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Am Fam Physician. 2018;97(9):562-564

Author disclosure: No relevant financial affiliations.

Key Clinical Issue

What is the effect of omega-3 fatty acid supplementation on cardiovascular outcomes?

Evidence-Based Answer

In patients with established cardiovascular disease or an increased risk of cardiovascular disease, omega-3 fatty acid supplementation has no effect on major adverse cardiac events, all-cause mortality, sudden cardiac death, coronary artery revascularization, or hypertension.1 (Strength of Recommendation [SOR]: A, based on consistent, good-quality patient-oriented evidence.)

Omega-3 fatty acids (source)OutcomeKey findingsNet change or RCT hazard ratio (95% confidence interval)Number and type of studiesStrength of evidence
Marine oil: EPA + DHA ± DPA* (mainly supplements or supplemented food)Major adverse cardiac eventsNo effect in RCTs0.96 (0.91 to 1.02)10 RCTs●●●
No association in observational studies of total dietary intake3 observational studies of total dietary intake
Unclear association in observational studies of fatty acid biomarkers2 observational studies of fatty acid biomarkers
All-cause deathNo effect in RCTs0.97 (0.92 to 1.03)17 RCTs●●●
No association in observational studies of total dietary intake3 observational studies of total dietary intake
Sudden cardiac deathNo effect in RCTs1.04 (0.92 to 1.17)9 RCTs●●●
No association in observational studies of total dietary intake1 observational study of total dietary intake
Coronary revascularizationNo effect in RCTsNot available6 RCTs●●●
No association in observational studies of total dietary intake1 observational study of total dietary intake
Atrial fibrillationNo effect in RCTsNot available3 RCTs●●○
Inconsistent findings in observational studies of total dietary intake3 observational studies of total dietary intake
Blood pressure (systolic, diastolic)No effectSystolic: 0.1 mm Hg (−0.2 to 0.4)29 RCTs●●●
Diastolic: −0.2 mm Hg (−0.4 to 0.5)
TriglyceridesDecrease−24 mg per dL (−31 to −18)41 RCTs●●●
High-density lipoprotein cholesterolIncrease0.9 mg per dL (0.2 to 1.6)34 RCTs●●●
Low-density lipoprotein cholesterolIncrease2.0 mg per dL (0.4 to 3.6)39 RCTs●●●
Total cholesterol: high-density lipoprotein cholesterol ratioDecrease−0.2 (−0.3 to −0.1)11 RCTs●●●

Practice Pointers

Omega-3 fatty acids, including eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid, are essential long-chain and very long-chain polyunsaturated fatty acids. They are found in fish and other seafood (marine oils), except for alpha-linolenic acid, which is found in walnuts, leafy green vegetables, and other oils. These omega-3 fatty acids have been made into supplements with claims of physiologic benefits, including inflammation regulation.1 Since the correlation between fish consumption and cardiovascular health was first identified, hundreds of studies have evaluated the effects of omega-3 fatty acids on cardiovascular outcomes. The American Heart Association has concluded that increased fish intake or use of omega-3 supplements is reasonable for the prevention of recurrent heart failure, recurrent coronary heart disease, and sudden cardiac death in patients with coronary heart disease. 2

The number of Americans using dietary supplements is increasing. An analysis of data from the National Health and Nutrition Examination Survey found that the use of fish oil supplements increased from 1.3% to 12% between 1999 and 2012.3 This Agency for Healthcare Research and Quality (AHRQ) review, which updates a 2004 systematic review, included 147 articles with 61 randomized controlled trials of relatively limited duration and 37 longitudinal observational studies from 2001 to 2015.4 Studies that analyzed levels of fish consumption without quantification of omega-3 fatty acid intake were excluded.1

The review found a high strength of evidence that omega-3 fatty acid supplementation has mixed effects on cholesterol levels, decreasing triglycerides, increasing high-density lipoprotein cholesterol and low-density lipoprotein cholesterol, and slightly decreasing total cholesterol (high-density lipoprotein cholesterol ratio).1 A high strength of evidence suggested that there is no benefit of omega-3 fatty acid supplementation for prevention of major adverse cardiac events (hazard ratio = 0.96; 95% confidence interval, 0.91 to 1.02). A high strength of evidence also showed no benefit for all-cause death and sudden cardiac death. These findings are consistent with the results of another recent meta-analysis of 10 clinical trials including nearly 80,000 individuals.5 The AHRQ review also concluded that there was no benefit of supplementation in patients with coronary revascularization and atrial fibrillation. For systolic and diastolic blood pressures, omega-3 fatty acid supplementation had no effects.1

Although omega-3 fatty acid supplementation affects several cholesterol measurements, there is strong evidence overall that in persons with cardiovascular disease or at increased risk of cardiovascular disease, supplementation does not affect patient-oriented outcomes, including major adverse cardiac events, all-cause death, sudden cardiac death, revascularization, or high blood pressure. Family physicians should not encourage patients to take these supplements to prevent heart disease. Instead, patients should be encouraged to eat a healthy, balanced diet,6 which can include foods high in omega-3 fatty acids.

Editor's Note: American Family Physician SOR ratings are different from the AHRQ Strength of Evidence (SOE) ratings.

The views expressed in this article are those of the authors and do not reflect the policy or position of the U.S. Army Medical Department, Department of the Army, Department of Defense, or the U.S. government.

The associated AHRQ product was funded under Contract No. HHSA 290-2012-00016-I Task Order 12 from the Agency for Healthcare Research and Quality (AHRQ), U.S. Department of Health and Human Services (HHS). The authors of this manuscript are responsible for its content. Statements in the manuscript do not necessarily represent the official views of or imply endorsement by AHRQ or HHS.

The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to produce evidence to improve health care and to make sure the evidence is understood and used. A key clinical question based on the AHRQ Effective Health Care Program systematic review of the literature is presented, followed by an evidence-based answer based on the review. AHRQ’s summary is accompanied by an interpretation by an AFP author that will help guide clinicians in making treatment decisions.

This series is coordinated by Kenny Lin, MD, MPH, deputy editor. A collection of Implementing AHRQ Effective Health Care Reviews published in AFP is available at https://www.aafp.org/afp/ahrq.

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