AgingNCT05732909
The Metabolic Effects of β-hydroxybutyrate on Working Skeletal Muscle
A study testing D-β-hydroxybutyrate/D 1,3 butanediol monoester in people with Aging and Metabolism Disorder, run by University of Aarhus at 1 site in Denmark.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 20 to 85 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Aging, Metabolism Disorder, Ketonemia
- What is being tested?
- D-β-hydroxybutyrate/D 1,3 butanediol monoester
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteDenmark
- Study dates
- 22 Dec 2022to 10 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 85 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
- Smoking.
- Drug abuse.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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.
After, participants will bike at a fixed intensity (~45% of Wmax) while lipid fluxes and glucose oxidation rates are measured by palmitate- and glucose tracer infusions and carbamide-corrected indirect calorimetry over 60 min. This was initially intended for both young and elderly individuals, but only involves the young group, as the elderly group had difficulties completing 60 min cycling.
Lastly on the study days, participants will perform a cycling test as a measure of performance starting at 70 % of Wmax for 5 min thereafter increasing by 10 % of Wmax every 1 min until exhaustion. Muscle biopsies are obtained before (both groups) and just following fixed intensity cycle work (only young group). Adipose tissue biopsies are collected at the beginning of the experimental day (both groups) before ketone/placebo ingestion and after the constant load cycle work (only young group). 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 (ActiGraph). Participants will log their diet 3 days prior to each experimental day. Participants are asked to ingest a similar diet 2 days before both experimental days and to withstand from strenuous exercise 2 days prior to both experimental days. Participants are asked not to make any significant changes to their lifestyle while taking part in the study.
- Conditions
- Aging, Metabolism Disorder, Ketonemia, Muscle Disorder
- Being tested
- D-β-hydroxybutyrate/D 1,3 butanediol monoester
- Medical subject headings
- Metabolic Diseases, Ketosis, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-β-hydroxybutyrate/D 1,3 butanediol monoesterDietary supplement
Ketone monoester
| Study group | Role | What they receive |
|---|---|---|
| First Ketone, then placebo | Experimental | 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. Receives: Dietary Supplement: D-β-hydroxybutyrate/D 1,3 butanediol monoester |
| First placebo, then ketone | Experimental | 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. Receives: Dietary Supplement: D-β-hydroxybutyrate/D 1,3 butanediol monoester |
What is being measured
The primary outcome is the main question the study is designed to answer.
Work efficiency
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.
Measured: Over 60 minutes on each of the two experimental days.
Secondary outcomes (21)
Oxidative capacity
Assessed by 31P-MRS as phosphocreatine resynthesis.
Measured: Over 20 minutes at each of the two experimental days.
Glucose oxidation rates (only young group)
Assessed by measuring tracer dilution from blood samples obtained during 3H-glucose infusion while cycling at a fixed intensity.
Measured: At 10 minute intervals over the last 30 min of the 90 min fixed intensity cycling on each experimental day.
Palmitate flux (only young group)
Assessed by measuring tracer dilution from blood samples obtained during 3H-palmitate infusion while cycling at a fixed intensity.
Measured: At 10 minute intervals over the last 30 min of the 90 min fixed intensity cycling on each experimental day.
ATP generation
ATP generated from different pathways (glycolytic, oxidative, phosphocreatine) assessed by 31P-MRS.
Measured: Over 30 minutes at each of the two experimental days.
Mitochondrial function
Assessed by high-resolution respirometry on muscle biopsies
Measured: Just before and immediately after the constant load cycling at each of the two experimental days.
Intramuscular pH
Measurements at rest rest and during work assessed by 31P-MRS
Measured: Over 60 minutes at each of the two experimental days.
Blood 3-OHB
Blood concentration measured by blood sampling
Measured: During each of the two experimental days
Blood glucose
Blood concentration measured by blood sampling
Measured: During each of the two experimental days
Blood free fatty acids
Blood concentration measured by blood sampling
Measured: During each of the two experimental days
Cycle performance
Assessed by a performance test on a bike ergometer with incremental load. The test continues until failure. The test outcome is the power generated at time of failure.
Measured: 5-8 minutes during each of the two experimental days
Rating of perceived exertion (only young group)
Subjective measure of exertion during cycling evaluated by reporting on a number assessment scale (Borg scale (6-20)).
Measured: After 30, 60 and 90 minutes of fixed intensity cycling and just after the incremental performance test.
Tibialis anterior fatigue
Tibialis anterior fatigue assessed by the dynamometer during 3 minutes of dorsiflexion at a fixed resistance.
Measured: Over 3 minutes on each of the two experimental days.
Blood growth hormone
Blood concentration measured by blood sampling
Measured: During experimental days
Blood insulin
Blood concentration measured by blood sampling
Measured: During each of the two experimental days
AMPK phosphorylation (only young group)
From muscle biopsies
Measured: Just before and immediately after the constant load cycling at each of the two experimental days.
