Higher ketogenic diet ratios confer protection from seizures without neurotoxicity

The present study was designed to establish a dose-response relationship fo r the efficacy of the ketogenic diet (KD). Sprague-Dawley rats were fed ket ogenic diets containing varying ratios of fats; (carbohydrates + proteins) whereas control animals were fed rodent chow. Unless otherwise indicated, a ll animals were fed calorie-restricted, isocaloric diets beginning at P37 a nd ketonemia, seizure threshold and neurotoxic effects were determined. Des pite being provided isocaloric quantities, animals fed lower ketogenic rati os gained weight relative to those fed diets having greater proportions of fats. A significantly increased metabolic rate was noted for animals fed a high-fat diet, suggesting a basis for the weight differences. Results also showed that the animals fed calorie-restricted high-fat diets exhibited sig nificant ketonemia and protection from pentylenetetrazole (PTZ)-induced sei zures. There were no detectable neurotoxic effects for any diet group. For animals of the same age, there was no correlation between beta-hydroxybutyr ate (beta-OHB) and seizure threshold. These findings suggest that beta-OHB is not directly involved in the anticonvulsant mechanism of the diet. Also, data presented here show that the conventional 4:1 ketogenic diet does not confer the greatest level of seizure protection. We conclude that a 6:1 ke togenic diet, which shows no evidence of neurotoxicity, may be maximally ef ficacious in rats. (C) 2000 Elsevier Science B.V. All rights reserved.