AUTHOR=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. , Valkovič Ladislav 

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

JOURNAL=Frontiers in Physiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.793987

DOI=10.3389/fphys.2022.793987

ISSN=1664-042X

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