The ketogenic diet for the treatment of epilepsy: a challenge for nutritional neuroscientists

The ketogenic diet (KD) is a high-fat, low-carbohydrate, adequate-protein diet that has been used for more than eight decades for the treatment of refractory epilepsy in children. Despite this long history, the mechanisms by which the KD exerts its anti-seizure action are not fully understood. Questions remain regarding several aspects of KD action, including its effects on brain biochemistry and energetics, neuronal membrane function and cellular network behavior. With the explosion of the KD use in the last 10 years, it is now imperative that we understand these factors in greater detail, in order to optimize the formulation, administration and fine-tuning of the diet. This review discusses what is known and what remains to be learned about the KD, with emphasis on clinical questions that can be approached in the laboratory. We encourage scientists with a primary interest in nutritional neuroscience to join with those of us in the epilepsy research community to address these urgent questions, for the benefit of children ravaged by intractable seizures.