NutritionKETO-GENETICNCT06668168
The Causal Role of Ketone Bodies in Obesity-associated Disease Prevention - Combining Genetic Epidemiology With a Randomised Trial to Infer Causality
A study testing Ketone Monoester (KE) and Ketogenic diet in people with Nutrition and Obesity and Overweight, run by University of Bath at 1 site in United Kingdom.
Trial summary
Excess weight increases the risk of several diseases including cardiovascular disease, type 2 diabetes, kidney disease and various cancers. There is a need for preventative strategies for obesity-associated disease, especially for people in the overweight and moderately obese ranges where pharmacological intervention… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Nutrition, Obesity and Overweight
- What is being tested?
- Ketone Monoester (KE) and Ketogenic diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 6 May 2025to 3 Jun 2026
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index: 25-45 kg/m2
- Waist circumference >93.9 (males) or >79.9 (females)
Who cannot join
- Glucose or lipid lowering medication
- Diagnosis of cardiovascular disease, renal failure, liver disease or type 2 diabetes
- Contraindications to a ketogenic diet (e.g., pancreatitis, liver failure, disorders of fat metabolism, primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency, porphyrias, or pyruvate kinase deficiency)
- Unable to understand English language
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Causal Role of Ketone Bodies in Obesity-Associated Disease Prevention - Combining Genetic Epidemiology With a Randomised Trial to Infer Causality
Excess weight increases the risk of several diseases including cardiovascular disease, type 2 diabetes, kidney disease and various cancers. There is a need for preventative strategies for obesity-associated disease, especially for people in the overweight and moderately obese ranges where pharmacological intervention may not be suitable.
Low-carbohydrate (ketogenic) diets are popular for weight control. Ketogenic diets increase circulating ketones, which can have favourable effects on cardiometabolic health markers. However, the ketogenic diet has a nutrient composition associated with harms (high-saturated fat/red meat, and low-fibre). The net effects of ketogenic diets on long-term health are unclear. Ketone supplements can increase circulating ketones and could provide benefits of ketosis without needing to adhere to a potentially harmful diet.
Read more
Establishing causality between complex exposures (e.g., diet) and long-term outcomes (e.g., disease), is challenging. The MRC \& NIHR Review of Nutrition and Human Health Research (2017) highlighted an "overreliance (as opposed to reasonable reliance) on observational studies" as a key barrier to progression in the field of nutrition and health. Randomised controlled trials (RCTs) facilitate causal inference, but for long-term outcomes are expensive, time-consuming, and often suffer from waning adherence. Mendelian randomization (MR) can estimate causal effects subject to key assumptions. A challenge to these assumptions includes complex behavioural exposures (e.g., diet), which could be intercorrelated with causal factors.
Our proposal will address these limitations with a novel combination of study designs to establish causal effects of ketosis (via diet and supplementation) on obesity-associated disease risk in humans.
The investigators will combine a tightly controlled, short-term RCT, with MR to link short-term responses to long-term endpoints. The investigators will examine the circulating (blood) and tissue-specific (adipose) transcriptomic and proteomic responses in the fasted and postprandial state in response to our dietary interventions and translate these to MR by identifying single-nucleotide polymorphisms from genome wide association studies. This approach overcomes limitations of RCTs and MR, as adherence to diets will be confirmed with controlled feeding, and intermediate molecular traits as exposure for MR are less likely to be intercorrelated with causal traits.
- Conditions
- Nutrition, Obesity and Overweight
- Being tested
- Ketone Monoester (KE), Ketogenic diet
- Keywords
- Ketogenic diet
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone Monoester (KE)Dietary supplement
25g ketone ester 3x/day. The ketone ester will be a beta-hydroxybutyrate monoester [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate].
Ketogenic dietBehavioural
Ketogenic diet (<50 g carbohydrate per day)
| Study group | Role | What they receive |
|---|---|---|
| CONTROL | No intervention | Not described |
| KETONE ESTER | Active comparator | Not described Receives: Dietary Supplement: Ketone Monoester (KE) |
| KETOGENIC DIET | Experimental | Not described Receives: Behavioral: Ketogenic diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma proteome
Plasma proteome at week 4 adjusted for baseline values
Measured: From baseline to week 4
Transcriptome of peripheral blood mononuclear cells
Transcriptome of peripheral blood mononuclear cells at week 4 adjusting for baseline values
Measured: From baseline to week 4
Transcriptome of adipose tissue
Transcriptome of subcutaneous abdominal adipose tissue at week 4 adjusting for baseline values
Measured: From baseline to week 4
Secondary outcomes (3)
Apolipoprotein B concentrations
Plasma apolipoprotein B concentrations at week 4 adjusted for baseline values.
