The American Journal of Clinical Nutrition · Nov 2026

(R)-1,3-butanediol (S)-lactate ester improves insulin sensitivity, modulates appetite hormones, and reduces urea excretion: a randomized controlled crossover trial in adults with obesity

By Kjær SK, Svart M, Bülow Pedersen MG et al.

Background Lactate and ketone bodies, such as (R)-β-hydroxybutyrate (βHB), are central to metabolic regulation, serving as important energy intermediates and signaling molecules. The molecule (R)-1,3-butanediol (S)-lactate ester (LaKe) is a new supplement that offers dual supplementation of lactate and βHB. Objectives This study aims to evaluate whether 28 d of LaKe supplementation followed by acute dosing would 1) improve insulin sensitivity and 2) influence appetite-regulating hormones, gastric emptying, substrate metabolism, and body weight. Methods In this randomized, double-blind, placebo-controlled crossover trial, 10 adults (males = 5, females = 5) with obesity consumed 25 mL (27.75 g) LaKe or noncaloric placebo twice daily for 28 d. Fasting blood and anthropometric measurements were obtained after each intervention period. Participants then ingested an additional dose of the assigned intervention, followed by 4-h serial blood sampling. Gastric emptying and lipolysis were assessed using an oral acetaminophen test and infusion of [9,10-³H] palmitate, respectively. Urea excretion rate was measured over 3 h. Whole-body insulin sensitivity (primary endpoint) was assessed using a hyperinsulinemic euglycemic clamp. Data were analyzed using linear mixed-effects models. Results Compared with placebo, LaKe increased βHB and lactate concentrations and improved insulin sensitivity by 28% [M value: 4.57 compared with 3.58 mg/kg lean body mass/min; pairwise difference: 1.00 (95% confidence interval: 0.28, 1.72) mg/kg lean body mass/min; P = 0.012]. LaKe consumption increased glucagon-like peptide-1, lowered ghrelin concentrations, delayed gastric emptying, reduced lipolysis (all P < 0.001), and decreased urea excretion rate (P = 0.037). Body weight was not affected by interventions, but participants increased their fat mass (P = 0.021). Conclusions Acute LaKe ingestion after 28 d of twice-daily supplementation enhanced whole-body insulin sensitivity, modulated appetite-regulating hormones, and lowered urea excretion, supporting its practical applicability and potential clinical application in the treatment and prevention of metabolic conditions. This trial was registered at www.clinicaltrial.gov as NCT05917873.

doi.org/10.1016/j.ajcnut.2026.101547 Open access Interventions