Healthy ParticipantsWAKMNCT07082309
The Effect of Ketone Monoesters on Skeletal Muscle Protein Synthesis and Whole-body Protein Metabolism.
A study testing Ketone Monoester (KE) and whey protein beverage in people with Healthy Participants, run by University of Exeter at 1 site in United Kingdom.
Trial summary
The ketone β-hydroxybutyrate (BHB) is endogenously produced during periods of low glucose availability, serving as an alternative metabolic fuel. Beyond its role as an energy substrate, BHB acts as a pleiotropic signalling molecule, modulating various physiological processes across multiple tissues. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- Ketone Monoester (KE) and whey protein beverage
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 4 Jun 2025to Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI 18-30
Who cannot join
- Body mass index (BMI) < 18.5 or > 30 kg/m2
- Age < 18 or > 40
- Regularly smokes
- Type 2 diabetes
- Cardiovascular disease, metabolic disease and hypertension (≥ 140/90 mmHg)
- Gastrointestinal disorders
- Use medicines that may impact protein metabolism or that are anti-inflammatory (determined at the screening)
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Health and Life Sciences
Exeter, Devon, EX1 2LU
Alistair Monteyne, PhD, +44 (0)1392 72 4774, a.monteyne2@exeter.ac.uk
Alistair Monteyne, PhD
About this study
The ketone β-hydroxybutyrate (BHB) is endogenously produced during periods of low glucose availability, serving as an alternative metabolic fuel. Beyond its role as an energy substrate, BHB acts as a pleiotropic signalling molecule, modulating various physiological processes across multiple tissues. BHB can also be ingested orally as a ketone monoester, transiently elevating plasma concentrations of BHB to a level similar to those seen following several days of fasting, thereby obviating the need for dietary manipulation. The influence of BHB on human skeletal muscle protein metabolism remains poorly understood, although emerging evidence suggests that BHB may play a role in regulating muscle protein turnover. As such, BHB supplementation may support skeletal muscle remodelling and offer therapeutic benefits, and investigating this is of considerable interest. This study will investigate the ability of oral BHB ingestion - co-ingested with protein - to stimulate skeletal muscle anabolism in young healthy adults. A dual amino acid stable isotope tracer approach will be utilised to determine postprandial (i.e., fed state) muscle protein synthesis (MPS) rates and whole-body amino acid kinetics, given BHBs systemic effects. This research will advance our understanding of the fundamental biology of exogenous ketosis and provide insight into the potential of BHB supplementation as a novel nutritional strategy to optimise muscle mass and quality.
Read the detailed description
The ketone body β-hydroxybutyrate (BHB) is produced endogenously during periods of low glucose availability (e.g., fasting or starvation) and provides an alternative metabolic fuel. BHB also acts as a metabolic signalling molecule, modulating physiological processes across multiple tissues, including skeletal muscle. However, the impact of exogenous ketosis on muscle protein turnover, which regulates muscle mass and modulates physical function, remains largely unexplored. As such, understanding how BHB affects skeletal muscle protein turnover is fundamentally important. The ingestion of 0.5g/kg body mass BHB appreciably increases plasma BHB concentrations for several hours, to ~3-5 mM; equivalent to several days of fasting. This offers a model to exogenously elevate plasma BHB concentrations and investigate how BHB interacts with feeding to affect postprandial protein metabolism, the period primarily responsible for driving changes in muscle quality and quantity.
An early study demonstrated that the infusion of BHB stimulates muscle protein synthesis rates (MPS), whilst only a single recent study has investigated the effect of oral BHB ingestion (exogenous ketosis) on MPS. Prior work demonstrated that the ingestion of an oral ketone monoester stimulated MPS, and it did so to a similar extent as 10 g whey protein or co-ingestion of the two, in healthy young males. While this study provides useful insights, several unanswered questions/objectives that justify the need for further investigation remain:
- To determine how BHB ingestion influences myofibrillar protein synthesis, plasma amino acid concentrations, and amino acid kinetics following the co-ingestion of a physiologically relevant meal-like protein dose.
- To examine how BHB ingestion affects plasma amino acid concentrations and kinetics following protein co-ingestion, addressing prior research limitations where differences in carbohydrate intake and postprandial insulin levels confounded the independent effects of ketones.
- To assess the impact of BHB ingestion on whole-body protein metabolism following protein co-ingestion, as previous studies have not examined its potential influence on protein breakdown, amino acid kinetics, and net protein balance.
- To investigate whether BHB ingestion influences mitochondrial muscle protein synthesis following protein co-ingestion, given its established effects on mitochondrial metabolism, yet unexamined role in mitochondrial protein turnover.
