OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Resveratrol – Generic

DRUG CLASS

Herbal and Dietary Supplements

SUMMARY INFORMATION

Fact Sheet at MedlinePlus, NLM

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Resveratrol	501-36-0	C14-H12-O3

ANNOTATED SELECTIVE BIBLIOGRAPHY

References updated: 30 November 2024

Abbreviations used: HDS, herbal and dietary supplements.

• Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 731-4.

  (Expert review of hepatotoxicity published in 1999; several herbal medications are discussed, but not resveratrol).
• Seeff L, Stickel F, Navarro VJ. Hepatotoxicity of herbals and dietary supplements. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 631-58.

  (Review of hepatotoxicity of herbal and dietary supplements; no mention of resveratrol).
• Resveratrol. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007: pp. 19-26.

  (Compilation of short monographs on herbal medications and dietary supplements).
• Stedman C. Herbal hepatotoxicity. Semin Liver Dis 2002; 22: 195-206. [PubMed: 12016550]

  (Review and description of patterns of liver injury, including discussion of potential risk factors, and herb-drug interactions).
• Schiano TD. Hepatotoxicity and complementary and alternative medicines. Clin Liver Dis 2003; 7: 453-73. [PubMed: 12879994]

  (Comprehensive review of herbal associated hepatotoxicity, including common patterns of presentation).
• Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444: 337-42. [PMC free article: PMC4990206] [PubMed: 17086191]

  (In mice fed a high caloric diet long term, resveratrol [22 mg/kg/day] supplementation increased life span, improved insulin sensitivity, and decreased hepatic fat).
• Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschöp MH. Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci USA 2008; 105: 9793-8. [PMC free article: PMC2474520] [PubMed: 18599449]

  (Mice with overexpression of SIRT1 were protected from the metabolic effects of a high fat diet, and had improved insulin sensitivity and less hepatic fat and inflammation with lower levels of inflammatory cytokines and higher antioxidant enzymes).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, 9% of cases were attributed to herbal medications, but no case attributed to resveratrol alone or in combination with other agents).
• García-Cortés M, Borraz Y, Lucena MI, Peláez G, Salmerón J, Diago M, Martínez-Sierra MC, et al. [Liver injury induced by "natural remedies": an analysis of cases submitted to the Spanish Liver Toxicity Registry]. Rev Esp Enferm Dig 2008; 100: 688-95. Spanish. [PubMed: 19159172]

  (Among 521 cases of drug induced liver injury submitted to Spanish registry, 13 [2%] were due to herbals; none were due to resveratrol).
• Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009; 29: 373-382. [PubMed: 19826971]

  (Overview of the regulatory environment, clinical patterns, and future directions in research with HDS; resveratrol is not listed as a potential hepatotoxin).
• Jacobsson I, Jönsson AK, Gerdén B, Hägg S. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden. Pharmacoepidemiol Drug Saf 2009; 18: 1039-47. [PubMed: 19650152]

  (Review of 778 spontaneous reports of adverse reactions to herbals to Swedish Registry; no instance was linked to resveratrol).
• Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, et al. Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res 2009 May; 53 Suppl 1: S7-15. [PubMed: 19194969]

  (Pharmacokinetic study of 4 doses of resveratrol vs placebo given every 4 hours for 48 hours in 40 volunteers; side effects included headache, dyspepsia and dizziness; "no clinically significant abnormalities were found in the laboratory parameters").
• Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, et al. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 2010; 70: 9003-11. [PMC free article: PMC2982884] [PubMed: 20935227]

  (Pharmacokinetic study of 4 doses of resveratrol [0.5-4 gm daily] for 29 days in 40 volunteers found occasional minor abdominal discomfort, nausea, diarrhea, flatulence and dizziness with higher doses, but no serious adverse events).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 [11%] were attributed to drug induced liver injury, of which 12 [9%] were due to herbals, including several herbal mixtures, usnic acid, Ma Huang, black cohosh, and Hydroxycut, but not resveratrol).
• Bishayee A, Darvesh AS, Politis T, McGory R. Resveratrol and liver disease: from bench to bedside and community. Liver Int 2010; 30: 1103-14. [PubMed: 20557453]

