A Novel Powder Formulation of the Ketone Ester, Bis Hexanoyl (R)-1,3-Butanediol, Rapidly Increases Circulating ß-Hydroxybutyrate Concentrations in Healthy Adults

Abstract

Objective: Growing interest in the metabolic state of ketosis has driven development of exogenous ketone products to induce ketosis without dietary changes. Bis hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester which, when consumed, increases blood beta-hydroxybutyrate (BHB) concentrations. BH-BD is formulated as a powder or ready-to-drink (RTD) beverage; the relative efficacy of these formulations is unknown, but hypothesized to be equivalent.

Methods: This randomized, observer-blinded, controlled, crossover decentralized study in healthy adults (n = 15, mean age = 33.7 years, mean BMI = 23.6 kg/m²) aimed to elucidate blood BHB and glucose concentrations before and 15, 30, 45, 60, 90 and 120 minutes following two serving sizes of reconstituted BH-BD powder (POW 25 g, POW 12.5 g), compared to a RTD BH-BD beverage (RTD 12.5 g), and a non-ketogenic control, all taken with a standard meal.

Results: All BH-BD products were well tolerated and increased BHB, inducing nutritional ketosis (BHB ≥0.5 mM) after ∼15 minutes, relative to the control. BHB remained elevated 2 h post-consumption. The control did not increase BHB. Ketosis was dose responsive; peak BHB concentration and area under the curve (AUC) were two-fold greater with POW 25 g compared to POW 12.5 g and RTD 12.5 g. There were no differences in peak BHB and AUC between matched powder and RTD formulas. Blood glucose increased in all conditions following the meal but there were neither significant differences in lowest observed concentrations, nor consistent differences at each time point between conditions. These results demonstrate that both powdered and RTD BH-BD formulations similarly induce ketosis with no differences in glucose concentrations in healthy adults.

Keywords:

• Ketones
• ketone ester
• ketone di-ester
• exogenous ketone
• beta-hydroxybutyrate

Acknowledgments

Thank you to Cosmin Beliciu at The National Food Laboratory for his assistance with packaging and shipping of study product. Thank you to Amy Boileau, Martin Ducker and Barbara Winters for their helpful comments on the protocol and manuscript.

Disclosure statement

B.J.S. has stock options in BHB Therapeutics Ltd., and Juvenescence Ltd. B.J.S. is an inventor on patents related to the use of ketone bodies. J.C.A. holds stock options in Juvenescence Limited and Juvenescence Life Sciences Limited. All other authors have no competing interests.

Author contributions

Conceptualization, B.J.S, J.C.A, K.M.N.; methodology, B.J.S, K.M.N, J.C.A; formal analysis, B.J.S; investigation, B.J.S, K.M.N.; data curation, B.J.S, K.M.N.; writing—original draft preparation, B.J.S, K.M.N.; writing—review and editing, B.J.S, J.C.A, K.M.N; visualization, B.J.S; project administration, B.J.S, K.M.N.; funding acquisition, B.J.S, J.C.A. All authors have read and agreed to the published version of the manuscript.

Data availability statement

The data presented here may be available upon reasonable request from the corresponding author and in accordance with intellectual property considerations.

Institutional review board statement

This study was conducted according to the guidelines of the Declaration of Helsinki (2004), and approved by WCG IRB (WIRB-Copernicus Group, Puyallup, WA) on July 26, 2021 (ID# 20213716).

Additional information

Funding

This work was funded by BHB Therapeutics (Ireland) Limited (“BHB Therapeutics”), which is licensed to develop products related to ketone bodies. BHB Therapeutics provided the study beverages used in this work.