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.

Publication Type
Journal Article
Year of Publication
Writing Group for the AREDS2 Research Group; Bonds, Denise E; Harrington, Molly; Worrall, Bradford B; Bertoni, Alain G; Eaton, Charles B; Hsia, Judy; Robinson, Jennifer; Clemons, Traci E; Fine, Lawrence J; Chew, Emily Y
JAMA Intern Med
Date Published
2014 May
Aged; Aged, 80 and over; Cardiovascular Diseases; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Lutein; Macular Degeneration; Male; Middle Aged; Risk; Treatment Outcome; Xanthophylls; Zeaxanthins

IMPORTANCE: Dietary supplements have been proposed as a mechanism to improve health and prevent disease.

OBJECTIVE: To determine if supplementing diet with long-chain ω-3 polyunsaturated fatty acids or with macular xanthophylls results in a reduced rate of cardiovascular disease (CVD).

DESIGN, SETTING, AND PARTICIPANTS: The Cardiovascular Outcome Study (COS) was an ancillary study of the Age-Related Eye Disease Study 2 (AREDS2), a factorial-designed randomized clinical trial of 4203 participants recruited from 82 US academic and community ophthalmology clinics, who were followed up for a median of 4.8 years. Individuals were eligible to participate if they were between the ages of 50 and 85 years, had intermediate or advanced age-related macular degeneration in 1 eye, and were willing to be randomized. Participants with stable, existing CVD (>12 months since initial event) were eligible to participate. Participants, staff, and outcome assessors were masked to intervention.

INTERVENTIONS: Daily supplementation with long-chain ω-3 polyunsaturated fatty acids (350-mg docosahexaenoic acid [DHA] + 650-mg eicosapentaenoic acid [EPA]), macular xanthophylls (10-mg lutein + 2-mg zeaxanthin), combination of the two, or matching placebos. These treatments were added to background therapy of the AREDS vitamin and mineral formulation for macular degeneration. MAIN OUTCOMES AND MEASURES A composite outcome of myocardial infarction, stroke, and cardiovascular death with 4 prespecified secondary combinations of the primary outcome with hospitalized heart failure, revascularization, or unstable angina.

RESULTS: Study participants were primarily white, married, and highly educated, with a median age at baseline of 74 years. A total of 602 cardiovascular events were adjudicated, and 459 were found to meet 1 of the study definitions for a CVD outcome. In intention-to-treat analysis, no reduction in the risk of CVD or secondary CVD outcomes was seen for the DHA + EPA (primary outcome: hazard ratio [HR], 0.95; 95% CI, 0.78-1.17) or lutein + zeaxanthin (primary outcome: HR, 0.94; 95% CI, 0.77-1.15) groups. No differences in adverse events or serious adverse event were seen by treatment group. The sample size was sufficient to detect a 25% reduction in CVD events with 80% power.

CONCLUSIONS AND RELEVANCE: Dietary supplementation of long-chain ω-3 polyunsaturated fatty acids or macular xanthophylls in addition to daily intake of minerals and vitamins did not reduce the risk of CVD in elderly participants with age-related macular degeneration.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.