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Physiol."],"abstract":"<jats:p>In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr\/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (<jats:sup>31<\/jats:sup>P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23\u201370 years for cardiac <jats:sup>31<\/jats:sup>P-MRS, and 16 aged 60\u201375 years for skeletal muscle <jats:sup>31<\/jats:sup>P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle <jats:sup>31<\/jats:sup>P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG<jats:sup>\u00ae<\/jats:sup>, was administered after the baseline scan. Administration was timed so that post-intervention <jats:sup>31<\/jats:sup>P-MRS would take place 30 min after deltaG<jats:sup>\u00ae<\/jats:sup> ingestion. The deltaG<jats:sup>\u00ae<\/jats:sup> ketone drink was well-tolerated by all participants. In participants who provided blood samples, post-intervention blood glucose, lactate and non-esterified fatty acid concentrations decreased significantly (\u221228.8%, <jats:italic>p<\/jats:italic> \u226a 0.001; \u221228.2%, <jats:italic>p<\/jats:italic> = 0.02; and \u221249.1%, <jats:italic>p<\/jats:italic> \u226a 0.001, respectively), while levels of the ketone body <jats:sc>D<\/jats:sc>-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol\/L after 30 min (<jats:italic>p<\/jats:italic> \u226a 0.001). There were no significant changes in cardiac PCr\/ATP or skeletal muscle metabolic parameters between baseline and post-intervention. Acute ketone supplementation caused mild ketosis in blood, with drops in glucose, lactate, and free fatty acids; however, such changes were not associated with changes in <jats:sup>31<\/jats:sup>P-MRS measures in the heart or in skeletal muscle. Future work may focus on the effect of longer-term ketone supplementation on tissue energetics in groups with compromised mitochondrial function.<\/jats:p>","DOI":"10.3389\/fphys.2022.793987","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T07:16:09Z","timestamp":1643613369000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of Acute Supplementation With the Ketone Ester (R)-3-Hydroxybutyl-(R)-3-Hydroxybutyrate (deltaG) in Healthy Volunteers by Cardiac and Skeletal Muscle 31P Magnetic Resonance Spectroscopy"],"prefix":"10.3389","volume":"13","author":[{"given":"Donnie","family":"Cameron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Soto-Mota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Willis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan E. 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