Ketogenic Therapy (KT) is a high fat, adequate protein, low carbohydrate diet used in the treatment of intractable epilepsy. Alterations in metabolism during KT result in seizure improvement. The literature is contradictory concerning possible adverse effects of KT on blood lipids and growth. During therapy, orally-fed patients usually receive a diet high in saturated fatty acids and tube-fed patients usually receive a diet high in omega 6 fatty acids. Preliminary analysis evaluating the incorporation of a balanced fatty acid profile found there were significant positive effects on blood lipids. A high fat diet could also alter the acylcarnitine profile due to carnitine’s major role in fatty acid metabolism. During starvation and fat loading, conditions similar to KT, the proportion of carnitine that is acetylated significantly increases. Additionally, acetyl-l-carnitine (ALC) has been shown to be neuroprotective. Monitoring of the acylcarnitine profile, specifically ALC, in patients on KT may be important in understanding mechanism of action.

Retrospective analysis was performed on the KT population at Shands to evaluate changes in growth and lipids. A prospective study was conducted in the General Clinical Research Center to more closely evaluate growth and blood lipids and to monitor changes in the acylcarnitine and metabolomic profile. A meal challenge test was performed to test changes in metabolites after ingestion of a keto meal.

Results indicate type of fat to be more important than amount of fat for increasing the risk of dyslipidemia in patients receiving KT. Children treated with the KT show significant changes in height over time and ambulation status is important in growth and energy needs. Overall, betahydroxybutyrate and glucose are maintained relatively constant. Stabilization of energy metabolism and an increase in ALC may be important in mechanism of action against seizures. An intervention with a balanced fat blend to improve dyslipidemia, indirect calorimetry for optimization of calorie needs to improve growth, and ALC supplementation to enhance alterations in metabolism induced by KT was designed based on these data in order to improve the health and/or efficacy of therapy. A system for use of metabolomics in this population to further understand mechanism was developed.