Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodiesReportar como inadecuado

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Nutrition and Metabolism

, 1:11

First Online: 19 October 2004Received: 29 July 2004Accepted: 19 October 2004


BackgroundThe high fat, low carbohydrate ketogenic diet KD was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction CR inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted SD-UR or restricted SD-R, and either a KD unrestricted KD-UR or restricted KD-R. All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once-week over a nine-week treatment period.

ResultsBody weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly p < 0.001 reduced in the SD-R and KD-R groups. Plasma β-hydroxybutyrate levels were significantly p < 0.001 increased in the SD-R and KD-R groups compared to their respective UR groups. Seizure susceptibility remained high in both UR-fed groups throughout the study, but was significantly reduced after three weeks in both R-fed groups.

ConclusionsThe results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone bodies for energy is predicted to manage EL epileptic seizures through multiple integrated changes of inhibitory and excitatory neural systems.

Lists of abbreviationsAEDantiepileptic drug

CRcaloric restriction

KDketogenic diet


SDstandard diet


Electronic supplementary materialThe online version of this article doi:10.1186-1743-7075-1-11 contains supplementary material, which is available to authorized users.

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Autor: John G Mantis - Nicole A Centeno - Mariana T Todorova - Richard McGowan - Thomas N Seyfried


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