Mechanistic Effect of Ketones on Cerebral Blood Flow

NCT06217159 | Completed

• 1 other identifier: MEKC
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebrovascular Function; Cerebral Blood Flow

Keywords

Cerebral Blood Flow; Beta-hydroxybutyrate (β-OHB); Cerebrovascular Function

Outcome Measures

Primary Outcomes (1)

• Resting cerebral blood flow (CBF)

  Measured via duplex ultrasound of the internal carotid artery and vertebral artery

  90-minutes

Secondary Outcomes (6)

• Plasma beta-hydroxybutyrate area under the curve

  90-minutes

• Blood pH

  90-minutes

• End-tidal CO2

  90-minutes

• Mean arterial pressure (MAP)

  90-minutes

• Cerebrovascular Reactivity of the Internal Carotid and Middle Cerebral Artery as assessed by Duplex Ultrasound and Transcranial Doppler Ultrasound, respectively.

  90-minutes

Study Arms (2)

Poikilocapnia

SHAM COMPARATOR

Room air-breathing

Dietary Supplement: Poikilocapnia

Normocapnia

EXPERIMENTAL

Breathing air mixture with slightly elevated CO2 to maintain PetCO2 to resting baseline levels

Dietary Supplement: Normocapnia

Interventions

Poikilocapnia DIETARY_SUPPLEMENT

Following ingestion of 0.6 g β-OHB/kg body weight ketone monoester, participants will wear a specialized face mask and breathe room air for 60 min. The face mask will be attached to an automated gas-blender system; however, only room air will be delivered.

Poikilocapnia

Normocapnia DIETARY_SUPPLEMENT

Following ingestion of 0.6 g β-OHB/kg body weight ketone monoester, participants will be outfitted with a specialized face mask and breathe air with a slightly higher concentration of CO2 to maintain PetCO2 to resting baseline values for 60 min. Gas will be continuously delivered by an automated gas-blender system.

Normocapnia

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Location

Study Officials

• Jeremy J Walsh, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: A randomized single-blind crossover design will be used to test 2 conditions. Participants will consume 60 mL of a supplement containing 0.6g/kg body weight of the ketone monoester (\[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate) in both conditions, and their PetCO2 will be maintained in the normocapnic conditions or not maintained in the poikilocapnic condition, in a randomized order.

Study Record Dates

• First Submitted: December 1, 2023
• First Posted: January 22, 2024
• Study Start: January 19, 2024
• Primary Completion: May 30, 2024
• Study Completion: August 31, 2024
• Last Updated: April 23, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 12 months and ending 36 months following article publication.
• Access Criteria: Anyone who wishes to access the data.

Locations

CA (1)