Resveratrol-What's all the hype about?

Resveratrol is a compound found largely in the skins of red grapes. It has gained a large amount of media attention and has been touted as having many beneficial effects on one’s health. Resveratrol 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.”

If one does a search of the literature and looks at well-accepted peer review journals, there is very little published to support any of these highly acclaimed effects of resveratrol. Research done by both Amgen and Pfizer and cast doubt on the manner in which the health supplement is said to work. Prominent researchers supposed that it worked by activating a certain gene, SIRT1. This activation is thought to produce the benefits of a caloric restriction diet even among those with high fat and high caloric intake. In 2009, Amgen scientists published in a volume of Chemical Biology and Drug Design, experimental results that indicate resveratrol does not, in fact, activate SIRT1. Pfizer scientists, in the Journal of Biological Chemistry in 2010 offers similar results, showing that resveratrol (and related substances such as SRT1720) do not active SIRT1 and did not reduce blood sugar in mice fed a high fat diet. Thus, to translate any mice studies into human studies is not possible and it may be that resveratrol doesn’t work at all. Despite what is heard on many of the nationally watched television shows on health, none of the claims have been every demonstrated in any valid human study.

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. 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 is the object of much speculation and research. 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 since dietary supplements are loosely regulated, it should not be assumed that the labeled dosage is accurate.

The anti-aging effects of resveratrol are also being studied. Recent 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. One of the studies was reported in a New York Times article that described how a researcher was taking resveratrol himself and had founded a pharmaceutical company to develop chemicals that mimic the role of resveratrol but at much lower doses. GlaxoSmithKline acquired his company, Sirtris for $720 million in 2007 and hopes to develop "drugs that target the sirtiuns, a recently discovered family of seven enzymes associated with the aging process." 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." Another supplement named Protandim, which contains mainly green tea extract and tumeric, has been shown to reduce TBARS(a measure of cellular oxidative stress) by 40% in human subjects, Decreasing cellular oxidative stress could also have profound anti-aging effects, but the long term results on humans for both Resveratrol and Protandim may never be known unless long term prospective human studies are performed.

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 resveratrol contains highly hydrophilic(water loving) and lipophilic(water hating) properties, it may provide more effective protection than other well-known antioxidants such as vitamin 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 To date, however, most of the research on resveratrol's antioxidant and anti-platelet properties has been done using test-tube or tissue-culture preparations and none have been tested in human trials. In addition, alcohol consumption raises triglyceride levels in the blood stream. Besides the negative effect on the cardiovascular profile, alcohol use and high triglycerides can cause pancreatitis.

Resveratrol is also being studied to see how it affects the initiation, promotion, and progression of cancer. With regard to tumor initiation, it has been shown to act as an antioxidant by inhibiting free radical formation and as an anti-mutagen in rat models. Studies related to progression have found that resveratrol induced human promyelocytic leukemia cell differentiation,inhibited enzymes that promote tumor growth, and exerted antitumor effects in neuroblastomas( the most common solid tumor in childhood). In animal studies, resveratrol was effective against tumors of the skin, breast, gastrointestinal tract, lung, and prostate gland. A recent review concluded that during the last decade, resveratrol has been shown to possess a fascinating spectrum of pharmacologic properties. Multiple biochemical and molecular actions seem to contribute to resveratrol effects against precancerous or cancer cells. Resveratrol affects all three discrete stages of carcinogenesis (initiation, promotion, and progression) by modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis, and metastasis. The anticancer property of resveratrol has been supported by its ability to inhibit proliferation of a wide variety of human tumor cells in vitro(in a test-tube), however, it’s role as a potentiator of breast cancer may limit it’s clinical use. Numerous preclinical animal studies to evaluate the potential of this drug for cancer chemo-prevention and chemotherapy are currently underway.

In summary, epidemiologic studies can find associations between the consumption of foods or dietary supplements and various health outcomes. Animal experiments can demonstrate what can happen in the species tested. However, only human clinical trials can determine whether supplementation is useful for humans. Resveratrol has not been tested in human clinical trials, and most clinical trials of other antioxidants have failed to demonstrate the benefits suggested by preliminary studies. Some substances—most notably beta- carotene—have even produced adverse effects.

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