Abstract
Purpose: :
Oxidative stress has been implicated in the development and progression of age-related macular degeneration (AMD). The Age-Related Eye Disease Study (AREDS) demonstrated that supplemental antioxidants and zinc can significantly decrease the risk of progressing to advanced AMD. Studies from our laboratory have shown that long-term supplementation prevents age-related blood plasma oxidation, as measured by biomarkers of oxidative stress. The purpose of this study is to determine if short-term AREDS antioxidant supplementation affects these biomarkers, possibly serving as a predictor of their efficacy.
Methods: :
Eighteen subjects, 11 with intermediate or advanced AMD (AREDS categories 3 or 4) and 7 age-matched controls, were admitted to the Vanderbilt General Clinical Research Center and placed on a controlled diet for 7 days. Antioxidant supplements were stopped two weeks prior to study enrollment. Dietary supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg ß-carotene, 80 mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 3. Blood was drawn on study days 3 and 7, and plasma concentrations of glutathione (GSH), cysteine (Cys), cystine (CySS), isoprostane (isoP) and isofuran (isoF) were determined.
Results: :
Short-term AREDS supplementation significantly lowered plasma levels of CySS in participants on a regulated diet (p = 0.034). No significant differences were observed for GSH, Cys, CySS/Cys, isoP, or isoF.
Conclusions: :
Our pilot interventional study shows that a 5-day course of antioxidant supplements can modify plasma levels of CySS, suggesting that this oxidative stress biomarker could help predict how likely an individual is to benefit from AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD therapies, particularly those hypothesized to affect redox status.
Clinical Trial: :
http://www.clinicaltrials.gov NCT00668213
Keywords: age-related macular degeneration • oxidation/oxidative or free radical damage • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials