Skip to main content

Advertisement

SpringerLink
Log in

The omega-3 index: From biomarker to risk marker to risk factor

  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Blood levels of omega-3 fatty acids reflect the interplay of metabolism and the intake of omega-3-rich foods (eg, oily fish). Multiple lines of evidence link reduced tissue and/or blood levels of omega-3 fatty acids, as reflected in the erythrocyte eicosapentaenoic acid plus docosahexaenoic acid level (ie, the omega-3 index), with increased risk for coronary heart disease, especially sudden cardiac death. The purpose of this review is to examine the extent to which biomarkers like the omega-3 index qualify as coronary heart disease risk markers and/or risk factors based on new criteria from the American Heart Association and older guidelines proposed in 1965 by Sir Austin Bradford Hill. These standards include consistency, strength of association, biological plausibility, coherence, dose-response relationship, clinical utility, cost effectiveness, and prospective validation. The omega-3 index appears to fulfill many of the requirements for a risk marker and, more importantly, for a risk factor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Harris WS, von Schacky C: The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med 2004, 39:212–220.

    Article  CAS  PubMed  Google Scholar 

  2. Siscovick DS, Raghunathan TE, King I, et al.: Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA 1995, 274:1363–1367.

    Article  CAS  PubMed  Google Scholar 

  3. Albert CM, Campos H, Stampfer MJ, et al.: Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 2002, 346:1113–1118.

    Article  CAS  PubMed  Google Scholar 

  4. Block RC, Harris WS, Reid KJ, et al.: EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls. Atherosclerosis 2007, 197:821–828.

    Article  PubMed  Google Scholar 

  5. Itomura M, Fujioka S, Hamazaki K, et al.: Factors influencing EPA+DHA levels in red blood cells in Japan. In Vivo 2008, 22:131–135.

    PubMed  Google Scholar 

  6. Barberger-Gateau P, Raffaitin C, Letenneur L, et al.: Dietary patterns and risk of dementia: the Three-City cohort study. Neurology 2007, 69:1921–1930.

    Article  CAS  PubMed  Google Scholar 

  7. Schaefer EJ, Bongard V, Beiser AS, et al.: Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol 2006, 63:1545–1550.

    Article  PubMed  Google Scholar 

  8. Chong EW, Kreis AJ, Wong TY, et al.: Dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis. Arch Ophthalmol 2008, 126:826–833.

    Article  PubMed  Google Scholar 

  9. Sun Q, Ma J, Campos H, et al.: Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women. Am J Clin Nutr 2007, 86:74–81.

    CAS  PubMed  Google Scholar 

  10. Harris WS: The omega-3 index as a risk factor for coronary heart disease. Am J Clin Nutr 2008, 87:1997S–2002S.

    CAS  PubMed  Google Scholar 

  11. Sun Q, Ma J, Campos H, et al.: Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction. Am J Clin Nutr 2008, 88:216–223.

    CAS  PubMed  Google Scholar 

  12. Harris WS, Poston WC, Haddock CK: Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 2007, 193:1–10.

    Article  CAS  PubMed  Google Scholar 

  13. Hlatky MA, Greenland P, Arnett DK, et al.: Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation 2009, 119:2408–2416.

    Article  PubMed  Google Scholar 

  14. Hill AB: The environment and disease: association or causation? Proc R Soc Med 1965, 58:295–300.

    CAS  PubMed  Google Scholar 

  15. Harris WS: International recommendations for consumption of long-chain omega-3 fatty acids. J Cardiovasc Med (Hagerstown) 2007, 8(Suppl 1):S50–S52.

    Google Scholar 

  16. Sekikawa A, Curb JD, Ueshima H, et al.: Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study. J Am Coll Cardiol 2008, 52:417–424.

    Article  CAS  PubMed  Google Scholar 

  17. Erkkila AT, Matthan NR, Herrington DM, et al.: Higher plasma docosahexaenoic acid is associated with reduced progression of coronary-artery atherosclerosis in women with established coronary artery disease. J Lipid Res 2006, 47:2814–2819.

    Article  CAS  PubMed  Google Scholar 

  18. Mozaffarian D, Lemaitre RN, Kuller LH, et al.: Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study. Circulation 2003, 107:1372–1377.

    Article  PubMed  Google Scholar 

  19. Block RC, Harris WS, Pottala JV: Determinants of blood cell omega-3 fatty acid content. Open Biomarkers J 2008, 1:1–6.

    Article  CAS  Google Scholar 

  20. He K, Song Y, Daviglus ML, et al.: Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation 2004, 109:2705–2711.

    Article  PubMed  Google Scholar 

  21. Iso H, Kobayashi M, Ishihara J, et al.: Intake of fish and n-3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation 2006, 113:195–202.

    Article  CAS  PubMed  Google Scholar 

  22. Shearer GC, Pottala JV, Spertus JA, et al.: Red blood cell fatty acid patterns and acute coronary syndrome. PLoS ONE 2009, 4:e5444.

    Article  PubMed  Google Scholar 

  23. Block RC, Harris WS, Reid KJ, et al.: Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes? Am Heart J 2008, 156:1117–1123.

    Article  CAS  PubMed  Google Scholar 

  24. Harris WS, Pottala JV, Sands SA, et al.: Comparison of the effects of fish and fish-oil capsules on the n 3 fatty acid content of blood cells and plasma phospholipids. Am J Clin Nutr 2007, 86:1621–1625.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Burr ML, Fehily AM, Gilbert JF, et al.: Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989, 2:757–761.

