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Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes

European Journal of Clinical Nutrition volume 57, pages 713–720 (2003)Cite this article

Abstract

Objective: Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus. However, fish oil may have deleterious effects on lipid peroxidation and glycemic control.

Design: In this study, 44 type 2 diabetic patients were randomized to vitamin E standardized (53.6 mg/day) supplementation (capsules) with 4 g daily of either fish oil (n=23) or corn oil (n=21) for 8 weeks preceded by a 4 week run-in period of corn oil supplementation. LDL was isolated by density gradient ultracentrifugation and oxidized in vitro with Cu2+. As a marker of in vivo oxidation malondialdehyde concentration in LDL (LDL-MDA) was measured.

Results: Fish oil reduced both mean lag time (before, 57.8; after, 48.8 min, P<0.001) and mean propagation rate (before, 0.018 ΔOD/min; after, 0.015 ΔOD/min, P<0.001), whereas corn oil had no influence on lag time and propagation rate. The changes in lag time and propagation rate differed significantly between fish oil and corn oil treatment. LDL-MDA changes differed borderline significantly between groups (FO, 110.4 pmol/mg protein; CO, 6.7 pmol/mg protein; P=0.057). Fish oil supplementation had no influence on glycemic control as assessed from HbA1c and fasting blood glucose.

Conclusion: According to our findings, fish oil supplementation leads to increased in vivo oxidation and increased in vitro oxidation susceptibility of LDL particles. More studies are needed to clarify the clinical importance of this finding.

Sponsorship: Financially supported by The Danish Heart Association and Dansk Droge A/S. Dansk Droge A/S generously provided the fish oil and corn oil capsules.

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References

  • Abuja, PM & Albertini, R (2001). Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clin. Chim. Acta, 306, (1–2) 1–17.

    Article  CAS  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 

  • Bruna, E, Petit, E, Beljean-Leymarie, M, Huynh, S & Nouvelot, A (1989). Specific susceptibility of docosahexaenoic acid and eicosapentaenoic acid to peroxidation in aquesous solution. Lipids, 24, (11) 970–975.

    Article  CAS  Google Scholar 

  • Burr, ML, Gilbert, JF & Holliday, RL (1989). Effects of changes in fat, fish and fiber intake on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet, II, 757–761.

    Article  Google Scholar 

  • Carbonneau, MA, Peuchant, E, Sess, D, Canioni, P & Clerc, M (1991). Free and bound malondialdehyde measured as thiobarbituric acid adduct by HPLC in serum and plasma. Clin. Chem., 37, 1423–1429.

    CAS  PubMed  Google Scholar 

  • Christopherson, SW & Glass, RL (1969). Preparation of milk fat methyl esters by alcoholysis in an essentially nonalcoholic solution. J. Dairy Sci., 52, 1289–1290.

    Article  CAS  Google Scholar 

  • De Deckere, E, Korver, O, Verschuren, PM & Katan, MB (1998). Health aspects of fish and n-3 polyunsaturated fatty acids from plant and marine origin. Eur. J. Clin. Nutr., 52, 749–753.

    Article  CAS  Google Scholar 

  • Esterbauer, H, Striegl, G, Puhl, H & Rotheneder, M (1989). Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic. Res. Commun., 6, 67–75.

    Article  CAS  Google Scholar 

  • Eritsland, J, Arnsen, 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 

  • Foulon, T, Richard, MJ, Payen, N, Bourrain, JL, Beani, JC, Laporte, F & Hadjian, A (1999). Effects of fish oil fatty acids on plasma lipids and lipoproteins and oxidant–antioxidant imbalance in healthy subjects. Scand. J. Clin. Invest., 59, 239–248.

    Article  CAS  Google Scholar 

  • Frankel, EN, Parks, EJ, Xu, R, Sshneeman, BO, Davis, PA & German, JB (1994). Effect of n-3 fatty acid-rich fish oil supplementation on the oxidation of low density lipoprotein. Lipids, 29, (4) 233–236.

