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.

Ketone monoester ingestion increased ATP production and time-torque derived work capacity in older but not young participants.

• Twelve young (20-25 years) and twelve older (65-85 years) healthy men participated in the study.
• Participants were matched by age-adjusted VO2max.
• The intervention was a randomized, crossover, double-blind design with ketone monoester or placebo on separate study days.
• A low-dose, continuous glucose infusion was administered on both days to block endogenous ketone production.
• The effect was specific to the older group, with no significant changes observed in the young group.

Ketosis improved peak power and increased both muscle relative decline in peak power and contraction-induced pH decline in older participants.

• Peak power improvements were observed only in the older group following ketone monoester ingestion.
• Ketones also increased the relative decline in peak power in older participants.
• Contraction-induced intramuscular pH decline was greater with ketone monoester in older participants.
• Intramuscular pH was assessed in the tibialis anterior through phosphorous MR spectroscopy (31P-MRS).
• No such effects were observed in the young group.

Ketosis had no effect on metabolic economy in either young or older participants.

• Metabolic economy was assessed in the tibialis anterior through phosphorous MR spectroscopy (31P-MRS) and dynamometer recordings.
• Neither the young nor the older group showed changes in metabolic economy following ketone monoester ingestion.
• The older group showed lower metabolic economy compared to the young group at baseline.
• This finding indicates that any ergogenic effects of ketones in older adults operate independently of changes in metabolic economy.

Oxidative capacity was similar between age groups and remained unaffected by ketone monoester ingestion.

• Oxidative capacity was assessed in the tibialis anterior using 31P-MRS.
• No significant differences in oxidative capacity were found between young and older participants.
• Ketone monoester had no effect on oxidative capacity in either group.
• This suggests the ergogenic effects of ketones in older adults are independent of changes in mitochondrial oxidative capacity.

Complex I + II mitochondrial respiration was lower in older compared to young participants, with no effect of ketone monoester.

• Mitochondrial function was assessed by high-resolution respirometry of the quadriceps femoris muscle.
• Complex I + II respiration was significantly lower in the older group compared to the young group.
• Ketone monoester ingestion did not alter Complex I + II respiration in either group.
• This finding indicates an age-related difference in mitochondrial respiratory capacity that is not modifiable by acute ketosis.

The study employed a controlled design using continuous glucose infusion to block endogenous ketone production on both intervention days.

• A low-dose, continuous glucose infusion was used to suppress endogenous ketone production.
• This design element ensured that any differences observed were attributable to exogenous ketone monoester rather than endogenously produced ketones.
• The study was pre-registered at clinicaltrials.gov (NCT05732909).
• The crossover design meant each participant received both ketone monoester and placebo on separate study days.

The findings support ketosis as a promising ergogenic therapy specifically for older adults.

• The authors describe the effects as 'age-specific,' with benefits confined to the older (65-85 years) group.
• The ergogenic effects in older adults were independent of changes in metabolic economy and mitochondrial function.
• The authors conclude that 'ketosis as a promising ergogenic therapy for older adults.'
• Ketosis may represent a therapeutic target for age-related impairments in skeletal muscle function.