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Drugs and Health Products

Resveratrol (Under Consultation)

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient.

Notes

  • By submitting a PLA referencing this monograph, the applicant is attesting that the product will comply fully with the recommended conditions of use outlined in this monograph. The conditions of use include methods of preparations, source materials, doses, durations of use, combinations of medicinal ingredients, and risk statements.
  • Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant's discretion.
  • The solidus (/) indicates that the terms and/or the statements are synonymous. Either term or statement may be selected by the applicant.

Date

March 7, 2014

Proper name(s)

  • trans-Resveratrol (Merck 2012)
  • (E)-5-(p-Hydroxystyryl)resorcinol (Merck 2012)
  • 5-[(1E)-2-(4-Hydroxyphenyl)ethenyl]-1,3-benzenediol (Merck 2012)

Common name(s)

Resveratrol (Merck 2012)

Source material(s)

  • Reynoutria japonica Houtt. - Root (Merck 2012; USDA 2011)
    (synonyms : Fallopia japonica Houtt.; Polygonum reynoutria Makino; Polygonum cuspidatum Siebold & Zucc.)
  • Vitis vinifera L. - Fruit (Bertelli and Das 2009; USDA 2009; Dani et al. 2007)
  • Synthetic (La Porte et al. 2010)

Route(s) of Administration

Oral

Dosage Form(s)

  • The acceptable pharmaceutical dosage forms include, but are not limited to capsules, chewables (e.g. gummies, tablets), liquids, powders, strips or tablets.
  • This monograph is not intended to include foods or food-like dosage forms such as bars, chewing gums or beverages.

Use or Purpose

Statement(s) to the effect of:

Provides antioxidants (Ghanim et al. 2010; Rocha et al. 2009).

Dose(s)

Statement(s) to the effect of:

Subpopulation(s)

Adult (≥ 18 years)

Quantity(ies)

Up to 1g resveratrol, per day (Cottart et al. 2013; Brown et al. 2010; Gaby 2006)

Duration of use

Statement(s) to the effect of:

Products providing more than 250 mg resveratrol per day:
For prolonged use, consult a health care practitioner (Vang et al. 2010)

Risk information

Statement(s) to the effect of:

Caution(s)/Warning(s)

  • If you are pregnant or breastfeeding, consult a health care practitioner prior to use.
  • If you are taking prescription medication, consult a healthcare practitioner prior to use as resveratrol may alter the effectiveness of these medications (Bransyo et al. 2011; Chow et al. 2010).

Contraindication(s)

No statement required

Known adverse reaction(s)

Products providing ≥ 0.5g of resveratrol per day:
May cause nausea, abdominal pain, and/or diarrhea (Brown et al. 2010; Chow et al. 2010).

Non-medicinal ingredients

Must be chosen from the current NNHPD Natural Health Products Ingredients Database (NHPID) and must meet the limitations outlined in the database.

