Hostname: page-component-848d4c4894-ttngx Total loading time: 0 Render date: 2024-06-02T14:01:38.031Z Has data issue: false hasContentIssue false
  • English
  • Français

Susceptibility of LDL to oxidative modification in healthy volunteers supplemented with low doses of n-3 polyunsaturated fatty acids

Published online by Cambridge University Press:  09 March 2007

Siobhán Higgins ,
Yvonne L. Carroll ,
Sinéad N. McCarthy ,
Bernice M. Corridan ,
Helen M. Roche ,
Julie M. W. Wallace ,
Nora M. O'Brien  and
Patrick A. Morrissey
Siobhán Higgins
Affiliation:
Division of Nutritional Sciences, Department of Food Science and Technology, University College Cork, Cork, Republic of Ireland
Yvonne L. Carroll
Affiliation:
Division of Nutritional Sciences, Department of Food Science and Technology, University College Cork, Cork, Republic of Ireland
Sinéad N. McCarthy
Affiliation:
Division of Nutritional Sciences, Department of Food Science and Technology, University College Cork, Cork, Republic of Ireland
Bernice M. Corridan
Affiliation:
Division of Nutritional Sciences, Department of Food Science and Technology, University College Cork, Cork, Republic of Ireland
Helen M. Roche
Affiliation:
Unit of Nutrition and Dietetics, Department of Clinical Medicine, Trinity Health Sciences Centre, St James Hospital, Dublin 8, Republic of Ireland
Julie M. W. Wallace
Affiliation:
Northern Ireland Centre for Diet and Health, University of Ulster, Coleraine, Co. Londonderry BT52 1SA, UK
Nora M. O'Brien
Affiliation:
Division of Nutritional Sciences, Department of Food Science and Technology, University College Cork, Cork, Republic of Ireland
Patrick A. Morrissey*
Affiliation:
Division of Nutritional Sciences, Department of Food Science and Technology, University College Cork, Cork, Republic of Ireland
*
*Corresponding author: Professor P. A. Morrissey, fax +353 21 270244 email p.morrissey@ucc.ie
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The objective of the present study was to evaluate the oxidative susceptibility of LDL in human volunteers following supplementation with various low doses (<1 g/d) of n–3 polyunsaturated fatty acids (PUFA). Sixty-two healthy volunteers (thirty-seven males and twenty-five females, aged 19–63 years) were recruited to take part in a randomised placebo-controlled trial. Volunteers were required to take 0.9, 0.6 or 0.3 g n–3 PUFA as fish oil or placebo capsules daily for 16 weeks. Susceptibility of LDL to oxidative modification was assessed by measuring the production of conjugated dienes and thiobarbituric acid-reactive substances in LDL oxidised by Cu2+ (15 μM) OR 2,2″-AZOBIS(2-AMIDINOPROPANE) DIHYDROCHLORIDE (1 Mm) for 5 h. Plasma fatty acid and LDL-fatty acid composition, cholesterol levels and antioxidant concentrations were also measured. While post-treatment n–3 PUFA compositions of plasma and LDL reflected the capsule contents, no meaningful differences in antioxidant concentrations or cholesterol levels were observed between the groups. Supplementation with low doses of n–3 PUFA as fish oil did not influence the oxidative susceptibility of LDL. The results of the present study suggest that moderate dietary intakes of n–3 PUFA do not significantly influence the susceptibility of LDL to oxidative modification in vitro.

Keywords

n-3 Polyunsaturated fatty acidsLDLFish oil supplementation
Type
Research Article
Information
British Journal of Nutrition , Volume 85 , Issue 1 , January 2001 , pp. 23 - 31
Copyright
Copyright © The Nutrition Society 2001