  (Extensive review of the in vitro and in vivo studies of resveratrol as a hepatoprotective agent against several forms of experimental liver injury, and the challenges of clinical studies of resveratrol in humans).
• Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health – A comprehensive review of human clinical trials. Mol Nutr Food Res 2011; 55: 1129-41. [PubMed: 21688389]

  (Review of the literature on pharmacokinetics, efficacy and safety of resveratrol in humans; few studies have been done, but none have reported severe adverse events or significant toxicities).
• Howells LM, Berry DP, Elliott PJ, Jacobson EW, Hoffmann E, Hegarty B, Brown K, et al. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases—safety, pharmacokinetics, and pharmacodynamics. Cancer Prev Res (Phila) 2011; 4: 1419-25. [PMC free article: PMC3173869] [PubMed: 21680702]

  (9 subjects scheduled to undergo hepatectomy for cancer metastases were given a micronized resveratrol [5 gm/day] or placebo for 14 days; peak plasma levels were variable and achieved in 2-4 hours with plasma half-life of 1 hour, and detectable levels in tissue at surgery).
• Walle T. Bioavailability of resveratrol. Ann N Y Acad Sci 2011; 1215: 9-15. [PubMed: 21261636]

  (Resveratrol exists as trans and cis isomers and is well absorbed orally but is rapidly metabolized by intestine and liver to sulfate and glucuronide conjugates).
• Yoshino J, Conte C, Fontana L, Mittendorfer B, Imai S, Schechtman KB, Gu C, Kunz I, et al. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab 2012; 16: 658-64. [PMC free article: PMC3496026] [PubMed: 23102619]

  (Controlled study of resveratrol [75 mg/day] vs placebo in 29 normal volunteers, found no change in weight, insulin sensitivity, serum enzyme levels or in SIRT1 expression [in muscle and adipose tissue] or AMP-K activity [in muscle tissue] after 12 weeks of therapy).
• Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int 2012; 32: 1543-56. [PubMed: 22928722]

  (A systematic compilation of all publications on the hepatotoxicity of specific herbals identified 185 publications on 60 different herbs, herbal drugs and supplements; none implicated resveratrol).
• Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, Reddy KR, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology 2014; 60:1399-408. [PMC free article: PMC4293199] [PubMed: 25043597]

  (Among 85 cases of HDS associated liver injury enrolled in a US prospective study between 2004 and 2013, resveratrol was not implicated in any case).
• Chachay VS, Macdonald GA, Martin JH, Whitehead JP, O'Moore-Sullivan TM, Lee P, Franklin M, et al. Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014;12:2092-2103. [PubMed: 24582567]

  (Among 20 overweight or obese men with hepatic steatosis treated with resveratrol [1500 mg] or placebo twice daily for 8 weeks, there was no change in body weight, hepatic steatosis, fasting blood glucose or lipid levels, while serum ALT and AST increased [median ALT rising from 25 to 63 U/L, AST from 35 to 45 U/L], with minimal increases in serum bilirubin and cytokeratin 18 but no symptoms; these changes were attributed to the high doses used).
• Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, Brewer JB, et al; Alzheimer's Disease Cooperative Study. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 2015; 85: 1383-91. [PMC free article: PMC4626244] [PubMed: 26362286]

  (Among 119 patients with Alzheimer disease treated with resveratrol [500 mg increasing to as much as 2000 mg daily] vs placebo for 52 weeks, there was no improvement in clinical or radiologic features and adverse event rates were similar between the 2 groups; no mention of ALT levels except that "routine laboratory tests were normal").
• Yiu EM, Tai G, Peverill RE, Lee KJ, Croft KD, Mori TA, Scheiber-Mojdehkar B, et al. An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels. J Neurol 2015; 262: 1344-53. [PubMed: 25845763]

  (Among 24 patients with Friedreich ataxia treated with resveratrol [1 gm vs 5 gm daily] for 12 weeks, adverse events more frequent with the higher dose included diarrhea [71% vs 8%], nausea [36% vs 8%] and skin rash [29% vs none], and 1 subject developed liver test abnormalities 4 weeks after starting high dose resveratrol [bilirubin not provided, ALT <2 times ULN, Alk P 4 times ULN], resolving 8 weeks after stopping).
• Chen S, Zhao X, Ran L, Wan J, Wang X, Qin Y, Shu F, et al. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Dig Liver Dis 2015; 47: 226-32. [PubMed: 25577300]

