Cerebral Blood Flow, Cerebrovascular Function
Conditions
Keywords
Cerebral Blood Flow, Beta-hydroxybutyrate (β-OHB), Cerebrovascular Function
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.
Interventions
DIETARY_SUPPLEMENTPoikilocapnia
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.
DIETARY_SUPPLEMENTNormocapnia
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.
Sponsors
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resting cerebral blood flow (CBF) | 90-minutes | Measured via duplex ultrasound of the internal carotid artery and vertebral artery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Plasma beta-hydroxybutyrate area under the curve | 90-minutes | Venous blood samples will be obtained via intravenous catheter |
| 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. |
| Middle Cerebral Artery Blood Velocity | 90-minutes | Measured via transcranial Doppler Ultrasound using a 2MHz probe |
| Mean arterial pressure (MAP) | 90-minutes | Automated blood pressure cuff measurements of brachial artery pressure in mmHg |
Countries
Canada
Outcome results
None listed