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

Abstract

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(-)-P-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 i 0.3 SEM) than in 1@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:l 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. SpeculationThe 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.

Ketosis and Epilepsy: 31P Spectroscopic Imaging at 4.1 T

“…Earlier studies performed in patients on the diet have failed to show any specific relation between success of diet with systemic changes induced by the diet, for example, pH, electrolytes, or cholesterol (4)(5)(6). In particular, the level of serum ketones does not specifically relate to degree of seizure control, although it has been shown that with resumption of a normal diet or by a glucose infusion, there is rapid loss of seizure control (6,7). Thus although ketosis is a requirement for seizure control, it is not the defining factor.…”

The Ketogenic Diet: Proposed Mechanisms of Action

“…Unfortunately, tests did not bear it out. In clinical studies, Huttenlocher 9 showed that the ketogenic diet did not make the blood acidic, and Al-Mudallal et al 10 later showed in animal studies that the ketogenic does not change the pH of either the blood or the brain.…”

“…Glucose is still present in the blood of patients on the ketogenic diet, usually in the low normal range. 9,13 This glucose is presumably entering into the brain and being used for energy. Even after some weeks of complete starvation, fats provide only about 60% of the brain's energy supply.…”

Avaliação do perfil metabólico, nutricional e efeitos adversos de crianças com epilepsia refratária em uso da dieta cetogênica

“…Elaborou-se uma tabela de freqüência das crises epilépticas para cada paciente, confrontando-a, em seguida, com a análise da freqüência de todos os tipos de crises de cada um, realizando, assim, um estudo comparativo e, por fim, utilizaram-se os seguintes critérios de Huttenlocher 7 …”