Specifications

References cited

  • Almeida L, Vaz-da-Silva M, Falcăo A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P. Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Molecular Nutrition & Food Research 2009;53 (1):S7-S15
  • Bertelli AA, Das DK. Grapes, wines, resveratrol, and heart health. Journal of Cardiovascular Pharmacology 2009;54(6):468-476.
  • Bhatt, JK, Thomas, S, Nanjan, MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutrition Research 2012;32(7):537-541.
  • Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, Mikolás E, Szijártó IA, Mérei A, Halmai R, Mészáros LG, Sümegi B, Wittmann. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. British Journal of Nutrition 2011;106(3):383-389.
  • Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher AJ, Brenner DE. Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in Healthy Volunteers: Safety, Pharmacokinetics, and Effect on the Insulin-like Growth Factor Axis. Cancer Research 2010; 70(22):9003-9011.
  • Chow HH, Garland LL, Hsu CH, Vining DR, Chew WM, Miller JA, Perloff M, Crowell JA, Alberts DS. Resveratrol Modulates Drug- and Carcinogen-Metabolizing Enzymes in a healthy Volunteer Study. Cancer Prevention Research 2010;3:1168-1175.
  • Cottart CH, Nivet-Antoine V, Beaudeux JL.Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans. Molecular Nutrition & Food Research 2013;Epub 1-15.
  • Dani C, Oliboni LS, Vanderlinde R, Bonatto D, Salvador M, Henriques JA. Phenolic content and antioxidant activities of white and purple juices manufactured with organically- or conventionally-produced grapes. Food and Chemical Toxicology 2007;45(12):2574-2580.
  • Gaby A. The Natural Pharmacy, 3rd edition. Healthnotes Inc.;2006.
  • Ghanim H, Sia CL, Abuaysheh S, Korzeniewski K, Patnaik P, Marumganti A, Chaudhuri A, Dandona P. An anti-inflammatory and Reactive Oxygen Species Suppressive Effects of an Extract of Polygonum Cuspidatum Containing Resveratrol. Journal of Clinical Endocrinology & Metabolism 2010;95(9):E1-E8.
  • La Porte C, Voduc N, Zhang G, Seguin I, Tardiff D, Singhal N, Cameron DW. Steady-State Pharmacokinetics and Tolerability of Trans-Resveratrol 2000 mg Twice Daily with Food, Quercetin and Alcohol (Ethanol) in Healthy Human Subjects. Clinical Pharmacokinetics 2010;49(7):449-454.
  • Merck 2012: The Merck Index Version 14.1. Next link will take you to another Web site MedicinesComplete - Merck. Whitehouse Station (NJ): Merck & Co., Inc. Copyright © 2006, 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. [Published 2006; Updated 2012; Accessed 2013 August 12].
  • PubChem 2007:Next link will take you to another Web site  PubChem Substance Database; National Center for Biotechnology Information. Chemicals & Bioassays. U.S. National Library of Medicine.[Accessed 2014 February 10]
  • Rocha KK, Souza GA, Ebaid GX, Seiva FR, Cataneo AC, Novelli EL. Resveratrol toxicity: Effects on risk factors for atherosclerosis and hepatic oxidative stress in standard and high-fat diets. Food and Chemical Toxicology 2009;47(6):1362-1367.
  • Tomé-Carneiro J, Gonzálvez M, Larrosa M, Yáńez-Gascón MJ, García-Almagro FJ, Ruiz-Ros JA, García-Conesa MT, Tomás-Barberán FA, Espín JC. One-year consumption of grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. American Journal of Cardiology 2012;110(3):356-363.
  • USDA 2011: ARS, National Genetic Resources Program. Germplasm Resources Information Network (GRIN).Next link will take you to another Web site GRIN Taxonomy for Plants. National Germplasm Resources Laboratory, Beltsville (MD). [Reynoutria japonica Houtt.; Last updated 2011 October 28; Accessed 2013 August 06].
  • USDA 2009: ARS, National Genetic Resources Program. Germplasm Resources Information Network (GRIN).Next link will take you to another Web site GRIN Taxonomy for Plants. National Germplasm Resources Laboratory, Beltsville (MD). [Vitis vinifera L.; Last updated 2009 May 23; Accessed 2013 August 06].
  • Vang, O. What is new for resveratrol? Is a new set of recommendations necessary? Annals of the New York Academy of Sciences 2013;1290(1):1-11.

