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

Abstract

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 pathways by which cells access and utilize energy, is critical 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.

Ketogenic diets, mitochondria, and neurological diseases

“…In an initial comparison of children under 10 years of age on a 60% MCT diet with the classic 3:1 KD, circulating levels of BHB were found to be by guest, on www.jlr.org Downloaded from models of epilepsy. However, clinical studies involving CR or intermittent fasting for epilepsy have yet to be conducted ( 67 ).…”

Potent anti-seizure effects of D-leucine

“…However, the efficacy of epilepsy medications has not improved substantially in the past 50 years. One underutilized option for these patients is metabolism-based therapy (Hartman and Stafstrom, 2013), with the high-fat, low-carbohydrate ketogenic diet being the most widely used form (Hartman et al, 2007; Neal et al, 2008). However, the full benefit of the ketogenic diet is hampered by difficulties with implementation.…”

The Ketogenic Diet and its Clinical Applications in Type I and II Diabetes

“…It has been shown that metabolic-based therapies, such as nutritional ketosis, are effective to contrast seizure disorders and various acute and chronic neurological disorders [1][2][3][4]. From a physiological perspective, glucose is the primary metabolic fuel for cells.…”