Use of supplemental long-chain omega-3 fatty acids and risk for cardiac death: An updated meta-analysis and review of research gaps

J Clin Lipidol. Sep-Oct 2017;11(5):1152-1160.e2. doi: 10.1016/j.jacl.2017.07.010. Epub 2017 Aug 2.


Background: Randomized controlled trials (RCTs) assessing use of long-chain omega-3 polyunsaturated fatty acids (LC-OM3), primarily eicosapentaenoic acid, and/or docosahexaenoic acid have shown mixed results.

Objective: The objectives of the study were to update and further explore the available RCT data regarding LC-OM3 supplementation and risk for cardiac death and to propose testable hypotheses for the mixed results obtained in RCTs regarding supplemental LC-OM3 use and cardiac risk.

Methods: A literature search was conducted using PubMed and Ovid/MEDLINE for RCTs assessing LC-OM3 supplements or pharmaceuticals with intervention periods of at least 6 months and reporting on the outcome of cardiac death. Meta-analysis was used to compare cumulative frequencies of cardiac death events between the LC-OM3 and control groups, including sensitivity and subset analyses.

Results: Fourteen RCTs were identified for the primary analysis (71,899 subjects). In the LC-OM3 arms, 1613 cardiac deaths were recorded (4.48% of subjects), compared with 1746 cardiac deaths in the control groups (4.87% of subjects). The pooled relative risk estimate showed an 8.0% (95% confidence interval 1.6%, 13.9%, P = .015) lower risk in the LC-OM3 arms vs controls. Subset analyses showed numerically larger effects (12.9%-29.1% lower risks, all P < .05) in subsets of RCTs with eicosapentaenoic acid + docosahexaenoic acid dosages >1 g/d and higher risk samples (secondary prevention, baseline mean or median triglycerides ≥150 mg/dL, low-density lipoprotein cholesterol ≥130 mg/dL, statin use <40% of subjects). Heterogeneity was low (I2 ≤ 15.5%, P > .05) for the primary and subset analyses.

Conclusion: LC-OM3 supplementation is associated with a modest reduction in cardiac death.

Keywords: Cardiac death; DHA; Docosahexaenoic acid; EPA; Eicosapentaenoic acid; Fish oil; Meta-analysis; Omega-3 fatty acids.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Death*
  • Dietary Supplements*
  • Fatty Acids, Omega-3 / chemistry
  • Fatty Acids, Omega-3 / pharmacology*
  • Humans
  • Randomized Controlled Trials as Topic
  • Risk


  • Fatty Acids, Omega-3