{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:56:11Z","timestamp":1790085371703,"version":"4.0.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> 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).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We undertook a randomized, parallel, open-label study in healthy adults (<jats:italic>n<\/jats:italic> = 33) to elucidate blood BHB, HEX and BDO concentrations for 8\u00a0h following consumption of three different serving sizes (SS) of BH-BD (12.5, 25 and 50\u00a0g\/day) before (Day 0) and after 7\u00a0days of daily BH-BD consumption (Day 7).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> 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. <jats:italic>In vitro<\/jats:italic> incubation of BH-BD in human plasma demonstrated BH-BD undergoes rapid spontaneous hydrolysis.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> 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\u00a0g nor displays consistent adaptation after 7\u00a0days of daily consumption.<\/jats:p>","DOI":"10.3389\/fphys.2023.1196535","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T01:37:38Z","timestamp":1687570658000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["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"],"prefix":"10.3389","volume":"14","author":[{"given":"Eunice","family":"Mah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traci M.","family":"Blonquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie N.","family":"Kaden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Beckman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Boileau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Anthony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna J.","family":"Stubbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/j.cell.2020.04.027","article-title":"Ketogenic diets alter the gut microbiome resulting in decreased intestinal Th17 cells","volume":"181","author":"Ang","year":"2020","journal-title":"Cell"},{"key":"B2","unstructured":"NonCompart: Noncompartmental analysis for pharmacokinetic data 2022\n            BaeK-S.\n          2022"},{"key":"B3","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1056\/NEJM197003192821209","article-title":"Starvation in man","volume":"282","author":"Cahill","year":"1970","journal-title":"N. 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