Ketonemia and Seizures: Metabolic and Anticonvulsant Effects of Two Ketogenic Diets in Childhood Epilepsy

Abstract

Extract: Metabolic effects of a new ketogenic regimen in which ketonemia is induced by feeding of medium chain triglycerides (MCT) are described, and comparisons are made with effects of the standard high fat ketogenic diet. Eighteen children maintained on the MCT diet for 3 months to 4 years failed to show elevations of serum cholesterol and had only a slight rise in serum total fatty acids, in contrast to the marked hyperlipidemia observed in children on the standard high fat diet. Long term use of the MCT diet did not affect pH of venous blood. Blood glucose fell below 50 mg/100 ml in one-third of the children, the lowest levels being reached 2–3 weeks after the start of the diet. Plasma D(–)-β-hydroxybutyrate (BHB) and acetoacetate rose gradually after institution of diet therapy, maximum levels being reached after about 1 month. Higher levels of BHB and acetoacetate were achieved in children under the age of 10 years (BHB = 4.3 mM ± 0.6 SEM, acetoacetate = 1.8 mM ± 0.3 SEM) than in 10–18 year olds (BHB = 1.6 mM ± 0.2 SEM, acetoacetate = 0.57 mM ± 0.08 SEM). Plasma BHB and acetoacetate levels in children maintained on a 3:1 high fat diet were similar to those in children on a 60% MCT diet. Plasma levels of BHB showed a significant correlation with anticonvulsant effect (P < 0.02). Both the ketonemia and the anticonvulsant action were reversed rapidly by intravenous infusion of glucose.

Speculation: The anticonvulsant effect of the standard ketogenic diet and of the MCT diet are dependent upon maintenance of blood levels of BHB above 2 mM and of acetoacetate above 0.6 mM. The data suggest that one or both of these compounds either have direct anticonvulsant effects or produce rapidly reversible changes in cerebral metabolism, which in turn affect cerebral excitability.