Abstract
Abstract: :
Purpose:To determine if antioxidant supplements will shift the plasma pool of age–related macular degeneration (ARMD) patients to a more reduced state as measured by glutathione and cysteine. Methods:The Age–Related Eye Disease Study (AREDS), sponsored by NEI, included a clinical trial to evaluate the effect of high doses of antioxidants and zinc on the progression to advanced ARMD. Participants with ARMD 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, as zinc oxide and copper, 2 mg as cupric oxide); (3) antioxidants plus zinc; or (4) placebo. At 2 study sites, blood specimens were obtained at 2 different time points, an average of 1.7 and 6.7 years after enrollment. Plasma glutathione (GSH), oxidized glutathione (GSSG), cysteine (Cys) and cystine (CySS) were measured by HPLC and redox potentials (EhGSH and EhCys) of the thiol/disulfide pools were calculated using the Nernst equation. The means of these metabolites for the antioxidants and no antioxidants groups were compared using analysis of variance. Results: At the first blood draw (n = 312), the means for the antioxidant group and no antioxidant group were not different for any of the metabolites. After five additional years of supplementation (n = 82) there was no difference in the means of GSH, GSSG, EhGSH or CySS between the two groups, but mean EhCys was significantly lower (more reduced) and mean Cys was significantly higher in the antioxidant group. EhCys and Cys After 5 Years of Antioxidant Supplementation
Conclusions:For these AREDS ARMD patients, the oxidation of the Cys/CySS pool was less in those subjects who received the AREDS antioxidant supplements. This should affect cysteine availability, cell growth, apoptosis, and immune status and may explain partially the beneficial effect of supplementation on progression to advanced ARMD.
Keywords: antioxidants • age–related macular degeneration • oxidation/oxidative or free radical damage