Cerebrovascular Function, Cognition
Conditions
Keywords
Cerebral Blood Flow, Cognition, Beta-hydroxybutyrate (β-OHB)
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTLow 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.
DIETARY_SUPPLEMENTHigh 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.
OTHERPlacebo
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.
Sponsors
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
A randomized double-blind placebo-controlled crossover design will be used to test 3 conditions. Participants will consume 60 mL of a supplement containing: 1) a low β-OHB dose (0.3g/kg) body weight of the ketone monoester; \[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate); 2) a high β-OHB dose (0.6g/kg body weight); or 3) a taste-matched calorie-free inert placebo drink.
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resting cerebral blood flow (CBF) | 2-hour | Measured via duplex ultrasound of the extra-cranial arteries (internal carotid and vertebral arteries). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function | 2-hour | The MST (Mnemonic Similarity Task) will be used to assess hippocampal-dependent memory and pattern separation. |
| Plasma beta-hydroxybutyrate area under the curve | 2-hour | Venous blood samples will be obtained via intravenous catheter |
| Brain-derived neurotrophic factor (BDNF) | 2-hour, then following completion of submaximal exercise bout | Serum and plasma BDNF measured in venous blood samples will be obtained via intravenous catheter |
| Oxygen uptake (VO2) | 2-hour, then during submaximal exercise (performed after 2-hour rest period) | Breath-by-breath analysis performed via metabolic cart |
| End-tidal CO2 | 2-hour, then during submaximal exercise (performed after 2-hour rest period) | Breath-by-breath analysis performed via PowerLab Gas Analyzer (AD Instruments) |
| Mean arterial pressure (MAP) | 2-hour | Automated blood pressure cuff measurement of brachial artery pressure in mmHg. |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORJeremy J Walsh, PhD
McMaster University
Outcome results
None listed