High plasma levels of α- and β-carotene are associated with a lower risk of atherosclerosis

Results from the Bruneck study


      Background and purpose: A large number of studies have contributed to the hypothesis that carotenoids, vitamins A and E are protective against atherosclerosis by acting as antioxidants. The aim of this study was to assess the relationship between plasma levels of carotenoids (α- and β- carotene, lutein, lycopene, zeaxanthin, β-cryptoxanthin), vitamins A and E, and atherosclerosis in the carotid and femoral arteries. Methods: This prospective and cross sectional study involved a randomly selected population sample of 392 men and women aged 45–65 years. Carotid and femoral artery atherosclerosis was assessed by high-resolution duplex ultrasound. Results: α- and β- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries (P=0.004) and with the 5-year incidence of atherosclerotic lesions in the carotid arteries (P=0.04). These findings were obtained after adjustment for other cardiovascular risk factors (sex, age, LDL (low density lipoproteins), ferritin, systolic blood pressure, smoking, categories of alcohol consumption, social status, C-reactive protein). Atherosclerosis risk gradually decreased with increasing plasma α- and β-carotene concentrations (P=0.004). No associations were found between vitamin A and E plasma levels and atherosclerosis. Conclusions: This study provides further epidemiological evidence of a protective role of high α- and β- carotene in early atherogenesis.


