Hostname: page-component-8448b6f56d-xtgtn Total loading time: 0 Render date: 2024-04-18T15:28:50.054Z Has data issue: false hasContentIssue false
  • English
  • Français

Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses

Published online by Cambridge University Press:  09 March 2007

Elizabeth C. Leigh-Firbank ,
Anne M. Minihane ,
David S. Leake ,
John W. Wright ,
Margaret C. Murphy ,
Bruce A. Griffin  and
Christine M. Williams
Elizabeth C. Leigh-Firbank
Affiliation:
The Hugh Sinclair Unit of Human Nutrition, The University of Reading, Reading, UK
Anne M. Minihane*
Affiliation:
The Hugh Sinclair Unit of Human Nutrition, The University of Reading, Reading, UK
David S. Leake
Affiliation:
School of Animal and Microbial Sciences, The University of Reading, Reading, UK
John W. Wright
Affiliation:
The Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, Guildford, UK
Margaret C. Murphy
Affiliation:
European Institute of Health and Medical Sciences, University of Surrey, Guildford, UK
Bruce A. Griffin
Affiliation:
The Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, Guildford, UK
Christine M. Williams
Affiliation:
The Hugh Sinclair Unit of Human Nutrition, The University of Reading, Reading, UK
*
*Corresponding author: Dr Anne M. Minihane, fax +44 118 9310080, email minihane@reading.ac.uk
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.

Fish-oil supplementation can reduce circulating triacylglycerol (TG) levels and cardiovascular risk. This study aimed to assess independent associations between changes in platelet eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and fasting and postprandial (PP) lipoprotein concentrations and LDL oxidation status, following fish-oil intervention. Fifty-five mildly hypertriacylglycerolaemic (TG 1·5–4·0 mmol/l) men completed a double-blind placebo controlled cross over study, where individuals consumed 6 g fish oil (3 g EPA+DHA) or 6 g olive oil (placebo)/d for two 6-week intervention periods, with a 12-week wash-out period in between. Fish-oil intervention resulted in a significant increase in the platelet phospholipid EPA (+491 %, P<0·001) and DHA (+44 %, P<0·001) content and a significant decrease in the arachidonic acid (-10 %, P<0·001) and γ-linolenic acid (-24 %, P<0·001) levels. A 30 % increase in ex vivo LDL oxidation (P<0·001) was observed. In addition, fish oil resulted in a significant decrease in fasting and PP TG levels (P<0·001), PP non-esterified fatty acid (NEFA) levels, and in the percentage LDL as LDL-3 (P=0·040), and an increase in LDL-cholesterol (P=0·027). In multivariate analysis, changes in platelet phospholipid DHA emerged as being independently associated with the rise in LDL-cholesterol, accounting for 16 % of the variability in this outcome measure (P=0·030). In contrast, increases in platelet EPA were independently associated with the reductions in fasting (P=0·046) and PP TG (P=0·023), and PP NEFA (P=0·015), explaining 15–20 % and 25 % of the variability in response respectively. Increases in platelet EPA+DHA were independently and positively associated with the increase in LDL oxidation (P=0·011). EPA and DHA may have differential effects on plasma lipids in mildly hypertriacylglycerolaemic men.

Keywords

Eicosapentaenoic acidDocosahexaenoic acidTriacylglyercolPlasma lipidLow-density lipoprotein oxidation
Type
Research Article
Information
British Journal of Nutrition , Volume 87 , Issue 5 , May 2002 , pp. 435 - 445
Copyright
Copyright © The Nutrition Society 2002

