*Result*: Kinetics, tolerability and safety of (R)-1,3-butanediol (S)-lactate ester (LaKe): A randomized controlled cross-over trial in adults with obesity.

Title:
Kinetics, tolerability and safety of (R)-1,3-butanediol (S)-lactate ester (LaKe): A randomized controlled cross-over trial in adults with obesity.
Authors:
Kjær SK; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus Univeristy, Aarhus, Denmark. Electronic address: simkjr@clin.au.dk., Rittig N; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus Univeristy, Aarhus, Denmark., Bruun JM; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus Univeristy, Aarhus, Denmark., Møller N; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus Univeristy, Aarhus, Denmark., Svart M; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus Univeristy, Aarhus, Denmark; Department of Internal Medicine, Regional Hospital Horsens, Horsens, Denmark.
Source:
Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2026 Feb; Vol. 165, pp. 106013. Date of Electronic Publication: 2025 Dec 12.
Publication Type:
Journal Article; Randomized Controlled Trial
Language:
English
Journal Info:
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8214983 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0295 (Electronic) Linking ISSN: 02732300 NLM ISO Abbreviation: Regul Toxicol Pharmacol Subsets: MEDLINE
Imprint Name(s):
Publication: <2003>- : Amsterdam : Elsevier
Original Publication: New York : Academic Press, [c1981-
Contributed Indexing:
Keywords: Esters; Humans: concentrations; Ketones; Lactate; Tolerability; pH
Substance Nomenclature:
0 (Butylene Glycols)
3XUS85K0RA (1,3-butylene glycol)
0 (Lactates)
33X04XA5AT (Lactic Acid)
Entry Date(s):
Date Created: 20251214 Date Completed: 20251226 Latest Revision: 20260112
Update Code:
20260130
DOI:
10.1016/j.yrtph.2025.106013
PMID:
41391659
Database:
MEDLINE

*Further Information*

*Hyperketonemia and hyperlactatemia can be induced by exogenous supplementation of each individual compound. In this study we examined the safety profile of (R)-1,3-butanediol (S)-lactate ester, a new lactate-ketone ester (LaKe). We hypothesized that 4 weeks of LaKe supplementation would induce hyperketonemia, hyperlactatemia, be feasible, tolerable, and safe. In this randomized, double-blind, placebo-controlled cross-over study, otherwise healthy adults with obesity (N = 10) received 25 mL (∼27.75 g) LaKe or taste-matched non-caloric placebo twice daily for 28 days, followed by an additional dose in a laboratory setting on day 29 with fasting and continuous blood sampling. Compliance was ≥80 % with no dropouts. 28 days of LaKe consumption was overall well tolerated but associated with mild to moderate gastrointestinal side effects without affecting organ function biomarkers. Following a 25 mL dose of LaKe, beta-hydroxybutyrate (βHB) and lactate concentrations peaked at 0.6 mmol/L (IQR 0.5-0.675 mmol/L) and 2.15 mmol (IQR 1.5-2.65 mmol/L), respectively, while blood gases and and electrolytes remained within normal ranges. LaKe elevates blood concentrations of both βHB and lactate. The consumption of LaKe twice daily for 28 days is well tolerated and safe, although associated with mild to moderate gastrointestinal side effects.
(Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)*

*Declaration of competing interest N. Møller is inventor on a patent related to LaKe and co-founder in Mmimetika Biosciences ApS that hold the commercial rights to exploit this patent. The other authers report no conflicts.*