Effects of ketogenic diets and ketone supplementation on the nervous system during development: Applications to autism spectrum disorders and schizophrenia

Schizophrenia and autism spectrum disorders (ASD) are among the neurodevelopmental disorders that have recently been conceptualized as disorders of brain energy metabolism. A variety of pathophysiological mechanisms might concur to the development of the disorders, to include altered brain glucose metabolism resulting in inefficient processing of glucose as the primary source of metabolic energy (ATP) via glycolysis as well as the abnormal functioning of the mitochondria. The ketogenic diet is a very low-carbohydrate, high-protein, and high-fat diet that induces a physiological state of ketosis in humans and other mammals. In the absence of glycolysis, ketone bodies enter the neural cell metabolism to produce ATP via the TCA cycle and might thus act as an alternative energy substrate. Preliminary data from preclinical and human studies confirm a measurable effect of dietary interventions to re-establish efficient brain energy metabolism.