Food and Behaviour Research

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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

Bot M, Brouwer IA, Roca M, Kohls E, Penninx BWJH, Watkins E, van Grootheest G, Cabout M, Hegerl U, Gili M, Owens M, Visser M (2019) JAMA.  2019 Mar;321(9): 858-868. doi: 10.1001/jama.2019.0556 

Web URL: Read this and related abstracts on PubMed here



Effects of nutritional interventions on the prevention of major depressive disorder (MDD) in overweight adults are unknown.


To examine the effect of 2 nutritional strategies (multinutrient supplementationfood-related behavioral activation therapy) and their combination for prevention of a new MDD episode in overweight adults with subsyndromal depressive symptoms.


This multicenter 2 × 2 factorial randomized clinical trial included overweight adults (body mass index, 25-40) with elevated depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] scores ≥5) and no MDD episode in the past 6 months from 4 European countries. A total of 1025 adults were randomized (July 30, 2015-October 12, 2016) and followed up for 1 year (October 13, 2017).


Daily multinutrient supplements (1412-mg omega-3 fatty acids, 30-μg selenium, 400-μg folic acid, and 20-μg vitamin D3 plus 100-mg calcium) vs placebo and 21 individual or group therapy sessions vs none (blinded to researchers) for 1 year. Participants were allocated to placebo without therapy (n = 257), placebo with therapy (n = 256), supplements without therapy (n = 256), and supplements with therapy (n = 256).


Cumulative 1-year onset of MDD via the Mini International Neuropsychiatric Interview at 3, 6, and 12 months. Logistic regression using effect-coded variables (-1 indicating control, 1 indicating intervention) evaluated intervention effects both individually and in combination (interaction) on MDD onset.


Among 1025 participants (mean age, 46.5 years; 772 women [75%]; mean BMI, 31.4), 779 (76%) completed the trial. During the 12-month follow-up, 105 (10%) developed MDD: 25 (9.7%) patients in the placebo without therapy, 26 (10.2%) in the placebo with therapy, 32 (12.5%) in the supplement without therapy, and 22 (8.6%) in the supplement with therapy group. None of the treatment strategies affected MDD onset. The odds ratio (OR) for supplements was 1.06 (95% CI, 0.87-1.29); for therapy, 0.93 (95% CI, 0.76-1.13); and for their combination, 0.93 (95% CI, 0.76-1.14; P for interaction, .48). One person in the supplementation with therapy group, died. Twenty-four patients in each of the placebo groups and 24 patients in the supplementation with therapy group were hospitalized, and 26 patients in the supplementation-only group were hospitalized.


Among overweight or obese adults with subsyndromal depressive symptomsmultinutrientsupplementation compared with placebo and food-related behavioral activation therapy compared with no therapy did not reduce episodes of major depressive disorder during 1 year. These findings do not support the use of these interventions for prevention of major depressive disorder.


Read the associated news article:
And see also the subsequent news and comments on the interpretation of findings from this study:
Unfortunately no conclusions can be drawn about the effects of either of the treatments, as the study was seriously statistically underpowered. (This is because far fewer participants actually developed depression during the 12month follow-up period than had been expected when the study was designed). 

In the discussion section of their paper, the authors also acknowledge that there were problems with the 'blinding' - i.e. that participants appeared to be able to tell which treatment they were receiving. This is another serious limitation that prevents any firm conclusions being drawn.

These and other problems mean that initial headlines such as 'nutritional supplements cannot prevent depression, research shows' are simply not justifiable.  As ever - more research is still needed.