A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss - AREDS Report No. 8

Background: Observational and experimental data suggest that antioxidant an d/or zinc supplements may delay progression of age-related macular degenera tion (AMD) and vision loss. Objective: To evaluate the effect of high-dose vitamins C and E, beta carot ene, and zinc supplements on AMD progression and visual acuity. Design: The Age-Related Eye Disease Study, an 11-center double-masked clini cal trial, enrolled participants in an AMD trial if they had extensive smal l drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20 /32 or better. Participants were randomly assigned to receive daily oral ta blets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; a nd beta carotene, 15 mg) (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, a s cupric oxide; (3) antioxidants plus zinc; or (4) placebo. Main Outcome Me asures: (1)Photographic assessment of progression to or treatment for advan ced AMD and (2) at least moderate visual acuity loss from baseline ( : 15 l etters). Primary analyses used repeated-measures logistic regression with a significance level of .01, unadjusted for covariates. Serum level measurem ents, medical histories, and mortality rates were used for safety monitorin g. Results: Average follow-up of the 3640 enrolled study participants, aged 55 -80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with plac ebo demonstrated a statistically significant odds reduction for the develop ment of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99 % confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxid ants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respe ctively. Participants with extensive small drusen, nonextensive intermediat e size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when the se 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% C I, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99 % CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduce d the odds of developing advanced AMD in this higher-risk group. The only s tatistically significant reduction in rates of at least moderate visual acu ity loss occurred in persons assigned to receive antioxidants plus zinc (OR , 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse ef fect was associated with any of the formulations. Conclusions: Persons older than 55 years should have dilated eye examinatio ns to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic at rophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye , and without contraindications such as smoking, should consider taking a s upplement of antioxidants plus zinc such as that used in this study.