BACKGROUND With ageing, skeletal muscles metabolism changes and muscle function declines. This may lead to muscle weakness and increased risk of developing metabolic diseases. Ketone bodies, namely 3-hydroxybutyrate (3-OHB), is an energy substrate that may change the metabolism and improve efficiency of skeletal muscles in a setting of ageing.~OBJECTIVE The study aims to investigate the effects of 3-OHB on skeletal muscle function and metabolism during muscle work in young and old individuals.~DESIGN Healthy young (20-25 years) and old (65-85 years) untrained males will be paired based on age corrected VO2-max. Participants will be evaluated in a double blinded cross-over design on two study days: One day with ketone ester ingestion (D-β-hydroxybutyrate/D 1,3 butanediol monoester), one day with ingestion of a volume and calorie matched placebo. Substrate levels will be maintained through a sipping protocol. During both conditions a low glucose dose will be continuously infused to block ketogenesis.~The order of the study days will be randomized and interspaced by at least 4 weeks.~On experimental days, participants meet fasted to perform voluntary contractions with tibialis anterior muscles in a MR compatible dynamometer while oxidative capacity, ATP generation, intramuscular pH, fatiguability and work efficiency is evaluated through 31P-MR spectroscopy. After, participants will bike at a fixed intensity (50% of VO2 max) while lipid fluxes and glucose oxidation rates are measured by palmitate- and glucose tracer infusions and carbamide-corrected indirect calorimetry. Lastly on the study days, participants will perform a VO2-max test as a measure of performance. Muscle biopsies are obtained before and just following fixed intensity cycle work. Adipose tissue biopsies are collected at the beginning of the experimental day before ketone/placebo ingestion and after the constant load cycle work. Blood samples are performed throughout the day to assess substrate levels, hormones and for proteomics analysis.~Before each study day, participant's activity level is measured for 7 days by accelerometry. Food intake will be reported by food questionnaire three days up to the study days.
The goal of this clinical trial is to test ketone bodies in healthy old and young individuals. The main question it aims to answer are:~• Do ketone bodies improve skeletal muscle function?~Participants will ingest a ketone monoester and skeletal muscle function will then be evaluated by:~Special magnetic imaging techniques~Intravenous infusion of tracer-marked nutrients~Performance tests on a ergometer bike and in a dynamometer~Researchers will compare the outcomes between the young and the old group to see if age has an effect on the outcome.