Anticonvulsant mechanisms of the ketogenic diet and caloric restriction

Many treatments have been proposed to control epileptic seizures, such as the ketogenic diet and caloric restriction. However, seizure control has not yet been improved completely in all patients. Probably, due to the lack of understanding regarding this neurological disorder pathogenesis or pathophysiology, including its molecular approach. Currently, there is not much information about the molecular processes and genes involved, and their relation to the possible beneficial effects of diet therapy on epilepsy. The ketogenic diet and caloric restriction are implicated in potential anti-seizure mechanisms related to the gut microbiome, metabolic pathways, hormones and neurotransmitters, mitochondria improvement, a role in inflammation, and oxidative stress, among others. In this review, we pretend to describe the molecular mechanism and the possible genes involved in the different ketogenic diet and caloric restriction mechanisms of action described to decrease neural excitability and, therefore, epileptic seizures, especially when conventional treatment is not enough to achieve control of epilepsy.