Vitamins E and C and medical record-confirmed age-related macular degeneration in a randomized trial of male physicians

Abstract

Purpose: To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of the diagnosis of age-related macular degeneration (AMD) in a large-scale randomized trial of male physicians.

Design: Randomized, double-masked, placebo-controlled trial.

Participants: We included 14 236 apparently healthy United States male physicians aged ≥50 years who did not report a diagnosis of AMD at baseline.

Methods: Participants were randomly assigned to receive 400 international units (IU) of vitamin E or placebo on alternate days, and 500 mg of vitamin C or placebo daily. Participants reported new diagnoses of AMD on annual questionnaires and medical record data were collected to confirm the reports.

Main outcome measures: Incident diagnosis of AMD responsible for a reduction in best-corrected visual acuity to ≤20/30.

Results: After 8 years of treatment and follow-up, a total of 193 incident cases of visually significant AMD were documented. There were 96 cases in the vitamin E group and 97 in the placebo group (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.78-1.37). For vitamin C, there were 97 cases in the active group and 96 in the placebo group (HR, 0.99; 95% CI, 0.75-1.31).

Conclusions: In a large-scale, randomized trial of United States male physicians, alternate-day use of 400 IU of vitamin E and/or daily use of 500 mg of vitamin C for 8 years had no appreciable beneficial or harmful effect on risk of incident diagnosis of AMD.

Trial registration: ClinicalTrials.gov NCT00270647.

Figure 1

Flow diagram of the vitamin E and vitamin C components of the Physicians’ Health Study (PHS) II. A total of 405 participants who had a diagnosis of age-related macular degeneration at baseline were excluded.

Figure 2

Cumulative incidence rates of age-related macular degeneration (AMD) in the vitamin E and vitamin C groups in the Physicians’ Health Study II.

Figure 3

Hazard ratios and 95% confidence intervals (CI) of age-related macular degeneration (AMD) comparing vitamin E alone, vitamin C alone, and vitamin E plus C groups with placebo (combined vitamin E and C placebo groups) in the Physicians’ Health Study II. Adjusted for age, Physicians’ Health Study cohort, and beta-carotene and multivitamin treatment assignment. The P value for interaction is based on a test of the null hypothesis of no difference in treatment effect across treatment combinations.