To elucidate the possible significance of ketone bodies in the mechanism of the ketogenic diet, researchers at Washington University School of Medicine, St Louis, MO, examined the effect of B-hydroxybutyrate and acetoacetate on excitatory and inhibitory synaptic transmission and spontaneous seizures in rat hippocampal slices and cultured hippocampal neurons. Ketone bodies had no effect on synaptic transmission in these models, and the hypothesis that ketone production is involved in the anticonvulsant action of the diet was not substantiated. 
COMMENT. Stafstrom CE and Spencer S, in an editorial comment, suggest that further studies on the possible anticonvulsant effects of ketones should be conducted in animals of different ages and after chronic ketogenic diet treatment . Perhaps further studies involving electrolyte changes induced by the diet would be more productive.
An electrolyte balance study in children with absence seizures treated with the ketogenic diet showed decreases in the blood pH, PC02, and standard bicarbonate during ketosis . The urinary excretion of electrolytes was increased and particularly that of calcium, magnesium and sodium, resulting in a negative balance of sodium, potassium, calcium, magnesium, phosphorus and nitrogen. The anticonvulsant action of the ketogenic diet was unrelated to diuresis, independent of acidosis, and was correlated with an increased urinary excretion and a negative balance of sodium and potassium, electrolytes known to affect the seizure threshold. Further reports of the mechanism of the diet are reviewed.