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

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.