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Juan Wu, Eunyoung Cho, Debra A Schaumberg, Srinivas Sastry, Walter Willett; Alpha-linolenic acid and risk of age-related macular degeneration: a prospective study over more than two decades of follow-up. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5129. doi: https://doi.org/.
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Marine-sourced long-chain omega-3 fatty acids (n-3) have been associated with lower risk of AMD in many observational studies. Alpha-linolenic acid (ALA) is the primary n-3 consumed in typical western diet due to its greater availability from plant sources and a small amount is endogenously converted to long-chain n-3. Thus, we aimed to investigate the association between long-term intake of ALA and risk of age-related macular degeneration (AMD).
This prospective study included 81,847 female participants in the Nurses’ Health Study who were ≥ 50 years old. We calculated the intake of ALA from validated food frequency questionnaires collected every four years beginning from 1984. By 2012, we confirmed 1,224 intermediate and 1,023 advanced AMD cases (96% wet AMD). Multivariate Cox proportional hazards model was used to estimate the relative risks (RR’s) and 95% confidence intervals (CI’s).
After adjusting for age, BMI, smoking and other suspected risk factors of AMD, cumulative averaged intake of ALA was positively associated with intermediate AMD (comparing extreme quintiles, multivariate RR = 1.32, 95% CI = 1.10 to 1.58; p trend < .001); the RR persisted after further adjustment for correlated dietary risk factors including DHA, linoleic acid, saturated fat and trans fat (RR = 1.30, 95% CI = 1.04 to 1.64; p trend = 0.02). Mayonnaise-type salad dressing, the leading contributor to both the intake and plasma level of ALA in this cohort, was associated with a 28% (95% CI = 1.06 to 1.55) increased risk of intermediate AMD comparing the highest quintile of intake to the lowest. We detected a small amount of understudied trans ALA isomers (0.05% of total fatty acids) in red blood cells among a subsample of women (n = 408) and mayonnaise also significantly predicted one of the trans ALA isomers (p < .001). Intake of ALA was not significantly associated with advanced AMD (RR = 1.09, 95% CI = 0.89 to 1.32; p trend = 0.61).
ALA does not appear to protect against AMD and may increase the risk of intermediate AMD. Whether trans ALA is responsible for the positive association deserves further investigation.
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