Ma. Puchowicz et al., Dog model of therapeutic, ketosis induced by oral administration of R,S-1,3-butanediol diacetoacetate, J NUTR BIOC, 11(5), 2000, pp. 281-287
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.