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Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infarction

European Journal of Clinical Nutrition volume 57, pages 793–800 (2003)Cite this article

Abstract

Objective: To assess the oxidative burden of a highly concentrated compound of n-3 PUFAs as compared to corn oil by measuring thiobarbituric acid–malondialdehyde complex (TBA–MDA) by HPLC. We also studied the influence on TBA–MDA of statins combined with n-3 PUFAs or corn oil.

Design: A prospective, randomised, double-blind, controlled study.

Setting: One hospital centre in Stavanger, Norway.

Subjects: A total of 300 subjects with an acute myocardial infarction (MI).

Interventions: Gelatine capsules, containing 850–882 mg EPA and DHA as concentrated ethylesters, or 1 g of corn oil, were ingested in a dose of two capsules twice a day for at least 1 y. Alpha-tocopherol (4 mg) was added to all capsules to protect the PUFAs against oxidation.

Results: After 1 y TBA–MDA increased modestly in the n-3 PUFA group (n=125), as compared to the corn oil group (n=130), P=0.027. Multiple linear regression analyses of fatty acids in serum total phospholipids (n=56) on TBA–MDA measured after 12 months intervention, showed no dependency. Performing best subsets regression, serum phospholipid concentration of arachidonic acid (20:4 n-6 PUFA) was identified as a predictor of TBA–MDA at 12 months follow-up, P=0.004.

We found no impact of statins on TBA–MDA.

Conclusion: TBA–MDA increased modestly after long-term intervention with n-3 PUFAs compared to corn oil post-MI, suggesting biological changes induced by n-3 PUFAs, rather than simply reflecting their concentration differences. The peroxidative potential of n-3 PUFAs was not modified by statin treatment.

Sponsorship: Pharmacia A/S and Pronova A/S, Norway.

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References

  • Alpert JS & Thygesen K (2000): The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J. 21, 1502–1513.

    Article  Google Scholar 

  • Anoopkumar-Dukie S, Walker RB & Daya S (2001): A sensitive and reliable method for the detection of lipid peroxidation in biological tissues. J. Pharm. Pharmacol. 53, 263–266.

    Article  CAS  Google Scholar 

  • Armstrong D & Browne R (1994): The analysis of free radicals, lipid peroxides, antioxidant enzymes and compounds related to oxidative stress as applied to the clinical chemistry laboratory. In Free Radicals in Diagnostic Medicine:A Systems Approach to Laboratory, Technology, Clinical Correlations, and Antioxidant Therapy, ed. D Armstrong, pp 43–58. New York: Plenum Press, XVI.

    Chapter  Google Scholar 

  • Arnesen E, Refsum H, Bonaa KH, Ueland PM, Forde OH & Nordrehaug JE (1995): Serum total homocysteine and coronary heart disease. Int. J. Epidemiol. 24, 704–709.

    Article  CAS  Google Scholar 

  • Avogaro P, Bittolo Bon G & Cazzolato G (1988): Presence of a modified low density lipoprotein in humans. Arteriosclerosis 8, 79–87.

    Article  CAS  Google Scholar 

  • Bittolo-Bon G, Cazzolato G, Alessandrini P, Soldan S, Casalino G & Avogaro P (1993): Effects of concentrated DHA and EPA supplementation on LDL peroxidation and vitamin E status in type HB hyperlipidemic patients. In Omega-3 Fatty Acids, eds CA Drevon, I Baksaas & HE Krokan, pp 51–58. Basel, Switzerland: Birkhauser-Verlag/Switzerland.

    Google Scholar 

  • Bonanome A, Biasia F, De Luca M, Munaretto G, Biffanti S, Pradella M & Pagnan A (1996): n-3 Fatty acids do not enhance LDL susceptibility to oxidation in hypertriacylglycerolemic hemodialyzed subjects. Am. J. Clin. Nutr. 63, 261–266.

    Article  CAS  Google Scholar 

  • Boyd HC, Gown AM, Wolfbauer G & Chait A (1989): Direct evidence for a protein recognized by a monoclonal antibody against oxidatively modified LDL in atherosclerotic lesions from a Watanabe heritable hyperlipidemic rabbit. Am. J. Pathol. 135, 815–824.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brude IR, Drevon CA, Hjermann I, Seljeflot I, Lund-Katz S, Saarem K, Sandstad B, Solvoll K, Halvorsen B, Arnesen H & Nenseter MS (1997): Peroxidation of LDL from combined-hyperlipidemic male smokers supplied with ω–3 fatty acids and antioxidants. Arterioscler. Thromb. Vasc. Biol. 17, 2576–2588.

