Review| Volume 208, ISSUE 2, P297-304, February 2010

Download started.


Wine and oxidative stress: Up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans

  • María Isabel Covas
    Corresponding author. Tel.: +34 93 3160734; fax: +34 933160796.
    Cardiovascular Risk and Nutrition Research Group (URLEC-CARIN), Institut Municipal d’ Investigació Mèdica (IMIM-Hospital del Mar), CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona Biomedical Research Park (PRBB), Carrer Doctor Aiguader, 88, 08003 Barcelona, Spain
    Search for articles by this author
  • Philippe Gambert
    INSERM Federative Research Institute 100 Health-CIST, University Hospital Le Bocage, BP 77908, 21079 Dijon, France
    Search for articles by this author
  • Montserrat Fitó
    Cardiovascular Risk and Nutrition Research Group (URLEC-CARIN), Institut Municipal d’ Investigació Mèdica (IMIM-Hospital del Mar), CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona Biomedical Research Park (PRBB), Carrer Doctor Aiguader, 88, 08003 Barcelona, Spain
    Search for articles by this author
  • Rafael de la Torre
    Human Pharmacology and Clinical Neurosciences Research Group, Institut Municipal d’ Investigació Mèdica (IMIM-Hospital del Mar), CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain
    Search for articles by this author


      Wine and alcohol consumption has been considered to be protective against coronary heart disease development, an oxidative stress associated disease. Wine contains polyphenols displaying antioxidant properties tested in in vitro and in vivo studies. Due to this, a general consensus exists, both among the general public and the scientific community, that wine, particularly red wine, is an antioxidant beverage. Alcohol consumption, however, is associated with oxidative damage. Several studies have been carried out on the antioxidant health benefits of wine and wine polyphenols. However, adequate scientific evidence (Level I or II) is required to be provided before recommendations or statements which can reach the general public can be formulated. Here, we summarize the state of the art of the up-to-date body of knowledge, and the extent to which there exists evidence of the benefits of moderate wine consumption on oxidative damage in humans. From the available data, there is no evidence, at present, that sustained wine consumption provides antioxidant benefits in healthy volunteers other than to counteract a possible pro-oxidative effect of the alcohol. On the contrary, data on the antioxidant protective effect of red wine in oxidative stress situations are promising. In this way, the postprandial oxidative stress after a meal, despite the diversity of biomarkers used for its evaluation, is counteracted by the ingestion of wine. Further studies are warranted.


      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


        • Covas M.I.
        The mediterranean diet and the role of alcohol.
        in: Victor R. Preedy Ronald R. Watson Compressive handbook of alcohol related pathology. Elsevier Science, 2004: 135-146 ([Chapter 12])
        • Bertelli A.A.E.
        Wine, research and cardiovascular disease: instructions for use.
        Atherosclerosis. 2007; 195: 242-247
        • Rodríguez Artalejo F.
        • Banegas J.R.
        • García Colmenero C.
        • del Rey Calero J.
        Lower consumption of wine and fish as a possible explanation for higher ischemic heart disease mortality in Spain's Mediterranean region.
        Int J Epidemiol. 1996; 25: 1196-1201
        • Tunstall-Pedoe H.
        • Kuulasma K.
        • Mahonen M.
        • et al.
        Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10 year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease.
        Lancet. 1999; 353: 1547-1557
        • Schröder H.
        • Marrugat J.
        • Fitó M.
        • Weinbrenner T.
        • Covas M.I.
        Alcohol consumption is directly associated with circulating oxidized low-density lipoprotein.
        Free Rad Biol Med. 2006; 40: 1474-1481
        • Yoshida R.
        • Shioji I.
        • Kishida A.
        • Ogawa Y.
        Moderate alcohol consumption reduces urinary 8-hydroxydeoxyguanosine by inducing of uric acid.
        Ind Health. 2001; 39: 322-329
        • Barden A.
        • Zilkens R.R.
        • Croft K.
        • et al.
        A reduction in alcohol consumption is associated with reduced plasma F2-isoprostanes and urinary 20-HETE excretion in men.
        Free Rad Biol Med. 2007; 42: 1730-1735
        • Hartman T.J.
        • Baer D.J.
        • Graham L.B.
        • et al.
        Moderate alcohol consumption and levels of antioxidant vitamins and isoprostanes in postmenopausal women.
        Eur J Clin Nutr. 2005; 59: 161-168
        • Beulens J.W.J.
        • Van der Berg R.
        • Kok F.J.
        • et al.
        Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity.
