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

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...

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Bibliographic Details
Published in:The Journal of nutritional biochemistry 2000-05, Vol.11 (5), p.281-287
Main Authors: Puchowicz, Michelle A, Smith, Chris L, Bomont, Catherine, Koshy, John, David, France, Brunengraber, Henri
Format: Article
Language:English
Subjects:
1,3-butanediol
acetoacetate esters
Biological and medical sciences
Diseases of the nervous system
epilepsy
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
ketogenic diet
ketone bodies
Medical sciences
Nervous system (semeiology, syndromes)
Neurology
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
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Summary: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.
ISSN:0955-2863
1873-4847
DOI:10.1016/S0955-2863(00)00079-6