Ketone Monoester Increases Skeletal Muscle Power and Energy Turnover in Older but Not Young Men Without Affecting Metabolic Economy: A Controlled, Double Blind, Cross‐Over Trial

ABSTRACT Aim Ketosis may represent a therapeutic target for age‐related impairments in skeletal muscle function. This study investigated acute effects of ketosis on metabolic economy, mitochondrial function, and contractile parameters in skeletal muscle of young and older adults. Methods Twelve young (20–25 years) and twelve older (65–85 years) healthy men, matched by age‐adjusted V̇O 2 max, participated in a randomized, crossover, double‐blind intervention with ingestion of ketone monoester or placebo on separate study days. On both days, a low‐dose, continuous glucose infusion blocked endogenous ketone production. Metabolic economy, oxidative capacity, muscle performance, intramuscular pH, and relative decline in peak power were assessed in the tibialis anterior through phosphorous MR spectroscopy ( 31 P‐MRS) and dynamometer recordings. Mitochondrial function of the quadriceps femoris muscle was assessed by high‐resolution respirometry. Results Ketosis had no effect on metabolic economy in either young or older participants. The older group showed lower metabolic economy compared to the young group. In older participants, ketones increased ATP production and time‐torque derived work capacity. Oxidative capacity was similar between groups and remained unaffected by ketones. In the older group, ketones improved peak power and increased both muscle relative decline in peak power and contraction‐induced pH decline. Complex I + II respiration was lower in older compared to young participants, with no effect of ketones. Conclusion Ketosis enhanced skeletal muscle work capacity and ATP production in older but not young adults, suggesting an age‐specific effect of ketone bodies on muscle function that operates independently of changes in metabolic economy and mitochondrial function. These findings support ketosis as a promising ergogenic therapy for older adults. Trial Registration The study was pre‐registered at clinicaltrials.gov (NCT05732909)