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Neurosci Biobehav Rev. 2018 Nov;94:11-16. doi: 10.1016/j.neubiorev.2018.07.020. Epub 2018 Jul 31.

Ketogenic diet as a metabolic therapy for mood disorders: Evidence and developments.

Author information

1
Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada; Department of Psychiatry, Federal University of São Paulo (Unifesp), São Paulo, Brazil. Electronic address: elisa.brietzke@unifesp.br.
2
Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada.
3
Unitat Docent de Psiquiatria i Psicologia Mèdica, Departament de Medicina, Universitat de València, Valencia Unitat de Salut Mental de Catarroja, Valencia Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto Carlos III, Madrid International Society for Nutritional Psychiatry Research (ISNPR), Spain.
4
Psychiatric Centre Copenhagen, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
5
Hospital Universitario de Alava-Santiago, CIBERSAM, EHU, Vitoria, Spain.
6
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Psychological Medicine, National University Health System, Singapore, Singapore.
7
Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto, Toronto, Canada; Brain and Cognition Discovery Foundation (BCDF), Toronto, Canada.

Abstract

Despite significant advances in pharmacological and non-pharmacological treatments, mood disorders remain a significant source of mental capital loss, with high rates of treatment resistance, requiring a coordinated effort in investigation and development of efficient, tolerable and accessible novel interventions. Ketogenic diet (KD) is a low-carb diet that substantially changes the energetic matrix of the body including the brain. It has been established as an effective anticonvulsant treatment, and more recently, the role of KD for mental disorders has been explored. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including but not limited to, glutamate/GABA transmission, monoamine levels, mitochondrial function and biogenesis, neurotrophism, oxidative stress, insulin dysfunction and inflammation. Preclinical studies, case reports and case series have demonstrated antidepressant and mood stabilizing effects of KD, however, to date, no clinical trials for depression or bipolar disorder have been conducted. Because of its potential pleiotropic benefits, KD should be considered as a promising intervention in research in mood disorder therapeutics, especially in treatment resistant presentations.

KEYWORDS:

Bipolar disorder; Ketogenic diet; Ketones; Major depressive disorders; Metabolic syndrome; Mood disorders

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