Dietary intake of α-linolenic acid and risk of age-related macular degeneration

Abstract

Background: The relation between α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and age-related macular degeneration (AMD) is unclear. European researchers reported that ≤40% of ALA can be present as trans forms.Objective: We aimed to evaluate the associations between intake of ALA and intermediate and advanced AMD.Design: Seventy-five thousand eight hundred eighty-nine women from the Nurses' Health Study and 38,961 men from Health Professionals Follow-Up Study were followed up from 1984 to 2012 and from 1986 to 2010, respectively. We assessed dietary intake by a validated food-frequency questionnaire at baseline and every 4 y thereafter. One thousand five hundred eighty-nine incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) were confirmed by medical record review.Results: The multivariable-adjusted HR for intermediate AMD comparing ALA intake at the top quintile to the bottom quintile was 1.28 (95% CI: 1.05, 1.56; P-trend = 0.01) in the analyses combining 2 cohorts. The HR in each cohort was in the positive direction but reached statistical significance only in the women. However, the positive association was apparent only in the pre-2002 era in each cohort and not afterward (P-time interaction = 0.003). ALA intake was not associated with advanced AMD in either time period. Using gas-liquid chromatography, we identified both cis ALA (mean ± SD: 0.13% ± 0.04%) and trans ALA isomers (0.05% ± 0.01%) in 395 erythrocyte samples collected in 1989-1990. In stepwise regression models, mayonnaise was the leading predictor of erythrocyte concentrations of cis ALA and one isomer of trans ALA. We also found trans ALA in mayonnaise samples.Conclusions: A high intake of ALA was associated with an increased risk of intermediate AMD before 2002 but not afterward. The period before 2002 coincides with the same time period when trans ALA was found in food and participants' blood; this finding deserves further study.

Keywords: age-related macular degeneration; food-frequency questionnaire; omega-3 fatty acids; prospective cohort study; trans fat; α-linolenic acid.

FIGURE 1

The associations of primary α-linolenic acid–containing foods with intermediate and advanced AMD. Each food was modeled as a continuous variable in a multivariate Cox regression model that included age (continuous), race (Caucasian or not), BMI (in kg/m²: <18.5, 18.5–23, 23–25, 25–30, 30–35, or >35), pack-years of smoking (never, 1–9, 10–24, 25–44, 45–64, or ≥65 y), physical activity (<3, 3–8.9, 9–17.9, 18–26.9, or ≥27 h metabolic equivalent tasks/wk), current aspirin use (≥1 tablet/wk or none), history of hypertension, history of hypercholesterolemia, and total calories (quintiles). In the Nurses’ Health Study, models were additionally adjusted for postmenopausal status and menopausal hormone use (never, current, and past). AMD, age-related macular degeneration.

FIGURE 2

Partial gas-liquid chromatography of trans and cis ALA isomers. ALA-A and ALA-B are trans ALAs with 2 trans bonds; ALA-C and ALA-D are trans ALAs with 1 trans bond. In all erythrocyte (A) and mayonnaise (B and C) samples, the amount of trans ALA-A was extremely low and could not always be identified. ALA, α-linolenic acid.