Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Metabolic syndrome, diabetes mellitus, cardiovascular and neurodegenerative diseases

Fish oil omega-3 fatty acids and cardio-metabolic health, alone or with statins

European Journal of Clinical Nutrition volume 67, pages 536–540 (2013)Cite this article

Subjects

Abstract

The impact of the fish-derived omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease (CVD) and type 2 diabetes incidence and risk has been widely investigated. Although the balance of evidence suggests substantial benefits with respect to CVD mortality, there is little evidence for an impact of these fatty acids on insulin sensitivity and diabetes incidence, despite very promising data from animal models. The focus here will be the plasma lipid modulatory effects of EPA and DHA and will include an exploration of the potential and demonstrated complementarity between statins and EPA/DHA on overall CVD risk and the plasma cholesterol and triglyceride profile. Although there is some justification for greater general population and patient EPA+DHA intakes, an often overlooked major obstacle is that global fish stocks are limited and insufficient to meet demands. The potential of emerging ‘non-fish foods’ to provide affordable and sustainable sources of EPA+DHA will also be briefly discussed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Nichols M, Townsend N, Scarborough P, Rayner M European Heart Network and European Society of Cardiology: European Cardiovascular Disease Statistics 2012.

  2. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937–952.

    Article  Google Scholar 

  3. Calder PC . Mechanisms of action of (n-3) fatty acids. J Nutr 2012; 142: 592S–599SS.

    Article  CAS  Google Scholar 

  4. Roth EM, Harris WS . Fish oil for primary and secondary prevention of coronary heart disease. Curr Atheroscler Rep 2010; 12: 66–72.

    Article  CAS  Google Scholar 

  5. Aranceta J, Perez-Rodrigo C . Recommended dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids: a systematic review. Br J Nutr 2012; 107 (Suppl 2), S8–22.

    Article  CAS  Google Scholar 

  6. Pan A, Chen M, Chowdhury R, Wu JH, Sun Q, Campos H et al. alpha-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr 2012; 96: 1262–1273.

    Article  CAS  Google Scholar 

  7. Burdge GC . Metabolism of alpha-linolenic acid in humans. Prostaglandins Leukot Essent Fatty Acids 2006; 75: 161–168.

    Article  CAS  Google Scholar 

  8. Burdge GC, Finnegan YE, Minihane AM, Williams CM, Wootton SA . Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men. Br J Nutr 2003; 90: 311–321.

    Article  CAS  Google Scholar 

  9. Welch AA, Shakya-Shrestha S, Lentjes MA, Wareham NJ, Khaw KT . Dietary intake and status of n-3 polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meat-eaters, vegetarians, and vegans and the product-precursor ratio [corrected] of alpha-linolenic acid to long-chain n-3 polyunsaturated fatty acids: results from the EPIC-Norfolk cohort. Am J Clin Nutr 2010; 92: 1040–1051.

    Article  CAS  Google Scholar 

  10. Scientific Advisory Committee on Nutrition (SACN) and Committee on Toxicology (COT). Advice on Fish Consumption: Benefits and Risks. TSO. The Stationary Office: Norwich, UK, 2004.

  11. Kris-Etherton PM, Harris WS, Appel LJ . Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002; 106: 2747–2757.

    Article  Google Scholar 

  12. NICE. Post Myocardial Infarction Secondary Prevention in primary and Secondary Care for Patients Following a Myocardial Infarction. Royal College of General Practioners, 2007.

  13. Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PR . Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids 2003; 38: 391–398.

    Article  CAS  Google Scholar 

  14. Kennedy ET, Luo H, Ausman LM . Cost implications of alternative sources of (n-3) fatty acid consumption in the United States. J Nutr 2012; 142: 605S–609SS.

    Article  CAS  Google Scholar 

  15. Vigerust NF, Bjorndal B, Bohov P, Brattelid T, Svardal A, Berge RK . Krill oil versus fish oil in modulation of inflammation and lipid metabolism in mice transgenic for TNF-alpha. Eur J Nutr 2012, e-pub ahead of print 28 August 2012.

  16. Adarme-Vega TC, Lim DK, Timmins M, Vernen F, Li Y, Schenk PM . Microalgal biofactories: a promising approach towards sustainable omega-3 fatty acid production. Microb Cell Fact 2012; 11: 96.

