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.