title: 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.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00345176.
authors.affiliation: Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Denise E
authors.initials: DE
authors.lastname: Bonds
authors.affiliation: EMMES Corporation, Rockville, Maryland.
authors.forename: Molly
authors.initials: M
authors.lastname: Harrington
authors.affiliation: Department of Neurology, School of Medicine, University of Virginia, Charlottesville.
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.affiliation: Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Alain G
authors.initials: AG
authors.lastname: Bertoni
authors.affiliation: Department of Family Medicine and Epidemiology, Division of Biology and Medicine, Alpert Medical School and the School of Public Health of Brown University, Providence, Rhode Island.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Eaton
authors.affiliation: AstraZeneca LLP, Washington, DC.
authors.forename: Judy
authors.initials: J
authors.lastname: Hsia
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City8Department of Medicine, University of Iowa, Iowa City.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Robinson
authors.affiliation: EMMES Corporation, Rockville, Maryland.
authors.forename: Traci E
authors.initials: TE
authors.lastname: Clemons
authors.affiliation: Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Fine
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D014975:Lutein / Q000008:administration & dosage*; D008268:Macular Degeneration / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012306:Risk; D016896:Treatment Outcome; D024341:Xanthophylls / Q000008:administration & dosage*; D065146:Zeaxanthins
chemical_list: D015525:Fatty Acids, Omega-3; D024341:Xanthophylls; D065146:Zeaxanthins; D014975:Lutein