Brain HealthKETO-BRAINNCT07711990
Effects of Acute Ketone Supplementation on the Brain
A study testing Ketone Ester Drink in people with Brain Health, run by Christopher Crabtree at 1 site in United States.
Trial summary
The purpose of this study is to determine how a ketone ester supplement affects brain function, brain blood flow, and brain metabolism in healthy middle-aged and older adults. Ketones are naturally produced by the body during periods of fasting or carbohydrate restriction and serve as an alternative fuel source for… Read more about this study
- Who is it for?
- Ages 45 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Brain Health
- What is being tested?
- Ketone Ester Drink
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2026to Dec 2029
- 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 45 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥45 years and ≤65 years
- Able to comply with study requirements including presenting for each test session following an overnight fast and not following a ketogenic diet during the duration of the study.
- BMI between 18.5 and 30 kg/m2
Who cannot join
- Non-English Speaking
- Currently taking a ketone ester supplement, ketone salt supplement, or on a ketogenic diet
- Pregnancy, a urine pregnancy test will be given to all women before scanning to confirm nonpregnant status
- Currently breastfeeding
- Allergies to components in the test products, including milk protein, and not lactose intolerant
- History of high blood pressure
Show all 14Show fewer
- History of alcoholism (previous 2 years)
- History of illicit drug use
- History of head trauma involving loss of consciousness or skull fracture
- Diagnosed neurological disease
- Taking psychiatric prescriptive medications (antipsychotics, antidepressants, or barbiturates) or over-the-counter (OTC) medications (other than those taken as nutritional supplements for non-therapeutic indications)
- Current smoker
- Currently consuming a habitual ketogenic diet, or was consuming a habitual ketogenic diet in the past three months
- Any condition or material in the body that is a contraindication for MRI procedures
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The Ohio State University
Columbus, Ohio, 43210
Christopher Crabtree, Ph.D., 614-688-5623, Chrisstopher.Crabtree@osumc.edu
About this study
Official title: Effects of Acute Ketone Supplementation on the Brain [KETO-BRAIN]
The purpose of this study is to determine how a ketone ester supplement affects brain function, brain blood flow, and brain metabolism in healthy middle-aged and older adults. Ketones are naturally produced by the body during periods of fasting or carbohydrate restriction and serve as an alternative fuel source for the brain. Researchers are interested in whether increasing blood ketone levels through supplementation can alter brain activity and blood flow in ways that may support healthy brain function.
Participants will consume a ketone ester supplement and a placebo in separate study visits. Brain imaging, blood measurements, and cognitive testing will be used to evaluate the effects of each intervention. Findings from this study will help researchers better understand how ketones influence the healthy aging brain and may provide preliminary data for future studies in populations at risk for cognitive decline.
Read the detailed description
Alzheimer's disease and other age-related neurodegenerative conditions are associated with changes in brain energy metabolism that can occur years before symptoms develop. One of the earliest findings in these conditions is reduced utilization of glucose by certain brain regions. Ketones, including beta-hydroxybutyrate, can serve as an alternative fuel source for the brain and may help support brain metabolism when glucose utilization is impaired. Experimental evidence also suggests ketones may influence cerebral blood flow, neurotransmitter balance, and functional brain connectivity.
Despite growing interest in ketone supplementation, the acute effects of ketone esters on multiple aspects of human brain function have not been comprehensively evaluated. This study will investigate whether acute ketone ester ingestion alters cerebral blood flow, brain neurochemistry, resting-state brain connectivity, and cognitive performance in healthy adults.
This is a randomized, double-blind, placebo-controlled crossover study. Participants will complete two intervention periods, receiving a ketone ester supplement during one period and a calorie-matched placebo during the other. The order of interventions will be randomized and separated by a washout period of 3 to 7 days. Participants will consume study beverages for two days prior to each testing session and will undergo detailed testing following an overnight fast.