    Article  CAS  PubMed  Google Scholar 

  27. Marchioli R, Barzi F, Bomba E, et al.: Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation 2002, 105:1897–1903.

    Article  CAS  PubMed  Google Scholar 

  28. GISSI-HF investigators: Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008, 372:1223–1230.

    Article  Google Scholar 

  29. Yokoyama M, Origasa H, Matsuzaki M, 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  PubMed  Google Scholar 

  30. Schmier JK, Rachman NJ, Halpern MT: The cost-effectiveness of omega-3 supplements for prevention of secondary coronary events. Manag Care 2006, 15:43–50.

    PubMed  Google Scholar 

  31. Lamotte M, Annemans L, Kawalec P, et al.: A multi-country health-economic evaluation of highly concentrated n-3 polyunsaturated fatty acids in the secondary prevention after myocardial infarction. Herz 2006, 3(Suppl):74–82.

    Google Scholar 

  32. Albert CM, Cook NR, Gaziano JM, et al.: Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA 2008, 299:2027–2036.

    Article  CAS  PubMed  Google Scholar 

  33. Harris WS, Mozaffarian D, Lefevre M, et al.: Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J Nutr 2009, 139:804S–819S.

    Article  CAS  PubMed  Google Scholar 

  34. Harris WS, Miller M, Tighe AP, et al.: Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis 2008, 197:12–24.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  36. Stillwell W, Shaikh SR, Zerouga M, et al.: Docosahexaenoic acid affects cell signaling by altering lipid rafts. Reprod Nutr Dev 2005, 45:559–579.

    Article  CAS  PubMed  Google Scholar 

  37. Siddiqui RA, Harvey KA, Zaloga GP: Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health. J Nutr Biochem 2008, 19:417–437.

    Article  CAS  PubMed  Google Scholar 

  38. Leaf A, Albert CM, Josephson M, et al.: Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Circulation 2005, 112:2762–2768.

    Article  CAS  PubMed  Google Scholar 

  39. Farzaneh-Far R, Harris WS, Garg S, et al.: Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: The Heart and Soul Study. Atherosclerosis 2008 Dec 14 (Epub ahead of print).

  40. Amin AA, Menon RA, Reid KJ, et al.: Acute coronary syndrome patients with depression have low blood cell membrane omega-3 fatty acid levels. Psychosom Med 2008, 70:856–862.

    Article  CAS  PubMed  Google Scholar 

  41. Augood C, Chakravarthy U, Young I, et al.: Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration. Am J Clin Nutr 2008, 88:398–406.

    CAS  PubMed  Google Scholar 

  42. Kamada T, Yamashita T, Baba Y, et al.: Dietary sardine oil increases erythrocyte membrane fluidity in diabetic patients. Diabetes 1986, 35:604–611.

    Article  CAS  PubMed  Google Scholar 

  43. Stillwell W, Wassall SR: Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids 2003, 126:1–27.

    Article  CAS  PubMed  Google Scholar 

  44. Ma DW, Seo J, Switzer KC, et al.: n-3 PUFA and membrane microdomains: a new frontier in bioactive lipid research. J Nutr Biochem 2004, 15:700–706.

    Article  CAS  PubMed  Google Scholar 

  45. Li Q, Wang M, Tan L, et al.: Docosahexaenoic acid changes lipid composition and interleukin-2 receptor signaling in membrane rafts. J Lipid Res 2005, 46:1904–1913.

    Article  CAS  PubMed  Google Scholar 

  46. Akbar M, Calderon F, Wen Z, et al.: Docosahexaenoic acid: a positive modulator of Akt signaling in neuronal survival. Proc Natl Acad Sci U S A 2005, 102:10858–10863.

    Article  CAS  PubMed  Google Scholar 

  47. Calder PC: n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006, 83:1505S–1519S.

    CAS  PubMed  Google Scholar 

  48. Blok WL, Katan MB, van der Meer JW: Modulation of inflammation and cytokine production by dietary (n-3) fatty acids. J Nutr 1996, 126:1515–1533.

    CAS  PubMed  Google Scholar 

  49. Leaf A, Kang JX, Xiao YF, et al.: 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  PubMed  Google Scholar 

  50. London B, Albert C, Anderson ME, et al.: Omega-3 fatty acids and cardiac arrhythmias: prior studies and recommendations for future research: a report from the National Heart, Lung, and Blood Institute and Office Of Dietary Supplements Omega-3 Fatty Acids and their Role in Cardiac Arrhythmogenesis Workshop. Circulation 2007, 116:e320–e335.

    Article  CAS  PubMed  Google Scholar 

  51. Davidson MH: Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol 2006, 98:27i–33i.

    Article  CAS  PubMed  Google Scholar 

  52. Deckelbaum RJ, Worgall TS, Seo T: n-3 fatty acids and gene expression. Am J Clin Nutr 2006, 83:1520S–1525S.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiovascular Health Research Center, Sanford Research/USD and Sanford School of Medicine, University of South Dakota, 1100 E. 21st Street, Suite 700, Sioux Falls, SD, 57105, USA

    William S. Harris

Authors
  1. William S. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William S. Harris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harris, W.S. The omega-3 index: From biomarker to risk marker to risk factor. Curr Atheroscler Rep 11, 411–417 (2009). https://doi.org/10.1007/s11883-009-0062-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-009-0062-2

Keywords

Search

Navigation