Micronutrients and Supplements Info: Resveratrol

Resveratrol

Description

Resveratrol is a phytoalexin, a group of substances produced by plants as a defence mechanism when infected by a bacteria or fungus.

Function

In addition to its antibacterial and antifungal action in pants, resveratrol has been widely studied for its protective action against cardiovascular diseases and cancer.

Sources

Resveratrol is mainly found in some types of wine-making grapes; therefore, its main dietary source is red wine. It is also provided as dietary supplement.

Toxicity

No toxicity or drug interaction is reported. Naturally, increasing red wine consumption for the sole purpose of increasing the level of resveratrol may also potentially increase the risks link to alcohol consumption and may not necessarily be recommended. Alcohol should be avoided during pregnancy.

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Additional Sources of Information

Resveratrol - Wikipedia

Resveratrol - Linus Pauling Institute

Scientific References

A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. Barger JL, Kayo T, Vann JM, et al. PLoS One. 2008;3(6):e2264.

Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Goldberg DM, Yan J, Soleas GJ. Clin Biochem. 2003;36(1):79-87.

Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. Ferrero ME, Bertelli AE, Fulgenzi A, et al. Am J Clin Nutr. 1998;68(6):1208-1214.

Alcohol and coronary heart disease: a meta-analysis. Corrao G, Rubbiati L, Bagnardi V,

Alcohol intake and diet in France, the prominent role of lifestyle. Ruidavets JB, Bataille V, Dallongeville J, et al. Eur Heart J. 2004;25(13):1153-1162.

Alcohol-free red wine prevents arterial thrombosis in dietary-induced hypercholesterolemic rats: experimental support for the 'French paradox'. De Curtis A, Murzilli S, Di Castelnuovo A, et al. J Thromb Haemost. 2005;3(2):346-350.

Analysis of resveratrol as a lung cancer chemopreventive agent in A/J mice exposed to benzo[a]pyrene. Berge G, Ovrebo S, Eilertsen E, Haugen A, Mollerup S. Br J Cancer. 2004;91(7):1380-1383.

Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Donnelly LE, Newton R, Kennedy GE, et al. Am J Physiol Lung Cell Mol Physiol. 2004;287(4):L774-783.

Antiplatelet activity of synthetic and natural resveratrol in red wine. Bertelli AA, Giovannini L, Giannessi D, et al. Int J Tissue React. 1995;17(1):1-3.

Atherosclerotic Vascular Disease Conference: Writing Group III: pathophysiology. Faxon DP, Fuster V, Libby P, et al. Circulation. 2004;109(21):2617-2625.

Better psychological functioning and higher social status may largely explain the apparent health benefits of wine: a study of wine and beer drinking in young Danish adults. Mortensen EL, Jensen HH, Sanders SA, Reinisch JM. Arch Intern Med. 2001;161(15):1844-1848.

Bioavailability of trans-resveratrol from red wine in humans. Vitaglione P, Sforza S, Galaverna G, et al. Mol Nutr Food Res. 2005;49(5):495-504.

Biological effects of resveratrol. Fremont L. Life Sci. 2000;66(8):663-673.

Calorie restriction and aging: review of the literature and implications for studies in humans. Heilbronn LK, Ravussin E. Am J Clin Nutr. 2003;78(3):361-369.

Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Jang M, Cai L, Udeani GO, et al. Science. 1997;275(5297):218-220.

Cardiovascular protective effects of resveratrol. Bradamante S, Barenghi L, Villa A. Cardiovasc Drug Rev. 2004;22(3):169-188.

Cell-cycle dysregulation and anticancer therapy. Stewart ZA, Westfall MD, Pietenpol JA. Trends Pharmacol Sci. 2003;24(3):139-145.

Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Shankar S, Singh G, Srivastava RK. Front Biosci. 2007;12:4839-4854.

Chemopreventive effect of trans-resveratrol--a phytoalexin against colonic aberrant crypt foci and cell proliferation in 1,2-dimethylhydrazine induced colon carcinogenesis. Sengottuvelan M, Viswanathan P, Nalini N. Carcinogenesis. 2006;27(5):1038-1046.

Concentration of the phytoalexin resveratrol in wine. Siemann EH, Creasey LL. Am J Enol Vitic. 1992;43(1):49-52.

C-reactive protein and other inflammatory risk markers in acute coronary syndromes. Blake GJ, Ridker PM. J Am Coll Cardiol. 2003;41(4 Suppl S):37S-42S.

Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independently of inhibition of lipid peroxidation in the artery wall. Stocker R, O'Halloran RA. Am J Clin Nutr. 2004;79(1):123-130.

Determination of piceid and resveratrol in Spanish wines deriving from Monastrell (Vitis vinifera L.) grape variety. Moreno-Labanda JF, Mallavia R, Perez-Fons L, Lizama V, Saura D, Micol V. J Agric Food Chem. 2004;52(17):5396-5403.

Dietary resveratrol does not affect intestinal tumorigenesis in Apc(Min/+) mice. Ziegler CC, Rainwater L, Whelan J, McEntee MF. J Nutr. 2004;134(1):5-10.

Dietary supplementation of resveratrol suppresses colonic tumour incidence in 1,2-dimethylhydrazine-treated rats by modulating biotransforming enzymes and aberrant crypt foci development. Sengottuvelan M, Nalini N. Br J Nutr. 2006;96(1):145-153.

Direct gas chromatographic-mass spectrometric method to assay cis-resveratrol in wines: preliminary survey of its concentration in commercial wines. Goldberg DM, Karumanchiri A, Ng E, Yan J, Eleftherios P, Soleas G. J Agric Food Chem. 1995;43(5):1245-1250.

Does diet or alcohol explain the French paradox? Criqui MH, Ringel BL. Lancet. 1994;344(8939-8940):1719-1723.

Drink to your health? Klatsky AL. Sci Am. 2003;288(2):74-81.

Effect of resveratrol on platelet aggregation in vivo and in vitro. Wang Z, Zou J, Huang Y, Cao K, Xu Y, Wu JMChin. Med J (Engl). 2002;115(3):378-380.

Effect of trans-resveratrol on the thrombogenicity and atherogenicity in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Fukao H, Ijiri Y, Miura M, et al. Blood Coagul Fibrinolysis. 2004;15(6):441-446.

Effects of phenolics on vascular endothelial function. Duffy SJ, Vita JA. Curr Opin Lipidol. 2003;14(1):21-27.

Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Wang Z, Huang Y, Zou J, Cao K, Xu Y, Wu JM. Int J Mol Med. 2002;9(1):77-79.

Efficiency and mechanism of the antioxidant action of trans-resveratrol and its analogues in the radical liposome oxidation. Stojanovic S, Sprinz H, Brede O. Arch Biochem Biophys. 2001;391(1):79-89.

Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM. Cancer Res. 2001;61(20):7456-7463.

Evaluation of butylated hydroxyanisole, myo-inositol, curcumin, esculetin, resveratrol and lycopene as inhibitors of benzo[a]pyrene plus 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. Hecht SS, Kenney PM, Wang M, et al. Cancer Lett. 1999;137(2):123-130.

Extraction of phenolics and changes in antioxidant activity of red wines during vinification. Burns J, Gardner PT, Matthews D, Duthie GG, Lean ME, Crozier A. J Agric Food Chem. 2001;49(12):5797-5808.

Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. St Leger AS, Cochrane AL, Moore F. Lancet. 1979;1(8124):1017-1020.

Genome-scale analysis of resveratrol-induced gene expression profile in human ovarian cancer cells using a cDNA microarray. Yang SH, Kim JS, Oh TJ, et al. Int J Oncol. 2003;22(4):741-750.

High absorption but very low bioavailability of oral resveratrol in humans. Walle T, Hsieh F, Delegge MH, Oatis JE, Jr., Walle UK. Drug Metab Dispos. 2004;32(12):1377-1382.

Influence of lipophilicity on the interactions of hydroxy stilbenes with cytochrome P450 3A4. Regev-Shoshani G, Shoseyov O, Kerem Z. Biochem Biophys Res Commun. 2004;323(2):668-673.

Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Ciolino HP, Yeh GC. Mol Pharmacol. 1999;56(4):760-767.

Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Piver B, Berthou F, Dreano Y, Lucas D. Toxicol Lett. 2001;125(1-3):83-91.

Inhibition of human LDL oxidation by resveratrol. Frankel EN, Waterhouse AL, Kinsella JE. Lancet. 1993;341(8852):1103-1104.

Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation. Lin MT, Yen ML, Lin CY, Kuo ML. Mol Pharmacol. 2003;64(5):1029-1036.