At each testing visit, participants will provide fingerstick blood samples to measure ketone and glucose concentrations, complete standardized cognitive testing, and undergo advanced magnetic resonance imaging (MRI). Brain imaging will include arterial spin labeling (ASL) to evaluate cerebral blood flow, proton magnetic resonance spectroscopy (1H-MRS) to assess brain metabolite and neurotransmitter concentrations, and functional MRI (fMRI) to assess resting-state brain network connectivity. Cardiac MRI measures will also be collected to explore relationships between cardiovascular and cerebrovascular responses.
The primary goal is to determine whether acute ketone supplementation changes cerebral blood flow, brain metabolite concentrations, and functional brain connectivity compared with placebo. Secondary analyses will evaluate relationships between blood ketone concentrations, imaging measures, and cognitive performance. Results from this pilot study will provide important mechanistic information regarding how ketones affect the healthy aging brain and will support the development of future clinical trials in populations at risk for cognitive impairment.
The study lasts about two weeks. There are two main test days with 3-7 days in between. Each testing session will last up to 3.5 hours at most.
- Conditions
- Brain Health
- Being tested
- Ketone Ester Drink, Placebo
- Keywords
- ketone supplement, brain MRI, brain MRS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone Ester DrinkDietary supplement
The ketone ester beverage contains 25 g of C8 Diester emulsified in a matrix of water, whey protein concentrate, modified gum acacia, natural and artificial flavors and cocoa powder. It contains 210 kcal, 0.5 g fat, 2 g carbohydrates, and 2 g protein. Dose consumed is 50 g, 2 times per day for 2 days.
The placebo (PL) will be calorie and volume matched to the KE and be formulated with standard dietary ingredients.
PlaceboDietary supplement
The placebo drink will be calorie and volume matched to the KE and be formulated with standard dietary ingredients.
| Study group | Role | What they receive |
|---|---|---|
| Ketone Supplement drink | Active comparator | Drink contains 25 g of C8 Diester , 50g consumed total per day using split dose Receives: Dietary Supplement: Ketone Ester Drink |
| Placebo Drink | Placebo comparator | Drink contains no ketones, kcal and volume matched Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral Blood Flow
To detect a clinically meaningful difference in cerebral blood flow (CBF) between ketone ester and placebo conditions in healthy adults
Measured: Acute response following 2-day lead in
Brain Glutamate Concentration
To detect a difference in brain glutamate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Brain GABA Concentration
To detect a difference in brain gamma-aminobutyric acid (GABA) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Brain Lactate Concentration
To detect a difference in brain lactate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Brain Choline Concentration
To detect a difference in brain choline concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Brain N-Acetylaspartate (NAA) Concentration
To detect a difference in brain N-acetylaspartate (NAA) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Brain Glucose Concentration
To detect a difference in brain glucose concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Brain Beta-Hydroxybutyrate (BHB) Concentration
To detect a difference in brain beta-hydroxybutyrate (BHB) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Functional Brain Connectivity
Change in resting-state brain network connectivity measured using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI).
Measured: Acute response following 2-day lead in
Brain Acetoacetate Concentration
To detect a difference in brain acetoacetate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Brain Glutamine Concentration
To detect a difference in brain glutamine concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Measured: Acute response following 2-day lead in
Secondary outcomes (3)
Blood Ketone Concentration
Blood beta-hydroxybutyrate concentrations measured by fingerstick testing.
Measured: Acute response following 2-day lead in
Blood Glucose Concentration
Blood glucose concentrations measured by fingerstick testing.
Measured: Acute response following 2-day lead in
Cognitive Performance (RBANS Total Scale Score)
Total Scale Score on the RBANS, comparing ketone ester and placebo conditions in healthy adults.
