LAUSR

A high-fat diet with appropriate protein and low carbohydrate content, widely known as the ketogenic diet (KD), is considered as an effective non-pharmacotherapeutic treatment option for certain types of epilepsies. Several preclinical and clinical studies have been carried out to elucidate its mechanism of antiepileptic action. Ketone bodies produced after KD's breakdown interacts with cellular excito-inhibitory processes and inhibits abnormal neuronal firing. The generated ketone bodies decrease glutamate release by inhibiting the Vesicular glutamate transporter 1 and alters the transmembrane potential by hyperpolarization. Apart from their effect on the well-known pathogenic mechanisms of epilepsy, some recent studies have shown the interaction of KD metabolites with novel neuronal targets, particularly adenosine receptors, adenosine triphosphate sensitive potassium channel, mammalian target of rapamycin, histone deacetylase, hydroxycarboxylic acid receptors, and the NLR family pyrin domain containing 3 inflammasome to suppress seizures. The role of KD in augmenting gut microbiota as a potential mechanism in epileptic seizures suppression has been established. Furthermore, some recent findings also support the beneficial effect of KD against epilepsy-associated comorbidities. Despite several advantages of the KD in epilepsy management, its use is also associated with a wide range of side effects. Hypoglycemia, excessive ketosis, acidosis, renal stones, cardiomyopathies, and other metabolic disturbances are the primary adverse effects observed with the use of KD. However, in some recent studies, modified KD has been tested with lesser side effects and better tolerability. The present review discusses the molecular mechanism of KD and its role in managing epilepsy and its associated comorbidities.