title: Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate.
abstract: (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester) has been developed as an oral source of ketones, which may be utilized for energy. In a 28-day toxicity study, Crl:WI (Wistar) rats received diets containing, as 30% of the calories, ketone monoester (12 and 15 g/kg body weight/day for male and female rats, respectively). Control groups received either carbohydrate- or fat-based diets. Rats in the test group consumed less feed and gained less weight than control animals; similar findings have been documented in studies of ketogenic diets. Between-group differences were noted in selected hematology, coagulation, and serum chemistry parameters; however, values were within normal physiological ranges and/or were not accompanied by other changes indicative of toxicity. Upon gross and microscopic evaluation, there were no findings associated with the ketone monoester. In a developmental toxicity study, pregnant Crl:WI (Han) rats were administered 2g/kg body weight/day ketone monoester or water (control) via gavage on days 6 through 20 of gestation. No Caesarean-sectioning or litter parameters were affected by the test article. The overall incidence of fetal alterations was higher in the test group; however, there were no specific alterations attributable to the test substance. The results of these studies support the safety of ketone monoester.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. kieran.clarke@dpag.ox.ac.uk
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.forename: Kirill
authors.initials: K
authors.lastname: Tchabanenko
authors.forename: Robert
authors.initials: R
authors.lastname: Pawlosky
authors.forename: Emma
authors.initials: E
authors.lastname: Carter
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Knight
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murray
authors.forename: Lowri E
authors.initials: LE
authors.lastname: Cochlin
authors.forename: M Todd
authors.initials: MT
authors.lastname: King
authors.forename: Andrea W
authors.initials: AW
authors.lastname: Wong
authors.forename: Ashley
authors.initials: A
authors.lastname: Roberts
authors.forename: Jeremy
authors.initials: J
authors.lastname: Robertson
authors.forename: Richard L
authors.initials: RL
authors.lastname: Veech
mesh_terms: D000818:Animals; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake; D004734:Energy Metabolism / Q000187:drug effects; D004952:Esters; D005260:Female; D006885:Hydroxybutyrates / Q000378:metabolism / Q000633:toxicity*; D007659:Ketones / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D059551:Toxicity Tests, Subacute
chemical_list: C576699:(R)-3-hydroxybutyl (R)-3-hydroxybutyrate; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004952:Esters; D006885:Hydroxybutyrates; D007659:Ketones