Omega 3 Fatty Acids and Cardiovascular Outcomes: Systematic Review and Meta-Analysis

Background—Early trials evaluating the effect of omega 3 fatty acids (&ohgr;-3 FA) reported benefits for mortality and cardiovascular events but recent larger studies trials have variable findings. We assessed the effects of &ohgr;-3 FA on cardiovascular and other important clinical outcomes. Methods and Results—We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for all randomized studies using dietary supplements, dietary interventions, or both. The primary outcome was a composite of cardiovascular events (mostly myocardial infarction, stroke, and cardiovascular death). Secondary outcomes were arrhythmia, cerebrovascular events, hemorrhagic stroke, ischemic stroke, coronary revascularization, heart failure, total mortality, nonvascular mortality, and end-stage kidney disease. Twenty studies including 63030 participants were included. There was no overall effect of &ohgr;-3 FA on composite cardiovascular events (relative risk [RR]=0.96; 95% confidence interval [CI], 0.90–1.03; P=0.24) or on total mortality (RR=0.95; 95% CI, 0.86–1.04; P=0.28). &ohgr;-3 FA did protect against vascular death (RR=0.86; 95% CI, 0.75–0.99; P=0.03) but not coronary events (RR=0.86; 95% CI, 0.67–1.11; P=0.24). There was no effect on arrhythmia (RR=0.99; 95% CI, 0.85–1.16; P=0.92) or cerebrovascular events (RR=1.03; 95% CI, 0.92–1.16; P=0.59). Adverse events were more common in the treatment group than the placebo group (RR=1.18, 95% CI, 1.02–1.37; P=0.03), predominantly because of an excess of gastrointestinal side effects. Conclusions—&ohgr;-3 FA may protect against vascular disease, but the evidence is not clear-cut, and any benefits are almost certainly not as great as previously believed.

[1]  S. Yusuf,et al.  n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. , 2012, The New England journal of medicine.

[2]  H. Seo,et al.  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. , 2012, Archives of internal medicine.

[3]  K. Swedberg.  n-3 Fatty acids in cardiovascular disease. , 2011, The New England journal of medicine.

[4]  M. Gold.  Efficacy and Safety of Prescription Omega-3 Fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation: A Randomized Controlled Trial , 2011 .

[5]  P. Galan,et al.  Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial , 2010, BMJ : British Medical Journal.

[6]  J. Geleijnse,et al.  n-3 fatty acids and cardiovascular events after myocardial infarction. , 2010, The New England journal of medicine.

[7]  G. Einvik,et al.  A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk , 2010, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[8]  J. Brophy,et al.  Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials , 2010, BMC cardiovascular disorders.

[9]  D. Grobbee,et al.  Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis , 2010, The Lancet.

[10]  Risc Investigators,et al.  protocolEfficacy of n-3 polyunsaturated fatty acids and feasibility of optimizing preventive strategies in patients at high cardiovascular risk : rationale , design and baseline characteristics of the Rischio and Prevenzione study , a large randomised trial in general practice , 2010 .

[11]  R. Uauy,et al.  Fats and Fatty Acids in Human Nutrition: Introduction , 2009, Annals of Nutrition and Metabolism.

[12]  Fats and fatty acids in human nutrition. Proceedings of the Joint FAO/WHO Expert Consultation. November 10-14, 2008. Geneva, Switzerland. , 2009, Annals of nutrition & metabolism.

[13]  M. Dorgan,et al.  Effect of fish oil on arrhythmias and mortality: systematic review , 2008, BMJ : British Medical Journal.

[14]  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 , 2008, The Lancet.

[15]  L. Tavazzi,et al.  ect of n-3 polyunsaturated fatty acids in patients with chronic heart failure ( the GISSI-HF trial ) : a randomised , double-blind , placebo-controlled trial , 1980 .

[16]  Y. Matsuzawa,et al.  Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis , 2007, The Lancet.

[17]  Dariush Mozaffarian,et al.  Fish intake, contaminants, and human health: evaluating the risks and the benefits. , 2006, JAMA.

[18]  Ethan M Balk,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. , 2006, The American journal of clinical nutrition.

[19]  E. Schmidt,et al.  N-3 fatty acids as secondary prevention against cardiovascular events in patients who undergo chronic hemodialysis: a randomized, placebo-controlled intervention trial. , 2006, Clinical journal of the American Society of Nephrology : CJASN.

[20]  R. Hauer,et al.  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. , 2006, JAMA.

[21]  A. Tonkin,et al.  National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand: position statement on lipid management--2005. , 2005 .

[22]  M. Josephson,et al.  Prevention of Fatal Arrhythmias in High-Risk Subjects by Fish Oil n-3 Fatty Acid Intake , 2005, Circulation.

[23]  S. Chugh,et al.  Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. , 2005, JAMA.

[24]  V. Rastogi,et al.  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 , 1997, Cardiovascular Drugs and Therapy.

[25]  Thomas R. Riley,et al.  A Randomized Double-blind Placebo-controlled Trial , 2004 .

[26]  P. Elwood,et al.  Lack of benefit of dietary advice to men with angina: results of a controlled trial , 2003, European Journal of Clinical Nutrition.

[27]  Lawrence J Appel,et al.  Omega-3 Fatty Acids and Cardiovascular Disease: New Recommendations From the American Heart Association , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[28]  G. Albrektsen,et al.  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. , 2001, The American journal of clinical nutrition.

[29]  GISSI-Prevenzione Investigators,et al.  Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial , 1999, The Lancet.

[30]  Roberto Marchioli,et al.  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. , 1999 .

[31]  T. Larson,et al.  The Long-Term Outcome of Patients with IgA Nephropathy Treated with Fish Oil in a Controlled Trial , 1999 .

[32]  H. Arnesen,et al.  n-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study , 1999 .

[33]  K. Theisen,et al.  The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. , 1999, Annals of internal medicine.

[34]  H. Arnesen,et al.  N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial. , 1999, Journal of the American College of Cardiology.

[35]  T. Larson,et al.  The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group. , 1999, Journal of the American Society of Nephrology : JASN.

[36]  O. Hänninen,et al.  Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation. , 1997, Prostaglandins, leukotrienes, and essential fatty acids.

[37]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[38]  T. Mori,et al.  Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[39]  The Funding , 1995, Journal of the Royal College of Physicians of London.

[40]  E. Bergstralh,et al.  A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. , 1994, The New England journal of medicine.

[41]  P. Touboul,et al.  Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease , 1994, The Lancet.

[42]  D. Yue,et al.  The effects of dietary n - 3 fatty acid in animal models of type 1 and type 2 diabetes. , 1990, Diabetes research and clinical practice.

[43]  P. Elwood,et al.  EFFECTS OF CHANGES IN FAT, FISH, AND FIBRE INTAKES ON DEATH AND MYOCARDIAL REINFARCTION: DIET AND REINFARCTION TRIAL (DART) , 1989, The Lancet.

[44]  J. Dyerberg,et al.  Fatty acid composition of the plasma lipids in Greenland Eskimos. , 1975, The American journal of clinical nutrition.