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P. Sternberg, S.E. Moriarty–Craige, D.P. Jones, M. Lynn, S. Bressler, G. Gensler; Effects of Long Term Zinc Supplementation on Plasma Thiol Metabolites and Redox Status in ARMD Patients . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3302.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: This was an ancillary study to the Age–Related Eye Disease Study (AREDS), a randomized clinical trial to evaluate the effects of high doses of antioxidants and zinc supplementation on the progression of ARMD. The purpose of the study is to determine the effect of zinc on blood plasma thiol metabolites and redox status in a cohort of age–related macular degeneration (ARMD) patients. Methods: Subjects with ARMD were randomized to one of four treatment groups: 1) antioxidants (vitamin C, 500mg; vitamin E, 400IU, and beta carotene, 15mg); 2) zinc (80mg zinc oxide, 2mg cupric oxide); 3) antioxidants plus zinc; or 4) placebo. Blood specimens were obtained from subjects at two study sites (Wilmer and Emory) at two different time points (20 vs. 80 months after randomization). Blood specimens were analyzed for glutathione (GSH), oxidized glutathione (GSSG), cysteine (Cys), and cystine (CySS). Redox status for glutathione (Eh GSH) and cysteine (Eh Cys) were calculated using the Nernst equation. Results: At the initial blood draw, there was no difference in either plasma thiol redox status or thiol metabolites between the zinc and no zinc groups. At the second blood draw, zinc supplementation had no effect on a time related oxidation of the plasma GSH redox status (–110 vs –112 mV). There was no significant change in the plasma Cys redox status either. However, the patients receiving zinc supplementation demonstrated a significantly lower total Cys (Cys+CySS) as compared to those not receiving zinc (121.6 vs 142.1 µM) at the second blood draw. Conclusions: Despite its protective effect against the progression of AMD, zinc supplementation had no effect on time–related changes in plasma thiol /disulfide redox status. Although considered as a redox inactive compound, long term zinc supplementation did lead to changes in the plasma Cys/CySS pool. This effect may contribute to the benefits of zinc as reported in the AREDS.
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