    Article  CAS  Google Scholar 

  • Burstein M, Scholnick HR & Morfin R (1970): Rapid method for the isolation of lipoprotein from human serum by precipitation with polyanions. J. Lipid. Res. 11, 583–595.

    CAS  PubMed  Google Scholar 

  • Cavalca V, Cighetti G, Bamonti F, Loaldi A, Bortone L, Novembrino C, De Franceschi M, Belardinelli R & Guazzi MD (2001): Oxidative stress and homocysteine in coronary artery disease. Clin. Chem. 47, 887–892.

    CAS  PubMed  Google Scholar 

  • Connor SL & Connor WE (1997): Are fish oils beneficial in the prevention and treatment of coronary artery disease? Am. J. Clin. Nutr. 66 (Suppl), S1020–S1031.

    Article  Google Scholar 

  • Cosgrove JP, Church DF & Pryor WA (1987): The kinetics of the autoxidation of polyunsaturated fatty acids. Lipids 22, 299–304.

    Article  CAS  Google Scholar 

  • Dargel R (1992): Lipid peroxidation—a common pathogenetic mechanism? Exp. Toxicol Pathol. 44, 169–181.

    Article  CAS  Google Scholar 

  • Diaz-Velez CR, Garcia-Castineiras S, Mendoza-Ramos E & Hernandez-Lopez E (1996): Increased malondialdehyde in peripheral blood of patients with congestive heart failure. Am. Heart J. 131, 146–152.

    Article  CAS  Google Scholar 

  • Duthie GG, Beattie JA, Arthur JR, Franklin M, Morrice PC & James WPT (1994): Blood antioxidants and indices of lipid peroxidation in subjects with angina pectoris. Nutrition 10, 313–316.

    CAS  PubMed  Google Scholar 

  • Eritsland J, Arnesen H, Seljeflot I & Høstmark AT (1995): Long-term metabolic effects of n-3 polyunsaturated fatty acids in patients with coronary artery disease. Am. J. Clin. Nutr. 61, 831–836.

    Article  CAS  Google Scholar 

  • Frankel EN, Parks EJ, Xu R, Schneeman BO, Davis PA & German JB (1994): Effect of n-3 fatty acid-rich fish oil supplementation on the oxidation of low density lipoproteins. Lipids 29, 233–236.

    Article  CAS  Google Scholar 

  • Gerhardt W, Waldenstrøm J, Horder M, Hofvendahl S, Billstrøm R, Ljungdahl R, Berning H & Bagger P (1982): Creatine kinase and creatine kinase B-subunit activity in serum in cases of suspected myocardial infarction. Clin. Chem. 28, 277–283.

    CAS  PubMed  Google Scholar 

  • GISSI-Prevenzione Investigators (1999): Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 354, 447–455.

  • Gutteridge JM (1986): Aspects to consider when detecting and measuring lipid peroxidation. Free Radic. Res. Commun. 1, 173–184.

    Article  CAS  Google Scholar 

  • Halliwell B & Chirico S (1993): Lipid peroxidation: its mechanism, measurement, and significance. Am. J. Clin. Nutr. 57 (Suppl), S715–S725.

    Article  Google Scholar 

  • Hansen JB, Berge RK, Nordøy A & Bønaa KH (1998): Lipid peroxidation of isolated chylomicrons and oxidative status in plasma after intake of highly purified eicosapentaenoic or docosahexaenoic acids. Lipids 33, 1123–1129.

    Article  CAS  Google Scholar 

  • Harats D, Dabach Y, Hollander G, Ben-Naim M, Schwartz R, Berry EM, Stein O & Stein Y (1991): Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins. Atherosclerosis 90, 127–139.

    Article  CAS  Google Scholar 

  • Hetland Ø, Gøransson L & Nilsen DWT (1995): Cardiac troponin-T immunoassay on biotin–streptavidin-coated microplates, preliminary performance in acute myocardial infarction. Scand. J. Clin. Lab. Invest. 55, 701–713.

    Article  CAS  Google Scholar 

  • Higdon JV, Liu J, Du SH, Morrow JD, Ames BN & Wander RC (2000): Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F2-isoprostanes. Am. J. Clin. Nutr. 72, 714–722.

    Article  CAS  Google Scholar 

  • Janero DR (1990): Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Rad. Biol. Med. 9, 515–540.

