+Marine omega-3 fatty acids may reduce the risk of depression and improve mood. However, current evidence is mixed regarding whether omega-3 fatty acids reduce depressive symptoms. A large, randomized controlled trial has yet to assess whether omega-3 supplementation prevents or reduces depression risk. The VITAL-DEP randomized controlled trial investigated whether daily Vitamin D3 and omega-3 fatty acids can reduce depression risk compared to placebo. This current study discusses the results of omega-3 supplementation. Adults (18 353 included in the primary analysis) aged 50 years or over (50+ men and 55+ women) were randomized to receive Vitamin D3, marine omega-3 fatty acids, or matching placebos between November 2011 and March 2014. They were followed up annually, and this continued until the end of randomized treatment on December 31, 2017, with a median treatment duration of 5.3 years (IQR: 5.0-5.7). The co-primary outcomes were depression risk and longitudinal mood scores using PHQ-8 scores (range 0-24; higher scores indicate worse mood). There were 651 cases of depression/clinically relevant depressive symptoms in the omega-3 treatment cohort (13.9 per 1000 person-years) compared to 583 cases in the placebo arm (12.3 per 1000 person-years), resulting in an adjusted hazard ratio (HR) of 1.13 (95% CI: 1.01-1.26; p= 0.03). Furthermore, the mean change in PHQ-8 scores between the omega-3 cohort and placebo group over the entire follow-up period was 0.03 points (95% CI: -0.01-0.07; p= 0.19). Surprisingly, the omega-3 cohort had a small but significant increased risk of first-time depression (HR: 1.17 [95% CI: 1.03-1.33]) and no increased risk of recurrent depression (HR: 1.02 [95% CI: 0.82-1.27]) compared to the placebo group. Overall, adults without baseline depression who received omega-3 supplements did not have a decreased risk of developing depression (there was a small statistically significant increase in risk) or change in mood scores compared to placebo; therefore, the use of omega-3 to prevent depression in adults is not supported. This study was strengthened by its large, diverse cohort, a long duration of treatment, and a high proportion of participants with long-term follow-up. Notably, this study did not directly measure brain levels of omega-3 fatty acids; therefore, despite increased blood levels of fatty acids in the treatment group, it is not clear whether this was correlated with elevated brain levels.
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