Effects of n‐3 fatty acids on cognitive decline: A randomized, double‐blind, placebo‐controlled trial in stable myocardial infarction patients

Abstract Background Epidemiological studies suggest a protective effect of n‐3 fatty acids derived from fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) against cognitive decline. For α‐linolenic acid (ALA) obtained from vegetable sources, the effect on cognitive decline is unknown. We examined the effect of n‐3 fatty acid supplementation on cognitive decline in coronary heart disease patients. Methods The analysis included 2911 coronary patients (78% men) aged 60 to 80 years who participated in a double‐blind placebo‐controlled trial of n‐3 fatty acids and cardiovascular diseases (Alpha Omega Trial). By using a 2 × 2 factorial design, patients were randomly assigned to margarines that provided 400 mg/d of EPA–DHA, 2 g/d of ALA, both EPA–DHA and ALA, or placebo for 40 months. Cognitive function was assessed by the Mini‐Mental State Examination (MMSE) at baseline and after 40 months. The effect of n‐3 fatty acids on change in MMSE score was assessed using analysis of variance. Logistic regression analysis was used to examine the effects on risk of cognitive decline, defined as a decrease of 3 or more points in MMSE score or incidence of dementia. Results Patients in the active treatment groups had an additional intake of 384 mg of EPA–DHA, 1.9 g of ALA, or both. The overall MMSE score in this cohort was 28.3 ± 1.6 points, which decreased by 0.67 ± 2.25 points during follow‐up. Changes in MMSE score during intervention did not differ significantly between EPA–DHA and placebo (−0.65 vs −0.69 points, P = .44) or between ALA and placebo (−0.60 vs −0.74 points, P = .12). The risk of cognitive decline was 1.03 (95% confidence interval: 0.84–1.26, P = .80) for EPA–DHA (vs placebo) and 0.90 (0.74–1.10, P = .31) for ALA (vs placebo). Conclusion This large intervention study showed no effect of dietary doses of n‐3 fatty acids on global cognitive decline in coronary heart disease patients.