The aim, therefore, is to establish the effect of BHB and protein co-ingestion on myofibrillar protein synthesis rates, mitochondrial protein synthesis rates, and whole-body protein turnover. We will address this question by utilising a meal-like bolus of protein (0.3 g/kg whey protein), with and without 0.5g/kg body mass BHB (matching the test drinks caloric content via the addition of fat to minimally stimulate insulin secretion), whilst applying a dual-stable isotope tracer approach.
- Conditions
- Healthy Participants
- Being tested
- Ketone Monoester (KE) and whey protein beverage, Control
- Keywords
- ketone monoesters, muscle protein synthesis, amino acid metabolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone Monoester (KE) and whey protein beverageDietary supplement
Ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and whey protein (0.3 g/kg)
ControlDietary supplement
Placebo with bitter agent (Bitrex), to flavour match to ketone condition, whey protein (0.3 g/kg), and milk fat (to match the caloric content of the ketone condition).
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | Placebo with bitter agent (Bitrex), to flavour match to ketone condition, whey protein (0.3 g/kg), and milk fat (to match the caloric content of the ketone condition). Receives: Dietary Supplement: Control |
| Ketone monoester | Experimental | Ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and whey protein (0.3 g/kg) Receives: Dietary Supplement: Ketone Monoester (KE) and whey protein beverage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skeletal muscle protein synthesis rates (FSR)
Skeletal muscle protein synthesis rates
Measured: 5 hours (2 hours postabsorptive, 3 hours postprandial)
Secondary outcomes (4)
Plasma amino acid concentrations
Plasma amino acid concentrations
Measured: 5 hours
Whole-body phenylalanine kinetics assessed by stable isotope tracer methodology, including rate of appearance (Ra), rate of disappearance (Rd), hydroxylation rate, and net balance.
Whole-body kinetics of phenylalanine will be quantified using a primed continuous intravenous infusion of stable isotope-labelled phenylalanine and tyrosine tracers (e.g., L-[ring-²H₅]-phenylalanine and L-[³-¹³C]-tyrosine). Arterialised-venous blood samples will be collected at steady state to determine tracer enrichment in plasma.
The following parameters will be calculated:
Rate of appearance (Ra) of phenylalanine (μmol/kg/min), rate of disappearance (Rd) of phenylalanine (μmol/kg/min), hydroxylation rate of phenylalanine to tyrosine (μmol/kg/min) (derived from the appearance of labelled tyrosine from labelled phenylalanine), and net balance of phenylalanine (μmol/kg/min): calculated as the difference between Ra and Rd to assess overall protein balance.
Measured: 5 hours (2 hours postabsorptive, 3 hours postprandial)
Serum insulin concentrations
Serum insulin concentrations
Measured: 5 hours
Plasma beta hydroxybutyrate concentrations
Plasma beta hydroxybutyrate concentrations
Measured: 5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2025
- Study start4 Jun 2025
- Primary completionJul 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- 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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Exeter
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07082309
- Sponsor's protocol ID
- 9482953
- Acronym
- WAKM
- Status last verified
- Jul 2025
- First submitted
- 3 Jul 2025
- Last updated
- 24 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Ketone Monoesters on Skeletal Muscle Protein Synthesis and Whole-body Protein Metabolism.
- ClinicalTrials.gov ID
- NCT07082309
- Acronym / sponsor ID
- WAKM / 9482953
- Conditions
- Healthy Participants
- Keywords
- ketone monoesters, muscle protein synthesis, amino acid metabolism
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of ExeterUniversity, hospital or other
- Study start
- 4 Jun 2025 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 24 Jul 2025 (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 ketone β-hydroxybutyrate (BHB) is endogenously produced during periods of low glucose availability, serving as an alternative metabolic fuel. Beyond its role as an energy substrate, BHB acts as a pleiotropic signalling molecule, modulating various physiological processes across multiple tissues. BHB can also be ingested orally as a ketone monoester, transiently elevating plasma concentrations of BHB to a level similar to those seen following several days of fasting, thereby obviating the need for dietary manipulation. The influence of BHB on human skeletal muscle protein metabolism remains poorly understood, although emerging evidence suggests that BHB may play a role in regulating muscle protein turnover. As such, BHB supplementation may support skeletal muscle remodelling and offer therapeutic benefits, and investigating this is of considerable interest. This study will investigate the ability of oral BHB ingestion - co-ingested with protein - to stimulate skeletal muscle anabolism in young healthy adults. A dual amino acid stable isotope tracer approach will be utilised to determine postprandial (i.e., fed state) muscle protein synthesis (MPS) rates and whole-body amino acid kinetics, given BHBs systemic effects. This research will advance our understanding of the fundamental biology of exogenous ketosis and provide insight into the potential of BHB supplementation as a novel nutritional strategy to optimise muscle mass and quality.
