Wine, research and cardiovascular disease: Instructions for use

  • Alberto A.E. Bertelli
    Correspondence address: Alberto Bertelli, MD, PhD, Dipartimento di Morfologia Umana, Università degli Studi di Milano, Via Mangiagalli, 31, 20133 Milano, Italy. Tel.: +39 0250315384; fax: +39 0250315387.
    Department of Human Morphology, University of Milan, Milano, Italy
    Search for articles by this author


      The results of studies on the role of appropriate wine consumption in the prevention of cardiovascular disease are inconsistent, suggesting that the general approach to the issue needs to be revisited before further research is conducted. A number of points for consideration are raised: (1) the necessity to characterize wine analytically, as the content in important components of wine, such as resveratrol, is influenced considerably by regional factors, such as climate and local oenological procedures; (2) the bioavailability of the components of wine, which appears to be adequate as a broad range of biological effects have been documented at low concentrations that can be achieved by moderate chronic wine consumption; (3) the lack of importance of wine color, as also white wine consumption affords benefit, thanks to its content in the antioxidants caffeic acid, tyrosol and hydroxytyrosol, which are also found in olive oil; (4) the recommendation by WHO to “investigate the possible protective effects of ingredients other than alcohol in alcoholic beverages”.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Naissaides M.
        • Mamo J.C.L.
        • James A.P.
        • Pal S.
        The effect of chronic consumption of red wine on cardiovascular disease risk factors in postmenopausal women.
        Atherosclerosis. 2006; 185: 438-445
        • Norata G.D.
        • Marchesi P.
        • Passamonti S.
        • et al.
        Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice.
        Atherosclerosis. 2007; 191: 265-271
        • Blanco-Colio L.M.
        • Muñoz-García B.
        • Martín-Ventura J.L.
        • et al.
        Ethanol beverages containing polyphenols decrease nuclear factor kappa-B activation in mononuclear cells and circulating MCP-1 concentrations in healthy volunteers during a fat-enriched diet.
        Atherosclerosis. 2007; 192: 335-341
        • Pignatelli P.
        • Ghiselli A.
        • Buchetti B.
        • et al.
        Polyphenols synergistically inhibit oxidative stress in subjects given red and white wine.
        Atherosclerosis. 2006; 188: 77-83
        • Waterhouse A.L.
        Wine Phenolics.
        Ann N Y Acad Sci. 2002; 957: 21-36
        • Ruidavets J.B.
        • Teissedre P.L.
        • Ferrières J.
        • Carando S.
        • Bougard G.
        • Cabanis J.C.
        Catechin in the Mediterranean diet: vegetable, fruit or wine?.
        Atherosclerosis. 2000; 153: 107-117
        • Arts I.C.W.
        • Hollman P.C.H.
        • Feskens E.J.M.
        • Bas Bueno de Mesquita H.
        • Kromhout D.
        Catechin intake might explain the inverse relation between tea consumption and ischemic heart disease: the Zutphen Elderly Study.
        Am J Clin Nutr. 2001; 74: 227-232
        • Knekt P.
        • Kumpulainen J.
        • Järvinen R.
        • et al.
        Flavonoid intake and risk of chronic diseases.
        Am J Clin Nutr. 2002; 76: 560-568
      1. Shishodia S, Aggarawal BB, Resveratrol, a polyphenol for all seasons In: Resveratrol in health, Disease, CRC Press, 2006, pp. 1–15.

        • Tokusoglu Özlem
        • Ünal M.K.
        • Yemis F.
        Determination of the phytoalexin resveratrol (3,5,4′-trihydroxystilbene) in peanuts and pistachios by high-performance liquid chromatographic diode array (HPLC-DAD) and gas chromatography-mass spectrometry (GC–MS).
        J Agric Food Chem. 2005; 53: 5003-5009
        • Wang Y.
        • Catana F.
        • Yang Y.
        • Roderick R.
        • van Breemen R.B.
