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Am Fam Physician. 2014;90(9):662

Clinical Question

In older patients with macular degeneration, does omega-3 fatty acid supplementation decrease the likelihood of experiencing a cardiovascular outcome?

Bottom Line

Omega-3 fatty acid supplementation does not decrease the risk of cardiovascular outcomes in this older population. Although the numbers are small, supplementation may prevent heart disease in patients already at low risk; that is, patients without a history of cardiovascular disease (CVD) and who are not hypertensive. (Level of Evidence = 1b)


This study is a separate analysis of a study aimed at determining the effect of omega-3 fatty acids and macular xanthophylls (lutein and zeaxanthin) on the progression of age-related macular degeneration in patients between 50 and 85 years of age (average age = 74 years) who have intermediate or advanced age-related macular degeneration. Most patients (greater than 95%) were white, approximately 50% were current or former smokers, 13% had diabetes mellitus, and 19% had a history of CVD or cerebrovascular disease with no episodes in the 12 months before enrollment. After a 30-day trial with placebo to weed out nonadherent or second-thought patients, the 4,203 patients were randomized to receive (1) omega-3 fatty acids, (2) macular xanthophylls, (3) both, or (4) matching placebo for an average of 4.8 years. The fatty acids were docosahexaenoic acid (DHA), 350 mg, and eicosapentaenoic acid (EPA), 650 mg.

Using intention-to-treat analysis, the combined outcome of cardiovascular-related events (mortality and morbidity events) was not different among the patients receiving the fatty acids compared with patients not receiving them. This study had the ability to find a 25% reduction in these events if this difference occurred (at 80% power). Treatment with macular xanthophylls similarly did not affect cardiovascular outcomes. There was a reduction in cardiovascular-related events in patients without a history of CVD and in those without hypertension.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Uncertain

Setting: Outpatient (specialty)

Reference: BondsDEHarringtonMWorrallBBet alWriting Group for the AREDS2 Research Group. Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med2014; 174( 5): 763– 771.

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