The ketogenic diet: 1997

There has been a dramatic resurgence of interest in the ketogenic diet during the past several years. For many children with difficult-to-control epilepsy, the diet presents an alternative approach to trying multiple medications. The ketogenic diet's current success rate, when properly executed, greatly exceeds that of the medications which have recently become available. Its side effects, both cognitive and allergic, appear fewer than most available medications. The ketogenic diet is also cheaper than most new anticonvulsants. Even though we now know that the diet works, we still do not know how it works. Nor do we know how most anticonvulsants work. The mechanism of action of the ketogenic diet appears to rely on a fundamental change in the brain's metabolism from that of a glucose-based energy substrate to a ketone-based substrate. This change is, in some fashion, critical to the maintenance of seizure threshold. Why should the source of the energy make a difference in seizure threshold? The change in seizure threshold appears to occur without affecting the brain's ability to carry out its normal complex functions. Could the brain's utilization of an energy substrate for seizure control be different from its utilization of energy for normal brain function? If so it should it be possible to study the metabolic differences between the two and develop a biochemistry of epilepsy, which is differentiated from the biochemistry of normal cognition and function. The ketogenic diet is successful in controlling or ameliorating a broad spectrum of seizure types and etiologies. Perhaps then, common metabolic pathways, independent of seizure type, are used in the initiation and spread of electrical seizures. Based on clinical experience and limited research data, it would appear that different seizures and different epilepsies must have metabolic pathways in common that make them susceptible to treatment with a common metabolic therapy. If we could understand how the ketogenic diet "works," how changing from a glucose substrate' to a ketone body substrate is anticonvulsant, then perhaps a medication could be developed that would simulate the biochemical effects of the ketogenic diet. Such an approach would be a major departure in the study of the neuroscience of epilepsy. The ketogenic diet offers a new paradigm to think about epilepsy and its treatment, and perhaps will stimulate new approaches to this still often devastating condition.