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

Abstract

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.