Abstracts

Glucose uptake into the brain is greater during epileptic seizures than during most other brain activities suggesting a key role for glucose in the initiation and spread of seizure activity. Under conditions of fasting or caloric restriction (CR), however, brain cells can also derive energy from ketone bodies (acetoacetate and beta-hydroxybutyrate). Diet therapies for epilepsy are as old as the disease itself and the high fat, low carbohydrate ketogenic diet (KD) was developed as an alternative to fasting for seizure management. While the mechanisms by which KD inhibit seizures remain speculative, ketone bodies and alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR) inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a model of multifactorial idiopathic epilepsy. CR is a natural dietary therapy that involves the reduction of total dietary energy intake while maintaining adequate levels of essential vitamins and minerals. In this study, we compared the antiepileptic efficacy of the KD with that of CR in adult EL mice.
Adult EL mice (about 12 months old) that experienced at least 15 recurrent complex partial seizures were fed either a standard (chow) diet unrestricted (SD-UR) or restricted (SD-R), and either a KD unrestricted (KD-UR) or restricted (KD-R). Seizure susceptibility, body weights, and the levels of plasma glucose levels were measured once a week over an eight-week treatment period in each diet group.
Body weights and blood glucose levels remained stable over the eight-week testing period in the SD-UR and the KD-UR groups, but were significantly (p[lt] 0.001) reduced by about 25% in the SD-R and KD-R groups. Results from ketone body measurements will also be presented. Seizure susceptibility remained high in both UR diet groups, but decreased significantly (p[lt] 0.001) after two weeks in both R diet groups. Seizures were completely managed in both R groups after eight weeks of diet therapy.
The results indicate that seizure susceptibility is dependent on plasma glucose levels in EL mice fed either a SD or a KD diet and that seizure management depends more on the amount than on the origin of dietary calories. A reduction in plasma glucose levels coupled with an increase in plasma ketone levels is predicted to control the epileptic seizures in EL mice.
[Supported by: NIH grant (HD39722), and the Boston College Research Expense Fund.]