Wine and Health: A Paradigm for Alcohol and Antioxidants

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Wine and Health: A Paradigm for Alcohol and Antioxidants

Moderate alcohol consumption has been shown in many epidemiological investigations to prolong overall life expectancy by reducing the risk of certain diseases. Those that account most for this reduction are coronary heart disease and ischemic stroke, both of which are caused by atherosclerotic vascular disease. It has been claimed that these effects are beverage-specific, with red wine being the most potent. This review examines the relative contributions of ethanol and the polyphenolic antioxidants of red wine by considering their potential to inhibit atherogenesis and the mechanisms involved. There is good evidence, both in vitro and in vivo, that ethanol increases production and circulating levels of HDL-Cholesterol, and reduces clot formation by blocking thrombin activity as well as by inhibition of fibrinolysis. It also prevents migration of smooth-muscle cells to the intimal layer of arteries and reduces the incidence of Type II Diabetes Mellitus, a major risk factor for atherosclerotic disease. Red wine, in addition to ethanol, contains many polyphenolic antioxidants that are also present in fruit and vegetables (such as catechin and quercetin), as well as resveratrol that is almost restricted to grapes and red wine. These polyphenols, especially the last-named, have been shown by in vitro experiments to exhibit many potent properties conducive to preventing atherosclerosis. In addition to lowering clot formation, they diminish inflammatory reactions by down-regulating production of eicosanoids and cytokines, they prevent oxidation of LDL, reduce expression of cell-adhesion molecules, and increase NO production. However, investigations in whole animals and human subjects have yielded conflicting results. The above paradox can be explained by studies demonstrating that these polyphenols, when taken orally, are rapidly conjugated with glucuronide and sulfate by the small-intestinal mucosa prior to absorption, following which the deactivated water-soluble conjugates are quickly excreted by the kidney. The free biologically-active parent compounds appear in the circulation in very low concentrations and with a very rapid halflife. Uptake by relevant tissues could not be demonstrated. In line with this evidence, red and white wines have comparable effects when administered to humans that are essentially attributable to their alcohol content alone. These findings suggest that dietary antioxidants may be less effective than previously thought.

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  • Agarwal DP Seitz HK editors. Alcohol in health and disease. New York: Marcel Dekker 2001: 632pp.

  • Rehm JT Bondy SJ Sempos CT Vuong CV. Alcohol consumption and coronary heart disease mortality and morbidity. Am J Epidemiol 1997; 146: 495-501.

  • Klatsky AL Armstrong MA Friedman GD. Red wine white wine liquor beer and risk for coronary artery disease hospitalization. Am J Cardiol 1997; 80: 416-20.

  • Armstrong MA Midanik LT Klatsky AL. Alcohol consumption and utilization of health services in a health maintenance organization. Med Care 1998; 36: 1599-605.

  • Camargo CA Jr Stampfer MJ Glynn RJ Grodstein F Gaziano JM Manson JE et al. Moderate alcohol consumption and risk for angina pectoris or myocardial infarction in US male physicians. Ann Intern Med 1997; 375: 372-5.

  • Muntwyler J Henneckens CH Buering JE Gaziano JM. Mortality and light to moderate alcohol consumption after myocardial infarction. Lancet 1998; 352: 1882-5.

  • Sacco RL Elkind M Boden-Albala B Lin IF Kargman DE Hauser WA et al. The protective effect of moderate alcohol consumption on ischemic stroke. JAMA 1999; 281: 53-60.

  • Suter PM Vetter W. Alcohol and ischemic stroke. Nutr Rev 1999; 57: 310-4.

  • Hegele RA. The pathogenesis of atherosclerosis. Clin Chim Acta 1996; 246: 21-38.

  • Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med 1999; 340: 115-26.

  • Langer RD Criqui MH Reed DM. Lipoproteins and blood pressure as biological pathways for effects of moderate alcohol consumption on coronary heart disease. Circulation 1992; 85: 910-5.

  • Suh I Shaten J Cutler JA Kuller LH. Alcohol use and mortality from coronary heart disease: the role of high-density lipoprotein cholesterol. Ann Intern Med 1992; 116: 881-7.

  • Goldberg DM Garovic-Kocic V Diamandis EP Pace-Asciak CR. Wine: Does the colour count? Clin Chim Acta 1996; 246: 183-93.

  • Amarasuriya RN Gupta AK Civen M Homg Y-C Maeda T Kashyap MI. Ethanol stimulates lipoprotein A-I secretion by human hepatocytes: implications for a mechanism for atherosclerosis protection. Metabolism 1992; 41: 827-32.

  • Locher R Suter PM Vetter W. Ethanol suppresses smooth muscle cell proliferation in the post-prandial state: a new antiatherosclerotic mechanism of ethanol? Am J Clin Nutr 1998; 67: 338-41.