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        • Steinberg D.
        • Parathasarathy S.
        • Carew T.E.
        • Khoo J.C.
        • Witztum J.L.
        Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity.
        N. Engl. J. Med. 1989; 320: 915-924
        • Ross R.
        The pathogenesis of atherosclerosis: a perspective for the 1990s.
        Nature. 1993; 362: 801-809
        • Witztum J.L.
        The oxidation hypothesis of atherosclerosis.
        Lancet. 1994; 344: 793-795
        • Shaish A.
        • Daugherty A.
        • O'Sullivan F.
        • Shonfeld G.
        • Heinecke J.W.
        Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits.
        J. Clin. Invest. 1995; 96: 2075-2082
        • Bellizzi M.C.
        • Franklin M.F.
        • Duthie G.G.
        • James W.P.
        Vitamin E and coronary heart disease: the European paradox.
        Eur. J. Clin. Nutr. 1994; 48: 822-831
        • Knekt P.
        • Reunanen A.
        • Jarvinen R.
        • Seppanen R.
        • Heliovaara M.
        • Aromaa A.
        Antioxidant vitamin intake and coronary mortality in a longitudinal population study.
        Am. J. Epidemiol. 1994; 139: 1180-1189
        • Pandey D.K.
        • Shekelle R.
        • Selwyn B.J.
        • Tangney C.
        • Stamler J.
        Dietary vitamin C and beta-carotene and risk of death in middle-aged men: the Western Electric Study.
        Am. J. Epidemiol. 1995; 142: 1269-1278
        • Kushi L.H.
        • Folsom A.R.
        • Prineas R.J.
        • Mink P.J.
        • Wu Y.
        • Bostick R.M.
        Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women.
        New Engl. J. Med. 1996; 334: 1156-1162
        • Gey K.F.
        • Stahelin H.B.
        • Eichholzer M.
        Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study.
        Clin. Investig. 1993; 71: 3-6
        • Singh R.B.
        • Ghosh S.
        • Niaz M.A.
        • Singh R.
        • Beegum R.
        • Chibo H.
        • Shoumin Z.
        • Postiglione A.
        Dietary intake, plasma levels of antioxidant vitamins, and oxidative stress in relation to coronary artery disease in elderly subjects.
        Am. J. Cardiol. 1995; 76: 1233-1238
        • Morris D.L.
        • Kritchevsky S.B.
        • Davis C.E.
        Serum carotenoids and coronary heart disease: the Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study.
        J. Am. Med. Assoc. 1994; 272: 1439-1441
        • Street D.A.
        • Comstock G.W.
        • Salkeld R.M.
        • Schuep W.
        • Klag M.J.
        Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction?.
        Circulation. 1994; 90: 1154-1161
        • Riemersma R.A.
        • Wood D.A.
        • Macintyre C.C.
        • Elton R.A.
        • Gey K.F.
        • Oliver M.F.
        Risk of angina pectoris and plasma concentrations of vitamin A, C, and E and carotene.
        Lancet. 1991; 337: 1-5
        • Steinberg D.
        Clinical trials of antioxidants in atherosclerosis: are we doing the right thing?.
        Lancet. 1995; 346: 36-38
        • Dowd P.
        • Zheng Z.B.
        On the mechanism of the anticlotting action of vitamin E quinone.
        Proc. Natl. Acad. Sci. 1995; 92: 8171-8175
        • Calzada C.
        • Bruckdorfer K.R.
        • Rice-Evans C.A.
        The influence of antioxidant nutrients on platelet function in healthy volunteers.
        Atherosclerosis. 1997; 128: 97-105
        • Keaney J.F.
        • Simon D.I.
        • Freedman J.E.
        Vitamin E and vascular homeostasis: implications for atherosclerosis.
        FASEB J. 1999; 13: 965-976
        • Bonithon-Kopp C.
        • Coudray C.
        • Berr C.
        • Touboul P.J.
        • Fève J.M.
        • Favier A.
        • Ducimetière P.
        Combined effects of lipid peroxidation and antioxidant status on carotid atherosclerosis in a population aged 59–71 years: the EVA study.
        Am. J. Clin. Nutr. 1997; 65: 121-127
        • Kiechl S.
        • Willeit J.
        • Egger G.
        • Poewe W.
        • Oberhollenzer F.
        Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study.
        Circulation. 1997; 96: 3300-3307
        • Willeit J.
        • Kiechl S.
        Prevalence and risk factors of asymptomatic extracranial carotid artery atherosclerosis: a population-based study.
        Arterioscler. Thromb. 1993; 13: 661-668
        • Kiechl S.
        • Willeit J.
        The natural history of atherosclerosis. Part I: Incidence and progression.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 1484-1490
        • Kiechl S.
        • Willeit J.
        The natural history of atherosclerosis. Part II: vascular remodeling.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 1491-1498
        • Kiechl S.
        • Willeit J.
        • Egger Oberhollenzer M.
        • Aichner F.
        Alcohol consumption and carotid atherosclerosis: evidence of dose-dependent atherogenic and antiatherogenic effects: results from the Bruneck study.
        Stroke. 1994; 25: 1593-1598
        • Lowe G.M.
        • Bilton R.F.
        • Young A.J.
        • Graham J.M.
        • Ford T.C.
        • Billington D.
        Carotenoid profiles of human plasma lipoproteins.
        Biochem. Soc. Trans. 1996; 24: 171S
        • Abbey M.
        • Nestel P.J.
        • Baghurst P.A.
        Antioxidant vitamins and low-density lipoprotein oxidation.
        Am. J. Clin. Nutr. 1993; 58: 525-532
        • Jialal I.
        • Norkus E.P.
        • Cristol L.
        • Grundy S.M.
        Beta-carotene inhibits the oxidative modification of low-density lipoprotein.
        Biochim. Biophys. Acta. 1991; 1086: 134-138
        • Parker R.S.
        Carotenoids in human blood and tissues.
        J. Nutr. 1989; 119: 101-104
        • Kritchevsky S.B.
        • Shimakawa T.
        • Tell G.S.
        • et al.
        Dietary antioxidants and carotid artery wall thickness: the ARIC Study.
        Circulation. 1995; 92: 2142-2150
        • Kardinaal A.F.
        • Kok F.J.
        • Ringstad J.
        • et al.
        Antioxidants in adipose tissue and risk of myocardial infarction: the EURAMIC study.
        Lancet. 1993; 342: 1379-1384
        • Blot W.J.
        • Li J.Y.
        • Taylor P.R.
        • et al.
        Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population.
        J. Natl. Cancer Inst. 1993; 85: 1483-1492
        • Gaziano J.M.
        • Hennekens C.H.
        Antioxidant vitamins in the prevention of coronary artery disease.
        Cont. Int. Med. 1995; 7: 9-14
        • Hennekens C.H.
        • Buring J.E.
        • Manson J.E.
        • et al.
        Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.
        New Engl. J. Med. 1996; 334: 1145-1149
        • Alpha-Tocopherol, Beta carotene Cancer Prevention Study Group
        The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers.
        New Engl. J. Med. 1994; 330: 1029-1035
        • Omenn G.S.
        • Goodman G.E.
        • Thornquist M.D.
        • et al.
        Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.
        N. Engl. J. Med. 1996; 334: 1150-1155
        • Levin G.
        • Mokady S.
        Antioxidant activity of 9-cis compared to all-trans beta-carotene in vitro.
        Free Radic. Biol. Med. 1994; 17: 77-82
        • Ben-Amotz A.
        • Levy Y.
        Bioavailability of a natural isomer mixture compared with synthetic all-trans beta-carotene in human serum.
        Am. J. Clin. Nutr. 1996; 63: 729-734
        • Stampfer M.J.
        • Hennekens C.H.
        • Manson J.E.
        • Colditz G.A.
        • Rosner B.
        • Willett W.C.
        Vitamin E consumption and the risk of coronary disease in women.
        N. Engl. J. Med. 1993; 328: 1444-1449
        • Rimm E.B.
        • Stampfer M.J.
        • Ascherio A.
        • Giovannucci E.
        • Colditz G.A.
        • Willett M.C.
        Vitamin E consumption and the risk of coronary heart disease in men.
        N. Engl. J. Med. 1993; 328: 1450-1456
        • Spencer A.P.
        • Carson D.S.
        • Crouch M.A.
        Vitamin E and coronary artery disease.
        Arch. Intern. Med. 1999; 159: 1313-1319
        • Upston J.M.
        • Terentis A.C.
        • Stocker R.
        Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement.
        FASEB J. 1999; 13: 977-994