How does the ketogenic diet work? Four potential mechanisms

J Child Neurol. 2013 Aug;28(8):1027-33. doi: 10.1177/0883073813487598. Epub 2013 May 13.


The ketogenic diet and its newer variants are clinically useful in treating epilepsy. They can also have antiepileptogenic properties and can eventually have a role in treating other neurologic and nonneurologic conditions. Despite being nearly a century old, identifying the molecular underpinnings of the ketogenic diet has been challenging. However, recent studies provide experimental evidence for 4 distinct mechanisms that could contribute to the antiseizure and other beneficial effects of these diets. These mechanisms include carbohydrate reduction, activation of adenosine triphosphate (ATP)-sensitive potassium channels by mitochondrial metabolism, inhibition of the mammalian target of rapamycin pathway, and inhibition of glutamatergic excitatory synaptic transmission.

Keywords: ATP-sensitive K channel; Seizure; epilepsy; glucose; ketogenic diet; mammalian target of rapamycin; mechanism of action; vesicular glutamate transporters.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, Carbohydrate-Restricted
  • Diet, Ketogenic / methods*
  • Epilepsy / diet therapy*
  • Epilepsy / metabolism*
  • Humans
  • Potassium Channels
  • Synaptic Transmission / physiology


  • Potassium Channels