References

Äreng;gren, JJ, Hänninen, O, Julkunen, A, Fogelholm, L, Vidgren, H, Schwab, U, Pynnönen, O & Uusitupa, M (1996) Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. European Journal of Clinical Nutrition 50, 765–771.Google Scholar
AÅgren;, JJ, Väisänen, S, Hänninen, O, Muller, AD & Hornstra, G (1997) Hemostatic factors and platelet aggregration after fishenriched diet or fish oil or docosahexaenoic acid supplementation. Prostaglandins, Leukotrienes and Essential Fatty Acids 57, 419–421.CrossRefGoogle 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. American Journal of Clinical Nutrition 63, 261–266.CrossRefGoogle Scholar
British Nutrition Foundation (1993) Nutritional Aspects of Fish. Briefing Paper no: 10. London:British Nutrition Foundation.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 n -3 fatty acids and antioxidants. Arteriosclerosis, Thrombosis and Vascular Biology 17, 2576–2588.CrossRefGoogle Scholar
Buege, JA & Aust, SD (1978) Microsomal lipid peroxidation. Method in Enzymology 52, 302–310.CrossRefGoogle ScholarPubMed
Burr, ML, Fehily, AM, Gilbert, JF, Rodgers, S, Holliday, RM, Sweetnam, PM, Elwood, PC & Deadman, NM (1989) Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet ii, 757–761.CrossRefGoogle Scholar
Burton, GW, Webb, A & Ingold, KU (1985) A mild, rapid and efficient method of lipid extraction for use in determining vitamin E/lipid ratios. Lipids 20, 29–39.CrossRefGoogle ScholarPubMed
Calviello, G, Palozza, P, Franceschelli, P & Bartoli, GM (1997) Low-dose eicosapentaenoic or docosahexaenoic acid administration modifies fatty acid composition and does not affect susceptibility to oxidative stress in rat erythrocytes and tissues Lipids 32, 1075–1083.CrossRefGoogle Scholar
Chung, BH, Segrest, JP, Ray, MJ, Brunzell, JD, Hokanson, JE, Krauss, RM, Beaudrie, K & Cone, JT (1986) Single vertical spin density gradient ultracentrifugation Methods in Enzymology 128, 181–209.CrossRefGoogle ScholarPubMed
Esterbauer, H, Gebicki, J, Puhl, H & Jürgens, G (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL Free Radical Biology and Medicine 13, 341–390.CrossRefGoogle ScholarPubMed
Esterbauer, H & Jürgens, G (1993) Mechanistic and genetic aspects of susceptibility of LDL to oxidation. Current Opinion in Lipidology 4, 114–124.CrossRefGoogle 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 oxidation of low density lipoprotein. Lipids 29, 233–236.CrossRefGoogle Scholar
Frei, B & Gaziano, JM (1993) Content of antioxidants, preformed lipid hydroperoxides, and cholesterol as predictors of the susceptibility of human LDL to metal ion-dependent and -independent oxidation. Journal of Lipid Research 34, 2135–2145.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
Green, P, Fuchs, J, Schoenfeld, N, Leibovici, L, Lurie, Y, Beigel, Y, Rotenberg, Z, Mamet, R & Budowski, P (1990) Effects of fish-oil ingestion on cardiovascular risk factors in hyperlipidemic subjects in Israel: a randomized, double-blind cross-over study. American Journal of Clinical Nutrition 52, 1118–1124.CrossRefGoogle Scholar
Hansen, JB, Berge, RK, Nordøy, A & Bønna, 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.CrossRefGoogle Scholar
Harris, WS (1989) Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review. Journal of Lipid Research 30, 785–807.CrossRefGoogle ScholarPubMed
Harris, WS (1996) n-3 Fatty acids and lipoproteins: Comparison of results from human and animal studies. Lipids 31, 243–252.CrossRefGoogle ScholarPubMed
Hau, MF, Smelt, AHM, Bindels, AJGH, Sijbrands, EJG, van der Laarse, A, Onkenhout, W, van Duyvenvoorde, W & Princen, HMG (1996) Effects of fish oil on oxidation resistance of VLDL in hypertriglyceridemic patients. Arteriosclerosis, Thrombosis and Vascular Biology 16, 1197–1202.CrossRefGoogle ScholarPubMed
Hokanson, JE & Austin, MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population based prospective studies. Journal of Cardiovascular Risk 3, 213–219.CrossRefGoogle Scholar
Hornstra, G, Oostenbrug, GS & Vossen, RCRM (1994) Peroxidation of low density lipoproteins and endothelial phospholipids: effect of vitamin E and fatty acid composition. In Fatty Acids and Lipids: Biological Aspects. World Review in Nutrition and Dietetics. pp. 149–154 [C, Galli, AP, Simopoulos & E, Tremoli, editors]. Basel, Switzerland: Karger.Google Scholar
Kleinveld, HA, Hak-Lemmers, HLM, Stalenhoef, AFH & Demacker, PNM (1992) Improved measurement of low-density-lipoprotein susceptibility to copper-induced oxidation: application of a short procedure for isolating low-density lipoprotein. Clinical Chemistry 38, 2066–2072.CrossRefGoogle Scholar
Kromhout, D, Bosschieter, EB & Coulander, CDL (1985) The inverse relation between fish consumption and 20-year mortality from coronary heart disease. New England Journal of Medicine 312, 1205–1209.CrossRefGoogle ScholarPubMed
Lepage, G & Roy, CC (1986) Direct transesterification of all classes of lipids in a one-step reaction. Journal of Lipid Research 27, 114–120.CrossRefGoogle Scholar