Blood glucagon
Blood concentration measured by blood sampling
Measured: During each of the two experimental days
Blood pH
Assessed from arterial blood samples
Measured: During each of the two experimental days
Blood catecholamines
Blood concentration measured by blood sampling
Measured: During each of the two experimental days
Blood cortisol
Blood concentration measured by blood sampling
Measured: During each of the two experimental days
Intramuscular lipid content
Concentration measured in muscle biopsies
Measured: At the beginning and at the end of each of the two experimental days
Intramuscular glycogen content
Concentration measured in muscle biopsies
Measured: Just before and immediately after the constant load cycling at each of the two experimental days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2023
- Study start22 Dec 2022
- Primary completion10 Jan 2024
- Study completion10 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Two-day cross-over design.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Diabetes Academy, AP Moeller Foundation, Aarhus University Hospital, Novo Nordisk Foundation
- Responsible party
- Sponsor
- Investigators
- Niels Jessen, Professor, Study director, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05732909
- Sponsor's protocol ID
- ketomr
- Status last verified
- Jan 2023
- First submitted
- 17 Jan 2023
- Last updated
- 6 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Andersen OE, Larsen RG, Moller N, Stouge A, Ringgaard S, Overgaard K, Jessen N. 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. Acta Physiol (Oxf). 2026 Mar;242(3):e70161. doi: 10.1111/apha.70161.
PubMed 41644499
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Metabolic Effects of β-hydroxybutyrate on Working Skeletal Muscle
- ClinicalTrials.gov ID
- NCT05732909
- Acronym / sponsor ID
- ketomr
- Conditions
- Aging, Metabolism Disorder, Ketonemia, Muscle Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Danish Diabetes Academy, AP Moeller Foundation, Aarhus University Hospital, Novo Nordisk Foundation
- Study start
- 22 Dec 2022 (actual)
- Primary completion
- 10 Jan 2024 (actual)
- Study completion
- 10 Jan 2024 (actual)
- First posted
- 17 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
After, participants will bike at a fixed intensity (~45% of Wmax) while lipid fluxes and glucose oxidation rates are measured by palmitate- and glucose tracer infusions and carbamide-corrected indirect calorimetry over 60 min. This was initially intended for both young and elderly individuals, but only involves the young group, as the elderly group had difficulties completing 60 min cycling.
Lastly on the study days, participants will perform a cycling test as a measure of performance starting at 70 % of Wmax for 5 min thereafter increasing by 10 % of Wmax every 1 min until exhaustion. Muscle biopsies are obtained before (both groups) and just following fixed intensity cycle work (only young group). Adipose tissue biopsies are collected at the beginning of the experimental day (both groups) before ketone/placebo ingestion and after the constant load cycle work (only young group). 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 (ActiGraph). Participants will log their diet 3 days prior to each experimental day. Participants are asked to ingest a similar diet 2 days before both experimental days and to withstand from strenuous exercise 2 days prior to both experimental days. Participants are asked not to make any significant changes to their lifestyle while taking part in the study.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Two-day cross-over design.
| Arm | Type | Receives |
|---|---|---|
| First Ketone, then placebo | Experimental | Dietary Supplement: D-β-hydroxybutyrate/D 1,3 butanediol monoesterIngestion 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. |
| First placebo, then ketone | Experimental | Dietary Supplement: D-β-hydroxybutyrate/D 1,3 butanediol monoesterIngestion 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. |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
- Smoking.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-β-hydroxybutyrate/D 1,3 butanediol monoesterKetone monoester | Dietary supplement | First Ketone, then placebo, First placebo, then ketone |
Primary outcome
Work efficiency
Time frame: 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.
21 secondary outcomes
Oxidative capacity
Time frame: Over 20 minutes at each of the two experimental days.
Glucose oxidation rates (only young group)
Time frame: At 10 minute intervals over the last 30 min of the 90 min fixed intensity cycling on each experimental day.
Palmitate flux (only young group)
Time frame: At 10 minute intervals over the last 30 min of the 90 min fixed intensity cycling on each experimental day.
ATP generation
Time frame: Over 30 minutes at each of the two experimental days.
Mitochondrial function
Time frame: Just before and immediately after the constant load cycling at each of the two experimental days.
Intramuscular pH
Time frame: Over 60 minutes at each of the two experimental days.
Blood 3-OHB
Time frame: During each of the two experimental days
Blood glucose
Time frame: During each of the two experimental days
Blood free fatty acids
Time frame: During each of the two experimental days
Cycle performance
Time frame: 5-8 minutes during each of the two experimental days
Rating of perceived exertion (only young group)
Time frame: After 30, 60 and 90 minutes of fixed intensity cycling and just after the incremental performance test.
Tibialis anterior fatigue
Time frame: Over 3 minutes on each of the two experimental days.
Blood growth hormone
Time frame: During experimental days
Blood insulin
Time frame: During each of the two experimental days
AMPK phosphorylation (only young group)
Time frame: Just before and immediately after the constant load cycling at each of the two experimental days.
Blood glucagon
Time frame: During each of the two experimental days
Blood pH
Time frame: During each of the two experimental days
Blood catecholamines
Time frame: During each of the two experimental days
Blood cortisol
Time frame: During each of the two experimental days
Intramuscular lipid content
Time frame: At the beginning and at the end of each of the two experimental days
Intramuscular glycogen content
Time frame: Just before and immediately after the constant load cycling at each of the two experimental days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2026.
- Derived from this study: PubMed 41644499Andersen OE, Larsen RG, Moller N, Stouge A, Ringgaard S, Overgaard K, Jessen N. 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. Acta Physiol (Oxf). 2026 Mar;242(3):e70161. doi: 10.1111/apha.70161.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niels Jessen, Professor study director
Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing D-β-hydroxybutyrate/D 1,3 butanediol monoester in people with Aging and Metabolism Disorder, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Work efficiency (time frame: Over 60 minutes on each of the two experimental days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05732909, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2026; AzTrials last refreshed its copy on 7 Nov 2026.