Omega-3 fatty acid supplementation may increase the risk of incident depression (VITAL-DEP)

Reference

Okereke OI, Vyas CM, Mischoulon D, et al. Effect of long-term supplementation with marine omega-3 fatty acids vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores. A randomized clinical trial. JAMA 2021;326(23):2385-2394.

Synopsis

Current evidence is inconclusive whether long-term dietary supplementation with omega-3 fatty acids reduces the risk of depression in adults. These investigators identified 18,353 adults, 50 years or older, without depression or clinically relevant depressive symptoms at baseline. Eligible participants randomly received daily vitamin D (2000 IU/d), marine omega-3 (Omacor, a 1g fish oil capsule containing 465 mg eicosapentaenoic acid and 375 mg docosahexaenoic acid), or matching placebos in a 2 x 2 factorial design (concealed allocation assignment). The participants, masked to treatment group assignment, self-reported symptoms annually via mailed questionnaires. Complete follow-up occurred for 90.3% of participants for a median of 5.3 years. A new (incident) depression event was defined as a self-report of physician- or clinician-diagnosed depression, treatment for depression, or the presence of clinically relevant depressive symptoms on a validated scoring tool. The study was 99% powered to detect the minimal clinically important difference in depressive symptoms. Using intention-to-treat analysis, the incidence of new depression events was significantly increased in the omega-3 group compared with the placebo groups (13.9 vs 12.3 per 1000 person-years). No significant difference in depression events occurred between patients taking vitamin D vs placebo. No significant differences occurred in secondary outcomes between treatment subgroups, with the exception of an elevated risk of depression in women but not men when comparing omega-3 with placebo. However, this difference may be due only to chance since there were multiple secondary subgroup outcomes reported.