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 epilepsy to help control seizures by inducing a permanent state of ketosis. Esters of ketone bodies have been previously studied for their potential as parent eral and enteral nutrients. We tested in conscious dogs whether ketosis cou ld be induced by repeated ingestion of R,S-1,3-butanediol diacetoacetate wi th or without carbohydrates. This ester is a water-soluble precursor of ket one bodies. Two constraints were imposed on this preclinical study: The rat e of ester administration was limited to one half of the daily caloric requ irement and to one half of the liver to oxidize butanediol derived from est er hydrolysis. Under these conditions, the level of ketosis achieved in thi s dog model (0.8 mM) was lower than the level measured in children whose se izures were controlled by the ketogenic diet (1-3 mM). However, because hum ans may have a lower capacity for ketone body utilization than dogs, the do ses of R,S-butanediol diacetoacetate used in the present study might induce higher average ketone body concentrations in humans than in dogs. (C) Else vier Science Inc. 2000. All rights reserved.