The Ketogenic Diet and Brain Metabolism

Glucose ordinarily is the major brain fuel. However, the consumption of a diet high in fat evokes a brisk ketonemia (1–2 mmol/l) and provides brain with substrates (3-OH-butyrate and acetoacetate) that can furnish almost half of cerebral energy requirements. Such a diet also confers a potent anti-epileptic effect, even in patients whose epilepsy has proved refractory to anti-convulsant drugs. The precise basis of the therapeutic effect is not clear, but a ketogenic diet alters brain metabolism of many compounds, including the handling of neurotransmitter amino acids such as glutamate, aspartate, glutamine and GABA. This review summarizes some of these changes and considers how such adaptations might attenuate or even prevent a seizure diathesis.