    Article  CAS  Google Scholar 

  • Jayakumari N, Ambikakumari V, Balakrishnan KG & Subramonia IK (1992): Antioxidant status in relation to free radical production during stable and unstable angina syndromes. Atherosclerosis 94, 183–190.

    Article  CAS  Google Scholar 

  • Johansen O, Abdelnoor M, Brekke M, Seljeflot I, Høstmark AT & Arnesen H (2001): Predictors of restenosis after coronary angioplasty. A study on demographic and metabolic variables. Scand. Cardiovasc. J. 35, 86–91.

    Article  CAS  Google Scholar 

  • Johansen O, Seljeflot I, Høstmark AT & Arnesen H (1999): The effect of supplementation with omega-3 fatty acids on soluble markers of endothelial function in patients with coronary heart disease. Arterioscler. Thromb. Vasc. Biol. 19, 1681–1686.

    Article  CAS  Google Scholar 

  • Kharb S, Singh V, Ghalaut PS & Singh GP (2000): Oxidative stress after acute myocardial infarction: effect of thrombolytic treatment. J. Assoc. Physicians India 48, 578–580.

    CAS  PubMed  Google Scholar 

  • Kinsella JE, Lokesh B & Stone RA (1990): Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular disease: possible mechanisms. Am. J. Clin. Nutr. 52, 1–28.

    Article  CAS  Google Scholar 

  • Lapenna D, Ciofani G, Pierdominico SD, Giamberardino MA & Cuccurullo F (2001): Reaction conditions affecting the relationship between thiobarbituric acid reactivity and lipid peroxides in human plasma. Free Radic. Biol. Med. 31, 331–335.

    Article  CAS  Google Scholar 

  • Liu J, Yeo HC, Doniger SJ & Ames BN (1997): Assay of aldehydes from lipid peroxidation: gas chromatography–mass spectrometry compared to thiobarbituric acid. Anal. Biochem. 245, 161–166.

    Article  CAS  Google Scholar 

  • Mansoor MA, Svardal AM & Ueland PM (1992): Determination of the in vivo redox status of cysteine, cysteinglycine, homocysteine, and glutathione in human plasma. Anal. Biochem. 200, 218–229.

    Article  CAS  Google Scholar 

  • Meagher EA & FitzGerald GA (2000): Indices of lipid peroxidation in vivo: strengths and limitations. Free Radic. Biol. Med. 28, 1745–1750.

    Article  CAS  Google Scholar 

  • Meydani M, Natiello F, Goldin B, Free N, Woods M, Schaefer E, Blumberg JB & Gorbach SL (1991): Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women. J. Nutr. 121, 484–491.

    Article  CAS  Google Scholar 

  • Miwa K, Miyagi U & Fujita M (1995): Susceptibility of plasma low density lipoprotein to cupric ion-induced peroxidation in patients with variant angina. J. Am. Coll. Cardiol. 26, 632–638.

    Article  CAS  Google Scholar 

  • Muller Bardorff M, Hallermeayer K, Schroeder A, Ebert C, Borgya A, Gerhardt W, Remppis A, Zehelein J & Katus HA (1997): Improved troponin T ELISA specific for cardiac troponin T isoform: assay development and analytical and clinical validation. Clin. Chem. 43, 458–466.

    CAS  PubMed  Google Scholar 

  • Nenseter MS & Drevon CA (1996): Dietary polyunsaturates and peroxidation of low density lipoprotein. Curr. Opin. Lipidol. 7, 8–13.

    Article  CAS  Google Scholar 

  • Nenseter MS, Rustan AC, Lund-Katz S, Soyland E, Maelandsmo G, Phillips MC & Drevon CA (1992): Effects of dietary supplementation with n-3 polyunsaturated fatty acids on physical properties and metabolism of low density lipoproteins in humans. Arterioscl. Thromb. 12, 369–379.

    Article  CAS  Google Scholar 

  • Nilsen DWT, Albrektsen G, Landmark K, Moen S, Aarsland T & Woie L (2001): Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Am. J. Clin. Nutr. 74, 50–56.

    Article  CAS  Google Scholar 

  • Nordøy A, Bønaa KH, Nilsen H, Berge RK, Hansen JB & Ingebretsen OC (1998): Effects of simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. J. Int. Med. 243, 163–170.

