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 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.
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.
aLaboratory of Psychiatric Neuroscience, Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine
bCollege of Public Health, Medical and Veterinary Science, James Cook University, Townsville, Queensland, Australia
cDepartment of Postgraduate and Continuing Education, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA
Correspondence to Zoltán Sarnyai, MD, PhD, College of Public Health, Medical and Veterinary Science, James Cook University, 1 Solander Road, Douglas, QLD 4811, Australia. Tel: +61 7 4781 6992; e-mail: email@example.com