title: Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects.
abstract: Induction of mild states of hyperketonemia may improve physical and cognitive performance. In this study, we determined the kinetic parameters, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone monoester administered in the form of a meal replacement drink to healthy human volunteers. Plasma levels of β-hydroxybutyrate and acetoacetate were elevated following administration of a single dose of the ketone monoester, whether at 140, 357, or 714 mg/kg body weight, while the intact ester was not detected. Maximum plasma levels of ketones were attained within 1-2h, reaching 3.30 mM and 1.19 mM for β-hydroxybutyrate and acetoacetate, respectively, at the highest dose tested. The elimination half-life ranged from 0.8-3.1h for β-hydroxybutyrate and 8-14 h for acetoacetate. The ketone monoester was also administered at 140, 357, and 714 mg/kg body weight, three times daily, over 5 days (equivalent to 0.42, 1.07, and 2.14 g/kg/d). The ketone ester was generally well-tolerated, although some gastrointestinal effects were reported, when large volumes of milk-based drink were consumed, at the highest ketone monoester dose. Together, these results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels, compared with the inconvenience of preparing and consuming a ketogenic diet.
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: M
authors.initials: M
authors.lastname: Todd King
authors.forename: Kathy
authors.initials: K
authors.lastname: Musa-Veloso
authors.forename: Manki
authors.initials: M
authors.lastname: Ho
authors.forename: Ashley
authors.initials: A
authors.lastname: Roberts
authors.forename: Jeremy
authors.initials: J
authors.lastname: Robertson
authors.forename: Theodore B
authors.initials: TB
authors.lastname: Vanitallie
authors.forename: Richard L
authors.initials: RL
authors.lastname: Veech
mesh_terms: D000293:Adolescent; D000328:Adult; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007659:Ketones / Q000097:blood*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D006885:Hydroxybutyrates; D007659:Ketones