Effects of n-3 fatty acids on depressive symptoms and dispositional optimism after myocardial infarction

Abstract

Background: In patients who have experienced a myocardial infarction (MI), n-3 (omega-3) PUFA status is low, whereas the risk of depression is increased.

Objective: The objective was to assess whether the plant-derived α-linolenic acid (ALA) and the fish fatty acids EPA and DHA would improve affective states.

Design: In a secondary analysis of the randomized, double-blind, placebo-controlled Alpha Omega Trial, 4116 of 4837 (85.1%) patients (aged 60-80 y; 79.2% men) who had experienced an MI were included. Margarine spreads were used to deliver 400 mg EPA-DHA/d, 2 g ALA/d, both EPA-DHA and ALA, or a placebo for 40 mo. At 40 mo, the endpoints of depressive symptoms (15-item Geriatric Depression Scale) and dispositional optimism (a 4-item questionnaire and the Life Orientation Test-Revised) were analyzed by using a posttest-only design.

Results: The 4 randomly assigned groups did not differ in baseline characteristics. ALA supplementation significantly increased plasma cholesteryl ester concentrations of ALA by 69%, and EPA-DHA supplementation increased plasma cholesteryl ester concentrations of EPA and DHA by 61% and 30%, respectively. Depressive symptoms or dispositional optimism did not differ between groups with the use of n-3 fatty acids compared with placebo at the 40-mo follow-up. The standardized mean (±SE) differences in depressive symptoms were as follows: for EPA-DHA plus ALA (n = 1009) compared with placebo (n = 1030), -0.025 ± 0.044 (P = 0.57); for EPA-DHA (n = 1007) compared with placebo, -0.048 ± 0.044 (P = 0.28); and for ALA (n = 1022) compared with placebo, -0.047 ± 0.044 (P = 0.29).

Conclusions: In patients who had experienced an MI, low-dose EPA-DHA supplementation, ALA supplementation, or a combination of both did not affect depressive symptoms and dispositional optimism. These findings are in accord with those from previous trials in individuals without psychopathology or without severe depressive symptoms. This trial was registered at clinicaltrials.gov as NCT00127452.

FIGURE 1.

CONSORT (Consolidated Standards of Reporting Trials) diagram showing patient flow of men and women aged 60–80 y who had experienced an MI within 10 y before entering the study to receive 1 of 4 margarine spreads that were enriched with EPA-DHA, ALA, or both or placebo in a 2 × 2 factorial design. For the computation of the scores, the following missing items were allowed: total GDS-15 score, 1 or 2 out of 15; for the total LOT-R, 1 out of 6; and for the 4Q scores, 1 out of 4. ALA, α-linolenic acid; GDS-15, 15-item Geriatric Depression Scale; LOT-R, Life Orientation Test–Revised; MI, myocardial infarction; 4Q, 4-item optimism questionnaire.

FIGURE 2.

ALA, EPA, and DHA concentrations in plasma cholesteryl esters at baseline, 20 mo, and 40 mo in random samples of patients with coronary heart disease, according to n–3 fatty acid supplementation. Geometric mean (95% CI) values are presented on logarithmic scales. *P < 0.001 for group difference at that time point, as assessed by ANOVA. ALA, α-linolenic acid.

FIGURE 3.

Mean differences in depressive symptoms between prespecified subgroups, according to treatment group, in patients assigned to n−3 fatty acid supplementation groups compared with placebo. The horizontal bars represent SEs, and the vertical gray dotted lines indicate no mean difference. The size of the boxes is proportional to the number of patients. P values for the difference between the groups assigned to n−3 fatty acids compared with placebo are shown. GDS-15 scores were log-transformed because of their positively skewed distribution, and standardized scores were used in the analysis. The mean difference indicates the mean number of SDs in the GDS-15 score (ie, standardized z scores) by which the n–3 fatty acid–treated group was lower or higher than the placebo group at 40-mo follow-up. ALA, α-linolenic acid; GDS-15, 15-item Geriatric Depression Scale.