Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects.
Level 3 - non-randomized controlled study
Non-randomized phase 1 pharmacokinetic and safety trial in healthy volunteers
PubMed 22561291 · doi:10.1016/j.yrtph.2012.04.008
What was done
Healthy adult volunteers were administered the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in a meal-replacement drink. Pharmacokinetic parameters were evaluated after single doses of 140, 357, or 714 mg/kg body weight. Safety and tolerability were assessed following repeated dosing at the same dose levels given three times daily for 5 days (total daily intake of 0.42, 1.07, and 2.14 g/kg/day).
What was found
Single doses rapidly elevated blood ketones, reaching peak plasma concentrations within 1–2 hours of 3.30 mM for β-hydroxybutyrate and 1.19 mM for acetoacetate at the highest dose (714 mg/kg). Intact ester was not detected in plasma. Elimination half-lives were 0.8–3.1 hours for β-hydroxybutyrate and 8–14 hours for acetoacetate. Repeated dosing over 5 days was generally well-tolerated, though gastrointestinal side effects were reported at the highest dose when large volumes of the milk-based drink were consumed.
Why it matters
This study provides foundational human pharmacokinetic and short-term safety data showing that oral ketone monoester ingestion can rapidly induce acute nutritional ketosis without the dietary restriction of a ketogenic diet.
Limits
The abstract does not state the total sample size (n), participant sex/age demographics, or whether a placebo control group was used. Dosing duration was limited to 5 days, precluding assessment of chronic safety, and gastrointestinal adverse events occurred at high doses.
Cited by
- context Exogenous ketone ester supplementation was originally investigated and developed for preventing central nervous system oxygen toxicity.