Metabolic Dysfunctions in Epilepsy and Novel Metabolic Treatment Approaches

Abstract

Growing evidence suggests that dysfunction of metabolic processes such as glycolysis and the tricarboxylic acid (TCA) cycle in the brain plays an important role in the pathophysiology of epilepsy. Supplementation of compounds that enhance energy production has been shown to provide protection against seizures and/or associated damage in rodent seizure models in vivo. Therefore, metabolic treatments appear to be promising alternative approaches for epilepsy. Current dietary approaches such as the ketogenic diet (KD) and modified Atkins diet (MAD) are primarily effective in children, but the KD is unsuitable as a long-term treatment for adults. Potential metabolic treatment approaches include medium-chain fatty acids, TCA-cycle substrates, and triheptanoin. The mechanisms of action underlying the anticonvulsant effects of these substrates remain to be elucidated but possibly include inhibition of glycolysis (medium-chain fats) and fast β-oxidation of medium-chain fats, which is independent from transporters and/or replenishment of the TCA cycle (anaplerosis–triheptanoin).