The intracellular pH of the cerebral cortex was studied by the neutral red method in 15 adult rats maintained on ketogenic and control diets for 5-6 weeks. Rats fed the ketogenic diet had more than a 10-fold increase in plasma ketones, but no significant differences in cerebral pH or in cerebral metabolites and GABA levels were noted. The antiepileptic effect of the ketogenic diet was probably not mediated by cerebral acidosis or changes in cerebral GABA levels. [1]

COMMENT. The ketogenic diet used in the treatment of some forms of epilepsy in childhood was originally introduced at the Mayo Clinic [2], not at Johns Hopkins University, as some recent media publicity would have us believe. Furthermore, some of the earlier work relating to the mechanism of action of the ketogenic diet, not cited in the above paper, also originated at the Mayo Clinic [3]. Seizure susceptibility was not modified by a fat diet in normal animals, but an anticonvulsant effect was demonstrated in mice with a seizure threshold lowered by water intoxication and hypoelectrolytemia. In animals and in patients with absence seizures, the anticonvulsant effect of the ketogenic diet was unrelated to diuresis, independent of acidosis and ketosis, similar to the effects of acetazolamide, and correlated most closely with a negative balance of sodium and potassium.