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Increased α-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis

European Journal of Clinical Nutrition volume 58, pages 1083–1089 (2004)Cite this article

Abstract

Objective: To investigate the effects of increased alpha-linolenic acid (ALA)-intake on intima–media thickness (IMT), oxidized low-density lipoprotein (LDL) antibodies, soluble intercellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and interleukins 6 and 10.

Design: Randomized double-blind placebo-controlled trial.

Subjects: Moderately hypercholesterolaemic men and women (55±10 y) with two other cardiovascular risk factors (n=103).

Intervention: Participants were assigned to a margarine enriched with ALA (fatty acid composition 46% LA, 15% ALA) or linoleic acid (LA) (58% LA, 0.3% ALA) for 2 y.

Results: Dietary ALA intake was 2.3 en% among ALA users, and 0.4 en% among LA users. The 2-y progression rate of the mean carotid IMT (ALA and LA: +0.05 mm) and femoral IMT (ALA:+0.05 mm; LA:+0.04 mm) was similar, when adjusted for confounding variables. After 1 and 2 y, ALA users had a lower CRP level than LA users (net differences −0.53 and −0.56 mg/l, respectively, P<0.05). No significant effects were observed in oxidized LDL antibodies, and levels of sICAM-1, interleukins 6 and 10.

Conclusions: A six-fold increased ALA intake lowers CRP, when compared to a control diet high in LA. The present study found no effects on markers for atherosclerosis.

Sponsorship: The Dutch ‘Praeventiefonds’.

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References

  • Bemelmans WJE, Muskiet FAJ, Feskens EJM, Vries de JHM, Broer J, May JF & Meyboom-de Jong B (2000): Associations of alpha-linolenic acid and linoleic acid with risk factors for coronary heart disease. Eur. J. Clin. Nutr. 54, 865–871.

    Article  CAS  Google Scholar 

  • Bemelmans WJE, Broer J, Feskens EJM, Smit AJ, Muskiet FAJ, Lefrandt JF, Bom VJJ May JF & Meyboom-de Jong B (2002): Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN). Am. J. Clin. Nutr. 75, 221–227.

    Article  CAS  Google Scholar 

  • Berry EM (2001): Are diets high in omega-6 polyunsaturated fatty acids unhealthy? Eur. Heart. J. 3 (Suppl D), 37–41.

    Article  Google Scholar 

  • De Caterina R & Basta G (2001): n-3 Fatty acids and the inflammatory response–biological background. Eur. Heart J. 3 (Suppl D), 42–49.

    Article  Google Scholar 

  • Endres S (1996): n-3 polyunsaturated fatty acids and human cytokine synthesis. Lipids 31 (Suppl), 239–242.

    Article  Google Scholar 

  • Freese R, Mutanen V, Valstra LM & Salminen I (1994): Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/alpha-linolenic acid ratio on platelet aggregation. Thromb. Haemost. 71, 73–77.

    Article  CAS  Google Scholar 

  • Gabay C & Kushner I (1999): Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 340, 448–454.

    Article  CAS  Google Scholar 

  • Glass CK & Witztum JL (2001): Atherosclerosis. The road ahead. Cell 104, 503–516.

    Article  CAS  Google Scholar 

  • de Groot E, Zwinderman AH, van der Steen AFW, Ackerstaff RGA, van Montauban Swijndregt AD, Bom N, Lie KI & Bruschke AVG (1998): Variance components analysis of carotid and femoral intima–media thickness measurements. Ultrasound Med. Biol. 24, 825–832.

    Article  CAS  Google Scholar 

  • Hennig B, Meerarani P, Ramadass P, Watkins BA & Toborek M (2000): Fatty acid-mediated activation of vascular endothelial cells. Metabolism 49, 1006–1013.

    Article  CAS  Google Scholar 

  • Libby P (2002): Inflammation in atherosclerosis. Nature 420, 868–874.

    Article  CAS  Google Scholar 

  • de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P & Delaye J (1994): Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 343, 1454–1459.

    Article  CAS  Google Scholar 

  • Ma J, Folsom AR, Lewis L & Eckfeldt JH (1997): Relation of plasma phospholipid and cholesterol ester fatty acid composition to carotid artery intima–media thickness: the Atherosclerosis Risk in Communities (ARIC) study. Am. J. Clin. Nutr. 65, 551–559.

    Article  CAS  Google Scholar 

  • Mantzioris E, Cleland LG, Gibson RA, Neumann MA, Demasi M & James MJ (2000): Biochemical effects of a diet containing foods enriched with n-3 fatty acids. Am. J. Clin. Nutr. 72, 42–48.

    Article  CAS  Google Scholar 

  • Marchioli R & on behalf of the GISSI-Prevenzione investigators (2001): Treatment with n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione Trial. Eur. Heart. J. 3 (Suppl D), 85–97.

    Article  Google Scholar 

  • National Cholesterol Education Program (2001): Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in Adults (Adult Treatment Panel III). JAMA 285, 2486–2497.

  • Pakala R, Pakala R, Sheng WL & Benedict CR (1999): Eicosapentaenoic acid and docosahexaenoic acid block serotonin-induced smooth muscle cell proliferation. Arterioscler. Thromb. Vasc. Biol. 19, 2316–2322.

