Purpose: To determine the effects of zinc supplementation on plasma thiol metabolites and their redox status in a cohort of patients with age-related macular degeneration (AMD). Design: Randomized clinical trial that evaluated the effects of high doses of zinc and antioxidants on plasma biomarkers of oxidative stress. Methods: This was an ancillary study of the Age-Related Eye Disease Study (AREDS). Subjects with AMD were randomized to one of four treatment groups: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg), (2) zinc (80 mg zinc oxide, 2 mg cupric oxide), (3) antioxidants plus zinc, or (4) placebo. At 20 and 80 months after randomization, blood specimens were collected and analyzed for glutathione (GSH), oxidized glutathione (GSSG), cysteine (Cys), and cystine (CySS). Results: Although zinc supplementation had no apparent effect on plasma thiol/disulfide redox status at the first blood draw, the group of patients receiving zinc supplementation at the second blood draw had significantly less CySS compared with those not receiving zinc (54.9 vs 64.1 μM; P = .01). There was a time-dependent oxidation of the plasma GHS pool and was not affected by zinc supplementation. Conclusions: Because increased CySS level is associated with aging, oxidative stress, and age-related diseases, the apparent prevention of increased CySS by zinc supplementation warrants additional investigation.
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