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Melissa P. Osborn, Youngja Park, Dean P. Jones, Paul Sternberg, Jr., Milam A. Brantley, Jr.; Short-term Antioxidant and Zinc Supplementation Alters Metabolic Profiles. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5565.
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In the Age-Related Eye Disease Study (AREDS), five years of antioxidant and zinc supplementation reduced progression from intermediate to advanced age-related macular degeneration (AMD). While supplementation is beneficial overall, not all individuals are protected from AMD progression. Our past studies have shown that long-term supplementation is associated with changes in thiol redox status and that short-term supplementation can significantly alter redox status in a subgroup of patients. The purpose of this study was to investigate the differences in plasma metabolic composition before and after five days of AREDS therapy in AMD patients and controls.
Participants 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 the AREDS formula (vitamins C and E, β-carotene, zinc oxide, and cupric oxide) was instituted on Study Day 2. Blood was drawn on Days 2 and 7. Plasma samples from 10 patients with intermediate or advanced AMD (AREDS categories 3 or 4) and 5 controls underwent liquid chromatography with anion exchange column-Fourier-transform mass spectrometry using a Thermo LTQ-FT mass spectrometer and adaptive processing software. Individual m/z features were matched to two metabolomics databases. A False Discovery Rate of 0.05 was used to account for multiple testing. Principal component analysis and orthogonal partial least squares discriminatory analysis were performed to detect differences in metabolic profiles.
Levels of specific m/z features varied between Days 2 and 7, indicating that individual metabolites may be altered by AREDS supplementation. There was a 19% reduction in features unique to AMD and a 61% increase in features related to both AMD patients and controls. In this pilot study, no individual m/z features were statistically different between time points.
These data suggest that short-term response to AREDS supplementation, as determined by alterations in metabolic profiles, might be useful in predicting an individual’s long-term response to AREDS therapy. The increase in m/z features common to AMD patients and controls on a controlled diet suggests that AREDS treatment may "normalize" the metabolism of AMD patients to more closely resemble that of controls.
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