Ketogenic Diet for Schizophrenia: Clinical Implication

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


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

In This Article

Ketogenic Diet Restores Normal Brain Glucose and Energy Metabolism

Diets rich in fat and low in carbohydrates, such as the ketogenic diet mimic the effects of fasting. The consequential reduction in circulating insulin and insulin signalling promotes a metabolic shift toward fatty acids utilization.[38] Metabolically, the ketogenic diet leads to improved insulin sensitivity, decreased blood glucose levels and weight loss.[39] β-Hydroxybutyrate (BHB), the main circulating ketone body, is fully oxidized as an energy substrate in the brain.[11] Furthermore, it inhibits histone deacetylases and upregulates genes involved in metabolic regulation, protection against oxidative stress and inflammation.[40] Ketogenic diet has already been used successfully for treatment of neurological conditions associated with abnormal energy metabolism including epilepsy, amyotrophic lateral sclerosis, traumatic brain injury and Alzheimer's disease.[41–44] More recently, application of the ketogenic diet has been found to improve core symptoms of impaired sociability, communication and repetitive behaviours in animal models of autism.[41,45,46] The beneficial effects of the ketogenic diet to normalize brain energy metabolism is achieved by circumventing glycolysis, providing alternative energy substrates in the form of ketone bodies and resetting the processes underlying glucose and energy metabolism. Furthermore, ketogenic diet has been shown to improve mitochondrial biogenesis and bioenergetics.[47,48,49] In addition, the ketogenic diet reduces glutamate toxicity, promotes GABA inhibitory tone and reduces the formation of reactive oxygen species, all of which can enhance neuronal function.[50]