Supplementation with B vitamins or n-3 fatty acids and depressive symptoms in cardiovascular disease survivors: ancillary findings from the SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids (SU.FOL.OM3) randomized trial

Background: Dietary factors might affect depressive symptoms. Objective: In secondary data analyses, we examined effects of supplementation with B vitamins or n-3 (omega-3) fatty acids on depressive symptoms in cardiovascular disease survivors. Design: The SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids (SU.FOL.OM3) trial was a secondary prevention trial (2003-2009; n = 2501) in which individuals aged 45-80 y were randomly assigned, by using a 2 x 2 factorial design, to receive 0.56 mg 5-methyl-tetrahydrofolate and vitamins B-6 (3 mg) and B-12 (0.02 mg); EPA and DHA (600 mg) in a 2:1 ratio; B vitamins and n-3 fatty acids; or a placebo. Depressive symptoms were evaluated at years 3 and 5 with the 30-item Geriatric Depression Scale (GDS). Overall and sex-specific ORs and 95% CIs were estimated in 2000 participants by using factorial logistic regression. Results: After a median of 4.7 y of supplementation, there was no association between allocation to receive B vitamins and depressive symptoms. However, the allocation to receive n-3 fatty acids was positively associated with depressive symptoms (GDS >10) in men (adjusted OR: 1.28; 95% Cl: 1.03, 1.61) but not in women. Conclusions: We showed no beneficial effects of a long-term, low-dose supplementation with B vitamins or n-3 fatty acids on depressive symptoms in cardiovascular disease survivors. The adverse effects of n-3 fatty acids in men merit confirmation. This trial was registered at www.controlled-trials.com as ISRCTN41926726. Am J Clin Mar 2012;96:208-14.