This revised application proposes to study the efficacy of a multivitamin and cocoa extract supplementation in prevention of cataract and age-related macular degeneration (AMD), two leading causes of visual impairment in US adults. Recent findings from the Physicians? Health Study II, the only large-scale clinical trial of a daily multivitamin, indicated a significant reduction in cataract, but an elevated, though statistically non-significant, increased risk of AMD. These findings in men require confirmation in other men and extension to women. The proposed study will utilize resources and data from the COcoa-Supplement and Multivitamins Outcomes Study (COSMOS), a randomized, double-blind, placebo-controlled, 2x2 factorial trial testing a patented, high-quality cocoa extract supplement (Mars Symbioscience) and Centrum Silver multivitamin (Pfizer) in the prevention of cardiovascular disease and cancer among 12,000 women aged ?65 years and 6,000 men aged ?60 years with 4 years of treatment and follow-up. Woman participants will be drawn from the Women?s Health Initiative (WHI) cohort, and male participants will be drawn from a target population screened for participation (but not randomized) in the VITamin D and OmegA-3 TriaL (VITAL). Beginning in June, 2015 and continuing through 2016, willing and eligible respondents to an invitational mailing will be enrolled in a 3-month run-in. Those who demonstrate good compliance with pill taking during the run-in, and remain willing and eligible, will be randomly assigned to 1 of 4 treatment groups for 5 years. At 1-year intervals, participants will receive a new supply of pills and a follow-up questionnaire on compliance, possible side effects, and incidence of endpoints. We propose to document incident cataract and prevalent and incident AMD endpoints in the COSMOS cohort in order to evaluate the efficacy of multivitamin and cocoa extract supplements in cataract and AMD prevention. The primary aims of the proposed study are to test whether 1) a daily multivitamin will reduce the risk of cataract; 2) a daily multivitamin will reduce the risk of total AMD events, a composite of incident AMD plus cases of progression to advanced AMD (neovascular AMD plus central geographic atrophy) among participants with prevalent AMD at baseline. The effect of cocoa extract supplements (capsule containing 750 mg/d flavanols, including 75 mg (-)-epicatechin, and 90 mg theobromine) in reducing risks of AMD and cataract will be examined as secondary aims. This research is responsive to a program priority of the National Eye Institute?s Strategic Plan to improve diagnosis, treatment, and prevention of eye disease. We believe the proposed eye disease ancillary to COSMOS offers a unique opportunity to obtain a reliable, efficient, and informative evaluation of the efficacy of two extremely promising preventive agents for cataract and AMD at a fraction of the cost of separate trials.
Despite the wide-spread usage of multivitamin supplements, and the growing enthusiasm for cocoa supplements, definitive data on the balance of risks and benefits of these agents are lacking. Data from this large-scale randomized trial should clarify the role of multivitamin and cocoa supplements in the prevention of cataract and AMD, two leading causes of visual impairment in US men and women.
