Potential Side Effects of Resveratrol (Revised)

Potential Side Effects of Resveratrol

Some rat-studies suggest that resveratrol is safe at doses equivalent to 300-500 mg./day for short-term use. [4,5] The toxicity of prolonged intake of resveratrol is unknown, especially at high doses. It has been speculated that the side effects of oral intake of resveratrol include issues in collagen formation and nerve regeneration, or even heart failure. This unwanted toxic side effects are probably related to overdoses and prolonged use of resveratrol. In general, the toxic effect of most drugs or supplements mostly is caused by over-dosage, immediate absorption of large amount of active ingredient at a time or prolonged use.

In various cancer cell lines, the copper concentration is reported to be elevated. Resveratrol has also been shown to exhibit "prooxidant properties" in the presence of copper ions. In a study of 2005, plasmid bluescript SK(+) DNA was treated with increasing concentrations of resveratrol in the presence and absence of copper ions, transformed into competent DH5alpha cells and sequenced. The study shows a decrease in the transformation efficiency of the plasmid after resveratrol treatment, and although all types of mutations were recorded, point mutations (deletions/substitutions) were found to be the predominant ones. Resveratrol alone resulted in deletion of mainly guanine bases. In the chromatin of nucleus, copper ions are bound to guanine bases. This study suggests the mobilization of such endogenous copper by resveratrol resulting in "prooxidant DNA cleavage" at the site. Since the copper concentration is high in various cancer cell lines, this may explain the anticancer activities of resveratrol. [6]

Resveratrol is generally considered as a copper chelator. Thus, it is speculated that oral intake excessive amount of resveratrol orally may hinder the absorption of certain metal ions, especially copper ion, leading to copper deficiency. People with ischemic heart disease usually have decreased cardiac and leucocyte copper. It was found that copper deficiency decreases copper in hearts and other organs and cells and increases cholesterol in plasma. Abnormal physiology from deficiency includes abnormal electrocardiograms, glucose intolerance and hypertension.

Most commercial supplements are immediate-release or immediate-disintegrate dosage forms. Once, the users intake the supplements, the tablets or capsules disintegrate and release the actives within a short period of time. This sudden availability of a large amount of resveratrol in the gastric intestine tract can prevent the absorption of the copper and potentially lead to copper deficiency.

If this speculation is the case, the side effect of resveratrol is serious. Users may need to take copper supplements or to ensure their copper levels are within normal range.

[1] U.S. Patent Application 20070148689

[2] Noel, Joseph.; et al, Methods of producing polyketide synthase mutants and compositions and uses thereof, U.S. Patent Application 20040106175.

[3] Klevay L.M., Cardiovascular disease from copper deficiency --a history. J Nutr. 2000 Feb;130(2S Suppl):489S-492S.

[4] Neil E Levin et al, Pomeratrol™ Fact Sheet, NowFoods Online Publication, September 20, 2005

[5] Crowell JA et al, Resveratrol-associated renal toxicity. Toxicol Sci. 2004 Dec;82(2):614-9. Epub 2004 Aug 25.

[6] Ahmad A, Syed FA, Singh S, Hadi SM, Prooxidant activity of resveratrol in the presence of copper ions: mutagenicity in plasmid DNA. Toxicol Lett. 2005 Oct 15;159(1):1-12.