Measured: Acute response following 2-day lead in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2026
- Study start15 Jun 2026
- Primary completionDec 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain HealthStudies 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
- Model description
- This study uses a randomized, double-blind, placebo-controlled crossover design. Participants will complete two intervention periods in random order, receiving a ketone ester supplement during one period and a placebo during the other. Each intervention period includes a two-day supplementation lead-in followed by a testing visit. The two intervention periods are separated by a 3- to 7-day washout period. Investigators and participants will remain blinded to treatment assignment until study completion.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Christopher Crabtree
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Christopher Crabtree, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07711990
- Sponsor's protocol ID
- STUDY20251460
- Acronym
- KETO-BRAIN
- Status last verified
- Jul 2026
- First submitted
- 13 Jul 2026
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Decision on data sharing not yet finalized.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Acute Ketone Supplementation on the Brain [KETO-BRAIN]
- ClinicalTrials.gov ID
- NCT07711990
- Acronym / sponsor ID
- KETO-BRAIN / STUDY20251460
- Conditions
- Brain Health
- Keywords
- ketone supplement, brain MRI, brain MRS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Christopher CrabtreeUniversity, hospital or other
- Study start
- 15 Jun 2026 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 17 Jul 2026 (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 purpose of this study is to determine how a ketone ester supplement affects brain function, brain blood flow, and brain metabolism in healthy middle-aged and older adults. Ketones are naturally produced by the body during periods of fasting or carbohydrate restriction and serve as an alternative fuel source for the brain. Researchers are interested in whether increasing blood ketone levels through supplementation can alter brain activity and blood flow in ways that may support healthy brain function.
Participants will consume a ketone ester supplement and a placebo in separate study visits. Brain imaging, blood measurements, and cognitive testing will be used to evaluate the effects of each intervention. Findings from this study will help researchers better understand how ketones influence the healthy aging brain and may provide preliminary data for future studies in populations at risk for cognitive decline.
Detailed description
Alzheimer's disease and other age-related neurodegenerative conditions are associated with changes in brain energy metabolism that can occur years before symptoms develop. One of the earliest findings in these conditions is reduced utilization of glucose by certain brain regions. Ketones, including beta-hydroxybutyrate, can serve as an alternative fuel source for the brain and may help support brain metabolism when glucose utilization is impaired. Experimental evidence also suggests ketones may influence cerebral blood flow, neurotransmitter balance, and functional brain connectivity.
Despite growing interest in ketone supplementation, the acute effects of ketone esters on multiple aspects of human brain function have not been comprehensively evaluated. This study will investigate whether acute ketone ester ingestion alters cerebral blood flow, brain neurochemistry, resting-state brain connectivity, and cognitive performance in healthy adults.
This is a randomized, double-blind, placebo-controlled crossover study. Participants will complete two intervention periods, receiving a ketone ester supplement during one period and a calorie-matched placebo during the other. The order of interventions will be randomized and separated by a washout period of 3 to 7 days. Participants will consume study beverages for two days prior to each testing session and will undergo detailed testing following an overnight fast.
At each testing visit, participants will provide fingerstick blood samples to measure ketone and glucose concentrations, complete standardized cognitive testing, and undergo advanced magnetic resonance imaging (MRI). Brain imaging will include arterial spin labeling (ASL) to evaluate cerebral blood flow, proton magnetic resonance spectroscopy (1H-MRS) to assess brain metabolite and neurotransmitter concentrations, and functional MRI (fMRI) to assess resting-state brain network connectivity. Cardiac MRI measures will also be collected to explore relationships between cardiovascular and cerebrovascular responses.
The primary goal is to determine whether acute ketone supplementation changes cerebral blood flow, brain metabolite concentrations, and functional brain connectivity compared with placebo. Secondary analyses will evaluate relationships between blood ketone concentrations, imaging measures, and cognitive performance. Results from this pilot study will provide important mechanistic information regarding how ketones affect the healthy aging brain and will support the development of future clinical trials in populations at risk for cognitive impairment.
