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Supplements and food-related therapy do not prevent depression in overweight adults

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Where do diet and depression meet?

Though links between mental and physical health disorders have been established, this study from Bot et al. reinforces the murkiness of a nascent field like nutritional psychiatry, according to Michael Berk, MD, PhD, and Felice N. Jacka, PhD, of Deakin University in Victoria, Australia.

“Prevention of major depressive disorder is difficult to study,” they wrote, which makes a trial like this so important. However, its findings also emphasize the ambiguous nature of oft-touted remedies, specifically the “liberal and mostly non–evidence-based use of nutrient supplement combinations for psychiatric disorders.”

This study raises as many questions as it answers. Only 71% of those in the food-related behavioral activation therapy group attended more than 8 of the 21 offered sessions, and there is no way to prove how many followed the dietary restrictions. Those who did attend at least of 8 the sessions “showed a significant reduction in risk of depression,” however, which supports other trials that have associated dietary adherence and symptom improvement.

Diet is not a sole treatment for depression. However, the authors acknowledged that it is likely a piece of the complex puzzle that nutritional psychiatry wishes to solve. “These recent findings,” they wrote, “highlight that an integrated care package incorporating first-line psychological and pharmacological treatments, along with evidence-based lifestyle interventions addressing ... diet quality, may have a more robust effect on this burdensome disorder.”

These comments are adapted from an accompanying editorial (JAMA. 2019 Mar 5. doi: 10.1001/jama.2019.0273 ). Both coauthors reported conflicts of interest, including receiving grants, consulting fees, and research support from numerous boards, pharmaceutical companies, and foundations.



Multinutrient supplements and food-related therapy, together or separately, do not reduce major depressive disorder (MDD) episodes, according to a clinical trial of overweight adults with subsyndromal depressive symptoms.

“These findings do not support the use of these interventions for prevention of major depressive disorder in this population,” wrote lead author Mariska Bot, PhD, of Amsterdam University Medical Center, and her coauthors. The study was published in JAMA.

For this randomized clinical trial, Dr. Bot and her colleagues recruited 1,025 overweight adults from four European countries. All had at least mild depressive symptoms – determined through Patient Health Questionnaire–9 scores of 5 or higher – but no MDD episode in the last 6 months. The patients were allocated into four groups: placebo without therapy (n = 257), placebo with therapy (n = 256), supplements without therapy (n = 256), and supplements with therapy (n = 256). The supplements included 1,412 mg of omega-3 fatty acids, 30 mcg of selenium, 400 mcg of folic acid, and 20 mcg of vitamin D3 plus 100 mg of calcium. The therapy sessions were focused on food-related behavioral activation and emphasized a Mediterranean-style diet.

Only 779 (76%) of the patients completed the trial. Of the 105 participants who developed an MDD episode during 12-month follow-up, 25 (9.7%) were receiving placebo alone, 26 (10.2%) were receiving placebo with therapy, 32 (12.5%) were receiving supplements alone, and 22 (8.6%) were receiving supplements with therapy. Three of the four groups had 24 patients hospitalized, and the supplements-only group saw 26 patients hospitalized.

“This study showed that multinutrient supplements containing omega-3 [polyunsaturated fatty acids], vitamin D, folic acid, and selenium neither reduced depressive symptoms, anxiety symptoms nor improved health utility measures,” Dr. Bot and her coauthors wrote. “In fact, they appeared to result in slightly poorer depressive and anxiety symptoms scores compared with placebo.”

The authors acknowledged their study’s limitations, including a lower-than-expected onset of MDD, roughly a quarter of patients lost to follow-up, and the likelihood that patients in the placebo group might have realized that they were not taking a multivitamin. In addition, participants were not selected based on deficiencies in the nutrients provided, making it possible that “deficient individuals will be more likely to benefit from supplementation.”

The study was funded by the European Union FP7 MooDFOOD Project Multi-country Collaborative Project on the Role of Diet, Food-related Behavior, and Obesity in the Prevention of Depression. Dr. Bot reported no disclosures. Her coauthors reported receiving funding from numerous pharmaceutical companies, the European Union, and Guilford Press.

SOURCE: Bot M et al. JAMA. 2019 Mar 5. doi: 10.1001/jama.2019.0556.

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