Bis Hexanoyl (R)-1,3-Butanediol, a Novel Ketogenic Ester, Acutely Increases Circulating r- and s-ß-Hydroxybutyrate Concentrations in Healthy Adults

Background: Ketosis has been reported to benefit healthspan and resilience, which has driven considerable interest in development of exogenous ketones to induce ketosis without dietary changes. Bis hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone di-ester that can be used as a food ingredient that increases hepatic ketogenesis and blood beta-hydroxybutyrate (BHB) concentrations.

Methods: Here, we provide the first description of blood ketone and metabolite kinetics for up to five hours after consumption of a beverage containing BH-BD by healthy adults (n = 8) at rest in three randomized, cross-over conditions (25 g + Meal (FEDH); 12.5 g + Meal (FEDL) ; 25 g + Fasted (FASTH)).

Results: Consumption of BH-BD effectively raised plasma r-BHB concentrations to 0.8-1.7 mM in all conditions, and both peak r-BHB concentration and r-BHB area under the curve were greater with 25 g versus 12.5 g of BH-BD. Urinary excretion of r-BHB was <1 g. Plasma concentration of the non-physiological isoform s-BHB was increased to 20-60 µM in all conditions. BH-BD consumption decreased plasma glucose and free fatty acid concentrations; insulin was increased when BH-BD was consumed with a meal.

Conclusions: These results demonstrate that consumption of BH-BD effectively induces exogenous ketosis in healthy adults at rest.