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 Med. 2014 May;174(5):763-71. doi: 10.1001/jamainternmed.2014.328.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / prevention & control*
  • Dietary Supplements*
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Humans
  • Lutein / administration & dosage*
  • Macular Degeneration / drug therapy*
  • Male
  • Middle Aged
  • Risk
  • Treatment Outcome
  • Xanthophylls / administration & dosage*
  • Zeaxanthins

Substances

  • Fatty Acids, Omega-3
  • Xanthophylls
  • Zeaxanthins
  • Lutein

Associated data

  • ClinicalTrials.gov/NCT00345176