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World Psychiatry. 2019 Oct;18(3):308-324. doi: 10.1002/wps.20672.

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(1)(2)(3), Teasdale SB(4)(5), Allott K(3)(6), Siskind D(7)(8), Marx W(9), 
Cotter J(10), Veronese N(11)(12), Schuch F(13), Smith L(14), Solmi M(15)(16),
Carvalho AF(17)(18), Vancampfort D(19)(20), Berk M(6)(9), Stubbs B(21)(22),
Sarris J(1)(23).

Author information: 
(1)NICM Health Research Institute, Western Sydney University, Westmead,
Australia.
(2)Division of Psychology and Mental Health, Faculty of Biology, Medicine and
Health, University of Manchester, Manchester, UK.
(3)Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.
(4)School of Psychiatry, Faculty of Medicine, University of New South Wales,
Sydney, Australia.
(5)Keeping the Body in Mind Program, South Eastern Sydney Local Health District, 
Sydney, Australia.
(6)Orygen, The National Centre of Excellence in Youth Mental Health, Parkville,
Australia.
(7)Metro South Addiction and Mental Health Service, Brisbane, Australia.
(8)School of Medicine, University of Queensland, Brisbane, Australia.
(9)IMPACT Strategic Research Centre, School of Medicine, Deakin University,
Barwon Health, Australia.
(10)Cambridge Cognition, Cambridge, UK.
(11)Neuroscience Institute, National Research Council, Padua, Italy.
(12)Research Hospital, National Institute of Gastroenterology, IRCCS De Bellis,
Castellana Grotte, Bari, Italy.
(13)Department of Sports Methods and Techniques, Federal University of Santa
Maria, Santa Maria, Brazil.
(14)Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University,
Cambridge, UK.
(15)Department of Neurosciences, University of Padua, Padua, Italy.
(16)Padua Neuroscience Center, University of Padua, Padua, Italy.
(17)Centre for Addiction and Mental Health, Toronto, ON, Canada.
(18)Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
(19)KU Leuven Department of Rehabilitation Sciences, Leuven, Belgium.
(20)University Psychiatric Centre KU Leuven, Kortenberg, Belgium.
(21)South London and Maudsley NHS Foundation Trust, London, UK.
(22)Institute of Psychiatry, Psychology and Neuroscience, King's College London, 
London, UK.
(23)Professional Unit,  The Melbourne Clinic, Department of Psychiatry,
University of Melbourne, Melbourne, Australia.

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. Folate-based 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.

© 2019 World Psychiatric Association.

DOI: 10.1002/wps.20672 
PMID: 31496103 

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