    Article  CAS  Google Scholar 

  • Rallidis LS, Paschos G, Liakos GK, Velissaridou H, Anastasiadis G & Zampelas A (2003): Dietary α-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Atherosclerosis 167, 237–242.

    Article  CAS  Google Scholar 

  • Ridker PM (2003): Clinical application of C-reactive Protein for cardiovascular disease detection and prevention. Circulation 107, 363–369.

    Article  Google Scholar 

  • Ridker PM, Buring JE, Cook NR & Rifai N (2003): C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events. An 8-year follow-up of 14.719 initially healthy American women. Circulation 107, 391–397.

    Article  Google Scholar 

  • Ross R (1999): Atherosclerosis— an inflammatory disease. N. Engl. J. Med. 340, 115–126.

    Article  CAS  Google Scholar 

  • Sanders TA (2000): Polyunsaturated fatty acids in the food chain in Europe. Am. J. Clin. Nutr. 71 (Suppl 1), 176–178.

    Article  Google Scholar 

  • Sanderson P, Finnegan YE, Williams CM, Calder PC, Burdge GC, Wootton SA, Griffin BA, Millward DJ, Pegge NC & Bemelmans WJE (2002): UK Food Standards Agency alpha-linolenic acid workshop report. Br. J. Nutr. 88, 573–579.

    Article  CAS  Google Scholar 

  • von Schacky C (2000): n-3 Fatty acids and the prevention of coronary atherosclerosis. Am. J. Clin. Nutr. 71 (Suppl), 224–227.

    Article  Google Scholar 

  • Schaefer J (1997): Effects of dietary fatty acids on lipoproteins and cardiovascular disease risk: summary. Am. J. Clin. Nutr. 65 (Suppl 1), 1655–1656.

    Article  Google Scholar 

  • Schmidt EB, Kristensen SB, De Caterina R & Illingworth DR (1993): The effects of n-3 fatty acids on plasma lipids and lipoproteins and other cardiovascular risk factors in patients with hyperlipidemia. Atherosclerosis 103, 107–121.

    Article  CAS  Google Scholar 

  • Swets BP, Brouwer DA & Cohen Tervaert JW (2001): Patients with systemic vasculitis have increased levels of autoantibodies against oxidized LDL. Clin. Exp. Immunol. 124, 163–167.

    Article  CAS  Google Scholar 

  • Ubels FL, Terpstra WF & Smit AJ (1999): Carotid intima–media thickness: influence of drug treatment and clinical implications. Neth. J. Med. 55, 188–195.

    Article  CAS  Google Scholar 

  • Watts GF, Lewis B, Jackson P, Burke V, Lewis ES, Brunt JN & Coltart DJ (1995): Relationships between nutrient intake and progression/regression of coronary atherosclerosis as assessed by serial quantitative angiography. Can. J. Cardiol. 11 (Suppl G), 110–114.

    Google Scholar 

  • Wolkerstorfer A, Laan MP, Savelkoul HFJ, Neijens HJ, Mulder PG, Oudesluijs-Murphy AM, Sukhai RN & Oranje AP (1998): Soluble E-selectin, other markers of inflammation and disease severity in children with atopic dermatitis. Br. J. Dermatol. 138, 431–435.

    Article  CAS  Google Scholar 

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Acknowledgements

The present research was funded by the Dutch ‘Praeventiefonds, Grant No. 28-2757. We thank Unilever Research, Vlaardingen, The Netherlands, for production and storage of the margarines, The St Lucas Hospital in Winschoten for logistic support, Marian Bruin, Margreet Teune-Weessies, and Anne van Gessel for assessment of the IMT, and Jan Damoiseaux, from the University Hospital Maastricht, for valuable comments. Finally, Peter Heymans, Ruud Theunissen, and Roel Brandts are acknowledged for their technical support.

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Authors and Affiliations

  1. Department of General Practice, University of Groningen, Groningen, The Netherlands

    W J E Bemelmans & B Meyboom-de Jong

  2. Department of Medicine, Groningen University Hospital, Groningen, The Netherlands

    J D Lefrandt, P L van Haelst & A J Smit

  3. Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

    W J E Bemelmans & E J M Feskens

  4. Municipal Health Service Agency, City of Groningen, Groningen, The Netherlands

    J Broer

  5. Department of Cardiology, Groningen University Hospital, Groningen, The Netherlands

    J F May

  6. Department of Medicine, University Hospital Maastricht, Maastricht, The Netherlands

    J W Cohen Tervaert

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  1. W J E Bemelmans
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Contributions

Guarantor: B Meyboom-de Jong.

Contributors: All investigators contributed to the writing and editing of the manuscript. M-dJ supervised the MARGARIN project and is the guarantor. JB, JFM, AJS, JDL, and WJEB contributed to the design and implementation. EJMF contributed with nutritional expertise and JWCT and PvH with their immunological medical expertise.

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Correspondence to W J E Bemelmans.

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Bemelmans, W., Lefrandt, J., Feskens, E. et al. Increased α-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis. Eur J Clin Nutr 58, 1083–1089 (2004). https://doi.org/10.1038/sj.ejcn.1601938

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