Dataset Information

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

ABSTRACT:

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; V̇O_2max: 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 V̇O_2max) 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.

SUBMITTER: Mosquera-Lopez E

PROVIDER: S-EPMC12948831 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Mosquera-Lopez Erick E Louis Julien J Edwards Jason P JP Pugh Jamie J Viggars Mark R MR Owens Daniel J DJ Areta Jose L JL

European journal of applied physiology 20250917 2

<h4>Purpose</h4>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.<h4>Methods</h4>Following a randomised, double-blind, crossover design, recreationally active men (n = 9, age: 26 ± 5 (means ± SD) y; V̇O<sub>2max</sub>: 47 ± 4 mL·kg<sup>-1</sup>·min<sup>-1< ...[more]

PMID: 40960642

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Project description:Purpose: Recent research suggests that Ketone monoester (KME) supplementation may enhance skeletal muscle adaptation to exercise, possibly modulated be an increased secretion of erythropoietin (EPO) and increased muscle glycogen resynthesis, but the precise molecular pathways driving the response remain uncertain. Therefore, we aimed at characterising the modulation of skeletal muscle by KME through a genome-wide characterisation of the transcriptome early post-exercise. Methods: Following a randomized, double-blind, crossover design, recreationally active men [n= 9; age: 26 ± 5 (means ± SD); height: 1.80 ± 0.07 m; body mass: 80 ± 9 kg; V̇O2max: 47 ± 4 mL·kg-1·min-1]) completed two experimental trials where they ingested either 1.25 g/kg of KME (>96% (R)-3-hydroxybutyl (R)-3-hydroxybutyrate) or a taste-matched placebo (PLA) drink around exercise (90-min cycling at 60% of VO2max) in standardised conditions. . Venous blood samples were taken throughout baseline, exercise and recovery, and skeletal muscle biopsies were taken at baseline and 3-h post exercise. Results: KME intake elevated serum ßHB concentrations post-exercise to 3.3 ± 0.5 mM and remained elevated levels during recovery (range: ~4.0–4.7 mM). Remarkably, there was no marked upregulation or downregulation of differentially expressed genes at 3-h post-exercise with KME supplementation compared to PLA. Although, baseline serum EPO levels were higher in PLA (12.8 ± 3.9 IU/L) compared to KME (10.1 ± 5.7 IU/L) and remained slightly higher in PLA throughout recovery, there was not significant difference between conditions. Pre- and post- exercise muscle glycogen concentrate were similar between conditions (KME PRE: 501 ± 118 mmol/kg, KME POST, 284 ± 117 mmol/kg, PLA PRE: 492 ± 102 mmol/kg, PLA POST: 282 ± 184 mmol/kg). Conclusions: Our findings indicate that despite a sustained post-exercise increase in serum ßHB concentrations, KME supplementation did not induce transcriptional changes in skeletal muscle. Additionally, in contrast to previous studies, KME did not affect glycogen concentrations or serum EPO levels during the first 3-hours post-exercise.

Dataset Information

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

Purpose

Methods

Results

Conclusions

Publications

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

Similar Datasets

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