References reviewed

  • Baxter RA. Anti-aging properties of resveratrol: review and report of a potent new antioxidant skin care formulation. Journal of Cosmetic Dermatology 2008;7(1):2-7.
  • Bishayee A. Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical Trials. Cancer Prevention Research Published Online First;2009.
  • Boocock DJ, Patel KR, Faust GE, Normolle DP, Marczylo TH, Crowell JA, Brenner DE, Booth TD, Gescher A, Steward WP.Quantitation of trans-resveratrol and detection of its metabolites in human plasma and urine by high performance liquid chromatography. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2007;848:182-187.
  • Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2007;16:1246-1252.
  • ChemID 2012: National Institutes of Health. ChemIDplus advanced [online]. 2011. Resveratrol. Next link will take you to another Web site ChemIDplus Advanced Bethesda (MD): Specialized Information Services, United States National Library of Medicine, National Institutes of Health, United States Department of Health & Human Services. [Accessed 2011 May 9].
  • Darvesh AS, Carroll RT, Bishayee A, Geldenhuys WJ, Van der Schyf CJ. Oxidative stress and Alzheimer's disease: dietary polyphenols as potential therapeutic agents.Expert review of neurotherapeutics 2010;10(5):729-745.
  • Goldberg DM, Yan J, Soleas GJ.Ab sorption of three wine-related polyphenols in three different matrices by healthy subjects.Clinical Biochemistry 2003;36:79-87.
  • Hogan S, Canning C, Sun S, Sun X, Zhou K. Effects of Grape Pomace Antioxidant Extract on Oxidative Stress and Inflammation in Diet Induced Obese Mice. Journal of Agriculture and Food Chemistry 2010;58(21):11250-11256.
  • Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. The American journal of clinical nutrition 2010; 91:1590-1597.
  • Levi F, Pasche C, Lucchini F, Ghidoni R, Ferraroni M, La Vecchia C. Resveratrol and breast cancer risk. European Journal of Cancer Prevention 2005;14:139-142.
  • Mason, P. Dietary Supplements. 3rd edition. Cromwell Press. Blackwell Science Ltd. Trowbridge, Wiltshire 2007:276-278.
  • Meng X, Maliaki P, Lu H, Lee M-J, Yang CS.Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. Journal of Agriculture and Food Chemistry 2004;52:935-942.
  • Obrenovich ME, Nair NG, Beyaz A, Aliev G, Reddy VP. The role of polyphenolic antioxidants in health, disease, and aging. Rejuvenation research 2010;13(6):631-643.
  • Penumathsa SV, Maulik N. Resveratrol: a promising agent in promoting cardioprotection against coronary heart disease. Canadian journal of physiology and pharmacology 2009;87(4):275-286.
  • Puizina-Ivic N, Miric L, Carija A, Karlica D, Marasovic D. Modern approach to topical treatment of aging skin. Collegium antropologicum 2010;34(3):1145-1153.
  • Soleas GJ, Yan J, Goldberg DM. Ultrasensitivity assay for the three polyphenols (catechin, quercetin and resveratrol) and their conjugates in biological fluids utilizing gas chromatography with mass selective detection. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2002;757:161-172.
  • Toklu HZ, Sehirli O, Ersahin M, Süleymanoglu S, Yiginer O, Emekli-Alturfan E, Yarat A, Yegen BÇ, Sener G. Resveratrol improves cardiovascular function and reduces oxidative organ damage in the renal, cardiovascular and cerebral tissues of two-kidney, one-clip hypertensive rats. The Journal of pharmacy and pharmacology 2010;62(12):1784-1793.
  • Vitaglione P, Sforza S, Galaverna G, Ghidini C, Caporaso N, Vescovi PP, Fogliano V, Marchelli R. Bioavailability of trans-resveratrol from red wine in humans. Molecular nutrition and food research 2005;49:495-504.
  • Walle T, Hsieh F, DeLegge MH, Oatis JE, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug metabolism and disposition: the biological fate of chemicals.2004;32:1377-82.
  • Wang J, He D, Zhang Q, Han Y, Jin S, Qi F. Resveratrol Protects Against Cisplatin-Induced Cardiotoxicity by Alleviating Oxidative Damage. Cancer biotherapy and radiopharmaceuticals, 2009;24(6):675-680.
  • Wood LG, Wark PA, Garg ML. Antioxidant and anti-inflammatory effects of resveratrol in airway disease. Antioxid Redox Signal 2010 Nov 15;13(10):1513-5.
  • Zamora-Ros R, Urpí-Sardŕ M, Lamuela-Raventós RM, Estruch R, Vázquez-Agell M, Serrano-Martínez M, Jaeger W, Andres-Lacueva C. Diagnostic performance of urinary resveratrol metabolites as a biomarker of moderate wine consumption.Clinical Chemistry 2006;52:1373-80.
  • Zern TL, Wood RJ, Greene C, West KL, Liu Y, Aggarwal D, Shachter NS, Fernandez ML. Grape Polyphenols Exert a Cardioprotective Effect in Pre- and Postmenopausal Women by Lowering Plasma Lipids and Reducing Oxidative Stress. Journal of Nutrition 2005;135:1911-1917.