Detailed description
The ketone body β-hydroxybutyrate (BHB) is produced endogenously during periods of low glucose availability (e.g., fasting or starvation) and provides an alternative metabolic fuel. BHB also acts as a metabolic signalling molecule, modulating physiological processes across multiple tissues, including skeletal muscle. However, the impact of exogenous ketosis on muscle protein turnover, which regulates muscle mass and modulates physical function, remains largely unexplored. As such, understanding how BHB affects skeletal muscle protein turnover is fundamentally important. The ingestion of 0.5g/kg body mass BHB appreciably increases plasma BHB concentrations for several hours, to ~3-5 mM; equivalent to several days of fasting. This offers a model to exogenously elevate plasma BHB concentrations and investigate how BHB interacts with feeding to affect postprandial protein metabolism, the period primarily responsible for driving changes in muscle quality and quantity.
An early study demonstrated that the infusion of BHB stimulates muscle protein synthesis rates (MPS), whilst only a single recent study has investigated the effect of oral BHB ingestion (exogenous ketosis) on MPS. Prior work demonstrated that the ingestion of an oral ketone monoester stimulated MPS, and it did so to a similar extent as 10 g whey protein or co-ingestion of the two, in healthy young males. While this study provides useful insights, several unanswered questions/objectives that justify the need for further investigation remain:
- To determine how BHB ingestion influences myofibrillar protein synthesis, plasma amino acid concentrations, and amino acid kinetics following the co-ingestion of a physiologically relevant meal-like protein dose.
- To examine how BHB ingestion affects plasma amino acid concentrations and kinetics following protein co-ingestion, addressing prior research limitations where differences in carbohydrate intake and postprandial insulin levels confounded the independent effects of ketones.
- To assess the impact of BHB ingestion on whole-body protein metabolism following protein co-ingestion, as previous studies have not examined its potential influence on protein breakdown, amino acid kinetics, and net protein balance.
- To investigate whether BHB ingestion influences mitochondrial muscle protein synthesis following protein co-ingestion, given its established effects on mitochondrial metabolism, yet unexamined role in mitochondrial protein turnover.
The aim, therefore, is to establish the effect of BHB and protein co-ingestion on myofibrillar protein synthesis rates, mitochondrial protein synthesis rates, and whole-body protein turnover. We will address this question by utilising a meal-like bolus of protein (0.3 g/kg whey protein), with and without 0.5g/kg body mass BHB (matching the test drinks caloric content via the addition of fat to minimally stimulate insulin secretion), whilst applying a dual-stable isotope tracer approach.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Dietary Supplement: ControlPlacebo with bitter agent (Bitrex), to flavour match to ketone condition, whey protein (0.3 g/kg), and milk fat (to match the caloric content of the ketone condition). |
| Ketone monoester | Experimental | Dietary Supplement: Ketone Monoester (KE) and whey protein beverageKetone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and whey protein (0.3 g/kg) |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- BMI 18-30
Key exclusion criteria (8 listed)
- Body mass index (BMI) < 18.5 or > 30 kg/m2
- Age < 18 or > 40
- Regularly smokes
- Type 2 diabetes
- Cardiovascular disease, metabolic disease and hypertension (≥ 140/90 mmHg)
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 |
|---|---|---|
| Ketone Monoester (KE) and whey protein beverageKetone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) and whey protein (0.3 g/kg) | Dietary supplement | Ketone monoester |
| ControlPlacebo with bitter agent (Bitrex), to flavour match to ketone condition, whey protein (0.3 g/kg), and milk fat (to match the caloric content of the ketone condition). | Dietary supplement | Control |
Primary outcome
Skeletal muscle protein synthesis rates (FSR)
Time frame: 5 hours (2 hours postabsorptive, 3 hours postprandial)
Skeletal muscle protein synthesis rates
4 secondary outcomes
Plasma amino acid concentrations
Time frame: 5 hours
Whole-body phenylalanine kinetics assessed by stable isotope tracer methodology, including rate of appearance (Ra), rate of disappearance (Rd), hydroxylation rate, and net balance.
Time frame: 5 hours (2 hours postabsorptive, 3 hours postprandial)
Serum insulin concentrations
Time frame: 5 hours
Plasma beta hydroxybutyrate concentrations
Time frame: 5 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2025.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone Monoester (KE) and whey protein beverage in people with Healthy Participants, run by University of Exeter at 1 site in United Kingdom.
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 1 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 24 Jul 2025. 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 United Kingdom. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alistair Monteyne, PhD (+44 (0)1392 72 4774, a.monteyne2@exeter.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skeletal muscle protein synthesis rates (FSR) (time frame: 5 hours (2 hours postabsorptive, 3 hours postprandial)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jul 2025.