        An LC–MS method for analyzing total resveratrol in grape juice, cranberry juice and in wine.
        J Agric Food Chem. 2002; 50: 431-435
        • Meng X.
        • Maliakal P.
        • Lu H.
        • Lee M.J.
        • Yang C.S.
        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: 935-942
        • Lamuela-Raventós R.M.
        • Waterhouse A.L.
        Occurrence of resveratrol in selected California wines by a new HPLC method.
        J Agric Food Chem. 1993; 41: 521-523
        • Chu Q.
        • O’Dwyer M.
        • Zeece M.G.
        Direct analysis of resveratrol in wine by Micel capillary electrophoresis.
        J Agric Food Chem. 1998; 46: 509-513
        • Mattivi F.
        Solid phase extraction of trans-resveratrol form wines for HPLC analysis.
        Z Lebensm Unters Forsch. 1993; 196: 522-525
        • Goldberg D.M.
        • Karumanchiri A.
        • Ng E.
        • et al.
        Direct gas chromatographic-mass spectrometric method to assay cis-resveratrol in wines: preliminary survey of its concentration in commercial wines.
        J Agric Food Chem. 1995; 43: 1245-1250
        • Jeandet P.
        • Bessis R.
        • Maume B.F.
        • Meunier P.
        • Peyron D.
        • Trollat P.
        Effect of enological practices on the resveratrol isomer content of wine.
        J Agric Food Chem. 1995; 43: 316-319
        • Vrhovsek U.
        • Wendelin S.
        • Eder R.
        Effects of various vinification techniques on the concentration of cis-and trans-resveratrol and resveratrol glucoside isomers in wine.
        Am J Enol Vitic. 1997; 48: 214-219
        • Corder R.
        • Mullen W.
        • Khan N.Q.
        • et al.
        Red wine procyanidins and vascular health.
        Nature. 2006; 444: 566
        • Muller C.J.
        • Fugelsang K.C.
        Red wine but not white: the importance of fully characterizing wines used in health studies.
        Am J Clin Nutr. 1997; 66: 447-451
        • Kroon P.A.
        • Clifford M.N.
        • Crozier A.
        • et al.
        How should we assess the effects of exposure to dietary polyphenols in vitro?.
        Am J Clin Nutr. 2004; 80: 15-21
      2. Bertelli AAE. Pharmacokinetics and metabolism of resveratrol. In: Resveratrol in health and Disease, CRC Press, 2006, pp. 631–647.

        • Horn T.L.
        • Cwik M.J.
        • Morrissey R.L.
        • et al.
        Oncogenicity evaluation of resveratrol in p53 knockout mice.
        Food Chem Toxicol. 2007; 45: 55-63
        • Goldberg D.M.
        • Yan J.
        • Soleas G.J.
        Absorption of three wine-related polyphenols in three different matrices by healthy subjects.
        Clin Biochem. 2003; 36: 79-87
        • Bertelli A.A.E.
        • Giovannini L.
        • Stradi R.
        • Bertelli A.
        • Tillement J.P.
        Plasma, urine and tissue levels of trans-a and cis-resveratrol (3,4′,5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats.
        Int J Tissue Reac. 1996; 18: 67-71
        • Ferrero M.E.
        • Bertelli A.A.E.
        • Fulgenzi A.
        • et al.
        Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium.
        Am J Clin Nutr. 1998; 68: 1208-1214
        • Teel R.W.
        • Huynh H.
        Modulation by phytochemicals of cytochrome P450-linked enzyme activity.
        Cancer Lett. 1998; 133: 135-141
        • Leikert J.F.
        • Räthel T.R.
        • Wohlfart P.
        • et al.
        Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells.
        Circulation. 2002; 106: 1614-1617
        • Gu J.
        • Wang C.Q.
        • Fan H.H.
        • et al.
        Effects of resveratrol on endothelial progenitor cells and their contributions to reendothelialization in intima-injured rats.
