Multinutrient supplementation and food-related behavioral activation therapy do not reduce episodes of major depressive disorder (MDD) in overweight or obese adults, according to research published in JAMA. Previously, the effects of nutritional interventions on preventing MDD in overweight adults were unknown.

To examine the individual and combined effects of multinutrient supplementation and food-related behavioral therapy, researchers conducted a multicenter 2×2 factorial randomized clinical trial. The study enrolled 1025 overweight adults with a body mass index of between 25 and 40, elevated depressive symptoms, and no MDD episode within the past 6 months. In the cohort, 257 participants were given a placebo, 256 were given a placebo and therapy, 256 took daily multinutrient supplements without therapy, and 256 took supplements with therapy.

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Follow-up was conducted for 1 year and logistic regression using effect-coded variables evaluated the intervention effects on MDD onset. During the follow-up period, MDD occurred in 105 participants: 25 in the placebo without therapy group, 26 in the placebo with therapy group, 32 in the group receiving supplement without therapy, and 22 in the supplement and therapy group. These figures indicate that none of the treatment strategies reduced episodes of MDD.

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The study had several limiting factors. MDD onset was lower than expected, causing lower power to detect significant effects. In addition, approximately 25% of participants were lost to follow-up, causing potential attrition bias.

Researchers concluded, “These findings do not support the use of [multinutrient supplementation and food-related behavioral activation therapy] for prevention of [MDD] in this population.”   


Bot M, Brouwer IA, Roca M, et al. Effect of multinutrient supplementation and food-related behavioral activation therapy on prevention of major depressive disorder among overweight or obese adults with subsyndromal depressive symptoms: the MooDFOOD randomized clinical trial. JAMA. 2019;321(9):858-868.