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

Cameron, Donnie, Soto-Mota, Adrian, Willis, David R., Ellis, Jane, Procter, Nathan E. K., Greenwood, Richard, Saunders, Neil, Schulte, Rolf F., Vassiliou, Vassilios S., Tyler, Damian J., Schmid, Albrecht Ingo, Rodgers, Christopher T., Malcolm, Paul N., Clarke, Kieran, Frenneaux, Michael P. and Valkovič, Ladislav (2022) 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. Frontiers in Physiology, 13. ISSN 1664-042X

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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 (31P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23–70 years for cardiac 31P-MRS, and 16 aged 60–75 years for skeletal muscle 31P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle 31P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG®, was administered after the baseline scan. Administration was timed so that post-intervention 31P-MRS would take place 30 min after deltaG® ingestion. The deltaG® 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 (−28.8%, p ≪ 0.001; −28.2%, p = 0.02; and −49.1%, p ≪ 0.001, respectively), while levels of the ketone body D-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol/L after 30 min (p ≪ 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 31P-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.

Item Type: Article
Additional Information: This study was funded by a combination of seed funding awarded to DC by Norwich Medical School, University of East Anglia, funding from TdeltaS., Ltd., and funding from the Wellcome Trust (#221805/Z/20/Z and #098436/Z/12/B). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. LV is a Sir Henry Dale Fellow supported jointly by the Wellcome Trust and the Royal Society (#221805/Z/20/Z), and he also acknowledges the support of the Slovak Grant Agencies VEGA (#2/0003/20) and APVV (#19-0032). AS was supported by The Austrian Science Fund (FWF) Schrödinger Fellowship (J 4043). CR is funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (#098436/Z/12/B) and acknowledges support from the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). DT was funded by a Senior Research Fellowship from the British Heart Foundation (FS/19/18/34252). JE was funded by the Medical Research Council.
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 01 Feb 2022 09:30
Last Modified: 25 May 2022 00:26
URI: https://ueaeprints.uea.ac.uk/id/eprint/83243
DOI: 10.3389/fphys.2022.793987

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