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Purpose <p>Nutritional ketosis is purported to enhance skeletal muscle recovery and adaptation to exercise, yet precise adaptive mechanisms are unknown. We investigated the post-exercise molecular response to ketone monoesters (KME) in skeletal muscle by characterising the early transcriptomic response.</p> Methods <p>Following a randomised, double-blind, crossover design, recreationally active men (n = 9, age: 26 ± 5 (means ± SD) y; V̇O<sub>2max</sub>: 47 ± 4&#xa0;mL·kg<sup>−1</sup>·min<sup>−1</sup>) completed two experimental trials where they ingested either 1.25&#xa0;g·kg<sup>−1</sup> of KME or a taste-matched placebo (PLA) drink during exercise (90-min cycling at 60% of V̇O<sub>2max</sub>) and 3-h recovery. Blood samples were taken throughout for hormone and metabolite analyses, and muscle biopsies were taken at baseline and 3 h post-exercise for glycogen and genome-wide gene expression analyses.</p> Results <p>Recovery ßHB concentrations were higher in KME (4.1 ± 0.7&#xa0;mM) vs PLA (0.1 ± 0.0&#xa0;mM, <i>P</i> &lt; 0.001). Erythropoietin (EPO) showed a main effect of time (<i>P</i> = 0.044), but no condition effect (<i>P</i> = 0.087) or interaction (<i>P</i> = 0.318). Skeletal muscle glycogen decreased post-exercise (−57%, <i>P</i> &lt; 0.001) as expected, but showed no condition effect (<i>P</i> = 0.889) or interaction (<i>P</i> = 0.907). We measured the expression of 16,898 genes, and despite a clear time effect on the skeletal muscle transcriptome (1561 differentially expressed genes post vs pre-exercise; <i>q</i> &lt; 0.05 fold change &gt; ± 1.5), there was no effect of condition.</p> Conclusions <p>KME did not demonstrate an effect on EPO concentration, muscle glycogen or transcriptome, suggesting DNA translation is likely not a process directly regulated by acute ketonaemia that increases early post-exercise.</p>

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Acute nutritional ketosis during early recovery from aerobic exercise does not affect skeletal muscle transcriptomic response in humans

  • 期刊论文

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  • 发表日期：

    2025年9月17日

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  • Erick Mosquera-Lopez,
  • Julien Louis,
  • Jason P. Edwards,
  • Jamie Pugh,
  • Mark R. Viggars,
  • Daniel J. Owens,
  • Jose L. Areta

摘要

Purpose

Nutritional ketosis is purported to enhance skeletal muscle recovery and adaptation to exercise, yet precise adaptive mechanisms are unknown. We investigated the post-exercise molecular response to ketone monoesters (KME) in skeletal muscle by characterising the early transcriptomic response.

Methods

Following a randomised, double-blind, crossover design, recreationally active men (n = 9, age: 26 ± 5 (means ± SD) y; V̇O2max: 47 ± 4 mL·kg−1·min−1) completed two experimental trials where they ingested either 1.25 g·kg−1 of KME or a taste-matched placebo (PLA) drink during exercise (90-min cycling at 60% of V̇O2max) and 3-h recovery. Blood samples were taken throughout for hormone and metabolite analyses, and muscle biopsies were taken at baseline and 3 h post-exercise for glycogen and genome-wide gene expression analyses.

Results

Recovery ßHB concentrations were higher in KME (4.1 ± 0.7 mM) vs PLA (0.1 ± 0.0 mM, P < 0.001). Erythropoietin (EPO) showed a main effect of time (P = 0.044), but no condition effect (P = 0.087) or interaction (P = 0.318). Skeletal muscle glycogen decreased post-exercise (−57%, P < 0.001) as expected, but showed no condition effect (P = 0.889) or interaction (P = 0.907). We measured the expression of 16,898 genes, and despite a clear time effect on the skeletal muscle transcriptome (1561 differentially expressed genes post vs pre-exercise; q < 0.05 fold change > ± 1.5), there was no effect of condition.

Conclusions

KME did not demonstrate an effect on EPO concentration, muscle glycogen or transcriptome, suggesting DNA translation is likely not a process directly regulated by acute ketonaemia that increases early post-exercise.