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

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.