  (Among 60 patients with nonalcoholic fatty liver disease treated with resveratrol [300 mg twice daily] vs placebo for 3 months, median ALT levels decreased by 7 vs 1 U/L in placebo recipients, while ultrasound graded hepatic fat did not change).
• García-Cortés M, Robles-Díaz M, Ortega-Alonso A, Medina-Caliz I, Andrade RJ. Hepatotoxicity by dietary supplements: A tabular listing and clinical characteristics. Int J Mol Sci 2016; 17: 537. [PMC free article: PMC4848993] [PubMed: 27070596]

  (Listing of published cases of liver injury from HDS products, does not list resveratrol).
• Heebøll S, Kreuzfeldt M, Hamilton-Dutoit S, Kjær Poulsen M, Stødkilde-Jørgensen H, Møller HJ, Jessen N, et al. Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease. Scand J Gastroenterol. 2016;51:456-64. [PubMed: 26784973]

  (Among 28 adults with fatty liver and raised serum ALT levels treated with resveratrol [500 mg] or placebo 3 times daily for 6 months, there were no differences in changes in body weight, hepatic steatosis, blood glucose levels, lipids, and serum ALT and AST levels between the two arms; 1 treated patient developed fever and lymphopenia that resolved on stopping and recurred on restarting and another developed an asymptomatic rise in ALT levels [from 150 to ~380 U/L] that resolved despite continuing therapy).
• Brown AC. Liver toxicity related to herbs and dietary supplements: online table of case reports. Part 2 of 5 series. Food Chem Toxicol 2017; 107: 472-501. [PubMed: 27402097]

  (Description of an online compendium of cases of liver toxicity attributed to HDS products does not list or discuss resveratrol).
• Medina-Caliz I, Garcia-Cortes M, Gonzalez-Jimenez A, Cabello MR, Robles-Diaz M, Sanabria-Cabrera J, Sanjuan-Jimenez R, et al.; Spanish DILI Registry. Herbal and dietary supplement-induced liver injuries in the Spanish DILI Registry. Clin Gastroenterol Hepatol. 2018;16:1495-1502. [PubMed: 29307848]

  (Among 856 cases of hepatotoxicity enrolled in the Spanish DILI Registry between 1994 and 2016, 32 were attributed to herbal products, the most frequent cause being green tea [n=8] and Herbalife products [n=6], no mention of resveratrol).
• Asghari S, Rafraf M, Farzin L, Asghari-Jafarabadi M, Ghavami SM, Somi MH. Effects of pharmacologic dose of resveratrol supplementation on oxidative/antioxidative status biomarkers in nonalcoholic fatty liver disease patients: a randomized, double-blind, placebo-controlled Trial. Adv Pharm Bull. 2018;8:307-317. [PMC free article: PMC6046420] [PubMed: 30023333]

  (Among 60 overweight or obese adults with nonalcoholic fatty liver treated with resveratrol [600 mg] or placebo daily for 12 weeks, there were no significant changes in markers of oxidative stress or in serum levels of ALT, AST, Alk P or GGT; no mention of adverse events or individual elevations in serum ALT or AST).
• Kantartzis K, Fritsche L, Bombrich M, Machann J, Schick F, Staiger H, Kunz I, et al. Effects of resveratrol supplementation on liver fat content in overweight and insulin-resistant subjects: A randomized, double-blind, placebo-controlled clinical trial. Diabetes Obes Metab. 2018;20:1793-1797. [PubMed: 29484808]

  (Among 108 overweight or obese adults with fatty liver and insulin resistance treated with resveratrol [150 mg] or placebo daily for 12 weeks, there were no significant differences in changes in total, liver, or visceral fat [by magnetic resonance spectroscopy], fasting glucose or HbA1c levels, HOMA-IR, blood pressure, or liver enzymes levels between the two groups).
• Ballotin VR, Bigarella LG, Brandão ABM, Balbinot RA, Balbinot SS, Soldera J. Herb-induced liver injury: Systematic review and meta-analysis. World J Clin Cases. 2021;9:5490-5513. [PMC free article: PMC8281430] [PubMed: 34307603]