The study lasts about two weeks. There are two main test days with 3-7 days in between. Each testing session will last up to 3.5 hours at most.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- This study uses a randomized, double-blind, placebo-controlled crossover design. Participants will complete two intervention periods in random order, receiving a ketone ester supplement during one period and a placebo during the other. Each intervention period includes a two-day supplementation lead-in followed by a testing visit. The two intervention periods are separated by a 3- to 7-day washout period. Investigators and participants will remain blinded to treatment assignment until study completion.
| Arm | Type | Receives |
|---|---|---|
| Ketone Supplement drink | Active comparator | Dietary Supplement: Ketone Ester DrinkDrink contains 25 g of C8 Diester , 50g consumed total per day using split dose |
| Placebo Drink | Placebo comparator | Dietary Supplement: PlaceboDrink contains no ketones, kcal and volume matched |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥45 years and ≤65 years
- Able to comply with study requirements including presenting for each test session following an overnight fast and not following a ketogenic diet during the duration of the study.
- BMI between 18.5 and 30 kg/m2
Key exclusion criteria (14 listed)
- Non-English Speaking
- Currently taking a ketone ester supplement, ketone salt supplement, or on a ketogenic diet
- Pregnancy, a urine pregnancy test will be given to all women before scanning to confirm nonpregnant status
- Currently breastfeeding
- Allergies to components in the test products, including milk protein, and not lactose intolerant
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 Ester DrinkThe ketone ester beverage contains 25 g of C8 Diester emulsified in a matrix of water, whey protein concentrate, modified gum acacia, natural and artificial flavors and cocoa powder. It contains 210 kcal, 0.5 g fat, 2 g carbohydrates, and 2 g protein. Dose consumed is 50 g, 2 times per day for 2 days. The placebo (PL) will be calorie and volume matched to the KE and be formulated with standard dietary ingredients. | Dietary supplement | Ketone Supplement drink |
| PlaceboThe placebo drink will be calorie and volume matched to the KE and be formulated with standard dietary ingredients. | Dietary supplement | Placebo Drink |
Primary outcome
Cerebral Blood Flow
Time frame: Acute response following 2-day lead in
To detect a clinically meaningful difference in cerebral blood flow (CBF) between ketone ester and placebo conditions in healthy adults
Brain Glutamate Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain glutamate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Brain GABA Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain gamma-aminobutyric acid (GABA) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Brain Lactate Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain lactate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Brain Choline Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain choline concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Brain N-Acetylaspartate (NAA) Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain N-acetylaspartate (NAA) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Brain Glucose Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain glucose concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Brain Beta-Hydroxybutyrate (BHB) Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain beta-hydroxybutyrate (BHB) concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Functional Brain Connectivity
Time frame: Acute response following 2-day lead in
Change in resting-state brain network connectivity measured using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI).
Brain Acetoacetate Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain acetoacetate concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
Brain Glutamine Concentration
Time frame: Acute response following 2-day lead in
To detect a difference in brain glutamine concentration (mM) between ketone ester and placebo conditions in healthy adults, measured using proton magnetic resonance spectroscopy (1H-MRS).
3 secondary outcomes
Blood Ketone Concentration
Time frame: Acute response following 2-day lead in
Blood Glucose Concentration
Time frame: Acute response following 2-day lead in
Cognitive Performance (RBANS Total Scale Score)
Time frame: Acute response following 2-day lead in
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 17 Jul 2026.
- Individual participant dataSharing planned: Undecided. Decision on data sharing not yet finalized.
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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 Ester Drink in people with Brain Health, run by Christopher Crabtree at 1 site in United States.
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 3 inclusion and 14 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 17 Jul 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 States. 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. Some participants in this study may receive a placebo. 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 Christopher Crabtree, Ph.D. (614-688-5623, Christopher.Crabtree@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cerebral Blood Flow (time frame: Acute response following 2-day lead in). The study lists 11 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 17 Jul 2026.