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

Mosquera-Lopez, E ORCID: 0000-0002-0505-0352, Louis, J ORCID: 0000-0002-9109-0958, Edwards, JP ORCID: 0000-0003-1563-1924, Pugh, J ORCID: 0000-0002-5930-4709, Viggars, MR ORCID: 0000-0002-0722-7051, Owens, DJ ORCID: 0000-0002-1908-8677 and Areta, JL ORCID: 0000-0001-6918-1223 (2025) Acute nutritional ketosis during early recovery from aerobic exercise does not affect skeletal muscle transcriptomic response in humans. European Journal of Applied Physiology. ISSN 1439-6319

Preview

Text Acute nutritional ketosis during early recovery from aerobic exercise does not affect skeletal muscle transcriptomic response in humans..pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

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; 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.

Item Type:	Article
Uncontrolled Keywords:	Aerobic exercise; Erythropoietin; Gene expression profiling; Glycogen metabolism; Ketone supplementation; 32 Biomedical and Clinical Sciences; 42 Health Sciences; 4207 Sports Science and Exercise; Human Genome; Physical Activity; Clinical Trials and Supportive Activities; Nutrition; Genetics; Clinical Research; Musculoskeletal; 1106 Human Movement and Sports Sciences; Sport Sciences; 3202 Clinical sciences; 3208 Medical physiology; 4207 Sports science and exercise
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Publisher:	Springer
Date of acceptance:	5 September 2025
Date of first compliant Open Access:	22 September 2025
Date Deposited:	22 Sep 2025 14:49
Last Modified:	22 Sep 2025 15:00
DOI or ID number:	10.1007/s00421-025-05987-9
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27191

View Item