        Nutr Met Cardiovasc Dis. 2008; 18: 539-544
        • Videla L.A.
        • Valenzuela A.
        Alcohol ingestion, liver glutathione and lipoperoxidation: metabolic interrelations and pathological implications.
        Life Sci. 1987; 31: 2395-2407
        • Woolf S.H.
        • Battista R.N.
        • Anderson G.M.
        • Logan A.G.
        • Wang E.
        Assessing the clinical effectiveness of preventive manoeuvres: analytic principals and systematic methods in reviewing evidence and developing clinical practice recommendations. A report by the Canadian Task Force on the Periodic Health Examination.
        J Clin Epidemiol. 1990; 43: 891-905
        • Witzum J.L.
        The oxidation hypothesis of atherosclerosis.
        Lancet. 1994; 344: 793-795
        • Cooke M.S.
        • Evans M.D.
        • Dizdaroglou M.
        • Lunec J.
        Oxidative DNA damage: mechanisms, mutation, and disease.
        FASEB J. 2003; 17: 1195-1214
        • Andreassi M.A.
        Coronary atherosclerosis and somatic mutations: an overview of the contributive factors for oxidative DNA damage.
        Mutat Res. 2003; 543: 67-68
        • Nagata K.
        • Suzuki H.
        • Sakaguchi S.
        Common pathogenic mechanisms in the development progression of liver injury caused by non-alcoholic or alcoholic steatohepatitis.
        J Toxicol Sci. 2007; 32: 453-468
        • Catapano A.L.
        Antioxidant effects of flavonoids.
        Angiology. 1997; 48: 39-41
        • Modun D.
        • Music I.
        • Vukovic J.
        • et al.
        The increase in human plasma antioxidant capacity after red wine consumption is due to both plasma urate and wine polyphenols.
        Atherosclerosis. 2008; 197: 250-256
        • Devaraj S.
        • Vega-López S.
        • Kaul N.
        • et al.
        Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the lipoprotein profile.
        Lipids. 2002; 37: 931-934
        • Covas M.I.
        • Nyyssönen K.
        • Poulsen H.E.
        • et al.
        The effect of polyphenols in olive oil on heart disease risk factors.
        Ann Int Med. 2006; 145: 333-341
        • Ansell B.J.
        • Watson K.E.
        • Fogelman A.M.
        • et al.
        High-density lipoprotein function. Recent advances.
        J Am Coll Cardiol. 2005; 46: 1792-1798
        • Gouédard C.
        • Barouki R.
        • Morel Y.
        Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism.
        Moll Cell Biol. 2004; 24: 5209-5222
        • Nielsen S.E.
        • Young J.F.
        • Daneshvar B.
        • et al.
        Effect of parsley (Petroselium crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress.
        Br J Nutr. 1999; 81: 447-455
        • Hadi S.M.
        • Bhat S.H.
        • Azmi A.S.
        • et al.
        Oxidative breakage of cellular DNA by plant polyphenols: a putative mechanism for anticancer properties.
        Semin Cancer Biol. 2007; 17: 370-376
        • Vinson J.A.
        • Hontz B.A.
        Phenol antioxidant index: comparative antioxidant effectiveness of red and white wines.
        J Agric Food Chem. 1995; 43: 401-403
        • German J.B.
        • Walzem R.L.
        The health benefits of wine.
        Annu Rev Nutr. 2000; 20: 561-593
        • Ursini F.
        • Zamburlini A.
        • Cazzolato G.
        • et al.
        Postprandial plasma lipid hydroperoxides: a possible link between diet and atherosclerosis.
        Free Radic Biol Med. 1998; 25: 250-252
        • Bub A.
        • Wtzl B.
        • Heeb D.
        • Rechkemmer G.
        • Briviba K.
        Malvidin-3-glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice.
        Eur J Nutr. 2001; 40: 113-120
        • De Vries J.H.M.
        • Hollman P.C.H.
        • Van Amersfoort I.
        • Olyhof M.R.
        • Katan M.B.
        Red wine is a poor source of bioavailable phenol in men.
        J Nutr. 2001; 131: 745-748
        • Donovan J.L.
        • Bell J.R.
        • Kasim-Karakas S.
        • et al.
        Catechin is present as metabolites in human plasma after consumption of red wine.
        J Nutr. 1999; 129: 1662-1668
        • 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
        • Vitaglione P.
        • Sforza S.
        • Galaverna G.
        • et al.
        Bioavailability of trans-resveratrol from red wine in humans.
        Mol Nutr Food Res. 2005; 49: 495-504
        • Urpi-Sardà M.
