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Mini: Nutrient supplements for mental health disorders

Study under review: The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials.

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There are a few reasons to suspect that nutritional supplements could play a role in improving mental health. The first is that mental illnesses and poor nutrition are associated[1] with each other, which could lead to nutritional deficiencies in theory. And certain deficiencies have in fact been observed. For instance, zinc and folate deficiency is relatively common in people with depression[2] and schizophrenia[2]. Ditto for folate[3][4] and vitamin D[5][6]. Also, inflammation and oxidative stress have also been shown to play a role in some mental illnesses[7][8][9], and some nutritional supplements like omega-3 fatty acids[10] and N-acetylcysteine[11] could influence these processes, which could in turn help impact psychiatric conditions.

But just because nutritional supplements could help doesn’t mean they do. Fortunately, there’s been quite a bit of research looking into how supplements can affect mental health. But, due to just how much research is out there, it can be hard to figure out what the evidence supports and what it doesn’t. Fortunately, umbrella reviews can help with this.

We’ve covered several umbrella reviews in the past, but as a refresher: an umbrella review is a review of reviews. It takes a look at all reviews and (usually) meta-analyses around a given topic, and summarizes the state of the evidence.

Recently, a large umbrella review[12] took a look at the evidence for nutritional supplements’ impact on various mental illnesses. The fifteen authors scoured the literature using a preregistered protocol, looking for systematic reviews and meta-analyses for how supplements for nutrients commonly found in the human diet impact mental health and summarized the results. They excluded reviews that examined changes in diet and that looked at herbal supplements: they just stuck to things like supplemental vitamins, minerals, fatty acids, and amino acids. They ultimately uncovered 33 meta-analyses of randomized controlled trials, that covered 10,951 people.

Given that it took 15 people to write the umbrella review, it shouldn’t be a surprise that there’s lots and lots of details we’re skipping over in this Mini. Fortunately, the full text is open access, so you can check out the details yourself[12] if you’d like, and discuss the nuances in the Examine Members Facebook forum. Here, we’re just going to summarize the results of one of the stronger findings of the paper: the evidence for supplements that have “sufficient data”, which the authors defined as having results from meta-analyses involving more than 400 people. These results are summarized in Figure 1. These larger meta-analyses are less likely to have much random error in their estimates, which is part of the reason why they’re worth highlighting over smaller meta-analyses, which by their nature provide less accurate effect estimates. However, as you can see in the “author’s notes” column of Figure 1, even larger meta-analyses may not always be reliable.

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See other articles with similar topics: Nutrition, Supplementation, Depression, ADHD, Bipolar Disorder, Schizophrenia.

See other articles in Issue #61 (November 2019) of Study Deep Dives.

Other Articles in Issue #61 (November 2019)


  1. ^ Firth J, et al. Diet as a hot topic in psychiatry: a population-scale study of nutritional intake and inflammatory potential in severe mental illness. World Psychiatry. (2018)
  2. ^ a b Swardfager W, et al. Zinc in depression: a meta-analysis. Biol Psychiatry. (2013)
  3. ^ Gilbody S, Lightfoot T, Sheldon T. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. J Epidemiol Community Health. (2007)
  4. ^ Belbasis L, et al. Risk factors and peripheral biomarkers for schizophrenia spectrum disorders: an umbrella review of meta-analyses. Acta Psychiatr Scand. (2018)
  5. ^ Anglin RE, et al. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. (2013)
  6. ^ Belvederi Murri M, et al. Vitamin D and psychosis: mini meta-analysis. Schizophr Res. (2013)
  7. ^ Berk M, et al. So depression is an inflammatory disease, but where does the inflammation come from?. BMC Med. (2013)
  8. ^ Miller BJ, et al. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. (2011)
  9. ^ Berk M, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. (2011)
  10. ^ Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. (2002)
  11. ^ Dodd S, et al. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther. (2008)
  12. ^ a b Firth J, et al. The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry. (2019)