Multinutrient Supplementation for Prevention of Major Depressive Disorder in Overweight Adults.

Abstract

of Major Depressive Disorder in Overweight Adults To the Editor The MooDFOOD randomized clinical trial1 found that neither multinutrient supplementation nor food-related behavioral activation therapy reduced major depressive disorder episodes in overweight or obese adults with depressive symptoms. However, the low rate of conversion to major depressive disorder of only 10% after 12 months vs 33% expected means that the study was likely underpowered, and the interpretation that nutrients “showed no effect” was potentially incorrect. The authors discussed various single-nutrient studies showing no benefit in the treatment of depression before concluding that micronutrients are unlikely candidates for prevention. These are different questions. Meta-analyses show that omega-3 eicosapentaenoic fatty acid supplements can be effective in treating major depressive disorder but not subclinical depressive symptoms.2 For prevention, including approximately 1 g of eicosapentaenoic fatty acid in the MooDFOOD supplementation was thus a reasonable choice. We also query the choice of other nutrients, only 2 vitamins and 2 minerals at dosages below the recommended dietary allowance (400 μg of folic acid, 20 μg of vitamin D, 30 μg of selenium, 100 mg of calcium). This choice does not reflect current knowledge with respect either to specific nutrients most strongly implicated in depression3 and doses required or to the importance of combining a wide range of micronutrients at levels likely to confer benefits for optimal brain function and improve oxidative stress and inflammation.4,5 Another limitation the authors highlighted is the lack of any nutritional status measures. Costs and other practicalities make including such measures difficult, but without them, meaningful conclusions cannot be drawn. Before treatment, did these participants actually lack the nutrients that were supplied? If so, did supplementation normalize those deficiencies? Equally important, did they lack other nutrients not provided? Whenever individualized treatment is impractical, an overinclusive approach (within safe limits) to both nutrients and dosages seems preferable to risking some deficiencies remaining unaddressed.4 Overweight and obesity may affect both nutrient status and requirements and mood, so the high body mass index of this sample would limit generalization of any findings to other populations. Unfortunately, overall findings were inconclusive—although depression, anxiety, and health measures improved on average in all groups, suggesting trial participation itself was beneficial. Given the high prevalence and costs of depression, limitations of existing treatments, and evidence implicating nutritional factors, further large-scale, high-quality trials of both diet and supplement interventions are warranted.