A ketogenic diet increases the resistance to pentylenetetrazole-induced seizures in the rat.

Abstract

The purpose of this study was to test the hypothesis that a ketogenic diet would increase the resistance of rats to pentylenetetrazole (PTZ)-induced seizures and to understand the relation of ketonemia to seizure resistance. A freely consumed, high-fat (ketogenic) diet was administered to male Sprague-Dawley rats for 5-10 weeks, while control animals were fed either rodent chow or a high-carbohydrate diet. Ketonemia was measured as plasma levels of beta-hydroxybutyric acid (beta-OHB). Seizures were induced by tail-vein infusion of pentylenetetrazole. The ketogenic diet produced a highly significant (p<0.01) increase in beta-OHB levels within 5 days. Induction of seizures by PTZ 35 days after animals were placed on their respective diets showed that ketogenic animals had a significantly (p<0.01) increased threshold for seizure induction compared with those fed an isocaloric diet of either high-carbohydrate or normal rodent chow. Ketogenic animals did not exhibit increased seizure severity relative to controls, despite receiving consistently higher doses of PTZ. The ketogenic diet resulted in an increased seizure threshold, confirming the hypothesis, and seizure threshold was found to be a direct function of the level of ketonemia.