References

Abbey, M, Belling, B, Noakes, M, Hirata, F & Nestel, PJ (1993) Oxidation of low-density lipoproteins: intra-individual variability and the effect of dietary linoleate supplementation. American Journal of Clinical Nutrition 57, 391–398.Google Scholar
Ågren, 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 ScholarPubMed
Andrews, B, Burnand, K, Paganga, G, Browse, N, Rice-Evans, C, Sommerville, K, Leake, D & Taub, N (1995) Oxidisability of low-density lipoproteins in patients with carotid or femoral artery atherosclerosis. Atherosclerosis 112, 77–84.CrossRefGoogle ScholarPubMed
American Oil Chemists' Society (1990) Ce 8-89. Determination of Tocopherols and Tocotrienols in Vegetable Oil and Fats by HPLC, pp. 1–5: Champaign, IL: AOCS.Google Scholar
Austin, MA, Breslow, JL, Hennekens, CH, Buring, JE, Willett, WC & Krauss, RM (1988) Low density lipoprotein subclass patterns and risk of myocardial infarction. Journal of the American Medical Association 260, 917–921.Google ScholarPubMed
Berge, RK, Madsen, L, Vaagenes, H, Tronstad, KJ, Göttlicher, M & Rustan, AC (1999) In contrast with docosahexaenoic acid, eicosapentaenoic acid and hypolipidaemic derivatives decrease hepatic synthesis and secretion of triacylglycerol by decreased diacylglycerol acyltransferase activity and stimulation of fatty acid oxidation. Biochemistry Journal 343, 191–197.CrossRefGoogle ScholarPubMed
Berliner, JA, Territo, MC, Sevanian, A, Ramin, S, Kim, JA, Bamshad, B, Esterson, M & Fogelman, AM (1990) Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. Journal of Clinical Investigation 85, 1260–1266.CrossRefGoogle ScholarPubMed
Bonanome, A, Biasia, F, DeLuca, M, Munaretto, G, Biffanti, S, Pradella, M & Pagnan, A (1996) n-3 Fatty acids do not enhance LDL susceptibility to oxidation in hypertriglycerolemic hemodialyzed subjects. American Journal of Clinical Nutrition 63, 261–266.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 omega-3 fatty acids and antioxidants. Arteriosclerosis Thrombosis and Vascular Biology 17, 2576–2588.CrossRefGoogle ScholarPubMed
Burr, ML, Fehily, AM, Gilbert, JF, Rogers, 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
Buttriss, J (1999) n-3 Fatty Acids and Health: Briefing Paper. London: British Nutrition Foundation.CrossRefGoogle Scholar
Childs, MT, King, IB & Knopp, RH (1990) Divergent lipoprotein responses to fish oils with various ratios of eicosapentaenoic acid and docosahexaenoic acid. American Journal of Clinical Nutrition 52, 632–639.Google Scholar
Conquer, JA & Holub, BJ (1997) Dietary docosahexaenoic acid as a source of eicosapentaenoic acid in vegetarians and omnivores. Lipids 32, 314–345.Google Scholar
Davidson, MH, Maki, KC, Kalkowski, JA, Schaefer, EJ, Torri, SA & Drennan, KB (1997) Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidaemia: a randomized, double-blind placebo-controlled trial. Journal of the American College of Nutrition 16, 236–243.CrossRefGoogle ScholarPubMed
DeGraaf, J, Haklemmers, HLM, Hectors, MPC, Demacker, PNM, Hendriks, JCM & Stalenhoef, AFH (1991) Enhanced susceptibility to in vitro oxidation of the dense low-density lipoprotein subfraction in healthy subjects. Arteriosclerosis and Thrombosis 11, 298–306.CrossRefGoogle Scholar
Dieber-Rotheneder, M, Puhl, H, Waeg, G, Striegl, G & Esterbauer, H (1991) Effect of oral supplementation with D-α-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation. Journal of Lipid Research 32, 1325–1332.CrossRefGoogle ScholarPubMed
Esterbauer, H, Striegl, G, Puhl, H & Rotheneder, M (1989) Continuous monitoring of in vitro oxidation of human low-density lipoprotein. Free Radical Research Communications 6, 67–75.CrossRefGoogle ScholarPubMed
Folch, J, Lees, M & Sloane Stanley, GH (1957) A simple method for the isolation and purification of total lipides from animal studies. Journal of Biological Chemistry 226, 497–509.Google Scholar
Frayn, KN (1998) Non-esterified fatty acid metabolism and postprandial lipaemia. Atherosclerosis 141, S41–S46.CrossRefGoogle ScholarPubMed
Frayn, KN, Williams, CM & Arner, P (1996) Are increased non-esterified fatty acid concentrations a risk marker for coronary heart disease and other chronic diseases? Clinical Science 90, 243–253.CrossRefGoogle ScholarPubMed
Friedewald, WT & Levy, RI (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry 18, 499–502.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
