Cardiovascular Risk FactorNCT04236388
Short Term Ketone Supplementation and Cardiometabolic Health
A study testing Ketone drink in people with Cardiovascular Risk Factor, run by Virginia Polytechnic Institute and State University at 1 site in United States.
Trial summary
The purpose of this research study is to determine if short-term consumption of a dietary ketone drink, which increases the blood circulation concentrations of beta-hydroxybutyrate, a ketone, affects blood vessel health and cognitive health in adults. Read more about this study
- Who is it for?
- Ages 50 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Risk Factor
- What is being tested?
- Ketone drink
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Oct 2020to 25 May 2022
- 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 50 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ability to provide informed consent
- 50-75 years of age
- Systolic blood pressure <160 mmHg
- Diastolic blood pressure <100 mmHg
- Sedentary to recreationally active
- Body Mass Index <35 kg/m^2
- Postmenopausal women must be >1 year since last menses
Who cannot join
- Current smoker
- Pregnant or planning to become pregnant
- Dyslipidemia (Total cholesterol >240 mg/dL, LDL >160 mg/dL)
- Chronic clinical disease (e.g., inflammatory bowel disease/irritable bowel syndrome, unstable coronary heart disease, stroke, heart failure, diabetes, neurological disorders)
- Following an extreme dietary pattern or planning to change to one (e.g., low carbohydrate, carnivore)
- Not weight stable in the prior 3 months (>2 kg weight change)
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Polytechnic and State University
Blacksburg, Virginia, 24061
About this study
Official title: Short Term Dietary Ketone Drink Consumption and Cardiometabolic Health in Adults
The purpose of this research study is to determine if short-term consumption of a dietary ketone drink, which increases the blood circulation concentrations of beta-hydroxybutyrate, a ketone, affects blood vessel health and cognitive health in adults. Ketones are normally produced by the liver when people fast longer than 16-24 hours or eat a diet low in carbohydrates. Participants will be asked to randomly consume a dietary ketone drink and placebo (flavored water) for a 2-week period each in a crossover fashion with a 2-week washout period while maintaining habitual diet and physical activity patterns.
The investigators hypothesize that consumption of a ketone drink will reduce BP and improve vascular health by reducing aortic pulse wave velocity and increasing brachial artery flow mediated dilation. Furthermore, they hypothesize that ketone consumption will improve cognitive health by increasing attention and processing speed.
Read the detailed description
Objective: The objective of this study is threefold: 1) To establish feasibility and proof-of-concept for the efficacy of ketone supplementation in reducing blood pressure and improving vascular and cognitive function in older adults; 2) Establish proficiency and feasibility with the proposed cognitive function measurements; and 3) Obtain preliminary data for effect size generation.
Background: Age is the primary risk factor for cardiovascular disease. Middle age is a vulnerable period where cardiovascular risk factors, such as BP, begin to emerge and signs and symptoms of disease first becomes evident. Hypertension is present in 60-75% of adults in this demographic and associated with vascular dysfunction and cognitive decline. Low Carbohydrate High Fat (LCHF) ketogenic diets have become increasingly popular for improving cardiometabolic health but adherence is suboptimal due to their restrictive nature. Supplementation with ketone drinks increase plasma β-hydroxybutyrate and mimics the metabolic effects of LCHF ketogenic diets as well as lowers BP and improves vascular and cognitive function in rodent models. Whether ketone supplementation lowers BP and improves vascular and cognitive health in humans of any age is unknown.
Approach: A double-blind randomized 2x2 crossover design with 2 repeated measures in each period will be used. Pre-/post-test evaluation in each period will be used to evaluate the benefits to vascular and cognitive health ingestion with consumption of a ketone drink/placebo drink.
- Conditions
- Cardiovascular Risk Factor
- Being tested
- Ketone drink, Placebo drink
- Keywords
- D-β-hydroxybutyrate, low carbohydrate high fat diet, blood pressure, cognitive function, flow mediated dilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone drinkDietary supplement
Pre- and post-testing will be completed before and after participants receive 42 doses of ketone supplement drink over a 2-week period (3x/day for 14 days).
Placebo drinkDietary supplement
Pre- and post-testing will be completed before and after participants receive 42 doses of placebo supplement drink over a 2-week period (3x/day for 14 days).
| Study group | Role | What they receive |
|---|---|---|
| Dietary Ketone | Active comparator | Participants will consume three daily ketone drinks (one before each meal) for 2 weeks. Receives: Dietary Supplement: Ketone drink |
| Placebo | Placebo comparator | Participants will consume three daily placebo drinks (one before each meal) for 2 weeks. . Receives: Dietary Supplement: Placebo drink |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Arterial Stiffness after Supplementation
The blood flow and diameter in the common arteries in the neck will be measured from the image obtained from an ultrasound unit (GE Vivid S6) equipped with a high-resolution linear array transducer. For applanation tonometry, the carotid, brachial, radial and femoral artery pressure waveform and amplitude will be obtained by a fingertip probe incorporating a high-fidelity strain gauge transducer. Each of these measures are used to calculate arterial stiffness. These tests will be conducted two times separated by about 2 weeks. The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design). The supplement drink will be consumed 3 times per day, once before each meal.
