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Review
. 2023 Apr 17;9(3):e70.
doi: 10.1192/bjo.2023.36.

Efficacy of low carbohydrate and ketogenic diets in treating mood and anxiety disorders: systematic review and implications for clinical practice

Daniel M Dietch  1 , Jess Kerr-Gaffney  2 , Meghan Hockey  3 , Wolfgang Marx  3 , Anu Ruusunen  4 , Allan H Young  2 , Michael Berk  3 , Valeria Mondelli  5
Affiliations
Review

Efficacy of low carbohydrate and ketogenic diets in treating mood and anxiety disorders: systematic review and implications for clinical practice

Daniel M Dietch et al. BJPsych Open. .

Abstract

Background: There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders.

Aims: To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders.

Method: MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367.

Results: The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis; diet duration: 2 weeks to 3 years; n = 389; age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some individuals.

Conclusions: Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.

Keywords: Ketogenic diet; anxiety disorders; low carbohydrate diet; mood disorders; nutritional psychiatry.

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Conflict of interest statement

D.M.D. is a GP Partner in the National Health Service (NHS); he has received fees for presentations, including Royal College of Psychiatrists International Congress Edinburgh 2013 (travel and accommodation only), webinars for general practitioners, PRIMHE (Primary care Mental Health & Education), Network Locums and BMJ Masterclasses; he received an honorarium from Lundbeck for a symposium presentation at the British Association of Psychopharmacology 2019 Summer Meeting on ‘The primary/secondary care interface for treating depression: challenges and future perspectives’, which covered practical ways to improve to help patient care and there was no endorsement of any pharmaceutical treatment or product. J.K.-G. owns shares in AstraZeneca and GSK plc. M.H. is supported by an Australian Rotary Health PhD Scholarship. W.M. is currently funded by an NHMRC (National Health and Medical Research Council) Investigator Grant (#2008971) and a Multiple Sclerosis Research Australia early-career fellowship and has previously received funding from the Cancer Council Queensland and university grants/fellowships from La Trobe University, Deakin University, University of Queensland, and Bond University; he has received industry funding and has attended events funded by Cobram Estate Pty. Ltd., has received travel funding from Nutrition Society of Australia, and consultancy funding from Nutrition Research Australia and ParachuteBH; he has received speakers honoraria from The Cancer Council Queensland and the Princess Alexandra Research Foundation. A.H.Y. is Deputy Editor of BJPsych Open and did not take part in the review or decision-making process of this paper; he is employed by King's College London, is an Honorary Consultant at SLaM (South London and Maudsley) (NHS UK); his independent research is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at SLaM NHS Foundation Trust and King's College London; he has given paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Boehringer Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, Sage, Novartis, Neurocentrx; he is Principal Investigator in the Restore-Life VNS (vagus nerve stimulation) registry study funded by LivaNova, Principal Investigator on ESKETINTRD3004: ‘An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression’, Principal Investigator on ‘The Effects of Psilocybin on Cognitive Function in Healthy Participants’, Principal Investigator on ‘The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)’, UK Chief Investigator for Compass; COMP006 & COMP007 studies, UK Chief Investigator for Novartis MDD (Major Depressive Disorder) study MIJ821A12201; grant funding (past and present): NIMH (National Institute of Mental Health) (USA); CIHR (Canadian Institutes of Health Research) (Canada); NARSAD (National Alliance for Research in Schizophrenia and Affective Disorders) (USA); Stanley Medical Research Institute (USA); MRC (Medical Research Council) (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (British Medical Association) (UK); UBC-VGH (University of British Colombia - Vancouver General Hospital) Foundation (Canada); WEDC (Western Economic Diversification Canada) (Canada); MSFHR (Michael Smith Health Research) (Canada); NIHR (National Institute for Health Research) (UK); Janssen (UK) EU Horizon 2020. M.B. is supported by a NHMRC Senior Principal Research Fellowship and Leadership 3 Investigator grant (1156072 and 2017131); he has received grant/research support from National Health and Medical Research Council, Wellcome Trust, Medical Research Future Fund, Victorian Medical Research Acceleration Fund, Centre for Research Excellence CRE, Victorian Government Department of Jobs, Precincts and Regions and Victorian COVID-19 Research Fund; he received honoraria from Springer, Oxford University Press, Cambridge University Press, Allen and Unwin, Lundbeck, Controversias Barcelona, Servier, Medisquire, HealthEd, ANZJP, EPA, Janssen, Medplan, Milken Institute, RANZCP, Abbott India, ASCP, Headspace and Sandoz (past 3 years). V.M. has received research funding from Johnson & Johnson, a pharmaceutical company interested in the development of anti-inflammatory strategies for depression, but the research described in this paper is unrelated to this funding. V.M. is supported by MQ Brighter Futures grants (MQBF/1 IDEA) and (MQBF/4), by the Medical Research Foundation (Grant: MRF-160-0005-ELP-MONDE) and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the funders, the NHS, the NIHR or the Department of Health and Social Care.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram.
Fig. 2
Fig. 2
Schematic illustration of potential impact of low carbohydrate and ketogenic diets (LC/KD) on mood symptoms. Symptoms may improve as carbohydrate (CHO) intake drops, for example when intake is <25–50 g/day for >4 days, inducing nutritional ketosis, although further evidence is required. Adverse effects may be challenging for some, causing discontinuation of the diet and relapse of mood symptoms. Some individuals may make further attempts at a low carbohydrate (LC) or ketogenic diet (KD). Clinical supervision is required to manage potential adverse effects and adherence problems across all phases of ketogenic dietary interventions.
See this image and copyright information in PMC

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