mammals.4,5 A meta-analysis of 19 published studies on the effect of resveratrol on survival found that resveratrol acts as a life-extending agent.6 The effect is most potent in yeast and nematodes, with diminished reliability in most higher-order species. Findings of life extension in simpler laboratory organisms, combined with thousands of in vitro and in vivo studies supporting a role for resveratrol in either the prevention or treatment of chronic diseases, imply that resveratrol may have the potential to make a positive impact on human health.
Resveratrol has multiple mechanisms of action that may be related to its health benefits.1 Like most polyphenols, resveratrol has intrinsic antioxidant capacity, but it also induces the expression of a number of antioxidant enzymes, making it hard to decipher the precise contribution of each mechanism to an overall reduction in oxidative stress.7 Although most of the published studies on resveratrol were performed in vitro or in animal models, intense media coverage highlighting its potential applications in the prevention and treatment of age-related diseases has inspired many individuals to try it and many companies to develop resveratrol supplements. Because of the continued public interest and the explosion of resveratrol supplements on the market, a need exists to summarize the available clinical literature.
Recently published studies evaluating resveratrol's potential for primary prevention of chronic disease in healthy populations have generated both controversy in the scientific community and large-scale media attention.
In the clinical trial abstract reviewed here, intake of 40 mg/d of trans-resveratrol for 6 weeks was found to significantly reduce the plasma concentration of tumor necrosis factor-α and interleukin 6. These findings confirm the results of previous studies in rats8 and healthy humans.9,10 For example, in 2008, Bujanda et al found that the production of tumor necrosis factor-α decreased in rats treated with resveratrol.8 Ghanim et al (2010) found that resveratrol supplementation suppressed plasma concentration of tumor necrosis factor-α, interleukin 6, and C-reactive protein after 6 weeks in healthy humans while they did not observe any changes in these indices in the control group.9 In comparison, Ghanim et al (2011) found anti-inflammatory effects of resveratrol and polyphenol preparation supplement in healthy humans.10
Recently published studies evaluating resveratrol’s potential for primary prevention of chronic disease in healthy populations have generated both controversy in the scientific community and large-scale media attention. At first glance these studies do not appear consistent with the animal model research findings.11–13 But as Smoliga et al asked, “How does one define clinical improvement in individuals who are already clinically healthy at baseline?”14 Biomarkers that are responsive to treatment in people with chronic disease are not likely to be as sensitive to interventions in healthy humans, due to normal homeostatic control mechanisms.14 Smoliga and his colleagues, in their position paper, present a strong case for why clinical endpoints in primary prevention studies in nonclinical populations should not be used.14 The goal of research examining the effects of resveratrol (or any other dietary supplements) in already healthy groups should not be to make them healthier. Rather studies should be undertaken to examine disease prevention and maintain health over the long-term.
Most recently, a well-designed clinical trial by Gliemann et al13 published in the Journal of Physiology generated intense media coverage. The study reported that resveratrol may blunt the beneficial effects of exercise. If true this will add a significant piece of information to our use of resveratrol. A detailed review and analysis of this new study will be published in an upcoming issue of this journal.
In summary, both the health field and general population must be critical readers of any clinical trial to ensure accurate conclusions are drawn. Resveratrol has been shown to have a wide variety of health benefits for humans. One question is whether these short-term positive health findings will translate into long-term health benefits. Larger-scale, longer-term multisite trials are currently underway to elucidate resveratrol’s potential role and mechanisms of action for the treatment and prevention of age-related diseases. Both the scientific and general community anxiously await the results of these trials which will further our understanding of the dose-response of resveratrol and its clinical applicability in people.

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  2. Liu BL, Zhang X, Zhang W, Shen HN. New enlightenment of French Paradox: resveratrol's potential for cancer chemoprevention and anti-cancer therapy. Cancer Biol Ther. 2007; 6(12):1833-1836.
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  4. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006; 444(7117):337-342.
  5. Labbe A, Garand C, Cogger VC, et al. Resveratrol improves insulin resistance hyperglycemia and hepatosteatosis but not hypertriglyceridemia, inflammation, and life span in a mouse model for Werner syndrome. J Gerontol A Biol Sci Med Sci. 2011; 66(3):264-278.
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  7. Halliwell B. Dietary polyphenols: good, bad, or indifferent for your health? Cardiovasc Res. 2007;73(2):341-347.
  8. Bujanda L, Hijona E, Larzabal M, et al. Resveratrol inhibits nonalcoholic fatty liver disease in rats. BMC Gastroenterol. 2008;8:40
  9. Ghanim H, Sia CL, Abuaysheh S, et al. An anti-inflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab. 2010;95(9):E1-8.
  10. Ghanim H, Sia CL, Korzeniewski K, et al. A resveratrol and polyphenol preparation suppresses oxidative and inflammatory stress response to a high-fat, high-carbohydrate meal. J Clin Endocrinol Metab. 2011;96(5):1409–1414.
  11. Yoshino J, Conte C, Fontana L, et al. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab. 2012; 16:658-664.
  12. Poulsen MM, Vestergaard PF, Clasen BF, et al. High-dose resveratrol supplementation in obese men: An investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes. 2013; 62(4):1186-1195.
  13. Gliemann L, Schmidt JF, Olesen J, et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol. 2013;[Epub ahead of print].
  14. Smoliga JM, Sage Comombo E, Campen MJ. A healthier approach to clinical trials evaluating resveratrol for primary prevention of age-relted diseases in healthy populations. Aging. 2013;5(7):495-506.