Measured: From baseline to week 4
Urinary albumin concentrations
Urinary albumin concentrations at week 4 adjusting for baseline values
Measured: From baseline to week 4
Fasting glucose concentrations
Plasma fasting glucose concentrations at week 4 adjusting for baseline values
Measured: From baseline to week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2024
- Study start6 May 2025
- Primary completion3 Jun 2026
- Study completion3 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NutritionStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bath
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bristol, Imperial College London
- Responsible party
- Principal investigator, Javier Gonzalez, University of Bath
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06668168
- Sponsor's protocol ID
- 23-09665
- Acronym
- KETO-GENETIC
- Status last verified
- Jun 2026
- First submitted
- 30 Oct 2024
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Causal Role of Ketone Bodies in Obesity-Associated Disease Prevention - Combining Genetic Epidemiology With a Randomised Trial to Infer Causality
- ClinicalTrials.gov ID
- NCT06668168
- Acronym / sponsor ID
- KETO-GENETIC / 23-09665
- Conditions
- Nutrition, Obesity and Overweight
- Keywords
- Ketogenic diet
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- University of BathUniversity, hospital or other
- Collaborators
- University of Bristol, Imperial College London
- Study start
- 6 May 2025 (actual)
- Primary completion
- 3 Jun 2026 (actual)
- Study completion
- 3 Jun 2026 (actual)
- First posted
- 31 Oct 2024 (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.
Excess weight increases the risk of several diseases including cardiovascular disease, type 2 diabetes, kidney disease and various cancers. There is a need for preventative strategies for obesity-associated disease, especially for people in the overweight and moderately obese ranges where pharmacological intervention may not be suitable.
Low-carbohydrate (ketogenic) diets are popular for weight control. Ketogenic diets increase circulating ketones, which can have favourable effects on cardiometabolic health markers. However, the ketogenic diet has a nutrient composition associated with harms (high-saturated fat/red meat, and low-fibre). The net effects of ketogenic diets on long-term health are unclear. Ketone supplements can increase circulating ketones and could provide benefits of ketosis without needing to adhere to a potentially harmful diet.
Establishing causality between complex exposures (e.g., diet) and long-term outcomes (e.g., disease), is challenging. The MRC \& NIHR Review of Nutrition and Human Health Research (2017) highlighted an "overreliance (as opposed to reasonable reliance) on observational studies" as a key barrier to progression in the field of nutrition and health. Randomised controlled trials (RCTs) facilitate causal inference, but for long-term outcomes are expensive, time-consuming, and often suffer from waning adherence. Mendelian randomization (MR) can estimate causal effects subject to key assumptions. A challenge to these assumptions includes complex behavioural exposures (e.g., diet), which could be intercorrelated with causal factors.
Our proposal will address these limitations with a novel combination of study designs to establish causal effects of ketosis (via diet and supplementation) on obesity-associated disease risk in humans.
The investigators will combine a tightly controlled, short-term RCT, with MR to link short-term responses to long-term endpoints. The investigators will examine the circulating (blood) and tissue-specific (adipose) transcriptomic and proteomic responses in the fasted and postprandial state in response to our dietary interventions and translate these to MR by identifying single-nucleotide polymorphisms from genome wide association studies. This approach overcomes limitations of RCTs and MR, as adherence to diets will be confirmed with controlled feeding, and intermediate molecular traits as exposure for MR are less likely to be intercorrelated with causal traits.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CONTROL | No intervention | – |
| KETONE ESTER | Active comparator | Dietary Supplement: Ketone Monoester (KE) |
| KETOGENIC DIET | Experimental | Behavioral: Ketogenic diet |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Body mass index: 25-45 kg/m2
- Waist circumference >93.9 (males) or >79.9 (females)
Key exclusion criteria (4 listed)
- Glucose or lipid lowering medication
- Diagnosis of cardiovascular disease, renal failure, liver disease or type 2 diabetes
- Contraindications to a ketogenic diet (e.g., pancreatitis, liver failure, disorders of fat metabolism, primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency, porphyrias, or pyruvate kinase deficiency)
- Unable to understand English language
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)25g ketone ester 3x/day. The ketone ester will be a beta-hydroxybutyrate monoester [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate]. | Dietary supplement | KETONE ESTER |
| Ketogenic dietKetogenic diet (<50 g carbohydrate per day) | Behavioural | KETOGENIC DIET |
Primary outcome
Plasma proteome
Time frame: From baseline to week 4
Plasma proteome at week 4 adjusted for baseline values
Transcriptome of peripheral blood mononuclear cells
Time frame: From baseline to week 4
Transcriptome of peripheral blood mononuclear cells at week 4 adjusting for baseline values
Transcriptome of adipose tissue
Time frame: From baseline to week 4
Transcriptome of subcutaneous abdominal adipose tissue at week 4 adjusting for baseline values
3 secondary outcomes
Apolipoprotein B concentrations
Time frame: From baseline to week 4
Urinary albumin concentrations
Time frame: From baseline to week 4
Fasting glucose concentrations
Time frame: From baseline to week 4
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 15 Jun 2026.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Ketogenic diet in people with Nutrition and Obesity and Overweight, run by University of Bath 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 2 inclusion and 4 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 15 Jun 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 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?
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?
Plasma proteome (time frame: From baseline to week 4). The study lists 3 primary outcomes in all. 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 15 Jun 2026.