Measured: 45-minute measurement in laboratory
Change in Brachial Artery Function after Supplementation
Brachial artery function or flow mediated dilation (FMD), the blood flow and diameter of the brachial artery in the forearm (fMD), will be measured using a duplex ultrasound machine before and after the inflation of a blood pressure cuff on the forearm for 5 minutes and after placing a nitroglycerine tablet (0.4 mg) under the participant's tongue. This test will be conducted two times separated by about 2 weeks. The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design). The supplement drink will be consumed 3 times per day, once before each meal. Off-line analysis of baseline and post-reactive hyperemic diameters and velocities will be performed using edge detection software (Vascular Analysis Tools, Medical Imaging Applications, Inc.).
Measured: 30-minute measurement in laboratory
Secondary outcomes (4)
Change in Blood Pressure after Supplementation
Blood pressure measurements will be made under quiet, comfortable ambient laboratory conditions via mercury sphygmomanometry. Three consecutive measurements within 6mmHg will be averaged. This measurement will be conducted two times separated by about 2 weeks. The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design). The supplement drink will be consumed 3 times per day, once before each meal.
Measured: 15-minute measurement in laboratory
Change in Glucose Tolerance after Supplementation
Participants will complete an oral glucose tolerance test, which includes having each subject consume a sugary glucose drink (75 grams) and collecting small amounts (less than one half teaspoon) of blood every half hour (4 blood draws) for a 2-hour period. These tests will be conducted two times separated by about 2 weeks. Each participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design). The supplement drink will be consumed 3 times per day, once before each meal.
Measured: 2-hour test in laboratory
Change in 24-hour Area Under the Curve for Glucose Levels after Supplementation
Glucose will be monitored by a Continuous Glucose Monitor (CGM) sensor (Enlite Sensor, Medtronic, Inc. or FreeStyle Libre, Abbott) and this will be placed on the subject's abdomen or back of the upper arm in order to measure glucose continuously. The measured glucose levels will be assessed by an iPro2 Professional CGM, Medtronic, Inc. or FreeStyle Libre Pro CGM, Abbott and the CGM will be worn for consecutive 3 days. These tests will be conducted two times separated by about 2 weeks. The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design). The supplement drink will be consumed 3 times per day, once before each meal.
Measured: 3-day measurement during free living
Change in Executive Cognitive Function after Supplementation
Participants will be instructed to complete a set of computerized tasks to asses executive cognitive function (e.g., working memory), speed of processing, and semantic verbal fluency. These tests will be conducted two times separated by about 2 weeks. The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design). The supplement drink will be consumed 3 times per day, once before each meal.
Measured: 40-min measurement in laboratory
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2020
- Study start2 Oct 2020
- Primary completion17 Dec 2021
- Study completion25 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular Risk FactorStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Polytechnic Institute and State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kevin Davy, Virginia Polytechnic Institute and State University
- Investigators
- Kevin Davy, PhD, Principal investigator, Virginia Polytechnic Institute and State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04236388
- Sponsor's protocol ID
- 25-529
- Status last verified
- Mar 2026
- First submitted
- 16 Jan 2020
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Term Dietary Ketone Drink Consumption and Cardiometabolic Health in Adults
- ClinicalTrials.gov ID
- NCT04236388
- Acronym / sponsor ID
- 25-529
- Conditions
- Cardiovascular Risk Factor
- Keywords
- D-β-hydroxybutyrate, low carbohydrate high fat diet, blood pressure, cognitive function, flow mediated dilation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Virginia Polytechnic Institute and State UniversityUniversity, hospital or other
- Study start
- 2 Oct 2020 (actual)
- Primary completion
- 17 Dec 2021 (actual)
- Study completion
- 25 May 2022 (actual)
- First posted
- 22 Jan 2020 (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 research study is to determine if short-term consumption of a dietary ketone drink, which increases the blood circulation concentrations of beta-hydroxybutyrate, a ketone, affects blood vessel health and cognitive health in adults. Ketones are normally produced by the liver when people fast longer than 16-24 hours or eat a diet low in carbohydrates. Participants will be asked to randomly consume a dietary ketone drink and placebo (flavored water) for a 2-week period each in a crossover fashion with a 2-week washout period while maintaining habitual diet and physical activity patterns.
The investigators hypothesize that consumption of a ketone drink will reduce BP and improve vascular health by reducing aortic pulse wave velocity and increasing brachial artery flow mediated dilation. Furthermore, they hypothesize that ketone consumption will improve cognitive health by increasing attention and processing speed.
