Advertisement

Influence of α-linolenic acid and fish-oil on markers of cardiovascular risk in subjects with an atherogenic lipoprotein phenotype

      Abstract

      We tested the hypothesis that dietary α-linolenic acid (ALA) can exert effects on markers of cardiovascular risk similar to that produced by its longer chain counterparts in fish-oil. A dietary intervention study was undertaken to examine the effects of an ALA-enriched diet in 57 men expressing an atherogenic lipoprotein phenotype (ALP). Subjects were randomly assigned to one of three diets enriched either with flaxseed oil (FXO: high ALA, n = 21), sunflower oil (SO: high linoleic acid, n = 17), or SO with fish-oil (SOF n = 19) for 12 weeks, resulting in dietary intake ratios of n-6:n-3 PUFA of 0.5, 27.9 and 5.2, respectively. The relative abundance of ALA and EPA in erythrocyte membranes increased on the FXO diet (p < 0.001), whereas both EPA and DHA increased after fish-oil (p < 0.001). There were significant decreases in total plasma cholesterol within (FXO −12.3%, p = 0.001; SOF −7.6%, p = 0.014; SO −7.3%, p = 0.033) and between diets (p = 0.019), and decreases within diets after 12 weeks for HDL cholesterol on flaxseed oil (FXO −10%, p = 0.009), plasma TG (−23%, p < 0.001) and small, dense LDL (−22% p = 0.003) in fish-oil. Membrane DHA levels were inversely associated with the changes in plasma TG (p = 0.001) and small, dense LDL (p < 0.05) after fish-oil. In conclusion, fish-oil produced predictable changes in plasma lipids and small, dense LDL (sdLDL) that were not reproduced by the ALA-enriched diet. Membrane DHA levels appeared to be an important determinant of these fish-oil-induced effects.

      Abbreviations:

      ALA (α-Linolenic acid), FXO (Flaxseed oil), SO (Sunflower oil diet), SOF (Sunflower+fish-oil diet), EPA (Eicosapentaenoic acid), DHA (Docosahexanoic acid), LA (Linoleic acid), PUFA (Polyunsaturated fatty acids), LCP (Very long-chain polyunsaturated fatty acids)