Levels of cis- and trans-resveratrol and their glucosides in white and rosé Vitis vinifera wines from Spain. Romero-Perez AI, Lamuela-Raventos RM, Waterhouse AL, de la Torre-Boronat MC. J Agric Food Chem. 1996;44(8):2124-2128.

Mechanisms and applications of non-steroidal anti-inflammatory drugs in the chemoprevention of cancer. Steele VE, Hawk ET, Viner JL, Lubet RA. Mutat Res. 2003;523-524:137-144.

Metabolism and bioavailability of trans-resveratrol. Wenzel E, Somoza V. Mol Nutr Food Res. 2005;49(5):472-481.

Modulatory influence of dietary resveratrol during different phases of 1,2-dimethylhydrazine induced mucosal lipid-peroxidation, antioxidant status and aberrant crypt foci development in rat colon carcinogenesis. Sengottuvelan M, Senthilkumar R, Nalini N. Biochim Biophys Acta. 2006;1760(8):1175-1183.

Occurrence of resveratrol in edible peanuts. Sanders TH, McMichael RW, Jr., Hendrix KW. J Agric Food Chem. 2000;48(4):1243-1246.

Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Carluccio MA, Siculella L, Ancora MA, et al. Arterioscler Thromb Vasc Biol. 2003;23(4):622-629.

Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Boocock DJ, Faust GE, Patel KR, et al. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1246-1252.

Phytoalexin production potential of grape berries. Creasey LL, Coffee M. J Am Soc Hortic Sci. 1988;113(2):230-234.

Piceid, the major resveratrol derivative in grape juices. J Agric Food Chem. Romero-Perez AI, Ibern-Gomez M, Lamuela-Raventos RM, de La Torre-Boronat MC. 1999;47(4):1533-1536.

Plant foods and herbal sources of resveratrol. Burns J, Yokota T, Ashihara H, Lean ME, Crozier A. J Agric Food Chem. 2002;50(11):3337-3340.

Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Lekakis J, Rallidis LS, Andreadou I, et al. Eur J Cardiovasc Prev Rehabil. 2005;12(6):596-600.

Pro- and anti-angiogenesis effects of resveratrol. Chen Y, Tseng SH. Review. In Vivo. 2007;21(2):365-370.

Profound negative regulatory effects by resveratrol on vascular smooth muscle cells: a role of p53-p21(WAF1/CIP1) pathway. Mnjoyan ZH, Fujise K. Biochem Biophys Res Commun. 2003;311(2):546-552.

Relationship between mechanisms, bioavailibility, and preclinical chemopreventive efficacy of resveratrol: a conundrum. Gescher AJ, Steward WP. Cancer Epidemiol Biomarkers Prev. 2003;12(10):953-957.

Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Lin SJ, Defossez PA, Guarente L. Science. 2000;289(5487):2126-2128.

Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM. Endocrinology. 2000;141(10):3657-3667.

Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. Klinge CM, Blankenship KA, Risinger KE, et al. J Biol Chem. 2004.

Resveratrol and quercetin inhibit angiogenesis in vitro. Igura K, Ohta T, Kuroda Y, Kaji K. Cancer Lett. 2001;171(1):11-16.

Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. de la Lastra CA, Villegas I. Mol Nutr Food Res. 2005;49(5):405-430.

Resveratrol decreases early signaling events in washed platelets but has little effect on platalet in whole blood. Kirk RI, Deitch JA, Wu JM, Lerea KM. Blood Cells Mol Dis. 2000;26(2):144-150.

Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression. Tessitore L, Davit A, Sarotto I, Caderni G. Carcinogenesis. 2000;21(8):1619-1622.

Resveratrol improves health and survival of mice on a high-calorie diet. Baur JA, Pearson KJ, Price NL, et al. Nature. 2006;444(7117):337-342.

Resveratrol in the chemoprevention and chemotherapy of breast cancer. Tangkeangsirisin W, Serrero G. Bagchi D, Preuss HG, eds. In: Phytopharmaceuticals in Cancer Chemoprevention. Boca Raton: CRC Press; 2005:449-463.

Resveratrol increases serine15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Haider UG, Sorescu D, Griendling KK, Vollmar AM, Dirsch VM. Mol Pharmacol.

2003;63(4):925-932.

Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Joe AK, Liu H, Suzui M, Vural ME, Xiao D, Weinstein IB. Clin Cancer Res. 2002;8(3):893-903.

Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis. Schneider Y, Duranton B, Gosse F, Schleiffer R, Seiler N, Raul F. Nutr Cancer. 2001;39(1):102-107.

Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction. Woo JH, Lim JH, Kim YH, et al. Oncogene. 2004;23(10):1845-1853.

Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Chen ZH, Hurh YJ, Na HK, et al. Carcinogenesis. 2004;25(10):2005-2013.

Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents. Szewczuk LM, Forti L, Stivala LA, Penning TM. J Biol Chem. 2004;279(21):22727-22737.

Resveratrol is a potent inhibitor of the dioxygenase activity of lipoxygenase. Pinto MC, Garcia-Barrado JA, Macias P. J Agric Food Chem. 1999;47(12):4842-4846.

Resveratrol modulation of signal transduction in apoptosis and cell survival: a mini-review. Fulda S, Debatin KM. Cancer Detect Prev. 2006;30(3):217-223.

Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A. Curr Biol. 2006;16(3):296-300.

Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits. Wilson T, Knight TJ, Beitz DC, Lewis DS, Engen RL. Life Sci. 1996;59(1):PL15-21.

Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. Lu R, Serrero G. J Cell Physiol. 1999;179(3):297-304.

Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Gehm BD, McAndrews JM, Chien PY, Jameson JL. Proc Natl Acad Sci U S A. 1997;94(25):14138-14143.

Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Wallerath T, Deckert G, Ternes T, et al. Circulation. 2002;106(13):1652-1658.

Resveratrol, pterostilbene, and piceatannol in vaccinium berries. Rimando AM, Kalt W, Magee JB, Dewey J, Ballington JR. J Agric Food Chem. 2004;52(15):4713-4719.

Resveratrol: a molecule whose time has come? And gone? Soleas GJ, Diamandis EP, Goldberg DM. Clin Biochem. 1997;30(2):91-113.

Resveratrol-associated renal toxicity. Crowell JA, Korytko PJ, Morrissey RL, Booth TD, Levine BS. Toxicol Sci. 2004;82(2):614-619.

Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits. Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. BMJ. 1996;312(7033):731-736.

Role of oxidative modifications in atherosclerosis. Stocker R, Keaney JF, Jr. Physiol Rev. 2004;84(4):1381-1478.

Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Anticancer Res. 2004;24(5A):2783-2840.

Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. Mukamal KJ, Conigrave KM, Mittleman MA, et al. N Engl J Med. 2003;348(2):109-118.

Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Wood JG, Rogina B, Lavu S, et al. Nature. 2004;430(7000):686-689.

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Howitz KT, Bitterman KJ, Cohen HY, et al. Nature. 2003;425(6954):191-196.

Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Banerjee S, Bueso-Ramos C, Aggarwal BB. Cancer Res. 2002;62(17):4945-4954.

Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol. Tsai SH, Lin-Shiau SY, Lin JK. Br J Pharmacol. 1999;126(3):673-680.

Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol. Li ZG, Hong T, Shimada Y, et al. Carcinogenesis. 2002;23(9):1531-1536.

The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. Juan ME, Vinardell MP, Planas JM. J Nutr. 2002;132(2):257-260.

The health benefits of wine. German JB, Walzem RL. Annu Rev Nutr. 2000;20:561-593.

The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection against LDL oxidation. Brito P, Almeida LM, Dinis TC. Free Radic Res. 2002;36(6):621-631.

The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G, Goldberg DM. Clin Chim Acta. 1995;235(2):207-219.

Therapeutic potential of resveratrol: the in vivo evidence. Baur JA, Sinclair DA. Nat Rev Drug Discov. 2006;5(6):493-506.

trans-resveratrol content in commercial peanuts and peanut products. Sobolev VS, Cole RJ. J Agric Food Chem. 1999;47(4):1435-1439.

Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer. Gronbaek M, Becker U, Johansen D, et al. Ann Intern Med. 2000;133(6):411-419.

Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality. Wannamethee SG, Shaper AG. Am J Public Health. 1999;89(5):685-690.

Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. Meng X, Maliakal P, Lu H, Lee MJ, Yang CS. J Agric Food Chem. 2004;52(4):935-942.

Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. Chen CK, Pace-Asciak CR. Gen Pharmacol. 1996;27(2):363-366.

Wine, beer, and mortality in middle-aged men from eastern France. Renaud SC, Gueguen R, Siest G, Salamon R. Arch Intern Med. 1999;159(16):1865-1870.