Clinical trial NCT06032156: Ketone Dose and Cerebral Blood Flow Study
Official title: The Acute Effects of a High Versus Low Dose of a Ketone Monoester Supplement on Cerebral Blood Flow and Cognition
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cerebrovascular Function
Cognition
Keywords: Cerebral Blood Flow
Cognition
Beta-hydroxybutyrate (β-OHB)
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2023-09-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Resting cerebral blood flow (CBF)
timeFrame: 2-hour
Secondary outcomes:
measure: Cognitive Function
timeFrame: 2-hour
measure: Plasma beta-hydroxybutyrate area under the curve
timeFrame: 2-hour
measure: Brain-derived neurotrophic factor (BDNF)
timeFrame: 2-hour, then following completion of submaximal exercise bout
measure: Oxygen uptake (VO2)
timeFrame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
measure: End-tidal CO2
timeFrame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
measure: Mean arterial pressure (MAP)
timeFrame: 2-hour
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
Study officials:
affiliation: McMaster University
name: Jeremy J Walsh, PhD
role: PRINCIPAL_INVESTIGATOR
References: