Mechanisms underlying the anti-epileptic efficacy of the ketogenic diet

The clinical efficacy of the ketogenic diet (KD) has now been well-document ed. However, the underlying bases of KD antiepileptic efficacy are still a matter of speculation. A number of suggestions regarding underlying mechani sms have been offered, but all require rigorous testing. Development of app ropriate animal model systems, and clear statement of experimentally testab le hypotheses, are needed. Among the general hypotheses of interest are the following: (1) the KD alters the nature, and/or degree, of energy metaboli sm in the brain - therefore altering brain excitability; (2) the KD leads t o changes in cell (neuronal and perhaps glial) properties, which decrease e xcitability and dampen epileptiform discharge; (3) the KD induces changes i n neurotransmitter function and synaptic transmission - thus altering inhib itory-excitatory balance and discouraging hyper-synchronization; (4) the KD is associated with changes in a variety of circulating factors which act a s neuromodulators that can regulate CNS excitability; and (5) the KD gives rise to alterations in brain extracellular milieu, which serve to depress e xcitability and synchrony. An understanding of the mechanism underlying KD antiepileptic efficacy will help us not only to optimize the clinical use o f the ketogenic diet, but also to develop novel antiepileptic treatments. ( C) 1999 Elsevier Science B.V. All rights reserved.