  (Systematic review of the literature on herb induced liver injury identified 446 references describing 936 cases due to 79 different herbal products, the most common being He Shou Wu [91], green tea [90] Herbalife products [64], kava kava [62], and greater celandine [48]; no mention of resveratrol).
• Bessone F, García-Cortés M, Medina-Caliz I, Hernandez N, Parana R, Mendizabal M, Schinoni MI, et al. Herbal and dietary supplements-induced liver injury in Latin America: experience from the LATINDILI Network. Clin Gastroenterol Hepatol. 2022;20:e548-e563. [PubMed: 33434654]

  (Among 367 cases of hepatotoxicity enrolled in the Latin American DILI Network between 2011 and 2019, 29 [8%] were attributed to herbal products, the most frequent being green tea [n=7], Herbalife products [n=5] and garcinia [n=3], while resveratrol was not mentioned).
• Kasprzak-Drozd K, Niziński P, Kasprzak P, Kondracka A, Oniszczuk T, Rusinek A, Oniszczuk A. Does resveratrol improve metabolic dysfunction-associated steatotic liver disease (MASLD)? Int J Mol Sci. 2024;25:3746. [PMC free article: PMC11012111] [PubMed: 38612556]

  (Resveratrol showed promising effects in vitro and in animal models of nonalcoholic steatohepatitis [NASH], possibly by inhibiting the NF-κB pathway, activating SIRT1 and AMP kinase, modifying the microbiome, or decreasing inflammation; but clinical studies “have yielded inconclusive results”).
• Keramatzadeh S, Hosseini SA, Majdinasab N, Cheraghian B, Zilaee M. Effects of resveratrol supplementation on inflammatory markers, fatigue scale, fasting blood sugar and lipid profile in relapsing-remitting multiple sclerosis patients: a double-blind, randomized placebo-controlled trial. Nutr Neurosci. 2024:1-9. Epub ahead of print. [PubMed: 39565038]

  (Among 55 patients with multiple sclerosis treated with resveratrol [500 mg] vs placebo daily for 8 weeks, there were significant decreases in serum malondialdehyde and tumor necrosis factor alpha levels with treatment but no significant changes in fatigue, food intake, body weight, lipids or glucose levels compared to placebo; no mention of adverse events, ALT levels, or hepatotoxicity).
• Ahmadi-Mousavi B, Karami-Mohajeri S, Dabaghzadeh F, Soltani M, Oghabian Z, Sharifi H. The effects of resveratrol in a randomized clinical trial on drug-induced hyperlipidemia and psychiatric factors in people living with HIV. Curr HIV Res. 2024 Nov 8. Epub ahead of print. [PubMed: 39528454]

  (Among 41 adults with HIV infection treated with resveratrol [500 mg] or placebo once daily for one month, there were no differences in changes in cholesterol or triglyceride levels or in symptoms or measures of quality of life and sleep quality; no mention of adverse events or ALT levels).
• Nguyen C, Coudeyre E, Boutron I, Baron G, Daste C, Lefèvre-Colau MM, Sellam J, et al. Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL). PLoS Med. 2024;21:e1004440. [PMC free article: PMC11321588] [PubMed: 39137167]

  (Among 142 patients with painful knee osteoarthritis treated with resveratrol [40 mg] or placebo twice daily for 6 months, there were no differences in knee pain between the two groups, and total and severe adverse events rates were similar, with none judged to be related to the intervention; no mention of ALT levels or hepatotoxicity).
• Erol Doğan Ö, Karaca Çelik KE, Baş M, Alan EH, Çağın YF. Effects of Mediterranean diet, curcumin, and resveratrol on mild-to-moderate active ulcerative colitis: a multicenter randomized clinical trial. Nutrients. 2024;16:1504. [PMC free article: PMC11123867] [PubMed: 38794742]

  (Among 48 patients with ulcerative colitis placed on a “Mediterranean diet” and treated with curcumin [1600 mg], resveratrol [500 mg] or placebo daily for 8 weeks, improvements in CRP and sedimentation rate and in health related quality of life and inflammatory bowel disease symptom scores occurred in all three groups with no additional effects in those receiving resveratrol or curcumin; no mention of adverse events or ALT levels).