Supplements Failed to Improve Mood

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It is clear the human brain, like other tissues, is likely to be adversely impacted by a lack of one of more nutrients. It is also likely that excessive intake of things like saturated fat, cholesterol, salt, and a lack of beneficial phytochemicals that may disrupt blood flow to the brain, alter the gut’s microbiome, and/or increase inflammation, and/or promote weight gain and insulin resistance and so impair healthy brain function. The idea that something as simple as changing one’s diet could help prevent depression has seen some research suggesting improving one’s diet may have some merit for reducing depression. Two review articles have reported that people consuming or adopting healthier diets are less like to become or remain depressed (1,2).

A cross sectional study found depressive symptoms were more common in those consuming a less healthy diet (3). Of course, such data do not prove that poor diet is causing depression. It may be that those who are more depressed simply are less motivated to consume a healthy diet, exercise, get adequate sleep, and/or adopt other unhealthy habits.

One randomized controlled clinical trial did find that adopting a healthier diet did significantly reduce depression (4). Of course, getting people to adopt a healthier diet perhaps especially if they are already depressed is a challenge. Getting depressed people to take supplements would certainly be easier than a big change in dietary habits. This led Dr. Marjolein Visser to study whether supplements of nutrients associated with less depression might significantly reduce depression. Dr. Visser and her colleagues selected a combination of nutrients that earlier studies had suggested may impact mood. The supplements used in her double-blind randomized controlled clinical trial included the omega-3 PUFAs folate, selenium, and vitamin D3 plus calcium on overweight and obese people with some depressive symptoms. Subjects were divided into 4 groups of over 250 subjects each. One group received placebo supplements without diet therapy; a second group received placebo supplements with diet therapy to consume a Mediterranean-style diet; a third group received the food supplements but without any diet therapy; the fourth group received both the multi-nutrient food supplements and diet therapy to consume a Mediterranean-style diet. During the one year follow up period, 105 subjects developed major depressive disorder (MDD) according to the DSM 4 guidelines. Unfortunately, Dr. Visser’s results showed no reduction in the risk of her subjects progressing to MDD compared to the control group that got no dietary advice or supplements. While compliance with the dietary advice was not very good, compliance with supplements and placebos was reasonably good and yet the supplement group showed no beneficial effects on progressing to the development of MDD.

Indeed, if anything the subjects receiving placebos were actually a bit less likely to end up with MDD than those taking the food supplements with 10.5% who received supplements progressing to MDD compared to 9.9% of those who received placebos ending up with MDD. In terms of the diet therapy group, Dr. Visser noted slightly lower rates of MDD after one year in those who got the dietary therapy compared to those who did not. However, this modest improvement was not statistically significant. In response to a question about what her results tell us, Dr. Visser stated she feels confident saying that the supplements she tested are very unlikely to help prevent the progression of depressive symptoms to MDD. The impact of a healthier diet and other lifestyle factors need more study before any strong conclusions should be drawn (5).

Bottom Line: Dr. Vissner’s study certainly is not encouraging to those who believe that supplements of omega-3s, selenium, folate, vitamin D3, and calcium can prevent depression. There remains no reason to recommend these supplements for people hoping to prevent or reduce major depressive symptoms or MDD. While the advice to adopt a healthy Mediterranean diet failed to significantly reduce the progression to MDD in this recent UK study, there was at least a modest (albeit not significant) tendency to do so. Had compliance been better with the healthy Mediterranean diet, it is possible it’s effects might have significantly reduce depression. And while it is too soon to conclude that a healthy diet will reduce depression, there is certainly no reason not to recommend that depressed people adopt a healthier diet as well as regular exercise, getting adequate sleep, and other lifestyle changes that at least some studies have found do reduce the risk of numerous ills. The challenge will be to motivate already depressed people to adopt a healthier diet and lifestyle.  Deficiencies of some nutrients can adversely affect brain function and supplementation may be warranted if there is reason to suspect a deficiency may be contributing to cognitive ills. More research is needed as to what dietary advice is most likely to improve mood and help prevent MDD.

By James J. Kenney, PhD, FACN


  1. Lai JS, Hiles S, Bisquera A, Hure AJ, McEvoy M, Attia J. A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults. Am J Clin Nutr. 2014;99:181–97.
  2. Molendijk  M, Molero  P, Ortuño Sánchez-Pedreño  F, Van der Does  W, Angel Martínez-González  M.  Diet quality and depression risk: a systematic review and dose-response meta-analysis of prospective studies.  J Affect Disord. 2018;226:346-354. doi:10.1016/j.jad.2017.09.022.
  3. Paans  NPG, Bot  M, van Strien  T, Brouwer  IA, Visser  M, Penninx  BWJH.  Eating styles in major depressive disorder: Results from a large-scale study.  J Psychiatr Res. 2018;97:38-46. doi:10.1016/j.jpsychires.2017.11.003.
  4. Jacka  FN, O’Neil  A, Opie  R,  et al.  A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial).  BMC Med. 2017;15(1):23. doi:10.1186/s12916-017-0791-y.
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