The ketogenic diet inhibits epileptogenesis in EL mice: A genetic model for idiopathic epilepsy

Purpose: The ketogenic diet (KD) is a high-fat, low-carbohydrate and -prote in diet that has been used to treat refractory seizures in children for mor e than 75 years. However, little is known about how the KD inhibits seizure s or its effects on epileptogenesis. Several animal models of epilepsy have responded favorably to KD treatment, but the KD has not been studied in an imals with a genetic predisposition to seizures. Here we studied the antiep ileptogenic effect of the KD in EL mice, an animal model for human idiopath ic epilepsy. Methods: Young male EL mice (postnatal day 30) were randomly separated into two groups fed ad libitum with either the KD (treated, n = 21) or Agway ch ow (control, n = 19). The mice were weighed and tested for seizures once pe r week for a total of 10 weeks. The effects of the KD on plasma levels of k etone bodies and glucose were analyzed at several time points throughout th e study. Associative learning was compared between treated and control anim als using a water maze. Results: KD treatment delayed seizure onset in young male EL mice by 1 mont h; however, seizure protection was transient, inasmuch as the treated and c ontrol mice experienced a similar number and intensity of seizures after 6 weeks on the diet. Plasma glucose levels and associative learning were simi lar in the treated and control groups, but the plasma beta-hydroxybutyrate levels were significantly higher in mice on the KD. The level of ketosis, h owever, was not predictive of seizure protection in EL mice. Conclusion: The KD delayed seizure onset in EL mice, suggesting a transient protection against epileptogenesis. The KD did not influence plasma glucos e levels or associative learning. Therefore, the EL mouse may serve as a go od model to study the antiepileptogenic mechanisms of the KD.