Short Term Ketone Supplementation and Cardiometabolic Health

NCT04236388 | Completed DMC

• 1 other identifier: 25-529
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Cardiovascular Risk Factor

Keywords

D-β-hydroxybutyrate; low carbohydrate high fat diet; blood pressure; cognitive function; flow mediated dilation

Outcome Measures

Primary Outcomes (2)

• 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.

  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.).

  30-minute measurement in laboratory

Secondary Outcomes (4)

• Change in Blood Pressure after Supplementation

  15-minute measurement in laboratory

• Change in Glucose Tolerance after Supplementation

  2-hour test in laboratory

• Change in 24-hour Area Under the Curve for Glucose Levels after Supplementation

  3-day measurement during free living

• Change in Executive Cognitive Function after Supplementation

  40-min measurement in laboratory

Study Arms (2)

Dietary Ketone

ACTIVE COMPARATOR

Participants will consume three daily ketone drinks (one before each meal) for 2 weeks.

Dietary Supplement: Ketone drink

Placebo

PLACEBO COMPARATOR

Participants will consume three daily placebo drinks (one before each meal) for 2 weeks. .

Dietary Supplement: Placebo drink

Interventions

Ketone drink DIETARY_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).

Dietary Ketone

Placebo drink DIETARY_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).

Placebo

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Virginia Polytechnic Institute and State University: lead

Study Sites (1)

Virginia Polytechnic and State University

Blacksburg, Virginia, 24061, United States

Location

Study Officials

• Kevin Davy, PhD

  Virginia Polytechnic Institute and State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: January 22, 2020
• Study Start: October 2, 2020
• Primary Completion: December 17, 2021
• Study Completion: May 25, 2022
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)