Resveratrol (trans-3,5,4'-trihydroxystilbene), a compound found largely in the skins of red grapes, is a component of Ko-jo-kon, an oriental medicine used to treat diseases of the blood vessels, heart and liver . It came to scientific attention during the mid-1990s as a possible explanation for the "French Paradox"—the low incidence of heart disease among the French people, who eat a relatively high-fat diet . Since then, it has been touted by manufacturers and examined by scientific researchers as an antioxidant , an anti-cancer agent, and a phytoestrogen . It has also been advertised on the Internet as "The French Paradox in a bottle."
While present in other plants, such as eucalyptus, spruce, and lily, and in other foods such as mulberries and peanuts, resveratrol's most abundant natural sources are Vitis vinifera, labrusca, and muscadine grapes, which are used to make wines. It occurs in the vines, roots, seeds, and stalks, but its highest concentration is in the skin , which contains 50-100 micrograms (µg) per gram . Resveratrol is a phytoalexin, a class of antibiotic compounds produced as a part of a plant's defense system against disease . For example, in response to an invading fungus, resveratrol is synthesized from p-coumaroyl CoA and malonyl CoA . Since fungal infections are more common in cooler climates, grapes grown in cooler climates have a higher concentration .
The resveratrol content of wine is related to the length of time the grape skins are present during the fermentation process. Thus the concentration is significantly higher in red wine than in white wine, because the skins are removed earlier during white-wine production, lessening the amount that is extracted . Grape juice, which is not a fermented beverage, is not a significant source of resveratrol. Since wine is the most notable dietary source, it has been the object of much speculation and research. But a recent review noted that (a) the presence of resveratrol in the human diet is almost negligible, and a role for resveratrol in explaining the "French paradox," has likely been overestimated, and if resveratrol or similar compounds are proven useful against cardiovascular disease, a supplement (or drug) rather diet is likely to be the source .
Resveratrol is also available from supplement pills and liquids, in which it is sometimes combined with vitamins and/or other ingredients. It is also an ingredient in topical skin creams. The supplements are generally labeled as containing from 20 to 500 mg per tablet or capsule. However, the purity of these products is unknown. And, because dietary supplements are loosely regulated, it should not be assumed that the labeled dosage is accurate.
Many studies suggest that consuming alcohol (especially red wine) may reduce the incidence of coronary heart disease (CHD). Several studies have demonstrated that resveratrol has antioxidant properties. It is claimed that because it contains highly hydrophilic and lipophilic properties, it may provide more effective protection than other well-known antioxidants, such as vitamins C and E. On the other hand, it is less effective than the antioxidants quercetin and epicatechin found in red wine. Reduced platelet aggregation has also been demonstrated in studies on resveratrol, which could contribute to prevention of atherosclerosis. Prior to 2010, however, most of the research on resveratrol's antioxidant and anti-platelet properties was done using test-tube or tissue-culture preparations. Since that time, some human trials have been conducted, but the evidence is not yet sufficient to draw practical conclusions.
Many studies have found that resveratrol can affect the initiation, promotion, and progression of cancer, which has raised hopes that it has potential for both prevention and treatment. A recent review concluded that it is not a good drug candidate because it lacks potency, high efficacy, and target specificity. But researchers hope that similarly-structured derivatives can be found that will be useful.
Studies in laboratory mice have found increased survival and lower incidence of several diseases and conditions associated with aging, but the results are contradictory. Protective effects have been found in mice fed a high-fat or a low-calorie diet, but one study found that mice fed a standard diet beginning at age 12 months did not live longer. In 2009, after reviewing the animal studies, the highly respected Medical Letter concluded: "Resveratrol appears to produce some of the same effects as calorie-restricted diets that have reduced the incidence of age-related diseases in animals. Whether it has any benefit in humans remains to be established."
One of the mouse studies was reported in a New York Times article which described how a researcher was taking resveratrol himself and had founded Sirtris Pharmaceuticals to develop chemicals that mimic the role of resveratrol but at much lower doses. GlaxoSmithKline acquired Sirtris for $720 million in 2008 and hopes to develop drugs that target the sirtuins, a group of enzymes associated with the aging process . However, a spokesperson said recently that the company is focused on compounds other than resveratrol that can activate sirtuins .
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