  • Hendrickson RJ Okada SS Cahill PA Sitzman JV Redmond EM. Ethanol inhibits basal and flow-induced vascular smooth muscle cell migration in vitro. J Surg Res 1999; 84: 64-70.

  • Rubin R Rand ML. Alcohol and platelet function. Alcohol Clin Exp Res 1994; 18: 105-10.

  • Renaud SC Beswick AD Fehily AM Sharp DS Elwood PC. Alcohol and platelet aggregation: the Caerphilly prospective heart disease study. Am J Clin Nutr 55; 1992: 1012-7.

  • Hendriks HF Van de Gaag MS. Alcohol coagulation and fibrinolysis. Novartis Found Symp 1998; 216: 111-20.

  • Pace-Asciak CR Rounova O Hahn SE Diamandis EP Goldberg DM. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clim Chim Acta 1996; 246: 163-82.

  • Mennen LI Balkau B Vol S Caces E Eschwege E. Fibrinogen: a possible link between alcohol and cardio-vascular disease. DESIR Study Group. Arterioscler Thromb Vasc Dis 1999; 19: 887-92.

  • Ridker PM Vaughan DE Stampfer MJ Glynn RJ Hennekens CH. Association of moderate alcohol consumption and plasma concentration of endogenous tissue-type plasminogen activator. JAMA 1994; 272: 929-33.

  • Aikens ML Grenett HE Benza RL Tabengwa EM Davis GC Booyse FM. Alcohol-induced upregulation of plasminogen activators and fibrinolytic activity in cultured human endothelial cells. Alcohol Clin Exp Res 1998; 22: 375-81.

  • Kozarevic D Racic Z Gordon T Kaelber CT McGee D Zukel WJ. Drinking habits and other characteristics: the Yugoslavia Cardiovascular Disease Study. Am J Epidemiol 1982; 116: 287-301.

  • Rimm EB Chan J Stampfer MJ Colditz GA Willett WC. Prospective study of cigarette smoking alcohol use and the risk of diabetes in men. BMJ 1995; 310: 555-60.

  • Wannamethee SG Shaper AG Walker M Ebrahim S. Life style and 15-year survival free of heart attack stroke and diabetes in middle-aged British men. Arch Intern Med 1998; 158: 2433-40.

  • Tsumura K Hayashi T Suematsu C Endo G Fuji S Okada K. Daily alcohol consumption and the risk of type 2 diabetes in Japanese men: the Osaka Health Survey. Diabetes Care 1999; 22: 1432-7.

  • Facchini F Chen IY-D Reaven GM. Light to moderate alcohol intake is associated with enhanced insulin sensitivity. Diabetes Care 1994; 17: 115-9.

  • Huang CM Elin RJ Ruddel M Schmitz J Linnoila M. The effect of alcohol withdrawal on serum concentration of Lp(a) apolipoproteins A-I and B and lipids. Alcohol Clin Exp Res 1992; 16: 895-8.

  • Lieber CS. Hepatic metabolic and nutritional disorders of alcoholism: from pathogenesis to therapy. In: Agarwal DP Seitz HK editors. Alcohol in health and disease. New York: Marcel Dekker 2001: 335-68.

  • Soleas GJ Diamandis EP Goldberg DM. Resveratrol: a molecule whose time has come? and gone? Clin Biochem 1997; 30: 91-103.

  • Soleas GJ Diamandis EP Goldberg DM. The world of resveratrol. Adv Exp Biol Med 2001; 492: 159-82.

  • Goldberg DM Soleas GJ. Resveratrol: biochemistry cell biology and the potential role in disease prevention. In: Sandler M Pinder R editors. Wine: a scientific exploration. London: Taylor and Francis 2003: 160-98.

  • Dhaliwal DS Steinbrecher UP. Scavenger receptors and oxidized low density lipoproteins. Clin Chim Acta 1999; 286: 191-205.

  • Bertelli AA Giovannini L Stradi R Bertelli A Tillement JP. Plasma urine and tissue of trans-and cis-resveratrol (34'5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats. Int J Tiss React 1996; 18: 67-71.

  • Bertelli AA Giovannini L Stradi R Urien S Tillement JP Bertelli A. Kinetics of trans- and cis-resveratrol (34'5-trihydroxystilbene) after red wine oral administration in rats. Int J Clin Pharmacol Res 1996; 16: 67-71.

  • Juan ME Lamuela-Raventos RM De La Torre-Boronat MC Planas JM. Determination of trans-resveratrol in plasma by HPLC. Anal Chem 1999; 71: 747-50.

  • Soleas GJ Angelini M Grass L Diamandis EP Goldberg DM. Absorption of trans-resveratrol in rats. Methods Enzymol 2001; 335: 145-54.

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

  • Kuhnle G Spencer JP Chowrimootoo G Schroeter S Debnam ES Srai SK et al. Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochem Biophys Res Commun 2000; 272: 212-7.

