Lycopene, lutein and β-carotene as determinants of LDL conjugated dienes in serum


      Oxidative modification of low-density lipoprotein (LDL) in the vascular endothelium is considered to be important in the development of early atherosclerosis. The aim of this study was to investigate the main determinants of serum LDL conjugated dienes in women (n = 124) and men (n = 225). We focused on the influence of fat-soluble vitamins and carotenoids on the concentration of conjugated dienes in LDL. In multivariate linear regression models, including age, body mass index, diastolic blood pressure, symptomatic ischaemic heart disease (IHD) or IHD history, statin medication, leukocytes and serum triglycerides as covariates, plasma lycopene (standardized β = −0.33; P = 0.002) and lutein (standardized β = −0.22; P = 0.027) concentrations were the strongest determinants of serum LDL conjugated dienes in women, whereas plasma β-carotene (standardized β = −0.23; P = 0.002) was the most important factor in men. Furthermore, statin medication, diastolic blood pressure, age and serum triglycerides were significant determinants of LDL conjugated dienes. The regression model with lycopene contributed to 29% in women and 15% in men with β-carotene of the variation of serum LDL conjugated dienes. Results of the present study suggest that plasma lycopene, lutein and β-carotene are the most powerful antioxidants for explaining the content of in vivo oxidatively modified LDL in serum.


      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


        • Steinberg D.
        The LDL modification hypothesis of atherogenesis: an update.
        J Lipid Res. 2008; 15: 1-25
        • Stocker R.
        • Keaney Jr, J.F.
        Role of oxidative modifications in atherosclerosis.
        Physiol Rev. 2004; 84: 1381-1478
        • Abbey M.
        • Noakes M.
        • Nestel P.J.
        Dietary supplementation with orange and carrot juice in cigarette smokers lowers oxidation products in copper-oxidized low-density lipoproteins.
        J Am Diet Assoc. 1995; 95: 671-675
        • Salonen J.T.
        • Nyyssonen K.
        • Salonen R.
        • et al.
        Lipoprotein oxidation and progression of carotid atherosclerosis.
        Circulation. 1997; 95: 840-845
        • Halliwell B.
        Lipid peroxidation, antioxidants and cardiovascular disease: how should we move forward?.
        Cardiovasc Res. 2000; 47: 410-418
        • Hulthe J.
        Antibodies to oxidized LDL in atherosclerosis development—clinical and animal studies.
        Clin Chim Acta. 2004; 348: 1-8
        • Ahotupa M.
        • Vasankari T.J.
        Baseline diene conjugation in LDL lipids: an indicator of circulating oxidized LDL.
        Free Radic Biol Med. 1999; 27: 1141-1150
        • Kaikkonen J.
        • Tuomainen T.P.
        • Nyyssonen K.
        • Morrow J.D.
        • Salonen J.T.
        C18 hydroxy fatty acids as markers of lipid peroxidation ex vivo and in vivo.
        Scand J Clin Lab Invest. 2004; 64: 457-468
        • Ahotupa M.
        • Ruutu M.
        • Mantyla E.
        Simple methods of quantifying oxidation products and antioxidant potential of low density lipoproteins.
        Clin Biochem. 1996; 29: 139-144
        • Ahotupa M.
        • Marniemi J.
        • Lehtimaki T.
        • et al.
        Baseline diene conjugation in LDL lipids as a direct measure of in vivo LDL oxidation.
        Clin Biochem. 1998; 31: 257-261
        • Vasankari T.
        • Lehtonen-Veromaa M.
        • Mottonen T.
        • et al.
        Reduced mildly oxidized LDL in young female athletes.
        Atherosclerosis. 2000; 151: 399-405
        • Tapiero H.
        • Townsend D.M.
        • Tew K.D.
        The role of carotenoids in the prevention of human pathologies.
        Biomed Pharmacother. 2004; 58: 100
        • Upritchard J.E.
        • Sutherland W.H.
        • Mann J.I.
        Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes.
        Diabetes Care. 2000; 23: 733-738
        • Agarwal S.
        • Rao A.V.
        Tomato lycopene and low density lipoprotein oxidation: a human dietary intervention study.
        Lipids. 1998; 33: 981-984
        • Levy Y.
        • Kaplan M.
        • Ben-Amotz A.
        • Aviram M.
        Effect of dietary supplementation of beta-carotene on human monocyte-macrophage-mediated oxidation of low density lipoprotein.
        Isr J Med Sci. 1996; 32: 473-478
        • Dugas T.R.
        • Morel D.W.
        • Harrison E.
        Dietary supplementation with beta-carotene, but not with lycopene, inhibits endothelial cell-mediated oxidation of low-density lipoprotein.
        Free Radic Biol Med. 1999; 26: 1238-1244
        • Salonen J.T.