Detailed description
Objective: The objective of this study is threefold: 1) To establish feasibility and proof-of-concept for the efficacy of ketone supplementation in reducing blood pressure and improving vascular and cognitive function in older adults; 2) Establish proficiency and feasibility with the proposed cognitive function measurements; and 3) Obtain preliminary data for effect size generation.
Background: Age is the primary risk factor for cardiovascular disease. Middle age is a vulnerable period where cardiovascular risk factors, such as BP, begin to emerge and signs and symptoms of disease first becomes evident. Hypertension is present in 60-75% of adults in this demographic and associated with vascular dysfunction and cognitive decline. Low Carbohydrate High Fat (LCHF) ketogenic diets have become increasingly popular for improving cardiometabolic health but adherence is suboptimal due to their restrictive nature. Supplementation with ketone drinks increase plasma β-hydroxybutyrate and mimics the metabolic effects of LCHF ketogenic diets as well as lowers BP and improves vascular and cognitive function in rodent models. Whether ketone supplementation lowers BP and improves vascular and cognitive health in humans of any age is unknown.
Approach: A double-blind randomized 2x2 crossover design with 2 repeated measures in each period will be used. Pre-/post-test evaluation in each period will be used to evaluate the benefits to vascular and cognitive health ingestion with consumption of a ketone drink/placebo drink.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dietary Ketone | Active comparator | Dietary Supplement: Ketone drinkParticipants will consume three daily ketone drinks (one before each meal) for 2 weeks. |
| Placebo | Placebo comparator | Dietary Supplement: Placebo drinkParticipants will consume three daily placebo drinks (one before each meal) for 2 weeks. . |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Ability to provide informed consent
- 50-75 years of age
- Systolic blood pressure <160 mmHg
- Diastolic blood pressure <100 mmHg
- Sedentary to recreationally active
Key exclusion criteria (6 listed)
- Current smoker
- Pregnant or planning to become pregnant
- Dyslipidemia (Total cholesterol >240 mg/dL, LDL >160 mg/dL)
- Chronic clinical disease (e.g., inflammatory bowel disease/irritable bowel syndrome, unstable coronary heart disease, stroke, heart failure, diabetes, neurological disorders)
- Following an extreme dietary pattern or planning to change to one (e.g., low carbohydrate, carnivore)
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 drinkPre- and post-testing will be completed before and after participants receive 42 doses of ketone supplement drink over a 2-week period (3x/day for 14 days). | Dietary supplement | Dietary Ketone |
| Placebo drinkPre- and post-testing will be completed before and after participants receive 42 doses of placebo supplement drink over a 2-week period (3x/day for 14 days). | Dietary supplement | Placebo |
Primary outcome
Change in Arterial Stiffness after Supplementation
Time frame: 45-minute measurement in laboratory
The blood flow and diameter in the common arteries in the neck will be measured from the image obtained from an ultrasound unit (GE Vivid S6) equipped with a high-resolution linear array transducer. For applanation tonometry, the carotid, brachial, radial and femoral artery pressure waveform and amplitude will be obtained by a fingertip probe incorporating a high-fidelity strain gauge transducer. Each of these measures are used to calculate arterial stiffness. These tests will be conducted two times separated by about 2 weeks. The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design). The supplement drink will be consumed 3 times per day, once before each meal.
Change in Brachial Artery Function after Supplementation
Time frame: 30-minute measurement in laboratory
Brachial artery function or flow mediated dilation (FMD), the blood flow and diameter of the brachial artery in the forearm (fMD), will be measured using a duplex ultrasound machine before and after the inflation of a blood pressure cuff on the forearm for 5 minutes and after placing a nitroglycerine tablet (0.4 mg) under the participant's tongue. This test will be conducted two times separated by about 2 weeks. The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design). The supplement drink will be consumed 3 times per day, once before each meal. Off-line analysis of baseline and post-reactive hyperemic diameters and velocities will be performed using edge detection software (Vascular Analysis Tools, Medical Imaging Applications, Inc.).
4 secondary outcomes
Change in Blood Pressure after Supplementation
Time frame: 15-minute measurement in laboratory
Change in Glucose Tolerance after Supplementation
Time frame: 2-hour test in laboratory
Change in 24-hour Area Under the Curve for Glucose Levels after Supplementation
Time frame: 3-day measurement during free living
Change in Executive Cognitive Function after Supplementation
Time frame: 40-min measurement in laboratory
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 27 Mar 2026.
- 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. This study is not recruiting at the moment.
Kevin Davy, PhD principal investigator
Virginia Polytechnic Institute and State University
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 drink in people with Cardiovascular Risk Factor, run by Virginia Polytechnic Institute and State University 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 7 inclusion and 6 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 27 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 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?
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?
Change in Arterial Stiffness after Supplementation (time frame: 45-minute measurement in laboratory). The study lists 2 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 27 Mar 2026.