Since its first mention in a Japansee article in 1939¹, over the years many beneficial effects have been attributed to the natural compound, resveratrol—anticancer, anti-inflammatory, anti-aging—which is even used in skincare cosmetic. Although a large number of studies suggest its health benefits, recently some reports have been questioning these potentials.

Resveratrol is a natural phenol and antioxidant compound found in various colored vegetables and fruit, especially in the skin of red grape. Its name comes probably from the combination if the term resorcinol (chemical compund) and Veratrum (the plant where resveratrol was first isolated). It is thought to influence inflammation, aging, neuronal degeneration, and metabolism through the serine deacetylase, sirtuin-1 (SIRT-1), the cAMP pathway, or AMP-activated protein kinase². However the exact mechanism of action is not known. A new role for resveratrol as a partial agonist of the estrogen receptor alpha (ERalpha) has been recently described³. According to this study, resveratrol binds to the ERalpha that is recruited to the interleukin-6 (IL-6) promoter and alters the binding of coregulators, such as SIRT-1, and the activity of transcriptional activators, leading to reduced inflammation. Resveratrol was identified in a previous screening for ERalpha agonists that inhibit IL-6 transciption⁴; thus resveratrol may have a selective role on the ERalpha pathway, inhibiting inflammation without promoting cell proliferation.

The amount of resveratrol found in foods varies greatly. It is mainly found in the skin of red grapes, red wine, peanuts, berries, and in lower amount in cocoa powder and dark chocolate⁵. However, the amount of resveratrol in foods is thought to be not enough to justify and mediate its effects. To understand whether resveratrol levels present in the diet can influence inflammation, cancer, cardiovascular disease, and mortality in humans, a prospective cohort study has been conducted in the Chianti region in Italy (InCHIANTI—“Aging in the Chianti Region”), in a population-based sample of 783 community-dwelling men and women 65 years or older who consume a diet rich in resveratrol⁶. The group of researchers, who have been studying aging in this population for fifteen years, measured the concentration of resveratrol metabolites present in the urine and found that it was not associated with inflammatory markers, cardiovascular disease, or cancer. This study shows that the amount of resveratrol present in the diet is not responsible for beneficial health effects. It is possible that the health benefits that come from the diet consumed in that region are not due to resveratrol, but to other substances present in the food. On the other hand resveratrol is rapidly metabolized in sulfate and glucuronide conjugates and it has long been believed that this could limit its bioavailability. However, a study from the University of Leicester shows that resveratrol is not rendered ineffective after it is metabolized by the body: it can be generated by resveratrol sulfate and be even more effective than the un-metabolized compound⁷.

Supplements that contain high quantity of resveratrol are available in the market. However, people should be careful with them, because we still don’t know the repercussions of high amount of resveratrol on human health. A very recent study published on the June issue of The FASEB Journal shows that the use of resveratrol during pregnancy can have beneficial effects on the blood flow in the placenta and on the liver function (decreased placental inflammation and liver triglyceride deposition), but can increase fetal pancreatic mass and exocrine proliferation, leading to unknown consequences on the development of the fetus⁸.

To date, there are not definitive studies on the benefits of resveratrol. The literature is full of controversial or incomplete reports. Therefore, be careful in listening to advertisements that sell resveratrol as a health serum.

¹Takaoka M, Resveratrol, a new phenolic compound, from Veratrum grandiflorum. M Takaoka, Journal of the Chemical Society of Japan, 193 (2012):1090-1100.

²Tennen RI, Michishita-Kioi E, Chua KF. “Finding a target for resveratrol”. Cell 2012,148 (3): 387–9.

³Nwachukwu J,Srinivasan S, Bruno NE, Parent AA, Hughes TS, Pollock JA, Gjyshi O, Cavett V, Nowak J, Garcia-Ordonez RD, Houtman R, Griffin PR, Kojetin DJ, Katzenellenbogen JA, Conkright MD, Nettles KW. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network. eLife, (2014).

⁴Srinivasan S., Nwachukwu J.C., Parent AA, Cavett V, Nowak J, Hughes TS, Kojetin DJ, Katzenellenbogen JA, and Nettles KW. Ligand-binding dynamics rewire cellular signaling via estrogen receptor-alpha. Nat Chem Biol (2013) 9, 326-332.

⁵Hurst WJ, Glinski JA, Miller KB, Apgar J, Davey MH, Stuart DA. “Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products”. Journal of Agricultural and Food Chemistry (2008) 56 (18): 8374–8.

⁶Semba RD, Luigi Ferrucci L, Bartali B, Urpí-Sarda M, Zamora-Ros R, Sun K, Cherubini A, Bandinelli S, Andres-Lacueva C. Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults. JAMA Internal Medicine, (2014) May 12.

⁷Patel KR, Andreadi C, Britton RG, Horner-Glister E, Karmokar A, Sale S, Brown VA, Brenner DE, Singh R, Steward WP, Gescher AJ and Brown K. Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence. Science Translational Medicine, (2013) Oct 2;5(205).

⁸Roberts VHJ, Pound LD, Thorn SR, Gillingham MB, Thornburg KL, Friedman JE, Frias AE, and Grove KL. Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates. FASEB J. (2014) June 28:2466-2477.