Association between Dietary Xanthophyll Intake and Early Age-Related Macular Degeneration
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Purpose: No clinical trial has investigated the effect of lutein and zeaxanthin (xanthophyll) supplementation on early AMD, and results from observational studies have been mixed. Data from 10,295 adults enrolled in the Atherosclerosis Risk in Communities Study, an epidemiologic cohort (mean age 53.9 years), was used to examine the association between xanthophyll intake and prevalent early AMD. Potential effect modification by genetic risk factors and biomarkers of high density lipoprotein cholesterol (HDL) metabolism was explored. Methods: Xanthophyll intake was assessed at visit 1 (1987-89) with a food frequency questionnaire. AMD was assessed at visit 3 (1993-95) via non-mydriatic retinal imaging of a randomly-chosen eye. Plasma samples collected at visit 1 were used to measure lipid concentrations (HDL, HDL2, HDL3, and apolipoprotein A-1 [apo-A1]) and obtain DNA for genotyping of the Y402H complement factor H (CFH) rs1061170 and the A69S age-related maculopathy susceptibility 2 (ARMS2) rs10490924 polymorphisms. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for AMD by quintiles of xanthophyll intake, adjusted for age, sex, race, study center, and pack-years of smoking. To evaluate effect modification, the association between tertiles (T) of xanthophyll intake and AMD were stratified by genotype and by median cutpoints of HDL biomarkers. Results: Xanthophyll intake was not associated with AMD in the overall sample, in Caucasians (n=8,257), or African-Americans (n=2,038). Exploratory analyses showed that among Caucasians, higher xanthophyll intake was associated with decreased odds of AMD in carriers of the moderate-risk CT genotype (T3 vs. T1, OR=0.57, 95% CI 0.36-0.91, p for interaction=0.022), but not the low-risk TT (OR=1.33, 95% CI 0.82-2.16) or high-risk CC genotypes (OR=1.37, 95% CI 0.82-2.28) of CFH. No interactions were observed between xanthophyll intake and ARMS2 in Caucasians, or with either polymorphism in African-Americans. Moreover, higher xanthophyll intake trended towards decreased odds of AMD among participants with lower HDL (OR=0.79, 95% CI 0.57-1.09), but not higher HDL (OR=1.14, 95% CI 0.83-1.58, p for interaction=0.048). Stratification by HDL2 and apo-A1 revealed similar trends. Conclusion: Xanthophyll intake was not associated with early AMD in this biracial cohort of middle-aged adults. Further research is needed to clarify potential interactions with genetic susceptibility and HDL metabolism.