Identifying the Molecular Mechanism of the MCT (Ketogenic) Diet

Abstract

AbstractThe medium-chain triglyceride (MCT) ketogenic diet is a highly effective and commonly used approach for treating drug-resistant epilepsy. Due to the restrictive nature of the diet and compliance issues, it is mainly used in children. The diet is associated with elevated levels of ketone bodies and two MCT-derived fatty acids, decanoic and octanoic acid. The therapeutic role for decanoic acid and a range of novel related chemicals has been shown in seizure control in multiple acute in vitro and in vivo models. Furthermore, a principal mechanism of decanoic acid has been shown to be through direct inhibition of AMPA receptors, a key excitatory neurotransmitter receptor widely recognized as a therapeutic target for seizure control. These data suggest that a therapeutic mechanism of action of the MCT ketogenic diet may be through a direct fatty acid-dependent mechanism, independent of ketosis. This discovery will enable the development of an improved and, potentially, better-tolerated diet and the generation of a corresponding pharmaceutical approach. Thus, the MCT ketogenic diet should be more correctly termed the MCT diet, because the ketosis may not be necessary for seizure control.