        J Cardiovasc Pharmacol. 2006; 47: 711-721
        • Zini R.
        • Morin C.
        • Bertelli A.
        • Bertelli A.A.E.
        • Tillement J.P.
        Resveratrol-induced limitation of dysfunction of mitochondria isolated from rat brain in an anoxia-reoxygenation model.
        Life Sci. 2002; 71: 3091-3108
        • Bertelli A.A.E.
        • Giovannini L.
        • De Caterina R.
        • et al.
        Antiplatelet activity of cis-resveratrol.
        Drugs Exptl Cin Res. 1996; 22: 61-63
        • Dobrydneva Y.
        • Williams R.L.
        • Blackmore P.F.
        Trans-resveratrol inhibits calcium influx in thrombin-stimulated human platelets.
        Br J Pharmacol. 1999; 128: 149-157
        • Liew R.
        • Stagg M.A.
        • Macleod K.T.
        • Collins P.
        The red wine polyphenol, resveratrol, exerts acute direct actions on guinea-pig ventricular myocytes.
        Eur J Pharmacol. 2005; 519: 1-8
        • Zhang Y.
        • Liu Y.
        • Wang T.
        • et al.
        Resveratrol, a natural ingredient of grape skin: antiarrhythmic efficacy and ionic mechanisms.
        Biochem Biophys Res Commun. 2006; 340: 1192-1199
        • Plin C.
        • Tillement J.P.
        • Berdeaux A.
        • Morin D.
        Resveratrol protects against cold ischemia—warm rexoxygenation-induced damages to mitochondria and cells in rat liver.
        Eur J Pharmacol. 2005; 528: 162-168
      3. Bråkenhielm E, Cao R, Cao Y. Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB, Published online June 8, 2001.

        • Pellegatta F.
        • Bertelli A.A.E.
        • Staels B.
        • et al.
        Different short- and long-term effects of resveratrol on nuclear factor-kB phosphorylation and nuclear appearance in human endothelial cells.
        Am J Clin Nutr. 2003; 77: 1220-1228
        • Shen F.
        • Chen S.J.
        • Dong X.J.
        • et al.
        Suppression of IL-8 gene transcription by resveratrol in phorbol ester treated human monocytic cells.
        J Asian Nat Prod Res. 2003; 5: 151-157
        • Cignarella A.
        • Minici C.
        • Bolego C.
        • et al.
        Potential pro-inflammatory action of resveratrol in vascular smooth muscle cells from normal and diabetic rats.
        Nutr metab Cardiovasc Dis. 2006; 16: 322-329
        • Renaud S.
        • de Lorgeril M.
        Wine, alcohol, platelets and the French paradox for coronary heart disease.
        Lancet. 1992; 339: 1523-1526
        • Bertelli A.A.E.
        • Giovannini L.
        • Giannessi D.
        • et al.
        Antiplatelet activity of synthetic and natural resveratrol in red wine.
        Int J Tissue Reac. 1995; 17: 1-3
        • De Santi C.
        • Pietrabissa A.
        • Spisni R.
        • Mosca F.
        • Pacifici G.M.
        Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum.
        Xenobiotica. 2000; 30: 609-617
        • De Santi C.
        • Pietrabissa A.
        • Mosca F.
        • Pacifici G.M.
        Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver.
        Xenobiotica. 2000; 30: 1047-1054
        • Romero-Pérez A.I.
        • Lamuela-Raventós R.M.
        • Waterhouse A.L.
        • de la Torre-Boronat M.C.
        Levels of cis- and trans-resveratrol and their glucosides in white and Rosé Vitis vinifera wines from Spain.
        J Agric Food Chem. 1996; 44: 2124-2128
        • Chamkha M.
        • Cathala B.
        • Cheynier V.
        • Douillard R.
        Phenolic composition of champagnes from Cardonnay and Pinot Noir Vintages.
        J Agric Food Chem. 2003; 51: 3179-3184
        • El-Mohsen M.A.