        • Zamora-Ros R.
        • Lamuela-Raventós R.
        • et al.
        HPLC-tandem mass spectrometric method to characterize resveratrol metabolism in humans.
        Clin Chem. 2007; 53: 292-299
        • Cartron E.
        • Fouret G.
        • Carbonneau M.A.
        • et al.
        Red-wine beneficial long term effect on lipids but not on antioxidant characteristics in plasma in a study comparing three types of wine. Description of two O-methylated derivatives of gallic acid in humans.
        Free Rad Res. 2003; 37: 1021-1035
        • Zamora-Ros R.
        • Urpí-Sardà M.
        • Lamuela-Raventós R.
        • et al.
        • The PREDIMED study
        Resveratrol metabolites in urine as a biomarker of wine intake in free-living subjects.
        Free Radic Bio Med. 2009; 46: 1562-1566
        • Day A.J.
        • Bao Y.
        • Morgan M.R.A.
        • Williamson G.
        Conjugation position of quercetin glucuronides and effect on biological activity.
        Free Radic Biol Med. 2000; 29: 1234-1243
        • Santner S.J.
        • Fiel P.D.
        • Santen R.J.
        In situ estrogen production via estrone sulphatase pathway in breast tumours: relative importance versus aromatase pathway.
        J Clin Endocrinol Metab. 1984; 50: 29-33
        • Shimoi K.
        • Saka N.
        • Nozawa R.
        • et al.
        Deglucuronidation of a flavonoid, luteolin monoglucuronide, during inflammation.
        Drug Metab Dispos. 2001; 29: 1521-1554
        • Urpi-Sardá M.
        • Jáuregui O.
        • Lamuela-Raventós R.M.
        • et al.
        Uptake of diet resveratrol into the human low-density lipoprotein. Identification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry.
        Anal Chem. 2005; 77: 3149-3155
        • Arendt B.M.
        • Ellinger S.
        • Kekic K.
        • et al.
        Single and repeated moderate consumption of native or dealcoholized red wine show different effects on antioxidant parameters in blood and DNA strand breaks in peripheral leukocytes in healthy volunteers: a randomized controlled trial (ISRCTN68505294).
        J Nutr. 2005; 4: 33
        • Duthie G.G.
        • Pedersen M.W.
        • Gardner P.T.
        • et al.
        The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers.
        Eur J Clin Nutr. 1998; 52: 733-736
        • Kiviniemi T.O.
        • Saraste A.
        • Toikka J.O.
        • et al.
        A moderate dose of red wine, but not de-alcoholized red wine increases coronary flow reserve.
        Atherosclerosis. 2007; 195: 176-181
        • Caccetta R.A.A.
        • Croft K.D.
        • Beilin L.J.
        • Puckley I.B.
        Ingestion of red wine significantly increases plasma phenolic acid concentrations but does not acutely affect ex vivo lipoprotein oxidability.
        Am J Clin Nutr. 2000; 71: 67-74
        • Ziegler S.
        • Kostner K.
        • Thallinger C.
        • et al.
        Wine ingestion has no effect on lipid peroxidation products.
        Pharmacology. 2005; 75: 152-156
        • Greenrod W.
        • Stockley C.S.
        • Burcham P.
        • Abbey M.
        • Fenech M.
        Moderate acute intake of de-alcoholized red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo. Results of a comparative in vivo intervention study in younger men.
        Mut Res. 2005; 591: 290-300
        • Ceriello A.
        • Taboga C.
        • Tonutti L.
        • et al.
        Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment.
        Circulation. 2002; 106: 1211-1218
        • Maxwell S.
        • Crickdhank A.
        • Thorpe G.
        Red wine and antioxidant activity in serum.
        Lancet. 1994; 344: 193-194
        • Natella F.
        • Ghiselli A.
        • Guidi A.
        • Ursini F.
        • Scaccini C.
        Red wine mitigates the postprandial increase of LDL susceptibility to oxidation.
        Free Radic Biol Med. 2001; 30: 1036-1044
        • Ventura P.
        • Bini A.
        • Panini R.
        • et al.
        Red wine consumption prevents vascular oxidative stress induced by a high-fat meal in healthy volunteers.
        Int J Vitam Nutr Res. 2004; 74: 137-143
        • Gorelik S.
        • Ligumsky M.
        • Kohen R.
        • Kanner J.
        A novel function of red wine polyphenols in humans: prevention of absorption of cytotoxic lipid peroxidation products.
        FASEB J. 2008; 22: 41-46
        • Ceriello A.
        • Bortolotti N.
        • Motz E.