    Article  CAS  Google Scholar 

  • Friday, KE, Childs, MT, Tsunehara, CH, Fujimoto, WY, Bierman, EL & Ensinck, JW (1989). Elevated plasma glucose and lowered triglycerid levels from omega-3 fatty acid supplementation in type II diabetes. Diabetes Care, 12, 276–281.

    Article  CAS  Google Scholar 

  • Giesig, SP & Esterbauer, H (1994). Low density lipoprotein is saturable by pro-oxidant copper. FEBS Lett., 343, (3) 188–194.

    Article  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.

  • Giugliano, D, Ceriello, A & Paolisso, G (1996). Oxidative stress and diabetic vascular complications. Diabetes Care, 19, 257–267.

    Article  CAS  Google Scholar 

  • Haffner, SM & Lehto, S (1998). Mortality from coronary heart disease in subjects with type 2 diabetes and in non-diabetic subjects with and without prior myocardial infarction. New Engl. J. Med., 339, 229–234.

    Article  CAS  Google Scholar 

  • Higdon, JV, Liu, J, Du, S, 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 

  • Higdon, JV, Du, SH, Lee, YS, Wu, T & Wander, RC (2001). Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate. J. Lipid Res., 42, 407–418.

    CAS  PubMed  Google Scholar 

  • Lauridsen, ST & Mortensen, A (1999). Probucol selectively increases oxidation of atherogenic lipoproteins in cholesterol-fed mice and in Watanabe heritable hyperlipidemic rabbits. Atherosclerosis, 142, 169–178.

    Article  CAS  Google Scholar 

  • Lussier-Cacan, S, Dubreuil-Quidoz, S, Roederer, G, Leboeuf, N, Boulet, L, de Langavant, GC, Davignon, J & Naruszewicz, M (1993). Influence of probucol on enhanced LDL oxidation after fish oil treatment of hypertriglyceridemic patients. Arterioscler. Thromb., 13, 1790–1797.

    Article  CAS  Google Scholar 

  • Lyons, TJ & Jenkins, AJ (1997). Lipoprotein glycation and its metabolic consequences. Curr. Opin. Lipidol., 8, 174–180.

    Article  CAS  Google Scholar 

  • Montori, VM, Farmer, A, Wollan, PC & Dinneen, SF (2000). Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care, 23, 1407–1415.

    Article  CAS  Google Scholar 

  • Mori, TA, Dunstan, DW, Burke, V, Croft, KD, Rivera, JH, Beilin, LJ & Puddey, IB (1999). Effect of dietary fish and exercise training on urinary F2-isoprostane excretion in non-insulin-dependent diabetic patients. Metabolism, 48, 1402–1408.

    Article  CAS  Google Scholar 

  • Morrison, WR & Smith, LM (1964). Preparation of fatty acid methyl esters from lipids with boron fluoride–methanol. J. Lipid Res., 5, 600–608.

    CAS  PubMed  Google Scholar 

  • Nenseter, MS, Rustan, AC, Lund-Katz, S, Søyland, E, Mælandsmo, G, Philips, MC & Drevon, CA (1992). Effect of dietary supplementation with n-3 polyunsaturated fatty acids on physical properties and metabolism of low density lipoprotein in humans. Arterioscler. Thromb., 12, 369–379.

    Article  CAS  Google Scholar 

  • Petersen, M, Pedersen, H, Major-Pedersen, A, Jensen, T & Marckmann, P (2002). Effect of fish oil vs corn oil supplementation on LDL and HDL subclasses in type 2 diabetes patients. Diabetes Care, (in press)

  • Regnström, J, Nilsson, J, Tornvall, P, Landou, C & Hamsten, A (1992). Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man. Lancet, 339, 1183–1186.