Griffin, BA, Caslake, MJ, Yip, B, Tait, GW, Packard, CJ & Shepherd, J (1990) Rapid isolation of low density lipoprotein subfractions from plasma by density gradient ultracentrifugation. Atherosclerosis 83, 59–67.Google Scholar
Griffin, BA, Freeman, DJ, Tait, GW, Thomson, J, Caslake, MJ, Packard, CJ & Shepherd, J (1994) Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk. Atherosclerosis 106, 241–253.CrossRefGoogle ScholarPubMed
Griffin, BA, Minihane, AM, Furlonger, N, Chapman, C, Murphy, M, Williams, D, Wright, JJ & Williams, CM (1999) Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects. Clinical Science 97, 269–276.CrossRefGoogle Scholar
Hamilton, JG & Comai, K (1988) Separation of neutral lipid, free fatty-acid and phospholipid classes by normal phase HPLC. Lipids 23, 1150–1153.CrossRefGoogle ScholarPubMed
Harats, D, Dabach, Y, 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.CrossRefGoogle ScholarPubMed
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.Google Scholar
Harris, WS (1997) n-3 Fatty acids and serum lipoproteins: human studies. American Journal of Clinical Nutrition 65, S1645–S1654.CrossRefGoogle ScholarPubMed
Hau, MF, Smelt, AHM, Bindels, AJGH, Sijbrands, EJG, Vander-Laarse, A, Onkenhout, W, van Duyvenvoorde, W & Princen, HMG (1996) Effects of fish oil on oxidation resistance of VLDL in hypertriglyceridaemic patients. Arteriosclerosis Thrombosis and Vascular Biology 16, 1197–1202.Google Scholar
Higgins, S, McCarthy, SN, Corridan, BM, Roche, HM, Wallace, JMW, O'Brien, NM & Morrissey, PA (2000) Measurement of free cholesterol, cholesteryl esters and cholesteryl linoleate hydroperoxide in copper-oxidised low-density lipoprotein in healthy volunteers supplemented with low dose of n-3 polyunsaturated fatty acids. Nutrition Research 20, 1091–1102.CrossRefGoogle Scholar
Holvoet, P & Collen, D (1998) Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis 137, S33–S38.CrossRefGoogle ScholarPubMed
Hughes, GS, Ringer, TV, Watts, KC, DeLoof, MJ, Francom, SF & Spillers, CR (1990) Fish oil produces an atherogenic lipid profile in hypertensive men. Atherosclerosis 84, 229–237.CrossRefGoogle ScholarPubMed
Indu, M & Ghafoorunissa, (1992) n-3 Fatty acids in Indian diets comparison of the effects of precursor alpha-linolenic acid vs product long chain n-3 polyunsaturated fatty acids. Nutrition Research 12, 569–582.CrossRefGoogle Scholar
Jessup, W, Rankin, SM, de Whalley, CV, Hoult, JRS, Scott, J & Leake, DS (1990) α-Tocopherol consumption during low density lipoprotein oxidation. Biochemistry Journal 265, 399–405.CrossRefGoogle ScholarPubMed
Jialal, I, Fuller, CJ & Huet, BA (1995) The effect of α-tocopherol supplementation on LDL-oxidation. Arteriosclerosis Thrombosis and Vascular Biology 15, 190–198.CrossRefGoogle ScholarPubMed
Kendrick, JS & Higgins, JA (1999) Dietary fish oils inhibit early events in the assembly of very low density lipoproteins and target apoB for degradation within the rough endoplasmic reticulum of hamster hepatocytes. xJournal of Lipid Research 40, 504–514.CrossRefGoogle ScholarPubMed
Li, D, Devaraj, S, Fuller, C, Bucala, R & Jialal, I (1996) Effect of alpha-tocopherol on LDL oxidation and glycation: In vitro and in vivo studies. Journal of Lipid Research 37, 1978–1986.CrossRefGoogle ScholarPubMed
McNamara, JR, Huang, C, Massov, T, Leary, ET, Warnick, GR, Rubins, HB, Robins, SJ & Schaefer, EJ (1994) Modification of the dextran-Mg2+ high-density lipoprotein cholesterol precipitation method for use with previously frozen plasma. Clinical Chemistry 40, 233–239.Google Scholar
Mata, P, Alonso, R, LopezFarre, A, Ordovas, JM, Lahoz, C, Garces, C, Caramelo, C, Codoceo, R, Blazquez, E & deOya, M (1996) Effect of dietary fat saturation on LDL oxidation and monocyte adhesion to human endothelial cells in vitro. Arteriosclerosis Thrombosis and Vascular Biology 16, 1347–1355.CrossRefGoogle ScholarPubMed
Minihane, AM, Khan, S, Leigh-Firbank, EC, Talmud, P, Wright, JW, Murphy, MC, Griffin, BA & Williams, CM (2000 a) ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. Arteriosclerosis Thrombosis and Vascular Biology 20, 1990–1997.Google Scholar
Minihane, AM, Khan, S, Talmud, PJ, Williams, DL, Wright, JW, Murphy, MC, Griffin, BA & Williams, CM (2000 b) Lack of association between lipaemia and central adiposity in subjects with an atherogenic lipoprotein phenotype (ALP). International Journal of Obesity 24, 1097–1106.CrossRefGoogle ScholarPubMed
Mori, TA, Burke, V, Puddey, IB, Watts, GF, O'Neal, DN, Best, JD & Beilin, LJ (2000 a) Purified eicosapentaenoic and docosapentaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. American Journal of Clinical Nutrition 71, 1085–1094.CrossRefGoogle Scholar
