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Effects of Eicosapentanoic Acid and Docosahexanoic Acid on Mortality Across Diverse Settings: Systematic Review and Meta-Analysis of Randomized Trials and Prospective Cohorts
Technical Reviews, No. 17.4
Investigators: Thomas A Trikalinos, MD, Jounghee Lee, PhD, Denish Moorthy, MBBS, MS, Winifred W Yu, MS, RD, Joseph Lau, MD, Alice H Lichtenstein, DSc, and Mei Chung, PhD, MPH.
Author Information and AffiliationsStructured Abstract
Background:
Eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) intake may protect from cardiovascular or all-cause mortality.
Objective:
To synthesize evidence from randomized controlled trials (RCTs) and large prospective cohorts on the effects of EPA and DHA on cardiac, cardiovascular, or all-cause mortality.
Design:
We conducted a systematic review with random effects meta-analysis and mixed effects dose-response meta-regression. Included were RCTs of EPA and DHA supplementation (>4 weeks of intervention, <6 grams per day) and large prospective cohorts (>1000 people, >3 years of followup) quantifying DHA or EPA intake.
Results:
In RCTs, the summary relative risks for all-cause mortality (17 trials, 51,264 patients) and cardiovascular mortality (14 trials, 48,500 patients) were 0.95 (95% confidence interval, CI: 0.89, 1.01) and 0.89 (95% CI, 0.83, 0.96), respectively, with no evidence for heterogeneity. The effect of DHA and EPA was not significantly associated with population or study characteristics or supplement dose. In dose-response meta-regressions, mean EPA and DHA intake up to 0.20 grams daily was associated with decreased risk of cardiac, cardiovascular, or sudden cardiac death (odds ratio 0.64 per 0.20 grams average daily intake, 95% CI: 0.46, 0.89—data from 7 cohorts, 123,122 participants), with no significant change in risk (positive or negative) at higher mean intakes. Dose-response analyses were not statistically significant for other intake thresholds or alternative mortality definitions.
Conclusions:
The maximal positive effect of EPA and DHA appears to plateau at a mean daily intake of 0.20 grams. There is no evidence that the effect of EPA and DHA on mortality phenotypes differs across populations and settings.
Contents
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. HHSA 290-2007-10055-1.Prepared by: Tufts Medical Center Evidence-based Practice Center, Boston, Massachusetts
Suggested citation:
Trikalinos TA, Lee J, Moorthy D, Yu WW, Lau J, Lichtenstein AH, Chung M. Effects of Eicosapentanoic Acid and Docosahexanoic Acid on Mortality Across Diverse Settings: Systematic Review and Meta-analysis of Randomized Trials and Prospective Cohorts. Technical Review 17, Vol. 4. (Prepared by the Tufts Medical Center Evidence-based Practice Center under Contract No. HHSA 290-2007-10055-1.) AHRQ Publication No. 12-EHC040-EF. Rockville, MD: Agency for Healthcare Research and Quality; February 2012.
This work was prepared with support from the Office of Dietary Supplements (ODS) of the National Institutes of Health, through the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract Number HHSA 290-2007-10055-1). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of the Office of Dietary Supplements (ODS), National Institutes of Health; AHRQ; or of the U.S. Department of Health and Human Services.
The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. ODS, AHRQ, or the U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
None of the investigators has any affiliations or financial involvement (e.g., employment, consultancies, honoraria, stock options, expert testimony, grants or patents pending, or royalties) that conflict with material presented in this report.
- 1
540 Gaither Road, Rockville, MD 20850; www
.ahrq.gov.
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