        • Bayele H.
        • Kuhnle G.
        • et al.
        Distribution of [3H]trans-resveratrol in rat tissues following oral administration.
        Brit J Nutr. 2006; 96: 62-70
        • Urpí-Sardà M.
        • Jáuregui O.
        • Lamuela-Raventós R.M.
        • et al.
        Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry.
        Anal Chem. 2005; 77: 3149-3155
        • Jannin B.
        • Menzel M.
        • Berlot J.P.
        • et al.
        Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake.
        Biochem Pharmacol. 2004; 68: 1113-1118
        • de la Torre R.
        • Covas M.I.
        • Pujadas M.A.
        • Fitó M.
        • Farré M.
        Is dopamine behind the health benefits of red wine?.
        Eur J Nutr. 2006; 45: 307-310
        • Howitz K.T.
        • Bitterman K.J.
        • Cohen H.Y.
        • et al.
        Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.
        Nature. 2003; 425: 191-196
        • Baur J.A.
        • Pearson K.J.
        • Price N.L.
        • et al.
        Resveratrol improves health and survival of mice on a high-calorie diet.
        Nature. 2006; 444: 337-342
        • Kaeberlein M.
        • McDonagh T.
        • Heltweg B.
        • et al.
        Substrate-specific activation of sirtuins by resveratrol.
        J Biol Chem. 2005; 280: 17038-17045
        • Zini R.
        • Morin C.
        • Bertelli A.
        • Bertelli A.A.E.
        • Tillement J.P.
        Effrects of resveratrol on the rat brain respiratory chain.
        Drugs Exptl Clin Res. 1999; 25: 87-97
        • Klatsky A.L.
        • Friedman G.D.
        • Armstrong M.A.
        • Kipp H.
        Wine, liquor, beer and mortality.
        Am J Epidemiol. 2003; 158: 585-595
        • Whelan A.P.
        • Sutherland W.H.F.
        • McCormick M.P.
        • et al.
        Effects of white and red wine on endothelial function in subjects with coronary artery disease..
        Intern Med J. 2004; 34: 224-228
        • Williams M.J.A.
        • Sutherland W.H.F.
        • Whelan A.P.
        • McCormick M.P.
        • de Jong S.A.
        Acute effect of drinking red and white wines on circulating levels of inflammation-sensitive molecules in men with coronary artery disease.
        Metabolism. 2004; 53: 318-323
        • Kikura M.
        • lvey J.H.
        • Safon R.A.
        • Lee M.K.
        • Szlam F.
        The influence of red wine or white wine intake on platelet function and viscoelastic property of blood in volunteers.
        Platelets. 2004; 15: 37-41
        • Daher C.F.
        • Slaiby R.
        • Haddad N.
        • Boustany K.
        • Baroody G.M.
        Effect of acute and chronic moderate red or white wine consumption on fasted and postprandial lipemia in the rat.
        J Toxicol Environ Health. 2006; 69: 1117-1131
        • Bertelli A.A.E.
        Beneficial components of white wine.
        in: Preedy V.R. Watson R.R. Comprehensive handbook of alcohol related pathology. Elsevier, 2005: 389-392
        • Caccetta R.A.A.
        • Croft K.D.
        • Beilin L.J.
        • Puddey I.B.
        Ingestion of red wine significantly increases plasma phenolic acid concentrations but does not acutely affect ex vivo lipoprotein oxidizability.
        Am J Clin Nutr. 2000; 71: 67-74
        • Bertelli A.
        • Migliori M.
        • Bertelli A.A.E.
        • et al.
        Effect of some white wine phenols in preventing inflammatory cytokine release.
        Drugs Exptl Clin Res. 2002; 28: 11-15
        • Betés-Saura C.
        • Lacueva C.A.
        • Lamuela-Raventós R.M.
        Phenolics in white free run juices and wines from Penedès by high-performance liquid chromatography: changes during vinification.
        J Agric Food Chem. 1996; : 3040-3046
        • Bertelli A.A.E.