  • Andlauer W Kolb J Siebert K Furst P. Assessment of resveratrol bioavailability in the perfused small intestine of the rat. Drugs Exp Clin Res 2000; 26: 47-55.

  • De Santi C Pietrabissa A Spisni R Mosca F Pacifici GM. Sulphation of resveratrol a natural product present in grapes and wine in the human liver and duodenum. Xenobiotica 2000; 30: 609-17.

  • Soleas GJ Yan J Goldberg DM. Ultrasensitive assay for three polyphenols (catechin quercetin and resveeratrol) and their conjugates in biological fluids utilizing gas chromatography and mass selective detection. J Chromatogr B 2001; 757: 161-72.

  • Agarwal DP. Cardioprotective effects of light-moderate consumption of alcohol: a review of putative mechanisms. Alcohol Alcohol 2002; 37; 409-15.

  • Elkind MS Sciacca R Boden-Albala B Rundek T Paik MC Sacco RL. Moderate alcohol consumption reduces risk of ischemic stroke: the Northern Manhattan Study. Stroke 2006; 37: 13-9.

  • Kawamoto R Kohara K Tabara Y Miki T Ohtsuka N Kusonoki T et al. Alcohol consumption is associated with decreased insulin resistance independent of body mass index in Japanese community-dwelling men. Tohoku J Exp Med 2009; 218: 331-7.

  • Rist PM Berger K Buring JE Kase CS Gaziano JM Kurth L. Alcohol consumption and functional outcome after stroke in men. Stroke 2010; 41: 141-6.

  • Klatsky AL. Alcohol and cardiovascular health. Physiol Behav 2010; 100: 76-81.

  • Beulens JW Algra A Soedamah-Muthu SS Visseren FL Grobbee DE Van der Graaf Y Alcohol consumption and risk of recurrent cardiovascular events and mortality in patients with clinically manifest vascular disease and diabetes mellitus: The Second Manifestations of ARTerial (SMART) disease study. Atherosclerosis 2010; 212: 281-6.

  • Pietraszek A Gregersen S Hermansen K. Alcohol and type 2 diabetes. A review. Nutr Metab Cardiovasc Dis 2010; 20: 366-75.

  • Walle T Hsieh F DeLegge MH Oatis JE Jr Walle UK. High absorption but very low availability of oral resveratrol in humans. Drug Metab Dispos 2004; 32: 1377-82.

  • Wenzel E Somoza V. Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res 2005; 49: 472-81.

  • Wenzel E Soldo T Ebersdobler H Somoza V. Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats. Mol Nutr Food Res 2005; 49: 482-94.

  • Vitaglione P Sforza S Galaverna G Ghidini C Caporaso N Vescovi PP et al. Bioavailability of trans-reservation from red wine in humans. Mol Nutr Food Res 2005; 49: 495-504.

  • Catterall F King LJ Clifford MN Ioannides C. Bioavailability of dietary doses of 3H-labelled tea antioxidants (+)-catechin and (-)-epicatechin in rat. Xenobiotica 2003; 33: 743-53.

  • Spencer JP. Metabolism of tea flavonoids in the gastrointestinal tract. J Nutr 2003; 133: 3255S-61S.

  • Meng X Maliakal P Lu H Lee MJ Yang CS. 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: 935-42.

  • Silberberg M Morand C Manach C Scalbert A Remesy C. Co-administration of quercetin and catechin in rats alters their absorption but not their metabolism. Life Sci 2005; 77: 3156-67.

  • Mullen W Edwards CA Crozier A. Absorption excretion and metabolite profiling of methyl- glucuronyl- glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions. Br J Nutr 2006; 96: 107-16.

  • Sesso HD Buring JE Norkus EP Gaziano JM. Plasma lycopene other carotenoids and retinol and the risk of cardiovascular disease in men. Am J Clin Nutr 2005; 81: 990-7.

  • Hatzigeorgiou C Taylor AJ Feuerstein IM Bautista L O'Malley PG. Antioxidant vitamin intake and subclinical coronary atherosclerosis. Prev Cardiol 2006; 9: 75-81.

  • Tavani A Gallus S Negri E Parpinel M La Vecchia C. Dietary intake of carotenoids and retinol and the risk of acute myocardial infarction in Italy. Free Radic Res 2006; 40: 659-64.

  • Kirmizis D Chatzidimitriou D. Antiatherogenic effects of vitamin E: the search for the Holy Grail. Vasc Health Risk Manag 2009; 5: 767-74.

  • Saremi A Arora R. Vitamin E and cardiovascular disease. Am J Ther 2010; 17: e56-65.

  • Rimm EB. Alcohol consumption and coronary heart disease: good habits may be more important than just good wine. Am J Epidemiol 1996; 143: 1094-8.

  • Klatsky AL. Alcohol and cardiovascular diseases. Expert Rev Cardiovasc Ther 2009; 7: 499-506.

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