        • et al.
        Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation: a pleasant approach to the prevention of cardiovascular disease in diabetes.
        Eur J Clin Invest. 2001; 3: 322-328
        • Blackhurst D.M.
        • Marais A.D.
        Concomitant consumption of red wine and polyunsaturated fat acids in edible oils does not influence the peroxidation status of chylomicron lipids despite increasing plasma catechin concentration.
        Nutr Met Cardiovasc Dis. 2006; 16: 550-558
        • Nigdikar S.V.
        • Williams N.R.
        • Griffin B.A.
        • Howard A.N.
        Consumption of red wine polyphenols reduces the susceptibility of low-density lipoproteins to oxidation in vivo.
        Am J Clin Nutr. 1998; 68: 258-265
        • Tsang C.
        • Higgins S.
        • Duthie G.G.
        • et al.
        The influence of moderate red wine consumption on antioxidant status and indices of oxidative stress associated with CHD in healthy volunteers.
        Br J Nutr. 2005; 93: 233-240
        • Caccetta A.A.R.
        • Burke V.
        • Mori T.A.
        • et al.
        Red wine polyphenols in the absence of alcohol, reduce lipid peroxidative stress in smoking subjects.
        Free Rad Biol Med. 2001; 30: 636-642
        • Micallef M.
        • Lexis L.
        • Lewandowski P.
        Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans.
        Nutr J (BioMed Central). 2007; 6: 27
        • Otaolaurruchi E.
        • Fernández-Pachón M.S.
        • González A.G.
        • Troncoso A.M.
        • García-Parrilla M.C.
        Repeated red wine consumption and changes on plasma antioxidant capacity and endogenous antioxidants (uric acid and protein thiol groups).
        J Agric Food Chem. 2007; 55: 9713-9716
        • Addolorato G.
        • Leggio L.
        • Ojetti V.
        • et al.
        Effects of short-term moderate alcohol administration on oxidative stress and nutritional status in healthy males.
        Appetite. 2008; 50: 50-56
        • Guarda E.
        • Godoy I.
        • Foncea R.
        • et al.
        Red wine reduces oxidative stress in patients with acute coronary syndrome.
        Int J Cardiol. 2005; 104: 35-38
        • Marfella R.
        • Cacciapuoti F.
        • Siniscalchi M.
        • et al.
        Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with type 2 diabetes mellitus.
        Diabet Med. 2006; 23: 974-981
        • Weinbrenner T.
        • Cladellas M.
        • Covas M.I.
        • et al.
        High oxidative stress in patients with stable coronary heart disease.
        Atherosclerosis. 2003; 168: 99-106
        • Acín S.
        • Navarro M.A.
        • Arbonés-Mainar J.M.
        • et al.
        Hydroxytyrosol administration enhances atherosclerotic lesion development in apo E deficient mice.
        J Biochem. 2006; 140: 383-391
        • Halliwell B.
        Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies?.
        Arch Biochem Biophys. 2008; 476: 107-112
        • Halliwell B.
        • Whiteman M.
        Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?.
        Br J Pharmacol. 2004; 142: 231-255
        • Haliwell B.
        The wanderings of a free radical.
        Free Rad Biol Med. 2009; 46: 531-542
        • Shimada K.
        • Mokuno H.
        • Matsunaga E.
        • et al.
        Circulating oxidized low-density lipoprotein is an independent predictor for cardiac event in patients with coronary heart disease.
        Atherosclerosis. 2004; 174: 343-347
        • Blankenberg S.
        • Rupprecht H.J.
        • Bickel C.
        • et al.
        AtheroGene Investigators. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary heart disease.
        New Engl J Med. 2003; 349: 1605-1613
        • Sacanella E.
        • Vázquez-Agell M.
        • Mena M.P.
        • et al.
        Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial.
        Am J Clin Nutr. 2007; 86: 1463-1469
        • Vázquez-Agell M.
        • Sacanella E.
        • Tobias E.
        • et al.
        Inflammatory markers of atherosclerosis are decreased after moderate consumption of cava (sparkling wine) in men with low cardiovascular risk.
        J Nutr. 2007; 137: 2279-2284
        • Khansari N.
        • Shakiba Y.
        • Mahmoudi M.
        Chronic inflammation and oxidative stress as a major cause of age-related diseases.
        Recent Pat Inflamm Allergy Drug Discov. 2009; 31: 73-80
        • Hongjun L.
        • Colavitti R.
        • Rovira I.I.
        • Finkel T.
        Redox-dependent transcriptional regulation.
        Cir Res. 2005; 97: 967-974