Food and Behaviour Research

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

Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, Veronese N, Schuch F, Smith L, Solmi M, Carvalho AF, Vancampfort D, Berk M, Stubbs B, Sarris J (2019) World Psychiatry.  2019 Oct;18(3): 308-324. doi: 10.1002/wps.20672. 

Web URL: Read this and related abstracts on PubMed here. Free full text of this article is available online.


The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements.

Recently, a large number of 
meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders.

Our systematic search identified 33 
meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia.

supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications.

In conclusion, clinicians should be informed of the 
nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.


This comprensive review adds to the already substantial evidence showing the fundamental importance of nutrition to psychiatry.

The authors systematically reviewed all meta-analyses of clinical trials investigating specific nutrients for specific psychiatric conditions, and found several areas where clear benefits have already been established, notably:
  • long-chain omega-3 fatty acids for ADHD 
 as well as others where evidence is still emerging or preliminary, such as: 
  • Vitamin B9 (folate) for depression and schizophrenia - but particularly in a special form (methylfolate), rather than as folic acid
  • N-Acetyl Cysteine for depression, schizophrenia and other mental health conditions

The fact that the highest level of evidence (systematic reviews and meta-analyses of clinical trials) already supports some nutritional supplements as adjunctive treatments for mental health disorders is obviously very positive.

However, clinical trials of 'specific nutrients for specific conditions' can rarely address many important issues, such as:
  1. psychiatric disorders - as currently diagnosed - are highly heterogenous, and yet most clinical trials focus only on broad diagnostic categories
  2. co-occurence / overlap of different mental health problems in the same individual is very common, which adds to the clinical variability
  3. nutrients work in synergy - not in isolation  - and yet nutritional status is often unknown in clinical trials even for the nutrient being supplemented - let alone for other nutrients that may be needed for this to be effective 
For these reasons, meta-analyses of clinical trials are likely to understate the potential benefits that could be obtained from more individuaised nutritional management. 

Good clinical practice always involves considering the patient's individual symptom profile, and their overall diet and nutritional status, as well as their general health. 

As the authors note, these factors are also important in designing the further clinical trials still needed in many areas.

See the associated news articles:

For just some of the key reviews in this area, see also: