About Herbs, Botanicals & Other Products

Scientific Name
3,5,4'-trihydroxystilbene
Top
Clinical Summary

Resveratrol is a polyphenolic compound found in the skins of red grapes. It is also found in peanuts, mulberries, spruce, eucalyptus, and some Chinese herbs. Resveratrol has antioxidant and anti-inflammatory properties as evidenced by its cardioprotective effects. It reduces the oxidation of low density lipoproteins (LDL) and inhibits aggregation of platelets and may offer protection against atherogenesis and coronary heart disease (1) (2). In addition, resveratrol enhanced the longevity in preliminary studies of yeast cells (17) (18). It was also shown to cause an increase in cerebral blood flow in healthy volunteers while performing cognitive tasks (22).
Resveratrol was also shown to protect against cisplatin-induced cardiotoxicity via suppression of oxidative stress (21).

Several cell culture and animal studies show that resveratrol inhibits proliferation of cancer cells via apoptosis and by exerting anti-estrogenic effects (3) (4) (5) (6). However, contradictory data from other studies showed that it acts as a phytoestrogen and could activate genes that are normally regulated by estrogen (7) or androgen (8). Resveratrol was found to inactivate some enzymes of the CYP450 family in tumor cells (9) (10). Therefore cancer patients with hormone-sensitive diseases, such as estrogen receptor-positive breast cancer and prostate cancer should avoid resveratrol as it may stimulate the proliferation of certain tumor cells.

Top
Food Sources
  • Grape skin
  • Peanuts
  • Mulberries
  • Spruce
  • Eucalyptus
  • Polygonum cuspidatum or Japanase knowtweed
Top
Purported Uses
  • Atherosclerosis
  • Cancer prevention
  • Coronary heart disease
  • Inflammation
Top
Mechanism of Action

Resveratrol acts as an antioxidant and inhibits the oxidation of low density lipoproteins (LDL) (1), the aggregation of platelets, and eicosanoid synthesis (2) and induces platelet nitric oxide (NO) production (11), which may help protect against atherosclerosis and coronary heart disease. It also acts as an anti-inflammatory agent by inhibiting cyclooxygenase (COX) activity (12) and by releasing cytokines from macrophages in chronic obstructive pulmonary disease (COPD) (13). Laboratory studies show that resveratrol has estrogen-like properties and activates expression of genes that are regulated by estrogen (7) and androgen (8). Preliminary data suggest that resveratrol may have a role in increasing life span in yeast cells, which it does by activating a set of genes known as sirtuins (17) (18).

Other data from cell culture and animal experiments suggest that it plays a role in cancer chemoprevention during initiation, promotion, and progression of carcinogenesis (12) (14). In vivo studies also demonstrate the inhibitory effects of resveratrol on the growth of oral squamous carcinoma cells (4), human promyelocytic leukemia cells (6), human breast cancer cells (5), and neuroblastoma cells (3) resulting from induction of apoptosis and its anti-estrogenic properties. In addition, reduction in breast cancer cell migration and invasion was observed after treatment with resveratrol (15) (16). Resveratrol also inhibited the enzymes CYP1A1, CYP1A2, and CYP1B1 in tumor cells. This may be one of the mechanisms by which it exerts anti-tumor effects as some of these enzymes are known to be involved in the activation of procarcinogens and toxins (9) (10).

Top
Pharmacokinetics

Upon oral administration, resveratrol is rapidly absorbed in the gastrointestinal tract and undergoes glucoronidation and sulfation in the liver microsomes. After 1.5 h, peak plasma levels of resveratrol were detected (19). Resveratrol is rapidly excreted; more than 50% of the ingested resveratrol is eliminated in urine in 24 hrs (20).

Top
Contraindications

As resveratrol exhibits estrogen-like properties and activates transcription by estrogen receptor and androgen receptor that leads to stimulation of cancer cell proliferation, patients with hormone-sensitive cancers should avoid resveratrol (7).

