Red Blood Cell Membrane Fatty Acids and Incident Age-Related Macular Degeneration in Postmenopausal Women
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Background: Evidence exists for an association between high dietary intake of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and decreased risk for age-related macular degeneration (AMD), but data using blood biomarkers of fatty acids is limited. Red blood cell membrane (RBCM) fatty acids can be used as a long-term indicator of fatty acid intake, and are not biased by the same errors as measurement of dietary intake. Purpose: To evaluate the relationship between RBCM n-3 and n-6 PUFAs, dietary PUFAs, and fish intake, a rich source of n-3 PUFAs, and incident AMD in a cohort of postmenopausal women in the United States. Methods: We included 1174 postmenopausal women who participated in the Women’s Health Initiative hormone therapy trials, sight exam, and memory study. Women were age 63-79 with no AMD at baseline (2000-2002), assessed using graded fundus photographs. RBCM PUFAs were measured from fasting blood samples using gas chromatography with flame ionization detection and expressed as a percent of total fatty acids. Dietary PUFAs and fish intake were assessed via food frequency questionnaire. Self-reported incident AMD was collected through an annual mailed survey administered from 2005-2015. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for incident AMD by RBCM and dietary PUFAs (n-3, n-6, and a ratio of n-6/n-3) adjusting for age, pack-years of smoking, metabolic equivalents of recreational physical activity, dietary alcohol, and participation in the intervention or control arm of the hormone therapy, dietary modification, and calcium and vitamin D trials, as well as dietary energy for the dietary PUFAs. The HR for RBCM PUFAs indicate a one unit difference in fatty acid concentration (% of total RBCM fatty acids), while dietary PUFAs (% of total energy intake) were parameterized in tertiles, as well as continuously for the p for trend. Results: A total of 153 participants developed AMD during a median of 9.5 years of study follow-up. No significant relationship was found between incident AMD and overall RBCM n-3, n-6, or n-6/n-3 concentrations. An inverse, but statistically insignificant, association was found for risk of incident AMD with increasing concentrations of eicosapentaenoic acid (EPA), a type of n-3 PUFA (HR=0.80, 95% CI 0.42, 1.53). A direct and statistically insignificant association was found for alpha-linolenic acid (ALA) (HR=1.34, 95% CI 0.07, 24.37). Null associations were found between incident AMD and RBCM concentrations of docosahexaenoic acid (DHA), another n-3 PUFA of interest, DHA+EPA, the n-6 PUFAs linoleic acid (LA) and arachidonic acid (AA), and n-6/n-3. Dietary analyses also found no association between DHA+EPA, EPA, DHA, ALA, AA, or fish intake and risk of incident AMD. A significant positive association with incident AMD was found for those in the second tertile of dietary LA compared to the lowest (HR=1.74, 95% CI 1.15, 2.62, p for trend=0.46), and a significant positive association for those in the third compared to the lowest tertile of n-6/n-3 (HR=1.53, 95% CI 1.03-2.29, p for trend=0.01) in the adjusted model. Conclusions: RBCM n-3 and n-6 PUFAs were not associated with incident AMD in this prospective cohort. Overall, dietary analyses of PUFAs supported this conclusion, with the main exception of dietary n-6/n-3. This is the first study to the authors’ knowledge assessing incidence of early AMD using RBCM PUFAs, a long-term biomarker for dietary fatty acid intake.