    Article  Google Scholar 

  • Palozza P, Sgarlata E, Luberto C, Piccioni E, Anti M, Marra G, Armelao F, Franceschelli P & Bartoli GM (1996): n-3 Fatty acids induce oxidative modifications in human erythrocytes depending on dose and duration of dietary supplementation. Am. J. Clin. Nutr. 64, 297–304.

    Article  CAS  Google Scholar 

  • Phillipson BE, Rothrock DW, Connor WE, Harris WS & Illingworth DR (1985): Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N. Engl. J. Med. 312, 1210–1216.

    Article  CAS  Google Scholar 

  • Reaven PD, Grasse BJ & Tribble DL (1994): Effects of linoleate-enriched and oleate-enriched diets in combination with alpha-tocopherol on the susceptibility of LDL and LDL subfractions to oxidative modification in humans. Arterioscler. Thromb. 14, 557–566.

    Article  CAS  Google Scholar 

  • Reaven P, Parthasarathy S, Grasse BJ, Miller E, Almazan F, Mattson FH, Khoo JC, Steinberg D & Witztum JL (1991): Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans. Am. J. Clin. Nutr. 54, 701–706.

    Article  CAS  Google Scholar 

  • Reaven P, Parthasarathy S, Grasse BJ, Miller E, Steinberg D & Witztum JL (1993): Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects. J. Clin. Invest. 91, 668–676.

    Article  CAS  Google Scholar 

  • Ridker PM, Glynn RJ & Hennekens CH (1998): C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 97, 2007–2011.

    Article  CAS  Google Scholar 

  • Rosenfeld ME (1991): Oxidized LDL affects multiple atherogenic cellular responses. Circulation 83, 2137–2140.

    Article  CAS  Google Scholar 

  • Schmidt EB & Dyerberg J (1994): Omega-3 fatty acids: current status in cardiovascular medicine. Drugs 47, 405–424.

    Article  CAS  Google Scholar 

  • Steinberg D, Parthasarathy MD, Carew TE, Khoo JC & Witztum JL (1989): Beyond cholesterol. Modification of low-density lipoprotein that increases its atherogenicity. N. Engl. J. Med. 320, 915–924.

    Article  CAS  Google Scholar 

  • Wander RC, Du SH, Ketchum SO & Rowe KE (1996): Effects of interaction of RRR-alpha-tocopheryl acetate and fish oil on low-density-lipoprotein oxidation in postmenopausal women with and without hormone-replacement therapy. Am. J. Clin. Nutr. 63, 184–193.

    Article  CAS  Google Scholar 

  • Wander RC, Du SH & Thomas DR (1998): Influence of longchain polyunsaturated fatty acids on oxidation of low density lipoprotein. Prostaglandins Leuk. Essent. Fatty Acids 59, 143–151.

    Article  CAS  Google Scholar 

  • Wiklund O, Mattsson L, Bjornheden T, Camejo G & Bondjers G (1991): Uptake and degradation of low density lipoproteins in atherosclerotic rabbit aorta: role of local LDL modification. J. Lipid. Res. 32, 55–62.

    CAS  PubMed  Google Scholar 

  • Wong SHY, Knight JA, Hopfer SM, Zaharia O, Leach Jr CN & Sunderman Jr FW (1987): Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. Clin. Chem. 33, 214–220.

    CAS  PubMed  Google Scholar 

  • Yoshino K, Sano M, Fujita M & Tomita I (1991): Production of aliphatic aldehydes on peroxidation of various types of lipids. Chem. Pharm. Bull. 39, 1788–1791.

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful for the financial support by Pharmacia A/S and Pronova A/S, Norway. We acknowledge the support of Ole Kristensen, MD at the Department of Clinical Chemistry, Central Hospital in Rogaland. Finally, thanks are due to the project nurse, Solfrid Moen, Hjertelaget Research Foundation, Norway, and the steering committee of the ‘OFAMI’-study: Dennis WT Nilsen, Knud Landmark, Leik Woie and Michael Abdelnoor.

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  1. Department of Clinical Chemistry, Central Hospital in Rogaland, Stavanger, Norway

    H Grundt & M A Mansoor

  2. Department of Medicine, Central Hospital in Rogaland, Stavanger, Norway

    H Grundt & D W T Nilsen

  3. Department of Medicine, University of Tromsoe, Norway

    A Nordøy

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Grundt, H., Nilsen, D., Mansoor, M. et al. Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infarction. Eur J Clin Nutr 57, 793–800 (2003). https://doi.org/10.1038/sj.ejcn.1601730

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