Levine, PH, Fisher, M, Schneider, PB, Whitten, RH, Weiner, BH, Ockene, IS, Johnson, BF, Johnson, MH, Doyle, EM, Reindeau, PA & Hoogasian, JJ (1989) Dietary supplementation with omega-3 fatty acids prolongs platelet survival in hyperlipidemic patients with atherosclerosis. Archives of Internal Medicine 149, 1113–1116.CrossRefGoogle ScholarPubMed
Liu, J, Yeo, HC, Doniger, SJ & Ames, BN (1997) Assay of aldehydes from lipid peroxidation: gas chromatography-mass spectrometry compared to thiobarbituric acid. Analytical Biochemistry 245, 161–166.CrossRefGoogle ScholarPubMed
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. Arteriosclerosis and Thrombosis 13, 1790–1797.CrossRefGoogle ScholarPubMed
Markwell, MAK, Haas, SM, Tolbert, NE & Bieber, LL (1981) Protein determination in membrane and lipoprotein samples: manual and automated procedures. Methods in Enzymology 72, 296–298.CrossRefGoogle ScholarPubMed
Nair, PP, Judd, JT, Berlin, E, Taylor, PR, Shami, S, Sainz, E & Bhagavan, HN (1993) Dietary fish oil-induced changes in the distribution of α-tocopherol, retinol, and ²-carotene in plasma, red blood cells, and platelets: modulation by vitamin E. American Journal of Clinical Nutrition 58, 98–102.CrossRefGoogle ScholarPubMed
Nenseter, MS, Rustan, AC, Lund-Katz, S, Søyland, E, Maelandsmo, G, Phillips, 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. Arteriosclerosis and Thrombosis 12, 369–379.CrossRefGoogle ScholarPubMed
Oostenbrug, GS, Mensink, RP & Hornstra, G (1994) Effects of fish oil and vitamin E supplementation on copper-catalysed oxidation of human low density lipoprotein in vitro. European Journal of Clinical Nutrition 48, 895–898.Google ScholarPubMed
Roche, HM & Gibney, MJ (1996) Postprandial triacylglycerolaemia: the effect of low-fat dietary treatment with and without fish oil supplementation European Journal of Clinical Nutrition 50, 617–624.Google ScholarPubMed
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. Journal of Clinical Investigation 91, 668–676.CrossRefGoogle ScholarPubMed
Saito, H, Chang, KJ, Tamura, Y & Yoshida, S (1991) Ingestion of eicosapentaenoic acid-ethyl ester renders rabbit LDL less susceptible to Cu2+-catalyzed-oxidative modification. Biochemical and Biophysical Research Communications 175, 61–67.CrossRefGoogle ScholarPubMed
Sanders, TAB & Hinds, A (1992) The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein and vitamin E concentrations and haemostatic function in healthy male volunteers. British Journal of Nutrition 68, 163–173.CrossRefGoogle ScholarPubMed
Schmidt, EB, Lervang, HH, Varming, K, Madsen, P & Dyerberg, J (1992) Long-term supplementation with n-3 fatty acids, I: effects on blood lipids, haemostasis and blood pressure. Scandanavian Journal of Clinical and Laboratory Investigation 52, 221–228.CrossRefGoogle ScholarPubMed
Scott, KJ & Hart, DJ (1993) Further observations on problems associated with the analysis of carotenoids by HPLC-2: Column temperature Food Chemistry 47, 403–405.CrossRefGoogle Scholar
Scientific Committee for Food (1993) Nutrient and Energy Intakes for the European Community. Report of the Scientific Committee for Food, 31st series. Luxembourg: EU.Google Scholar
Steinberg, D, Parthasarathy, S, Carew, TE, Khoo, JC & Witztum, JL (1989) Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. New England Journal of Medicine 320, 915–924.Google ScholarPubMed
Suzukawa, M, Abbey, M, Howe, PRC & Nestel, PJ (1995) Effects of fish oil fatty acids on low density lipoprotein size, oxidisability, and uptake by macrophages. Journal of Lipid Research 36, 473–484.CrossRefGoogle ScholarPubMed
Thomas, MJ, Thornburg, T, Manning, J, Hooper, K & Rudel, LL (1999) Fatty acid composition of low-density lipoprotein influences its susceptibility to autooxidation. Biochemistry 33, 1828–1834.CrossRefGoogle Scholar
Turley, E, Wallace, JMW, Gilmore, WS & Strain, JJ (1998) Fish oil supplementation with and without added vitamin E differentially modulates plasma antioxidant concentrations in healthy women. Lipids 33, 1163–1167.CrossRefGoogle ScholarPubMed
Vaagenes, H, Muna, ZA, Madsen, L & Berge, RK (1998) Low doses of eicosapentaenoic acid, docosahexaenoic acid, and hypolipidemic eicosapentaenoic acid derivatives have no effect on lipid peroxidation in plasma Lipids 33, 1131–1137.CrossRefGoogle Scholar
Wallace, JMW, Turley, E, Gilmore, WS & Strain, JJ (1995) Dietary fish oil supplementation alters leukocyte function and cytokine production in healthy women Arteriosclerosis, Thrombosis and Vascular Biology 15, 185–189.CrossRefGoogle ScholarPubMed
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 women with and without hormone-replacement therapy. American Journal of Clinical Nutrition 63, 184–193.CrossRefGoogle ScholarPubMed
Wander, RC, Du, SH & Thomas DR (1998) Influence of long-chain polyunsaturated fatty acids on oxidation of low density lipoprotein. Prostaglandins, Leukotrienes and Essential Fatty Acids 59, 143–151.CrossRefGoogle ScholarPubMed
Whitman, SC, Fish, JR, Rand, ML & Rodgers, KA (1994) n-3 Fatty acid incorporation into LDL particles renders them more susceptible to oxidation in vitro but not necessarily more atherogenic in vivo. Arteriosclerosis and Thrombosis 14, 1170–1176.CrossRefGoogle Scholar