A randomized, open-label, parallel pilot study investigating metabolic product kinetics of the novel ketone ester, bis-hexanoyl (R)-1,3-butanediol, over one week of ingestion in healthy adults

• Published in: Frontiers in physiology Vol. 14; p. 1196535
• Main Authors: Mah, Eunice, Blonquist, Traci M, Kaden, Valerie N, Beckman, Dawn, Boileau, Amy C, Anthony, Joshua C, Stubbs, Brianna J
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.06.2023
• Subjects: beta-hydroxybutyrate (BHB); exogenous ketone; ketone di-ester; ketone ester; ketones; Physiology; beta-hydroxybutyrate (BHB); ketone ester; ketone di-ester; ketones; exogenous ketone
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2023.1196535

Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester that, when consumed, is hydrolyzed into hexanoic acid (HEX) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). We undertook a randomized, parallel, open-label study in healthy adults ( = 33) to elucidate blood BHB, HEX and BDO concentrations for 8 h following consumption of three different serving sizes (SS) of BH-BD (12.5, 25 and 50 g/day) before (Day 0) and after 7 days of daily BH-BD consumption (Day 7). Maximal concentration and area under the curve of all metabolites increased proportionally to SS and were greatest for BHB followed by BDO then HEX on both Day 0 and 7. Metabolite half-life tended to decrease with increasing SS for BHB and HEX. Time to peak concentration increased with increasing SS for BHB and BDO on both days. incubation of BH-BD in human plasma demonstrated BH-BD undergoes rapid spontaneous hydrolysis. These results demonstrate that orally ingested BH-BD is hydrolyzed into products that appear in the plasma and undergo conversion to BHB in a SS dependent manner, and that metabolism of BH-BD neither becomes saturated at serving sizes up to 50 g nor displays consistent adaptation after 7 days of daily consumption.