Dog model of therapeutic ketosis induced by oral administration of R, S-1,3-butanediol diacetoacetate

Michelle Puchowicz, Chris L. Smith, Catherine Bomont, John Koshy, France David, Henri Brunengraber

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A high-fat, almost carbohydrate-free diet is used in children with intractable epilepsy to help control seizures by inducing a permanent state of ketosis. Esters of ketone bodies have been previously studied for their potential as parenteral and enteral nutrients. We tested in conscious dogs whether ketosis could be induced by repeated ingestion of R, S-1,3-butanediol diacetoacetate with or without carbohydrates. This ester is a water-soluble precursor of ketone bodies. Two constraints were imposed on this preclinical study: The rate of ester administration was limited to one half of the daily caloric requirement and to one half of the capacity of the liver to oxidize butanediol derived from ester hydrolysis. Under these conditions, the level of ketosis achieved in this dog model (0.8 mM) was lower than the level measured in children whose seizures were controlled by the ketogenic diet (1-3 mM). However, because humans may have a lower capacity for ketone body utilization than dogs, the doses of R, S-butanediol diacetoacetate used in the present study might induce higher average ketone body concentrations in humans than in dogs.

Original languageEnglish (US)
Pages (from-to)281-287
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume11
Issue number5
DOIs
StatePublished - Jan 1 2000

Fingerprint

Ketone Bodies
Ketosis
Oral Administration
Esters
Dogs
Butylene Glycols
Nutrition
Seizures
Carbohydrates
Ketogenic Diet
Therapeutics
Liver
Nutrients
Small Intestine
Hydrolysis
Eating
Fats
Diet
Food
1,3-butanediol diacetoacetate

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Dog model of therapeutic ketosis induced by oral administration of R, S-1,3-butanediol diacetoacetate. / Puchowicz, Michelle; Smith, Chris L.; Bomont, Catherine; Koshy, John; David, France; Brunengraber, Henri.

In: Journal of Nutritional Biochemistry, Vol. 11, No. 5, 01.01.2000, p. 281-287.

Research output: Contribution to journalArticle

Puchowicz, Michelle ; Smith, Chris L. ; Bomont, Catherine ; Koshy, John ; David, France ; Brunengraber, Henri. / Dog model of therapeutic ketosis induced by oral administration of R, S-1,3-butanediol diacetoacetate. In: Journal of Nutritional Biochemistry. 2000 ; Vol. 11, No. 5. pp. 281-287.
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