Ketogenic Diet for Schizophrenia: Clinical Implication

Zoltán Sarnyai; Ann-Katrin Kraeuter; Christopher M. Palmer

Disclosures

Curr Opin Psychiatry. 2019;32(5):394-401. 

In This Article

Abstract and Introduction

Abstract

Purpose of review: The aim of this article is to review recent findings on the efficacy of ketogenic diet in preclinical models and in patients with schizophrenia. This review will also highlight emerging evidence for compromised glucose and energy metabolism in schizophrenia, which provides a strong rationale and a potential mechanism of action for ketogenic diet.

Recent findings: Recent transcriptomic, proteomic and metabolomic evidence from postmortem prefrontal cortical samples and in-vivo NMR spectroscopy results support the hypothesis that there is a bioenergetics dysfunction characterized by abnormal glucose handling and mitochondrial dysfunctions resulting in impaired synaptic communication in the brain of people with schizophrenia. Ketogenic diet, which provides alternative fuel to glucose for bioenergetic processes in the brain, normalizes schizophrenia-like behaviours in translationally relevant pharmacological and genetic mouse models. Furthermore, recent case studies demonstrate that ketogenic diet produces improvement in psychiatric symptoms as well as metabolic dysfunctions and body composition in patients with schizophrenia.

Summary: These results support that ketogenic diet may present a novel therapeutic approach through restoring brain energy metabolism in schizophrenia. Randomized controlled clinical trials are needed to further show the efficacy of ketogenic diet as a co-treatment to manage both clinical symptoms and metabolic abnormalities inherent to the disease and resulted by antipsychotic treatment.

Introduction

Schizophrenia is a devastating neurodevelopmental disorder characterized by a complex set of symptoms, including hallucinations, delusions, stereotyped behaviours, social withdrawal and impairment in executive function and attentional processes.[1,2] The currently used atypical antipsychotics, acting primarily through D2 dopamine serotonin 2A receptors, are only partially effective in managing some, but not all, symptoms and they result in considerable side effects, such as weight gain, metabolic syndrome and cardiovascular consequences that result in shortened life expectancy.[1] Unfortunately, these side effects are related to the primary pharmacological mechanism of action, making it difficult to introduce novel compounds without identifying alternative targets. The development of new, more effective pharmacological treatment is hampered by our limited understanding of the disease pathophysiology and the resulting lack of novel drug targets.[3] Recent conceptualization of disease mechanism includes alterations in brain glutamatergic neurotransmission,[4,5] systemic and central pro-inflammatory processes,[6,7] and impaired systemic and cerebral energy metabolism.[6,8,9] This article reviews the accumulating evidence for impaired glucose handling and metabolism as well as other bioenergetic processes, including mitochondrial function, in the brain to provide a rationale for targeted metabolic interventions focussing on recent preclinical and clinical results of the efficacy of ketogenic diet. Moreover, we will highlight the gaps in our knowledge with regards to the efficacy and safety of a potential therapeutic ketogenic diet intervention as a co-treatment with currently used antipsychotic drugs.

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