The ketogenic diet and epilepsy.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Kim
Do Young
DY
Barrow Neurological Institute, St. Joseph's Hospital & Medical Center, Phoenix, Arizona 85013, USA. doyoung.kim@chw.edu
Rho
Jong M
JM
D050528:Diet, Carbohydrate-Restricted; D004827:Epilepsy / Q000178:diet therapy*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis*; D007662:Ketosis / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000178:diet therapy; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D007657:Ketone Bodies; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1