Ketone Dose and Cerebral Blood Flow Study (kCBF)

The Acute Effects of a High Versus Low Dose of a Ketone Monoester Supplement on Cerebral Blood Flow and Cognition

Ketone bodies are produced by the liver during periods of food scarcity or severe carbohydrate restriction. Blood ketones are an alternative fuel source used by the brain, heart, and skeletal muscle during periods of fasting. Further, ketones bodies act as a signalling molecule that have pleiotropic effects that upregulate cellular stress-resistance pathways throughout the body.

Oral supplements containing exogenous ketones have recently become available and represent a novel tool for increasing plasma ketone bodies without the need for dietary restriction. Early evidence suggests that oral ketone supplements may enhance cerebral blood flow and improve cognition. However, the dose-dependent effects of a single ketone supplement on cerebral blood flow and cognition in young adults is currently unknown.

The purpose of this study is to characterize the effects of ingesting a high versus low dose of an oral ketone monoester on cerebral blood flow, circulating blood markers, and cognition in young adults.

As an exploratory aim, this study will investigate how oxygen uptake kinetics during submaximal exercise are impacted 2 hours after ingestion of a ketone supplement. Recent findings indicate that ketone supplementation may impair exercise performance due to the physiological stress (i.e., pH disturbances) imposed by an acute ketone dose. Delaying exercise onset by 2 hours after ingestion of a ketone supplement may enhance oxygen kinetics in a dose-dependent manner.

Study Overview

• Status: Completed
• Conditions: Cognition; Cerebrovascular Function
• Intervention / Treatment: Other: Placebo; Dietary supplement: High Dose β-OHB; Dietary supplement: Low Dose β-OHB

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- Between the ages of 18 and 35

Exclusion Criteria:

• Presence of obesity (body mass index > 30 kg/m^2)
• Presence of known cardiovascular disease
• Presence of type 2 diabetes
• History of cardiovascular events requiring hospitalization (i.e., heart attack)
• History of concussion(s) with persistent symptoms
• Currently following a ketogenic diet and/or taking ketone body supplements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Single dose of a taste-matched calorie-free placebo	Other: Placebo; Ingestion of a taste-matched calorie-free placebo drink followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.
Experimental: High Dose β-OHB; Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight)	Dietary supplement: High Dose β-OHB; Ingestion of a high dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.6 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.
Experimental: Low Dose β-OHB; Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight)	Dietary supplement: Low Dose β-OHB; Ingestion of a low dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.3 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting cerebral blood flow (CBF)	Measured via duplex ultrasound of the extra-cranial arteries (internal carotid and vertebral arteries).	2-hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Function	The MST (Mnemonic Similarity Task) will be used to assess hippocampal-dependent memory and pattern separation.	2-hour
Plasma beta-hydroxybutyrate area under the curve	Venous blood samples will be obtained via intravenous catheter	2-hour
Brain-derived neurotrophic factor (BDNF)	Serum and plasma BDNF measured in venous blood samples will be obtained via intravenous catheter	2-hour, then following completion of submaximal exercise bout
Oxygen uptake (VO2)	Breath-by-breath analysis performed via metabolic cart	2-hour, then during submaximal exercise (performed after 2-hour rest period)
End-tidal CO2	Breath-by-breath analysis performed via PowerLab Gas Analyzer (AD Instruments)	2-hour, then during submaximal exercise (performed after 2-hour rest period)
Mean arterial pressure (MAP)	Automated blood pressure cuff measurement of brachial artery pressure in mmHg.	2-hour

Collaborators and Investigators

• Sponsor: McMaster University
• Investigators: Principal Investigator: Jeremy J Walsh, PhD, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2023
• Primary Completion (Actual): May 30, 2024
• Study Completion (Actual): August 30, 2024

Study Registration Dates

• First Submitted: April 6, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Cognition; Cerebral Blood Flow; Beta-hydroxybutyrate (β-OHB)
• Other Study ID Numbers: kCBF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will share individual patient data (de-identified) with researchers upon request
• IPD Sharing Time Frame: Beginning 12 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Anyone who wishes to access the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No