      Keywords

      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:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • GISSI-Prevenzione Investigators
        Dietary supplementation with n-3 polyunsaturated fatty acids and Vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial.
        Lancet. 1999; 354: 447-455
        • Hu F.B.
        • Stamfer M.J.
        • Manson J.E.
        Dietary intake of α-linolenic acid and risk of fatal ischemic heart disease among women.
        Am J Clin Nutr. 1999; 69: 890-897
        • de Longeril M.
        • Salen P.
        • Martin J.-L.
        • Monjaud I.
        • Delaye J.
        • Mamelle N.
        Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction. Final report of the Lyon Heart Study.
        Circulation. 1999; 99: 779-785
        • Oomen C.M.
        • Ocke M.C.
        • Peskens E.J.
        • Kok F.J.
        • Kromhout D.
        Alpha-linolenic acid intake is not beneficially associated with 10-year risk of coronary artery disease incidence: the Zupten Elderly Study.
        Am J Clin Nutr. 2001; 74: 457-463
        • Djoussé L.
        • Folsom A.R.
        • Province M.A.
        • Hunt S.C.
        • Ellison R.C.
        Dietary linolenic acid and carotid atherosclerosis: the National, Heart, Lung, and Blood Institute Family Heart Study.
        Am J Clin Nutr. 2003; 77: 819-825
        • Guallar E.
        • Aro A.
        • Jimenez F.J.
        • et al.
        Omega-3 fatty acids in adipose tissue and risk of myocardial infraction: the EURAMIC Study.
        Arterioscler Thromb Vasc Biol. 1999; 19: 1111-1118
        • Pedersen J.I.
        • Ringstad J.
        • Almendingen K.
        • Haugen T.S.
        • Stensvold I.
        • Thelle D.S.
        Adipose tissue fatty acids and risk of myocardial infarction – a case-control study.
        Eur J Clin Nutr. 2000; 54: 618-625
        • Harris W.S.
        N-3 fatty acid and serum lipoproteins: human studies.
        Am J Clin Nutr. 1997; 65: 1645S-1654S
        • Minihane A-M.
        • Khan S.
        • Leigh-Firbank C.
        • et al.
        Apo E polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype.
        Arterioscler Thromb Vasc Biol. 2000; 20: 1990-1997
        • Connor S.L.
        • Connor W.E.
        Are fish oils beneficial in the prevention and treatment of coronary artery disease.
        Am J Clin Nutr. 1997; 66: 1020S-1031S
        • Wilkinson P.A.
        • Ah-Sing E.
        • Emery C.
        • et al.
        The importance of alpha-linolenic acid as a source of long chain n-3 polyunsaturated fatty acids and its influence on risk factors of cardiovascular disease.
        Proc Nutr Soc. 2000; 59: 16A
        • Folch J.M.
        • Lees M.
        • Sloane-Stanley G.H.
        A simple method for the isolation and purification of total lipids from animal tissues.
        J Biol Chem. 1957; 226: 497-509
        • Griffin B.A.
        • Caslake M.J.
        • Yip B.
        • Tait G.W.
        • Packard C.J.
        • Shepherd J.
        Rapid isolation of low density lipoprotein (LDL) subfractions from plasma by density gradient ultracentrifugation.
        Atherosclerosis. 1990; 83: 59-67
        • Meade T.W.
        • Ruddock V.
        • Stirling Y.
        • Chakrabarti R.
        • Miller G.J.
        Fibrionlytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study.
        Lancet. 1993; 342: 1076-1079
        • Miller G.J.
        • Bauer K.A.
        • Barzegar S.
        • Cooper J.A.
        • Rosenberg R.D.
        Increased activation of the haemostatic system in men at high risk of fatal coronary heart disease.
        Thromb Haemost. 1996; 75: 767-771
        • Gerster H.
        Can adults adequately convert α-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)?.
        Int J Vitam Nutr Res. 1998; 68: 159-173
        • Schacky von C.
        Omega-3 fatty acids and cardiovascular disease.
        Curr Opin Clin Nutr Med. 2004; : 131-136
        • Djoussé L.
        • Hunt S.C.
        • Arnett D.K.
        • Province A.
        • Eckfeldt J.H.
        • Ellison R.C.
        Dietary linolenic acid is inversely associated with plasma triacylglycerol: the National, Heart, Lung, and Blood Institute Family Heart Study.
        Am J Clin Nutr. 2003; 78: 1098-1102
        • Abbey M.
        • Clifton P.
        • Kestin M.
        • Belling B.
        • Nestel P.J.
        Effect of fish-oil on lipoproteins, lecithin: cholesterol acyltransferase, and lipid transfer protein activity in humans.
        Arteriosclerosis. 1990; 10: 85-94
        • Kelley D.S.
        • Nelson G.J.
        • Love J.E.
        • et al.
        Dietary α-linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans.
        Lipids. 1993; 28: 533-537
        • Pang D.
        • Allman-Farinelli A.
        • Wong T.
        • Barnes R.
        • Kingham K.M.
        Replacement of linoleic acid with α-linolenic acid does not alter blood lipids in normolipidaemic men.
        Br J Nutr. 1998; 80: 163-167
        • Singer P.
        • Berger I.
        • Wirth M.
        • Godicke W.
        • Jaeger W.
        • Voight S.
        Slow desaturation and elongation of linoleic and α-linolenic acids as a rationale of eicosapentaenoic acid-rich diet to lower blood pressure, and serum lipids in normal, hypertensive and hyperlipidemic subjects.
        Prostaglandins Leukot Med. 1986; 24: 173-193
        • Finnegan Y.E.
        • Minihane A.-M.
        • Leigh-Firbank E.C.
        • et al.
        Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects.
        Am J Clin Nutr. 2003; 77: 783-795
        • Baumstark M.W.
        • Frey I.
        • Berg A.
        • Keul J.
        Influence of n-3 fatty acids from fish oils on concentration of high- and low-density lipoprotein subfractions and their lipid and apolipoprotein composition.
        Clin Biochem. 1992; 25: 338-340
        • Burdge G.C.
        • Finnegan Y.E.
        • Minihane A.M.
        • Williams C.M.
        • Wootton S.A.
        Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C] alpha-linoleic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men.
        Br J Nutr. 2003; 90: 311-321
        • Leigh-Fairbank E.C.
        • Minihane A.-M.
        • Leake D.S.
        • et al.
        Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses.
        Br J Nutr. 2002; 87: 435-445
        • Berge R.K.
        • Madsen L.
        • Vaagenes H.
        • Tronstad K.J.
        • Gottlicher M.
        • Rustan A.C.
        In contrast with docosahexaenoic acid, eicosapentaenoic acid and hypolipidaemic derivatives decrease hepatic synthesis and secretion of triacylglycerol by decreased diacyglycerol acyltransferase activity and stimulation of fatty acid oxidation.
        Biochem J. 1999; 343: 191-197
        • Davidson M.H.
        • Maki K.C.
        • Kalkowski J.A.
        • Schaefer E.J.
        • Torri S.A.
        • Drennan K.B.
        Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomised, double-blind placebo-controlled trial.
        J Am Coll Nutr. 1997; 16: 234-236
        • Buckley R.
        • Shewring B.
        • Turner R.
        • Yaqoob P.
        • Minihane A.M.
        Circulating triacylglycerol and apo E levels in response to EPA and docosahexaenoic acid supplementation in adult human subjects.
        Br J Nutr. 2004; 92: 477-483
        • Mori T.A.
        • Burke V.
        • Puddey I.B.
        • et al.
        Purified eicosapentaenoic acid and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men.
        Am J Clin Nutr. 2000; 71: 1085-1095
        • Heath R.B.
        • Karpe F.
        • Milne R.W.
        • Burdge G.C.
        • Wootton S.A.
        • Frayn K.
        Selective partitioning of dietary fatty acids into the VLDL TG pool in the early postprandial period.
        J Lipid Res. 2003; 44: 2065-2072
        • Mutanen M.
        • Freese R.
        Fats, lipids and blood coagulation.
        Curr Opin Lipidol. 2001; 12: 25-29
        • Mahrabian M.
        • Peter J.B.
        • Barnard R.J.
        • Lusis A.J.
        Dietary regulation of fibrinolytic factors.
        Atherosclerosis. 1990; 84: 25-32
        • Mehta J.
        • Mehta P.
        • Lawson D.
        • Salden T.
        Plasma tissue plasminogen activator inhibitor levels in coronary disease: correlation with age and serum triglyceride concentration.
        J Am Coll Cardiol. 1987; 9: 263-268
        • Knapp H.R.
        Dietary fatty acids in human thrombosis and hemostasis.
        Am J Clin Nutr. 1997; 65: 1687S-1698S
        • Allman-Farinelli M.A.
        • Hall D.
        • Kingham K.
        • Pang D.
        • Petocz P.
        • Favaloro E.J.
        Comparison of the effects of two low fat diets with different α-linolenic:linoleic acid ratios on coagulation and fibrinolysis.
        Atherosclerosis. 1999; 142: 159-168