        • Migliori M.
        • Panichi V.
        • et al.
        Oxidative stress and inflammatory reaction modulation by white wine.
        Ann N Y Acad Sci. 2002; 957: 295-301
        • Di Tommaso D.
        • Calabrese R.
        • Rotilio D.
        Identification and quantitation of hydroxytyrosol in Italian Wines.
        J High Resol Chromatogr. 1998; 21: 549-553
        • Wiseman S.A.
        • Mathot J.N.
        • de Fouw N.J.
        • Tijburg L.B.
        Dietary non-tocopherol antioxidants present in extra virgin olive oil increase the resistance of low density lipoproteins to oxidation in rabbits.
        Atherosclerosis. 1996; 120: 15-23
        • Covas M.I.
        • de la Torre K.
        • Albadejo M.F.
        • et al.
        Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans.
        Free Rad Biology Med. 2006; 46: 608-616
        • Covas M.I.
        • Nyyssonen K.
        • Poulsen H.E.
        • et al.
        • for the EUROLIVE study group
        The effect of poplyphenols in olive oil on heart disease risk factors. A randomized trial.
        Ann Intern Med. 2006; 145: 333-341
        • Bertelli A.A.E.
        Stockpiling of raw material for oseltamivir is not justified.
        BMJ. 2006; 332: 178
        • Bianco A.
        • Brufani M.
        • Manna F.
        • Melchioni C.
        Synthesis of a carbocyclic sialic acid analogue for the inhibition of influenza virus neuraminidase.
        Carbohydrate Res. 2001; 332: 23-31
        • Nielsen N.B.
        • Schnohr P.
        • Jensen G.
        • Gronbaek M.
        Is the relationship between type of alcohol and mortality influenced by socio-economic status?.
        J Intern Med. 2004; 255: 280-288
        • Barefoot J.C.
        • Gronboek M.
        • Feaganes J.R.
        • McPherson R.S.
        • Williams R.B.
        • Siegler I.C.
        Alcoholic beverage preference, diet, and health habits in the UNC Alumni Heart Study.
        Am J Clin Nutr. 2002; 76: 466-472
        • Wannamethee S.G.
        • Camargo C.A.
        • Manson J.E.
        • Willett W.C.
        • Rimm E.B.
        Alcohol drinking patterns and risk of type 2 diabetes mellitus among younger women.
        Arch Intern Med. 2003; 163: 1329-1336
        • Stender S.
        • Dyerberg J.
        • Astrup A.
        High levels of industrially produced trans fat in popular fast foods.
        N Engl J Med. 2006; 354: 1650-1652
        • Lesschaeve I.
        • Noble A.C.
        Polyphenols: factors influencing their sensory properties and their effects on food and beverage preferences.
        Am J Clin Nutr. 2005; 81: 330S-335S
        • Mukamal K.J.
        • Cushman M.
        • Mittleman M.A.
        • Tracy R.
        • Siscovick D.S.
        Alcohol consumption and inflammatory markers in older adults: the cardiovascular health study.
        Atherosclerosis. 2004; 173: 79-87
        • Mukamal K.J.
        • Conigrave K.M.
        • Mittleman M.A.
        • et al.
        Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men.
        N Engl J Med. 2003; 348: 109-118
        • Marques-Vidal P.
        • Montaye M.
        • Haas B.
        • et al.
        Relationships between alcoholic beverages and cardiovascular risk factor levels in middle-aged men, the PRIME study.
        Atherosclerosis. 2001; 157: 431-440
        • Estruch R.
        • Sacanella E.
        • Badia E.
        • et al.
        Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial. Effects of wine on inflammatory markers.
        Atherosclerosis. 2004; 175: 117-123
      4. The World Health Report 2002 page 66.

      5. Cardiovascular disease risk factors: new areas for research. Report of a WHO scientific group, WHO Technical Report Series 841. Page 23, WHO, Geneva, 1994.