Different calorie restriction treatments have similar anti-seizure efficacy

PURPOSE Previous studies showed that a single oral administration of a synthetic ketone ester (1,3-butanediol acetoacetate diester, BD-AcAc2) could elevate blood ketones with promising acute anti-epileptic effects. The aim of the present work was to evaluate the tolerability of a prolonged administration of BD-AcAc2 and the anti-epileptic efficacy of such treatment. METHODS The threshold for seizure induction with progressive intravenous infusion of pentylenetrazole (PTZ) was evaluated in anesthetized Wistar rats after a ten-day oral administration of BD-AcAc2 (gavage). The effects of this treatment were compared to those of: (1) a ten-day water gavage administration, (2) a ten-day ketogenic diet, (3) a standard rodent chow diet. RESULTS Compared to the standard diet, all other treatments produced a calorie restriction and an elevation of the seizure threshold. CONCLUSION These results indicate that supplementation with an oral synthetic ketone can have anti-seizure effects, but the formulation has to be further ameliorated to be more palatable; further studies are also needed to better understand the role played by ketone bodies alone in vivo, without any calorie restriction.