Mori, TA, Watts, GF, Burke, V, Hilme, E, Puddey, IB & Beilin, LJ (2000 b) Differential effects of eicosapentaenoic acid on reactivity of the forearm microcirculation in hyperlipidemic, overweight men. Circulation 102, 1264–1269.Google Scholar
Nelson, GJ, Schmidt, PC, Bartolini, GL, Kelley, DS & Kyle, D (1997) The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 32, 1137–1146.CrossRefGoogle ScholarPubMed
Nestel, PJ, Connor, WE, Reardon, MR, Connor, S, Wong, S & Boston, R (1984) Suppression by diets rich in fish oil of very low density lipoprotein production in man. Journal of Clinical Investigation 74, 72–89.Google Scholar
Nilsson-Ehle, P, Garfinkel, A & Schotz, MC (1980) Lipolytic enzymes and plasma lipoprotein metabolism. Annual Reviews in Biochemistry 49, 667–693.Google Scholar
Oostenbrug, GS, Mensink, RP, Hardeman, MR, DeVries, T, Brouns, F & Hornstra, G (1997) Exercise performance, red blood cell deformability, and lipid peroxidation: effects of fish oil and vitamin E. Journal of Applied Physiology 83, 746–752.Google Scholar
Rambjør, GS, Wålen, AI, Windsor, SL & Harris, WS (1996) Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans. xLipids 31, S45–S49.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
Reaven, PD, Grasse, BJ & Tribble, DL (1994) Effects of linoleate-enriched and oleate-enriched diets in combination with α-tocopherol on the susceptibility of LDL and LDL subfractions to oxidative modification in humans. Arteriosclerosis and Thrombosis 14, 557–566.CrossRefGoogle ScholarPubMed
Regnstrom, 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.CrossRefGoogle ScholarPubMed
Sanders, TAB & Roshanai, F (1983) The influence of different types of omega-3 polyunsaturated fatty acids on blood-lipids and platelet-function in healthy volunteers. Clinical Science 64, 91–99.CrossRefGoogle ScholarPubMed
Steinberg, D (1997) Low density lipoprotein oxidation and its pathobiological significance. Journal of Biological Chemistry 272, 20963–20966.Google Scholar
Suzukawa, M, Abbey, M, Howe, PRC & Nestel, PJ (1995) Effects of fish-oil fatty acids on low-density-lipoprotein size, oxidizability, and uptake by macrophages. Journal of Lipid Research 36, 473–484.Google Scholar
Toshima, S, Hasegawa, A, Kurabayashi, M, Itabe, H, Takano, T, Sugano, J, Shimamura, K, Michishita, I, Suzuki, T & Nagai, R (2000) Circulating oxidized low density lipoprotein levels: a biochemical marker for coronary heart disease. Arteriosclerosis Thrombosis and Vascular Biology 20, 2243–2247.CrossRefGoogle Scholar
Vieira, OV, Laranjinha, JAN, Madeira, VMC & Almeida, LM (1996) Rapid isolation of low-density lipoproteins in a concentrated fraction free from water-soluble plasma antioxidants. Journal of Lipid Research 37, 2715–2721.CrossRefGoogle Scholar
Vidgren, HM, Ågren JJ, Schwab, U, Rissanen, T, Hanninen, O & Uusitupa, MIJ (1997) Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexaenoic acid-rich oil among healthy young men. Lipids 32, 697–705.CrossRefGoogle ScholarPubMed
Von Schacky, C & Weber, PC (1985) Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans. Journal of Clinical Investigation 76, 2246–2250.CrossRefGoogle ScholarPubMed
Voss, A, Reinhart, M, Sankarappa, S & Sprecher, H (1991) The metabolism of 7, 10, 13, 16, 19-docosapentaenoic acid to 4, 7, 10, 13, 16, 19-docosahexaenoic acid in rat liver is independent of 4-desaturase. Journal of Biological Chemistry 266, 19995–20000.Google Scholar
Weis, JR, Pitas, RE, Wilson, BD & Rodgers, GM (1991) Oxidised LDL increases cultured human endothelial cell tissue factor activity and reduces protein C activation. Federation of American Societies for Experimental Biology Journal 5, 2459–2465.Google Scholar
Willumsen, N, Hexeberg, S, Skorve, J, Lundquist, M & Berge, RK (1993) Docosahexaenoic acid shows no triglyceride-lowering effects but decreases the peroxisomal fatty acid oxidation in liver of rats. Journal of Lipid Research 34, 13–22.CrossRefGoogle ScholarPubMed
Wong, WH, Fisher, EA & Marsh, JB (1989) Effects of eicosapentaenoic acid and docosahexaenoic acid on apolipoprotein mRNA and secretion of very low density lipoprotein in HepG2 cells. Arteriosclerosis 9, 836–841.Google Scholar
Zuijdgeest-van Leeuwen, SD, Dagnelie, PC, Rietveld, T, van den Berg, JWO & Wilson, JHP (1999) Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions. British Journal of Nutrition 82, 481–488.CrossRefGoogle ScholarPubMed