title: Different calorie restriction treatments have similar anti-seizure efficacy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department Medicine and Surgery, University of Salerno, via Allende snc, Baronissi (SA), Italy. Electronic address: aviggiano@unisa.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Viggiano
authors.affiliation: Department of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 8 Tampa, FL, United States; External Pharmacy of Fatebenefratelli Hospital, Viale Principe di Napoli 14/A, Benevento, Italy. Electronic address: raf.pilla@gmail.com.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pilla
authors.affiliation: Savind, Inc., Seymour, IL, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Arnold
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Italy. Electronic address: marcellino.monda@unina2.it.
authors.forename: Marcellino
authors.initials: M
authors.lastname: Monda
authors.affiliation: Department of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 8 Tampa, FL, United States. Electronic address: ddagosti@health.usf.edu.
authors.forename: Dominic
authors.initials: D
authors.lastname: D'Agostino
authors.affiliation: Department Medicine and Surgery, University of Salerno, via Allende snc, Baronissi (SA), Italy.
authors.forename: Pio
authors.initials: P
authors.lastname: Zeppa
authors.affiliation: Department Medicine and Surgery, University of Salerno, via Allende snc, Baronissi (SA), Italy; UO Child and Adolescent Neuropsychiatry, Medical School, University of Salerno, Largo Città di Ippocrate snc, Salerno, Italy.
authors.forename: Giangennaro
authors.initials: G
authors.lastname: Coppola
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002072:Butylene Glycols / Q000008:administration & dosage / Q000097:blood; D031204:Caloric Restriction / Q000379:methods*; D003292:Convulsants / Q000633:toxicity; D055423:Diet, Ketogenic / Q000379:methods; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004569:Electroencephalography; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D001786:Blood Glucose; D002072:Butylene Glycols; D003292:Convulsants; C028491:1,3-butylene glycol; D010433:Pentylenetetrazole
keywords: Calorie restriction; Ketogenic diet; Seizure; Synthetic ketone