    Article  CAS  Google Scholar 

  17. Whelan J, Rust C . Innovative dietary sources of n-3 fatty acids. Ann Rev Nutr 2006; 26: 75–103.

    Article  CAS  Google Scholar 

  18. Sayanova O, Napier JA . Transgenic oilseed crops as an alternative to fish oils. Prostaglandins Leukot Essent Fatty Acids 2011; 85: 253–260.

    Article  CAS  Google Scholar 

  19. Dyerberg J, Bang HO . A hypothesis on the development of acute myocardial infarction in Greenlanders. Scand J Clin Lab Inves Suppl 1982; 161: 7–13.

    Article  CAS  Google Scholar 

  20. Kwak SM, Myung SK, Lee YJ, Seo HG . Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Int Med 2012; 172: 686–694.

    Article  CAS  Google Scholar 

  21. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS . Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA 2012; 308: 1024–1033.

    Article  CAS  Google Scholar 

  22. Delgado-Lista J, Perez-Martinez P, Lopez-Miranda J, Perez-Jimenez F . Long chain omega-3 fatty acids and cardiovascular disease: a systematic review. Br J Nutr 2012; 107 (Suppl 2), S201–S213.

    Article  CAS  Google Scholar 

  23. GISSI. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet 1999; 354: 447–455.

    Article  Google Scholar 

  24. Harris WS, Miller M, Tighe AP, Davidson MH, Schaefer EJ . Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis 2008; 197: 12–24.

    Article  CAS  Google Scholar 

  25. Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr 2006; 84: 5–17.

    Article  CAS  Google Scholar 

  26. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007; 369: 1090–1098.

    Article  CAS  Google Scholar 

  27. Musa-Veloso K, Binns MA, Kocenas A, Chung C, Rice H, Oppedal-Olsen H et al. Impact of low v. moderate intakes of long-chain n-3 fatty acids on risk of coronary heart disease. Br J Nutr 2011; 106: 1129–1141.

    Article  CAS  Google Scholar 

  28. Adkins Y, Kelley DS . Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids. J Nutr Biochem 2010; 21: 781–792.

    Article  CAS  Google Scholar 

  29. Leaf A, Kang JX, Xiao YF, Billman GE . Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation 2003; 107: 2646–2652.

    Article  Google Scholar 

  30. Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB . Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation 2005; 112: 1945–1952.

    Article  CAS  Google Scholar 

  31. Pase MP, Grima NA, Sarris J . Do long-chain n-3 fatty acids reduce arterial stiffness? A meta-analysis of randomised controlled trials. Br J Nutr 2011; 106: 974–980.

    Article  CAS  Google Scholar 

  32. Campbell F, Dickinson HO, Critchley JA, Ford GA, Bradburn M . A systematic review of fish-oil supplements for the prevention and treatment of hypertension. Eur J Prev Cardiol 2012; 20: 107–120.

    Article  Google Scholar 

  33. Calder PC . Fatty acids and inflammation: the cutting edge between food and pharma. Eur J Pharmacol 2011; 668 (Suppl 1), S50–S58.

    Article  CAS  Google Scholar 

  34. Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 2003; 361: 477–485.

    Article  CAS  Google Scholar 

  35. Harris WS . n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997; 65 (5 Suppl), 1645S–1654SS.

    Article  CAS  Google Scholar 

  36. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J . Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis 2006; 189: 19–30.

    Article  CAS  Google Scholar 

  37. Minihane AM, Khan S, Leigh-Firbank EC, Talmud P, Wright JW, Murphy MC et al. ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. Arterioscler Thromb Vasc Biol 2000; 20: 1990–1997.

    Article  CAS  Google Scholar 

  38. Mozaffarian D, Rimm EB . Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 2006; 296: 1885–1899.

    Article  CAS  Google Scholar 

  39. Albert CM, Hennekens CH, O’Donnell CJ, Ajani UA, Carey VJ, Willett WC et al. Fish consumption and risk of sudden cardiac death. JAMA 1998; 279: 23–28.

    Article  CAS  Google Scholar 

  40. Andersen G, Harnack K, Erbersdobler HF, Somoza V . Dietary eicosapentaenoic acid and docosahexaenoic acid are more effective than alpha-linolenic acid in improving insulin sensitivity in rats. Ann Nutr Metab 2008; 52: 250–256.