    Article  Google Scholar 

  • Sørensen, NS, Marckmann, P, Høy, C, van Duyvenvoorde, W & Princen, HMG (1998). Effect of fish-oil-enriched margarine on plasma lipids, low-density-lipoprotein particle composition, size, and susceptibility to oxidation. Am. J. Clin. Nutr., 68, 235–241.

    Article  Google Scholar 

  • Steiner, G (1995). Dyslipoproteinemias in diabetes. Clin. Invest. Med., 18, 282–287.

    CAS  PubMed  Google Scholar 

  • Suzukawa, M, Abbey, M, Howe, PRC & Nestel, PJ (1995). Effects of fish oil fatty acids on low density lipoprotein size, oxidizabiliy, and uptake by macrophages. J. Lipid Res., 36, 473–484.

    CAS  PubMed  Google Scholar 

  • Tribble, DL, Holl, LG, Wood, PD & Krauss, RM (1992). Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. Atherosclerosis, 3, 189–199.

    Article  Google Scholar 

  • Tsai, P & Lu, S (1997). Fish oil lowers plasma lipid concentrations and increases the susceptibility of low density lipoprotein to oxidative modification in healthy men. J. Formos. Med. Assoc., 96, 718–726.

    CAS  PubMed  Google Scholar 

  • Van de Vijver, LPL, Kardinaal, AFM, Van Duyvenvoorde, W, Kruijssen, DACM, Grobbee, KE, van Poppel, G & Princen, HMG (1999). Oxidation of LDL and extent of peripheral atherosclerosis. Free Radic. Res., 31, 129–139.

    Article  CAS  Google Scholar 

  • Vessby, B, Karlström, B, Boberg, M, Lithell, H & Berne, C (1992). Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients. Diabetes Med., 9, 126–133.

    Article  CAS  Google Scholar 

  • Wallin, B, Rosengren, B, Shertzer, HG & Camejo, G (1993). Lipoprotein oxidation and measurement of thiobarbituric acid reacting substances formation in a single microtiter plate: its use for evaluation of antioxidants. Anal. Biochem., 208, 10–15.

    Article  CAS  Google Scholar 

  • Wander, RC, Du, SH, Ketchum, SO & Rowe, KE (1996). Effects of interaction of RRR-α-tocopheryl acetate and fish oil on low-density lipoprotein oxidation in postmenopausal woman 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 long-chain polyunsaturated fatty acids on oxidation of low density lipoprotein. Prostaglandins Leukot. Essent. Fatty Acids, 59, (2) 143–151.

    Article  CAS  Google Scholar 

  • Yoshida, Y, Tsuchiya, J & Niki, E (1994). Interaction of α-tocopherol with copper and its effect on lipid peroxidation. Biochim. Biophys. Acta, 1200, (2) 85–92.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Research Department of Human Nutrition, The Royal Veterinaryand Agricultural University, Frederiksberg, Denmark

    H Pedersen, M Petersen & P Marckmann

  2. Steno Diabetes Center, Gentofte, Denmark

    A Major-Pedersen & T Jensen

  3. Department of Biochemistry and Nutrition, The Technical University of Denmark, Lyngby, Denmark

    N S Nielsen

  4. Department of Food Safety and Toxicology, Division of Biochemical and Molecular Toxicology, Danish Veterinary and Food Administration, Søborg, Denmark

    S T Lauridsen

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  1. H Pedersen
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Guarantor: Peter Marckmann.

Contributors: Helle Pederson, Martin Petersen, Artheline Major-Pedersen, Tonny Jensen, Søren Lauridsen, Nina Skall Nielsen.

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Correspondence to H Pedersen.

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Pedersen, H., Petersen, M., Major-Pedersen, A. et al. Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes. Eur J Clin Nutr 57, 713–720 (2003). https://doi.org/10.1038/sj.ejcn.1601602

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  • DOI: https://doi.org/10.1038/sj.ejcn.1601602

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