1. The VITAL-DEP randomized controlled trial demonstrated that long-term supplementation of omega-3 fatty acids in adults did not reduce the risk of depression or change mood scores using the PHQ-8 score compared to placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: 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.
Click to read the study in JAMA
Relevant Reading: A multi-national, multi-disciplinary Delphi consensus study on using omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the treatment of major depressive disorder
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