Top
Herb-Drug Interactions
  • Antiplatelet drugs: Because resveratrol inhibits platelet aggregation, concurrent use of other antiplatelet drugs may increase the risk of bleeding.
  • Cytochrome P450 substrates: Resveratrol inhibits CYP3A4, CYP2D6, CYP2C9, and induces CYP1A2, thereby affecting the levels of drugs that are metabolized by these enzymes (23).
Top
References
  1. Fauconneau B, et al. Comparative study of radical scavenger and antioxidant properties of phenolic compounds from Vitis vinifera cell cultures using in vitro tests. Life Sci 1997; 61(21):2103-2110.
  2. Pace-Asciak CR, et al. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 1995; 235(2):207-219.
  3. Chen Y, et al. Resveratrol-induced cellular apoptosis and cell cycle arrest in neuroblastoma cells and antitumor effects on neuroblastoma in mice. Surgery 2004; 136(1):57-66.
  4. ElAttar TM and Virji AS. Modulating effect of resveratrol and quercetin on oral cancer cell growth and proliferation. Anticancer Drugs 1999; 10(2):187-193.
  5. Lu R and Serrero G. Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. J Cell Physiol 1999; 179(3):297-304.
  6. Surh YJ, et al. Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HL-60) cells. Cancer Lett 1999; 140(1-2):1-10.
  7. Gehm BD, et al. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci USA 1997; 94(25):14138-14143.
  8. Wang TT, Hudson TS, Wang TC, et al. Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo. Carcinogenesis. Oct 2008;29(10):2001-2010.
  9. Chen ZH, et al. Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Carcinogenesis 2004; 25(10):2005-2013.
  10. Liu J, et al. Differential regulation of CYP1A1 and CYP1B1 expression in resveratrol-treated human medulloblastoma cells. Neurosci Lett 2004; 363(3):257-261.
  11. Gresele P, Pignatelli P, Guglielmini G, et al. Resveratrol, at concentrations attainable with moderate wine consumption, stimulates human platelet nitric oxide production. J Nutr. Sep 2008;138(9):1602-1608.
  12. Jang M, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997; 275(5297):218-220.
  13. Culpitt SV, et al. Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD. Thorax 2003; 58(11):942-946.
  14. Aggarwal BB, et al. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 2004; 24(5A):2783-2840.
  15. Tang FY, Su YC, Chen NC, et al. Resveratrol inhibits migration and invasion of human breast-cancer cells. Mol Nutr Food Res. Jun 2008;52(6):683-691.
  16. Tang FY, Chiang EP, Sun YC. Resveratrol inhibits heregulin-beta1-mediated matrix metalloproteinase-9 expression and cell invasion in human breast cancer cells. J Nutr Biochem. May 2008;19(5):287-294.
  17. Hall SS. Longevity research. In vino vitalis? Compounds activate life-extending genes. Science 2003; 301(5637):1165.
  18. Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003; 425(6954):191-196.
  19. Boocock DJ, Faust GE, Patel KR, et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev. Jun 2007;16(6):1246-1252.
  20. Meng X, et al. Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. J Agric Food Chem 2004; 52(4):935-942.
  21. Wang J, He D, Zhang Q, et al. Resveratrol protects against Cisplatin-induced cardiotoxicity by alleviating oxidative damage. Cancer Biother Radiopharm. 2009 Dec;24(6):675-80.
  22. Kennedy DO, Wightman EL, Reay JL, et al. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010 Jun;91(6):1590-7.
  23. Chow HH, Garland LL, Hsu CH, et al. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res (Phila Pa). 2010 Sep;3(9):1168-75.
Top
How It Works

Bottom Line: In laboratory studies, resveratrol was found to reduce inflammation and to have antitumor properties, but human studies have not been conducted.

A naturally occurring compound in the skin of red grapes and other botanicals, resveratrol has been shown to reduce inflammation. It also has antioxidant properties and may help to protect against atherosclerosis (thickening of arterial walls) and heart disease. Animal studies have shown that resveratrol has the ability to prevent certain cancer cells from dividing.

Top
Purported Uses
  • Atherosclerosis
    Laboratory studies have shown that resveratrol helps in preventing atherosclerosis.
  • Coronary heart disease
    There is limited scientific evidence to support this use.
  • Cancer prevention
    Several laboratory studies have demonstrated the ability of resveratrol in preventing growth of cancer cells. However, it is not clear if similar effects will be seen in humans.
  • Inflammation
    This use is supported by data from laboratory studies.
Top
Research Evidence

Clinical trials have not been conducted to test the efficacy of resveratrol in humans.

Top
Do Not Take If
  • You are taking antiplatelet drugs (resveratrol may increase the risk of bleeding).
  • If you are taking drugs that are substrates of Cytochrome P450 (Resveratrol may increase the risk of side effects of some drugs and make others less effective).
Top
Side Effects

Women who have estrogen receptor-positive cancers should not take resveratrol because it may cause certain cancer cells to multiply.

Top
E-mail your questions and comments to aboutherbs@mskcc.org.
Last updated: May 9, 2011