Home LiteratureArticle Details
PMID: 19609891 Published · ppublish English Journal Article Meta-Analysis Review Systematic Review

Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review.

Clinical cardiology ·Vol. 32 ·No. 7 ·2009-07-00 ·Pages 365-72

Marik PE, Varon J

Abstract

Epidemiologic data suggest that omega-3 fatty acids derived from fish oil reduce cardiovascular disease. The clinical benefit of dietary fish oil supplementation in preventing cardiovascular events in both high and low risk patients is unclear. To assess whether dietary supplements of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease cardiovascular events across a spectrum of patients. MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and citation review of relevant primary and review articles. Prospective, randomized, placebo-controlled clinical trials that evaluated clinical cardiovascular end points (cardiovascular death, sudden death, and nonfatal cardiovascular events) and all-cause mortality in patients randomized to EPA/DHA or placebo. We only included studies that used dietary supplements of EPA/DHA which were administered for at least 1 year. Data were abstracted on study design, study size, type and dose of omega-3 supplement, cardiovascular events, all-cause mortality, and duration of follow-up. Studies were grouped according to the risk of cardiovascular events (high risk and moderate risk). Meta-analytic techniques were used to analyze the data. We identified 11 studies that included a total of 39 044 patients. The studies included patients after recent myocardial infarction, those with an implanted cardioverter defibrillator, and patients with heart failure, peripheral vascular disease, and hypercholesterolemia. The average dose of EPA/DHA was 1.8 +/- 1.2 g/day and the mean duration of follow-up was 2.2 +/- 1.2 years. Dietary supplementation with omega-3 fatty acids significantly reduced the risk of cardiovascular deaths (odds ratio [OR]: 0.87, 95% confidence interval [CI]: 0.79-0.95, p = 0.002), sudden cardiac death (OR: 0.87, 95% CI: 0.76-0.99, p = 0.04), all-cause mortality (OR: 0.92, 95% CI: 0.85-0.99, p = 0.02), and nonfatal cardiovascular events (OR: 0.92, 95% CI: 0.85-0.99, p = 0.02). The mortality benefit was largely due to the studies which enrolled high risk patients, while the reduction in nonfatal cardiovascular events was noted in the moderate risk patients (secondary prevention only). Meta-regression failed to demonstrate a relationship between the daily dose of omega-3 fatty acid and clinical outcome. Dietary supplementation with omega-3 fatty acids should be considered in the secondary prevention of cardiovascular events.

