• Resveratrol

    Supplement Forms/Alternate Names :

    • Grape Skin

    Uses

    Principal Proposed Uses

    • None

    Other Proposed Uses

    You may have heard of the "French paradox." The French diet is very high in saturated fat and cholesterol (just think of pate de fois gras and croissants), yet France has one of the world's lowest rates of heart disease. One theory for this apparent discrepancy is that another major player in the French diet—red wine—protects the arteries of the heart. (Another possibility, perhaps even more likely, is that cutting down on saturated fat is less helpful than previously thought. See the High Cholesterol article and the Antioxidant article for more information.)
    Resveratrol is a natural antioxidant found in red wine. Antioxidants protect cells in the body from damage by free radicals, naturally occurring but harmful substances that are thought to play a role in cardiovascular disease . Resveratrol is also a phytoestrogen, a substance that mimics some of the effects of estrogen, while blocking others. Soy , another phytoestrogen, is thought to help prevent heart disease as well as cancer, and resveratrol might have similar effects. However, as yet none of these potential benefits of resveratrol have been documented in any meaningful way, and there is some evidence that resveratrol taken by mouth is broken down before it enters the bloodstream.

    Sources

    Resveratrol is not an essential nutrient. It is found in red wine as well as in red grape skins and seeds and purple grape juice. Peanuts also contain a small amount of resveratrol. Resveratrol supplements are available as well.

    Therapeutic Dosages

    Because there haven't been any clinical studies, the optimal therapeutic dosage hasn't been established for resveratrol. Based on animal studies, a reasonable therapeutic dosage might be about 500 mg daily.

    Therapeutic Uses

    Very preliminary evidence, such as the results of test tube studies , suggests that resveratrol may help prevent heart disease , 2-5 and cancer . 9-14 However, not all studies have been favorable. 6,7,8,15 Furthermore, there is some evidence that resveratrol is immediately broken down by the human liver, and thereby does not, in fact, enter the blood stream at any significant level. 16 In any case, only double-blind studies can prove a treatment effective, and none have been reported with resveratrol. (For information on why such studies are essential, see Why Does This Database Rely on Double-Blind Studies? )

    Safety Issues

    Resveratrol has a chemical structure similar to that of the synthetic estrogenic hormone diethylstilbestrol and it has estrogenic effects. According to one study, it might stimulate the growth of breast cancer cells. 15 For this reason, resveratrol should be avoided by women who have had breast cancer or are at high risk of developing it. Maximum safe dosages for children, pregnant or nursing women, or those with severe liver or kidney disease have not been determined.

    References

    1 Gehm BD, McAndrews JM, Chien PY, et al. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci U S A . 1997;94:14138-14143.

    2 Goldberg DM. More on antioxidant activity of resveratrol in red wine [letter]. Clin Chem . 1996;42:113-114.

    3 Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine. Am J Enol Vitic. 1992;43:49-52.

    4 Kopp P. Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the ‘French paradox’? Eur J Endocrinol . 1998;138:619-620.

    5 Rotondo S, Rajtar G, Manarini S, et al. Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function. Br J Pharmacol . 1998;123:1691-1699.

    6 Turrens JF, Lariccia J, Nair MG. Resveratrol has no effect on lipoprotein profile and does not prevent peroxidation of serum lipids in normal rats. Free Radic Res . 1997;27:557-562.

    7 Pace-Asciak CR, Rounova O, Hahn SE, et al. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clin Chim Acta. 1996;246:163-182.

    8 Wilson T, Knight TJ, Beitz DC, et al. Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits. Life Sci . 1996;59:PL15-PL21.

    9 Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science . 1997;275:218-220.

    10 Mgbonyebi OP, Russo J, Russo IH. Antiproliferative effect of synthetic resveratrol on human breast epithelial cells. Int J Oncol . 1998;12:865-869.

    11 Subbaramaiah K, Chung WJ, Michaluart P, et al. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem . 1998;273:21875-21882..

    12 Clement MV, Hirpara JL, Chawdhury SH, et al. Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells. Blood . 1998;92:996-1002.

    13 Johnson JL, Maddipati KR. Paradoxical effects of resveratrol on the two prostaglandin H synthases. Prostaglandins Other Lipid Mediat . 1998;56:131-143.

    14 ElAttar TM, Virji AS. Modulating effect of resveratrol and quercetin on oral cancer cell growth and proliferation. Anticancer Drugs. 1999;10:187-193.

    15 Gehm BD, McAndrews JM, Chien PY, et al. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci U S A . 1997;94:14138-14143.

    16 Walle T, Hsieh F, DeLegge MH et al. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos . 2004;32:1377-82.

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