How Does the Ketogenic Diet Work? Four Potential Mechanisms

Abstract

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.