Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.

Systematic review and meta-analysis of randomized controlled trials in people without age-related macular degeneration at baseline, drawn mainly from the general population in Finland, Australia, and the United States. Participants included healthy men and women, including Finnish older men, male physicians, and female health professionals.

Trials evaluated antioxidant supplements used orally versus placebo, including vitamin E at 50 mg/day, 500 IU/day, 400 IU on alternate days, or 600 IU on alternate days; beta-carotene at 20 mg/day or 50 mg every other day; vitamin C at 500 mg/day; and a daily multivitamin formulation (Centrum Silver). Treatment duration ranged from 4 to 12 years across the included randomized trials.

Antioxidant vitamin and mineral supplements did not prevent age-related macular degeneration overall. Vitamin E showed little to no effect on any AMD (RR 0.97, 95% CI 0.90 to 1.06) or late AMD (RR 1.22, 95% CI 0.89 to 1.67); beta-carotene was also null for any AMD (RR 1.00, 95% CI 0.88 to 1.14) and late AMD (RR 0.90, 95% CI 0.65 to 1.24); and vitamin C showed little or no effect on any AMD (RR 0.96, 95% CI 0.79 to 1.18) or late AMD (RR 0.94, 95% CI 0.61 to 1.46). Multivitamins may slightly increase any AMD risk (RR 1.21, 95% CI 1.02 to 1.43) and had no clear effect on late AMD (RR 1.22, 95% CI 0.88 to 1.69).

Evidence was limited for several interventions, with only one trial each for vitamin C and multivitamin and substantial imprecision for late AMD and subtype outcomes. Adverse effects were inconsistently reported across eye studies, and safety concerns from other trials, especially beta-carotene and lung cancer risk in smokers, limit reassurance. The included populations were mostly specific healthier subgroups from high-income countries, reducing generalizability.