Mechanistic Effect of Ketones on Cerebral Blood Flow

Not Applicable

Completed

• Conditions: Cerebral Blood Flow; Cerebrovascular Function
• Interventions: Dietary Supplement: Poikilocapnia; Dietary Supplement: Normocapnia

• Registration Number: NCT06217159
• Lead Sponsor: McMaster University

Brief Summary

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 (CBF). However, a higher dose of a ketone monoester has been shown to slightly lower blood pH and reduce end-tidal CO2 (PetCO2) due to compensatory hyperventilation, which is accompanied by parallel reductions in CBF. Whether reductions in PetCO2 causes reductions in CBF is currently unknown.

The purpose of this study is to investigate the effect of manipulating PetCO2 at normocapnia (PetCO2 maintained at baseline) or poikilocapnia (no PetCO2 targeting; breathing room air), following the ingestion of a dose of a ketone monoester on CBF and cerebrovascular reactivity to CO2 in young adults.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-12-01
• Study First Submitted QC: 2024-01-10
• Study Start: 2024-01-19
• Study First Posted: 2024-01-22
• Primary Completion: 2024-05-30
• Study Completion: 2024-08-31
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• Having a normal blood pressure (≤125/≤85 mmHg)
• Between the ages of 18 and 35

Exclusion Criteria

• Individuals who are obese (body mass index > 30 kg/m^2)
• Individuals who smoke
• Individuals with respiratory illnesses
• A history of type 2 diabetes, hypoglycemia, or cardiovascular diseases (i.e. heart attack, stroke)
• Individuals currently following a ketogenic diet or taking ketone supplements
• Individuals with a history of concussion(s) with persistent symptoms
• Individuals participating in elite-level physical training (i.e. varsity athletics)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Poikilocapnia	Poikilocapnia	Room air-breathing
Normocapnia	Normocapnia	Breathing air mixture with slightly elevated CO2 to maintain PetCO2 to resting baseline levels

Primary Outcome Measures

Name	Time	Method
Resting cerebral blood flow (CBF)	90-minutes	Measured via duplex ultrasound of the internal carotid artery and vertebral artery

Secondary Outcome Measures

Name	Time	Method
Plasma beta-hydroxybutyrate area under the curve	90-minutes	Venous blood samples will be obtained via intravenous catheter
Middle Cerebral Artery Blood Velocity	90-minutes	Measured via transcranial Doppler Ultrasound using a 2MHz probe
Cerebrovascular Reactivity of the Internal Carotid and Middle Cerebral Artery as assessed by Duplex Ultrasound and Transcranial Doppler Ultrasound, respectively.	90-minutes	Automated gas-blender used to apply sequential gas delivery using an algorithm to target end-tidal CO2 at +3mmHg, +6mmHg, and +9mmHg above baseline, using five-minute step-wise stages. Simultaneously, changes in cerebral blood flow in the internal carotid artery and the middle cerebral artery will be assessed using duplex ultrasound and transcranial Doppler ultrasound, respectively. The final minute of each stage will be analyzed to characterize the slope of cerebrovascular reactivity to CO2 in the internal carotid artery and the middle cerebral artery.
Blood pH	90-minutes	Venous blood samples will be obtained via intravenous catheter
End-tidal CO2	90-minutes	Breath-by-breath analysis performed via RespirAct (RespirAct, Thornhill Research, Toronto, ON, Canada).
Mean arterial pressure (MAP)	90-minutes	Automated blood pressure cuff measurements of brachial artery pressure in mmHg

Trial Locations

Locations (1)

McMaster University; 🇨🇦 Hamilton, Ontario, Canada