    Article  CAS  Google Scholar 

  41. Nettleton JA, Katz R . n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc 2005; 105: 428–440.

    Article  CAS  Google Scholar 

  42. Tierney AC, McMonagle J, Shaw DI, Gulseth HL, Helal O, Saris WH et al. Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome--LIPGENE: a European randomized dietary intervention study. Int J Obes (Lond) 2011; 35: 800–809.

    Article  CAS  Google Scholar 

  43. Hartweg J, Perera R, Montori V, Dinneen S, Neil HA, Farmer A . Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database Syst Rev 2008; CD003205.

  44. Wu JH, Micha R, Imamura F, Pan A, Biggs ML, Ajaz O et al. Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. Br J Nutr 2012; 107 (Suppl 2), S214–S227.

    Article  CAS  Google Scholar 

  45. Wallin A, Di Giuseppe D, Orsini N, Patel PS, Forouhi NG, Wolk A . Fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes: systematic review and meta-analysis of prospective studies. Diabetes Care 2012; 35: 918–929.

    Article  CAS  Google Scholar 

  46. Austin MA . Triglyceride, small, dense low-density lipoprotein, and the atherogenic lipoprotein phenotype. Curr Atheroscler Rep 2000; 2: 200–207.

    Article  CAS  Google Scholar 

  47. Jackson KG, Poppitt SD, Minihane AM . Postprandial lipemia and cardiovascular disease risk: Interrelationships between dietary, physiological and genetic determinants. Atherosclerosis 2012; 220: 22–33.

    Article  CAS  Google Scholar 

  48. Caslake MJ, Miles EA, Kofler BM, Lietz G, Curtis P, Armah CK et al. Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study. Am J Clin Nutr 2008; 88: 618–629.

    Article  CAS  Google Scholar 

  49. Buckley R, Shewring B, Turner R, Yaqoob P, Minihane AM . Circulating triacylglycerol and apoE levels in response to EPA and docosahexaenoic acid supplementation in adult human subjects. Br J Nutr 2004; 92: 477–483.

    Article  CAS  Google Scholar 

  50. Cottin SC, Sanders TA, Hall WL . The differential effects of EPA and DHA on cardiovascular risk factors. Proc Nutr Soc 2011; 70: 215–231.

    Article  CAS  Google Scholar 

  51. Mozaffarian D, Wu JH . (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr 2012; 142: 614S–625S.

    Article  CAS  Google Scholar 

  52. Gotto AM, Moon JE . Management of cardiovascular risk: the importance of meeting lipid targets. Am J Cardiol 2012; 110 (1 Suppl), 3A–14A.

    Article  CAS  Google Scholar 

  53. Maki KC, Bays HE, Dicklin MR . Treatment options for the management of hypertriglyceridemia: Strategies based on the best-available evidence. J Clin Lipidol 2012; 6: 413–426.

    Article  Google Scholar 

  54. NICE. TA94: Statins for the Prevention of Cardiovascular Events. National Institute for Health and Clinical Excellence: London, 2006.

  55. Dujovne CA, Williams CD, Ito MK . What combination therapy with a statin, if any, would you recommend? Curr Atheroscler Rep 2011; 13: 12–22.

    Article  Google Scholar 

  56. Gotto AM, Moon JE . Recent clinical studies of the effects of lipid-modifying therapies. Am J Cardiol 2012; 110 (1 Suppl), 15A–26A.

    Article  CAS  Google Scholar 

  57. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 2008; 200: 135–140.

    Article  CAS  Google Scholar 

  58. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR Study). Am J Cardiol 2012; 110: 984–992.

    Article  CAS  Google Scholar 

  59. Maki KC, Bays HE, Dicklin MR, Johnson SL, Shabbout M . Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia. J Clin Lipidol 2011; 5: 483–492.

    Article  Google Scholar 

  60. Carroll MD, Lacher DA, Sorlie PD, Cleeman JI, Gordon DJ, Wolz M et al. Trends in serum lipids and lipoproteins of adults, 1960-2002. JAMA 2005; 294: 1773–1781.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK

    Anne Marie Minihane

Authors
  1. Anne Marie Minihane
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Marie Minihane.

Ethics declarations

Competing interests

The author declares no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marie Minihane, A. Fish oil omega-3 fatty acids and cardio-metabolic health, alone or with statins. Eur J Clin Nutr 67, 536–540 (2013). https://doi.org/10.1038/ejcn.2013.19

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2013.19

Keywords

This article is cited by

Search

Advanced search

Quick links