The Metabolic Effects of β-hydroxybutyrate on Working Skeletal Muscle
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Work efficiency
研究概览
简要总结
The goal of this clinical trial is to test ketone bodies in healthy elderly 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 within the young and elderly groups and between the young and the elderly group to investigate if age has an effect on the outcomes.
详细描述
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 beta-hydroxybutyrate ingested as a monoester on skeletal muscle function and metabolism during muscle work in young and elderly individuals.
DESIGN Healthy young (20-25 years) and elderly (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-beta-hydroxybutyrate/D-1,3-butanediol; KetoneAid Pro KE4), one day with ingestion of a volume and calorie and taste matched placebo (lipid emulsion). Blood ketone levels will be kept elevated through a sipping protocol. During both conditions a low glucose dose will be continuously infused to block physiological 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male 20-25 years old (n = 12) OR male 65-85 years old (n = 12)
- •BMI range: 19 to 27
- •Stable weight (< 5% change over last 6 months)
- •Less than 3 x 60 min of structured exercise per week.
排除标准
- •Medication that affect energy metabolism.
- •Non-MR-compatible metals or electric devices in the body.
- •Anaemia or bleeding disorders.
- •Heart, lung or other disease that affects the subjects ability to exercise.
- •Drug abuse.
- •Lack of compliance.
- •Known allergy towards local anaesthetics.
- •Any condition that the principal investigator considers unsuitable for the subject's ability to complete the study.
研究组 & 干预措施
First Ketone, then placebo
Ingestion of ketone monoester D-β-hydroxybutyrate / D 1,3 butanediol monoester on first experimental day and ingestion of a fat placebo drink on the second experimental day.
干预措施: D-β-hydroxybutyrate/D 1,3 butanediol monoester (Dietary Supplement)
First placebo, then ketone
Ingestion of a fat placebo drink on the first experimental day followed by ingestion of ketone monoester D-β-hydroxybutyrate / D 1,3 butanediol monoester on the second experimental day.
干预措施: D-β-hydroxybutyrate/D 1,3 butanediol monoester (Dietary Supplement)
结局指标
主要结局
Work efficiency
时间窗: Over 60 minutes on each of the two experimental days.
External work performed by the ankle during dorsiflexion per ATP consumed. ATP consumption is assessed by 31P-MRS while external force is measured by the dynamometer.
次要结局
- Palmitate flux (only young group)(At 10 minute intervals over the last 30 min of the 90 min fixed intensity cycling on each experimental day.)
- Blood free fatty acids(During each of the two experimental days)
- Cycle performance(5-8 minutes during each of the two experimental days)
- Blood glucagon(During each of the two experimental days)
- Glucose oxidation rates (only young group)(At 10 minute intervals over the last 30 min of the 90 min fixed intensity cycling on each experimental day.)
- Tibialis anterior fatigue(Over 3 minutes on each of the two experimental days.)
- Blood catecholamines(During each of the two experimental days)
- Intramuscular glycogen content(Just before and immediately after the constant load cycling at each of the two experimental days.)
- Oxidative capacity(Over 20 minutes at each of the two experimental days.)
- ATP generation(Over 30 minutes at each of the two experimental days.)
- Intramuscular pH(Over 60 minutes at each of the two experimental days.)
- Intramuscular lipid content(At the beginning and at the end of each of the two experimental days)
- Mitochondrial function(Just before and immediately after the constant load cycling at each of the two experimental days.)
- Blood 3-OHB(During each of the two experimental days)
- Blood pH(During each of the two experimental days)
- Blood growth hormone(During experimental days)
- Blood insulin(During each of the two experimental days)
- Blood glucose(During each of the two experimental days)
- Rating of perceived exertion (only young group)(After 30, 60 and 90 minutes of fixed intensity cycling and just after the incremental performance test.)
- AMPK phosphorylation (only young group)(Just before and immediately after the constant load cycling at each of the two experimental days.)
- Blood cortisol(During each of the two experimental days)