Different calorie restriction treatments have similar anti-seizure efficacy

Seizure. 2016 Feb;35:45-9. doi: 10.1016/j.seizure.2016.01.003. Epub 2016 Jan 7.


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.

Keywords: Calorie restriction; Ketogenic diet; Seizure; Synthetic ketone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Anticonvulsants / therapeutic use
  • Blood Glucose / drug effects
  • Blood Glucose / physiology
  • Body Weight / drug effects
  • Body Weight / physiology
  • Butylene Glycols / administration & dosage
  • Butylene Glycols / blood
  • Caloric Restriction / methods*
  • Convulsants / toxicity
  • Diet, Ketogenic / methods
  • Disease Models, Animal
  • Drug Administration Schedule
  • Electroencephalography
  • Male
  • Medulla Oblongata / pathology
  • Medulla Oblongata / ultrastructure
  • Microscopy, Electron, Scanning
  • Pentylenetetrazole / toxicity
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / therapy*
  • Treatment Outcome*


  • Anticonvulsants
  • Blood Glucose
  • Butylene Glycols
  • Convulsants
  • 1,3-butylene glycol
  • Pentylenetetrazole