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 ORCID: https://orcid.org/0000-0001-9841-6909, Soto-Mota, Adrian, Willis, David R., Ellis, Jane, Procter, Nathan E. K., Greenwood, Richard, Saunders, Neil, Schulte, Rolf F., Vassiliou, Vassilios S. ORCID: https://orcid.org/0000-0002-4005-7752, 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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Abstract

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: 24 Oct 2022 06:47
URI: https://ueaeprints.uea.ac.uk/id/eprint/83243
DOI: 10.3389/fphys.2022.793987

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