Lipid metabolism and therapy: Edited by Philip C. Calder and Richard J. DeckelbaumThe ketogenic diet and epilepsyKim, Do Young; Rho, Jong MAuthor Information Barrow Neurological Institute, St. Joseph's Hospital & Medical Center, Phoenix, Arizona USA Correspondence to Do Young Kim, DVM, PhD, Neurology Research, NRC 4th Fl., Barrow Neurological Institute and, St. Joseph's Hospital & Medical Center, 350 W. Thomas Road, Phoenix, AZ 85013, USA Tel: +1 602 406 3156; fax: +1 602 406 5779; e-mail: [email protected] Current Opinion in Clinical Nutrition and Metabolic Care: March 2008 - Volume 11 - Issue 2 - p 113-120 doi: 10.1097/MCO.0b013e3282f44c06 Buy Metrics Abstract Purpose of review The ketogenic diet has long been used to treat medically refractory epilepsy. The mechanisms underlying its clinical effects, however, have remained a mystery. The evidence to date suggests that a fundamental shift from glycolysis to intermediary metabolism induced by the ketogenic diet is necessary and sufficient for clinical efficacy. This notion is supported by a growing number of studies indicating that glucose restriction, ketone bodies and polyunsaturated fatty acids may all play mechanistic roles, possibly by enhancing mitochondrial respiration and ATP production, and decreasing reactive oxygen species production. Recent findings Recent reports indicate that ketone bodies can reduce oxidative stress and that fatty acid-induced mitochondrial uncoupling may also yield similar protective effects. Ketone bodies may attenuate spontaneous firing of ATP-sensitive potassium channels in central neurons, and pharmacological inhibition of glycolysis has been shown to retard epileptogenesis in a rat kindling model. Summary While the mechanisms underlying the broad clinical efficacy of the ketogenic diet remain unclear, there is growing evidence that the ketogenic diet alters the fundamental biochemistry of neurons in a manner that not only inhibits neuronal hyperexcitability but also induces a protective effect. Thus, the ketogenic diet may ultimately be useful in the treatment of a variety of neurological disorders. © 2008 Lippincott Williams & Wilkins, Inc.