Harnessing the power of metabolism for seizure prevention: focus on dietary treatments

The continued occurrence of refractory seizures in at least one-third of children and adults with epilepsy, despite the availability of almost 15 conventional and novel anticonvulsant drugs, speaks to a dire need to develop novel therapeutic approaches. Cellular metabolism, the critical pathway by which cells access and utilize energy, is essential for normal neuronal function. Furthermore, mounting evidence suggests direct links between energy metabolism and cellular excitability. The high-fat, low-carbohydrate ketogenic diet has been used as a treatment for drug-refractory epilepsy for almost a century. Yet, the multitude of alternative therapies to target aspects of cellular metabolism and hyperexcitability is almost untapped. Approaches discussed in this review offer a wide diversity of therapeutic targets that might be exploited by investigators in the search for safer and more effective epilepsy treatments.