MeSH Terms
Cardiovascular Diseases/drug therapy,etiology,mortality,prevention & control Dietary Supplements Docosahexaenoic Acids/administration & dosage Eicosapentaenoic Acid/administration & dosage Evidence-Based Medicine Humans Odds Ratio Prospective Studies Randomized Controlled Trials as Topic Risk Assessment Risk Factors Secondary Prevention Treatment Outcome
Chemicals
Docosahexaenoic Acids Eicosapentaenoic Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Marik Paul E
Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. [email protected]
Varon Joseph
References (57)
57 references, click to expand
  1. A MUFA-rich diet improves posprandial glucose, lipid and GLP-1 responses in insulin-resistant subjects.
    J Am Coll Nutr. 2007 Oct;26(5):434-44 PMID: 17914131
  2. n-3 polyunsaturated fatty acids inhibit the antigen-presenting function of human monocytes.
    Am J Clin Nutr. 2000 Jan;71(1 Suppl):357S-60S PMID: 10617997
  3. Fish consumption and risk of sudden cardiac death.
    JAMA. 1998 Jan 7;279(1):23-8 PMID: 9424039
  4. Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men.
    Circulation. 1995 Feb 1;91(3):645-55 PMID: 7828289
  5. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials.
    Am J Med. 2002 Mar;112(4):298-304 PMID: 11893369
  6. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial.
    JAMA. 2006 Jun 14;295(22):2613-9 PMID: 16772624
  7. Long-term treatment with eicosapentaenoic acid augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilatation in patients with coronary artery disease.
    J Cardiovasc Pharmacol. 1999 Apr;33(4):633-40 PMID: 10218735
  8. Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins.
    Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3542-6 PMID: 8622972
  9. Red blood cell omega-3 fatty acids and the risk of ventricular arrhythmias in patients with heart failure.
    Am Heart J. 2008 Jun;155(6):971-7 PMID: 18513506
  10. Plasma lipids and lipoproteins in Greenlandic west coast Eskimos.
    Acta Med Scand. 1972 Jul-Aug;192(1-2):85-94 PMID: 5052396
  11. Measuring inconsistency in meta-analyses.
    BMJ. 2003 Sep 6;327(7414):557-60 PMID: 12958120
  12. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial.
    Ann Intern Med. 1999 Apr 6;130(7):554-62 PMID: 10189324
  13. Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group.
    J Am Coll Cardiol. 1995 Jun;25(7):1492-8 PMID: 7759696
  14. Quantifying heterogeneity in a meta-analysis.
    Stat Med. 2002 Jun 15;21(11):1539-58 PMID: 12111919
  15. Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis.
    CMAJ. 2008 Jan 15;178(2):157-64 PMID: 18195289
  16. Omega-3 fatty acids and ventricular arrhythmias: nothing is simple.
    Am Heart J. 2008 Jun;155(6):967-70 PMID: 18513505
  17. Omega 3-fatty acids: health benefits and cellular mechanisms of action.
    Mini Rev Med Chem. 2004 Oct;4(8):859-71 PMID: 15544547
  18. The role of fish oil in arrhythmia prevention.
    J Cardiopulm Rehabil Prev. 2008 Mar-Apr;28(2):92-8 PMID: 18360184
  19. The inverse relation between fish consumption and 20-year mortality from coronary heart disease.
    N Engl J Med. 1985 May 9;312(19):1205-9 PMID: 3990713
  20. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial.
    Ann Intern Med. 2006 Jul 4;145(1):1-11 PMID: 16818923
  21. Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake.
    Circulation. 2005 Nov 1;112(18):2762-8 PMID: 16267249
  22. Regulation of gene transcription by polyunsaturated fatty acids.
    Prog Lipid Res. 1993;32(2):139-49 PMID: 7902585
  23. The effect of supplementation with omega-3 fatty acids on soluble markers of endothelial function in patients with coronary heart disease.
    Arterioscler Thromb Vasc Biol. 1999 Jul;19(7):1681-6 PMID: 10397685
  24. The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population.
    Int J Epidemiol. 1995 Apr;24(2):340-5 PMID: 7635594
  25. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells.
    Arterioscler Thromb. 1994 Nov;14(11):1829-36 PMID: 7524649
  26. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival--4.
    Cardiovasc Drugs Ther. 1997 Jul;11(3):485-91 PMID: 9310278
  27. Blood levels of long-chain n-3 fatty acids and the risk of sudden death.
    N Engl J Med. 2002 Apr 11;346(15):1113-8 PMID: 11948270
  28. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia.
    Int J Clin Lab Res. 1999;29(1):22-5 PMID: 10356659
  29. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses.
    Lancet. 1999 Nov 27;354(9193):1896-900 PMID: 10584742
  30. Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos.
    Lancet. 1971 Jun 5;1(7710):1143-5 PMID: 4102857
  31. Mechanisms of increased survival after lipopolysaccharide-induced endotoxic shock in mice consuming olive oil-enriched diet.
    Shock. 2005 Feb;23(2):173-8 PMID: 15665734
  32. Omega-3 fatty acids for cardioprotection.
    Mayo Clin Proc. 2008 Mar;83(3):324-32 PMID: 18316000
  33. Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events.
    Atherosclerosis. 2007 Jul;193(1):1-10 PMID: 17507020
  34. Lack of benefit of dietary advice to men with angina: results of a controlled trial.
    Eur J Clin Nutr. 2003 Feb;57(2):193-200 PMID: 12571649
  35. 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 Oct 4;372(9645):1223-30 PMID: 18757090
  36. 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 Sep 4;116(10):e320-35 PMID: 17768297
  37. The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil.
    Am J Clin Nutr. 1996 Jan;63(1):116-22 PMID: 8604658
  38. Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements.
    Appl Physiol Nutr Metab. 2007 Aug;32(4):619-34 PMID: 17622276
  39. Lipid modulation and systemic inflammation.
    Crit Care Clin. 2001 Jan;17(1):201-17 PMID: 11219230
  40. Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease.
    Clin Nutr. 1998 Dec;17(6):265-71 PMID: 10205349
  41. A comparison of statistical methods for combining event rates from clinical trials.
    Stat Med. 1989 Feb;8(2):141-51 PMID: 2704896
  42. Potentiation of ADP-induced platelet aggregation by mercury compounds.
    Thromb Res. 1990 Mar 1;57(5):795-801 PMID: 2339370
  43. Effect of pravastatin and omega-3 fatty acids on plasma lipids and lipoproteins in patients with combined hyperlipidemia.
    Arterioscler Thromb. 1993 Dec;13(12):1755-62 PMID: 8241095
  44. Omega 3 fatty acids for prevention and treatment of cardiovascular disease.
    Cochrane Database Syst Rev. 2004 Oct 18;(4):CD003177 PMID: 15495044
  45. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.
    Lancet. 2007 Mar 31;369(9567):1090-8 PMID: 17398308
  46. 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 Aug 7;354(9177):447-55 PMID: 10465168
  47. Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol.
    Am J Clin Nutr. 2001 Jul;74(1):50-6 PMID: 11451717
  48. Fish consumption and the 30-year risk of fatal myocardial infarction.
    N Engl J Med. 1997 Apr 10;336(15):1046-53 PMID: 9091800
  49. Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies.
    Circulation. 2004 Jun 8;109(22):2705-11 PMID: 15184295
  50. The chronic intake of a Mediterranean diet enriched in virgin olive oil, decreases nuclear transcription factor kappaB activation in peripheral blood mononuclear cells from healthy men.
    Atherosclerosis. 2007 Oct;194(2):e141-6 PMID: 17204269
  51. Dietary lipids: ancestral ligands and regulators of cell signaling pathways.
    Crit Care Med. 1999 Aug;27(8):1646-8 PMID: 10470779
  52. 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 Jul;84(1):5-17 PMID: 16825676
  53. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART).
    Lancet. 1989 Sep 30;2(8666):757-61 PMID: 2571009
  54. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial.
    JAMA. 2005 Jun 15;293(23):2884-91 PMID: 15956633
  55. Olive oil and the cardiovascular system.
    Pharmacol Res. 2007 Mar;55(3):175-86 PMID: 17321749
  56. Pro- and antiarrhythmic properties of a diet rich in fish oil.
    Cardiovasc Res. 2007 Jan 15;73(2):316-25 PMID: 16859661
  57. n-3 Fatty acids and cardiovascular disease: mechanisms underlying beneficial effects.
    Am J Clin Nutr. 2008 Jun;87(6):2003S-9S PMID: 18541602
Article Info
Journal
Clinical cardiology
Abbr.
Clin Cardiol
ISSN
1932-8737
Published
2009-07-00
Pages
365-72
Language
English
Region
United States
NLM ID
7903272
PMCID
PMC6653319
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]