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.

Highlights

  • Cardiac and skeletal muscle function declines with age, impairing quality of life in older individuals in a vicious cycle of decreased physical activity and muscle loss

  • Studies in mice have shown that declining skeletal muscle functional capacity with age is correlated with mitochondrial dysfunction, with uncoupled mitochondrial respiration, increased reactive oxygen species generation, and altered glucose homeostasis being more apparent in older animals (Jang et al, 2010; Lee et al, 2010)

  • Of the 16 participants recruited for skeletal muscle MRS, the 31P-MRS datasets of four were excluded due to hardware failure and a further two were discarded due to insufficient PCr breakdown

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Summary

Introduction

Cardiac and skeletal muscle function declines with age, impairing quality of life in older individuals in a vicious cycle of decreased physical activity and muscle loss. Even in relatively healthy older adults, the progressive loss of skeletal muscle mass and overall diminished strength with ageing can eventually develop into sarcopenia (Cruz-Jentoft et al, 2010), a condition estimated to affect up to 10% of the global population (Shafiee et al, 2017). The causes of this phenomenon are multi-factorial: hormonal changes with age, denervation of neuromuscular junctions, increased adiposity of skeletal muscle, and inflammatory infiltration, oxidation, or glycation of actin and myosin filaments may all contribute to the development of sarcopenia (Degens, 2007; Cruz-Jentoft et al, 2010; Walston, 2012; Marty et al, 2017; Shafiee et al, 2017). Uncoupled mitochondrial respiration has been documented in heart failure, (Neubauer, 2007) when circulating free-fatty acid concentrations are high

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