        Is there a continuing need for longitudinal epidemiologic research? The kuopio ischaemic heart disease risk factor study.
        Ann Clin Res. 1988; 20: 46-50
        • Mursu J.
        • Voutilainen S.
        • Nurmi T.
        • et al.
        Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans.
        Free Radic Biol Med. 2004; 37: 1351-1359
        • Karppi J.
        • Nurmi T.
        • Olmedilla-Alonso B.
        • Granado-Lorencio F.
        • Nyyssonen K.
        Simultaneous measurement of retinol, alpha-tocopherol and six carotenoids in human plasma by using an isocratic reversed-phase HPLC method.
        J Chromatogr B: Anal Technol Biomed Life Sci. 2008; 867: 226-232
        • International Federation of Clinical Chemistry and Laboratory Medicine
        IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International federation of clinical chemistry and laboratory medicine. Part 7. Certification of four reference materials for the determination of enzymatic activity of gamma-glutamyltransferase, lactate dehydrogenase, alanine aminotransferase and creatine kinase accord.
        Clin Chem Lab Med. 2002; 40: 739-745
        • Mursu J.
        • Nurmi T.
        • Tuomainen T.P.
        • et al.
        The intake of flavonoids and carotid atherosclerosis: the kuopio ischaemic heart disease risk factor study.
        Br J Nutr. 2007; 98: 814-818
        • Jordan P.
        • Brubacher D.
        • Moser U.
        • Stahelin H.B.
        • Gey K.F.
        Vitamin E and vitamin A concentrations in plasma adjusted for cholesterol and triglycerides by multiple regression.
        Clin Chem. 1995; 41: 924-927
        • Porkkala-Sarataho E.
        • Nyyssonen K.
        • Salonen J.T.
        Increased oxidation resistance of atherogenic plasma lipoproteins at high vitamin E levels in non-vitamin E supplemented men.
        Atherosclerosis. 1996; 124: 83-94
        • Parks E.J.
        • German J.B.
        • Davis P.A.
        • et al.
        Reduced oxidative susceptibility of LDL from patients participating in an intensive atherosclerosis treatment program.
        Am J Clin Nutr. 1998; 68: 778-785
        • Carpenter K.L.
        • van der Veen C.
        • Hird R.
        • et al.
        The carotenoids beta-carotene, canthaxanthin and zeaxanthin inhibit macrophage-mediated LDL oxidation.
        FEBS Lett. 1997; 401: 262-266
        • Hininger I.A.
        • Meyer-Wenger A.
        • Moser U.
        • et al.
        No significant effects of lutein, lycopene or beta-carotene supplementation on biological markers of oxidative stress and LDL oxidizability in healthy adult subjects.
        J Am Coll Nutr. 2001; 20: 232-238
        • Silaste M.L.
        • Alfthan G.
        • Aro A.
        • Kesaniemi Y.A.
        • Horkko S.
        Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation.
        Br J Nutr. 2007; 98: 1251-1258
        • Visioli F.
        • Riso P.
        • Grande S.
        • Galli C.
        • Porrini M.
        Protective activity of tomato products on in vivo markers of lipid oxidation.
        Eur J Nutr. 2003; 42: 201-206
        • Porrini M.
        • Riso P.
        • Brusamolino A.
        • et al.
        Daily intake of a formulated tomato drink affects carotenoid plasma and lymphocyte concentrations and improves cellular antioxidant protection.
        Br J Nutr. 2005; 93: 93-99
        • Wolters M.
        • Hahn A.
        LDL susceptibility to copper-induced oxidation after administration of a single dose of free or esterified beta-cryptoxanthin.
        Ann Nutr Metab. 2004; 48: 163-168
        • Kioskias S.
        • Gordon M.H.
        Dietary supplementation with a natural carotenoid mixture decreases oxidative stress.
        Eur J Clin Nutr. 2003; 57: 1135-1140
        • Lin Y.
        • Burri B.J.
        • Neidlinger T.R.
        • et al.
        Estimating the concentration of β-carotene required for maximal protection of low-density lipoproteins in women.
        Am J Clin Nutr. 1998; 67: 837-845
        • Milde J.
        • Elstner E.F.
        • Grassmann J.
        Synergistic effects of phenolics and carotenoids on human low-density lipoprotein oxidation.
        Mol Nutr Food Res. 2007; 51: 956-961
      1. Peroxidation mechanism. Available at (read 1.4.2009).

        • McNulty H.
        • Jacob R.F.
        • Mason R.P.
        Biologic activity of carotenoids related to distinct membrane physicochemical interactions.
        Am J Cardiol. 2008; 22: 20D-29D
        • Miller N.J.
        • Sampson J.
        • Candeias L.P.
        • Bramley P.M.
        • Rice-Evans C.A.
        Antioxidant activities of carotenes and xanthophylls.
        FEBS Lett. 1996; 22: 240-242
        • Holvoet P.
        • Mertens A.
        • Verhamme P.
        • et al.
        Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease.
        Arterioscler Thromb Vasc Biol. 2001; 21: 844-848
        • Keaney Jr, J.F.
        • Larson M.G.
        • Vasan R.S.
        • et al.
        Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the framingham study.
        Arterioscler Thromb Vasc Biol. 2003; 23: 434-439
        • Linna M.S.
        • Borg P.
        • Kukkonen-Harjula K.
        • et al.
        Successful weight maintenance preserves lower levels of oxidized LDL achieved by weight reduction in obese men.
        Int J Obes (Lond). 2007; 31: 245-253
        • Vasankari T.
        • Fogelholm M.
        • Kukkonen-Harjula K.
        • et al.
        Reduced oxidized low-density lipoprotein after weight reduction in obese premenopausal women.
        Int J Obes Relat Metab Disord. 2001; 25: 205-211
        • Krajcovicova-Kudlackova M.
        • Valachovicova M.
        • Paukova V.
        • Dusinska M.
        Effects of diet and age on oxidative damage products in healthy subjects.
        Physiol Res. 2008; 57: 647-651
        • Wakatsuki A.
        • Okatani Y.
        • Ikenoue N.
        • et al.
        Effect of lower dose of oral conjugated equine estrogen on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women.
        Circulation. 2003; 108: 808-813
        • Memon R.A.
        • Staprans I.
        • Noor M.
        • et al.
        Infection and inflammation induce LDL oxidation in vivo.
        Arterioscler Thromb Vasc Biol. 2000; 20: 1536-1542
        • Panza J.A.
        • Garcia C.E.
        • Kilcoyne C.M.
        • Quyyumi A.A.
        • Cannon III, R.O.
        Impaired endothelium-dependent vasodilation in patients with essential hypertension. Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway.
        Circulation. 1995; 91: 1732-1738
        • Engelhard Y.N.
        • Gazer B.
        • Paran E.
        Natural antioxidants from tomato extract reduce blood pressure in patients with grade-1 hypertension: a double-blind, placebo-controlled pilot study.
        Am Heart J. 2006; 151: 100
        • Rosenson R.S.
        Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities.
        Atherosclerosis. 2004; 173: 1-12
        • Lapointe A.
        • Couillard C.
        • Piche M.E.
        • et al.
        Circulating oxidized LDL is associated with parameters of the metabolic syndrome in postmenopausal women.
        Atherosclerosis. 2007; 191: 362-368
        • Muda P.
        • Kampus P.
        • Teesalu R.
        • et al.
        Effects of amlodipine and candesartan on oxidized LDL level in patients with mild to moderate essential hypertension.
        Blood Press. 2006; 15: 313-318
        • Vasankari T.
        • Ahotupa M.
        • Viikari J.
        • et al.
        Effects of statin therapy on circulating conjugated dienes, a measure of LDL oxidation.
        Atherosclerosis. 2005; 179: 207-209
        • Jula A.
        • Marniemi J.
        • Huupponen R.
        • et al.
        Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial.
        JAMA. 2002; 287: 598-605
        • Mates J.M.
        Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology.
        Toxicology. 2000; 153: 83-104
        • Caner M.
        • Karter Y.
        • Uzun H.
        • et al.
        Oxidative stress in human in sustained and white coat hypertension.
        Int J Clin Pract. 2006; 60: 1565-1571
        • Forstermann U.
        Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies.
        Nat Clin Pract Cardiovasc Med. 2008; 5: 338-349
        • Uzun H.
        • Karter Y.
        • Aydin S.
        • et al.
        Oxidative stress in white coat hypertension; role of paraoxonase.
        J Hum Hypertens. 2004; 18: 523-528
        • Nyyssonen K.
        • Porkkala-Sarataho E.
        • Kaikkonen J.
        • Salonen J.T.
        Ascorbate and urate are the strongest determinants of plasma antioxidative capacity and serum lipid resistance to oxidation in Finnish men.
        Atherosclerosis. 1997; 130: 223-233
        • Niskanen L.K.
        • Laaksonen D.E.
        • Nyyssonen K.
        • et al.
        Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study.
        Arch Intern Med. 2004; 164: 1546-1551
        • Rissanen T.H.
        • Voutilainen S.
        • Virtanen J.K.
        • et al.
        Low intake of fruits, berries and vegetables is associated with excess mortality in men: the kuopio ischaemic heart disease risk factor (KIHD) study.
        J Nutr. 2003; 133: 199-204
      2. Rissanen T. Association of lycopene and dietary intake of fruits, berries and vegetables with atherosclerosis and cardiovascular diseases: epidemiologic evidence, Kuopio; 2003, p. 73 [36]s.