Possible mechanism for the effect of ketogenic diet in cases of uncontrolled seizures. The reconsideration of acetone theory.

High fat and low carbohydrate diet, designated ketogenic diet, has been successfully used for the treatment of intractable epilepsy in a portion of patients, particularly in children. Several hypotheses have been worked out for the explanation of its beneficial effects, among others acetone has been raised as a causative factor. However, despite the endeavours the mode of action of the diet is still an enigma. And it is also not known why the diet is effective in some patients, while in others it is without any effect. Here a possible way for the effect of ketogenic diet is proposed in which the central point of seizure preventing effect of the diet is the metabolism of acetone. The proposal nominates S-D-lactoylglutathione, an intermediate of acetone metabolism, as a factor being responsible for seizure controlling effect of ketogenic diet and on the other hand, a sequence of evidence is given for the support of suggestion. S-D-lactoylglutathione would exert its effect by the influence of K(+) channels. The proposal also gives an explanation of why only a portion of patients benefit while on the diet. A proposition is also made for the future directions of research involving the measurement of intermediates of S-D-glutathione breakdown in the cerebrospinal fluid and clinical trials with selected groups of patients. The establishment of this specific mechanism for the ketogenic diet may lead to novel strategies for the investigation and the treatment of intractable epilepsies.