MooDFOOD: 1,025 adults, a year of supplements and food-focused therapy, and no effect on new depression
The largest trial in the set: 1,025 overweight adults with low-grade symptoms, a 2 x 2 design of a multinutrient supplement and food-related behavioural activation. 10% developed major depression; supplement OR 1.06, therapy OR 0.93.
Well-supported by good-quality research. how we score evidence
Caveat on this rating: A prevention trial in overweight adults without current major depression; the food arm was a behavioural therapy, not a whole-diet change; so it does not test what the small treatment trials tested. Twenty four percent did not complete. Several authors disclose pharmaceutical fees.
The biggest randomised test of a food-based approach to depression found nothing, and the authors said so without hedging. It is the row that keeps the small positive trials honest.
Significant findings
"This multicenter 2 x 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."
The interventions: "Daily multinutrient supplements (1412-mg omega-3 fatty acids, 30-ug selenium, 400-ug folic acid, and 20-ug vitamin D3 plus 100-mg calcium) vs placebo and 21 individual or group therapy sessions vs none (blinded to researchers) for 1 year."
"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)."
The conclusion: "These findings do not support the use of these interventions for prevention of major depressive disorder."
The other direction
This is a prevention trial in people who did not have major depression, not a treatment trial in people who did, so it does not test what SMILES tested. The food arm was a behavioural therapy about eating, not a whole-diet change with a dietician, and the supplement arm was a pill. A null result in a different population with a different intervention limits the small trials' claims; it does not overturn them. Twenty four percent did not complete the year. Several authors disclose fees from pharmaceutical companies, on the record.
What this does not show
It does not show that diet has no effect on existing depression. It does not test a Mediterranean diet. It does not compare with any treatment. It does not tell anyone to stop taking a supplement or start one, and this row does not either.
Worth asking
Was the intervention the thing that failed, or was it the wrong intervention for the question?
Source
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; MooDFOOD Prevention Trial Investigators (2019)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1001/jama.2019.0556
DOI: 10.1001/jama.2019.0556
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Funding not disclosed
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 1,025
- Preregistered
- Yes
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 29, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "strong evidence". Well-supported by good-quality research. It scores 76 out of 100 on our published rubric. One caveat travels with that badge: A prevention trial in overweight adults without current major depression; the food arm was a behavioural therapy, not a whole-diet change; so it does not test what the small treatment trials tested. Twenty four percent did not complete. Several authors disclose pharmaceutical fees. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
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; MooDFOOD Prevention Trial Investigators (2019). Published in: Top-tier peer-reviewed journal. DOI: 10.1001/jama.2019.0556. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Randomised controlled trial. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.