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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
20
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.
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.
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.
McMaster University
Hamilton, Ontario, Canada
Resting cerebral blood flow (CBF)
Measured via duplex ultrasound of the extra-cranial arteries (internal carotid and vertebral arteries).
Time frame: 2-hour
Cognitive Function
The MST (Mnemonic Similarity Task) will be used to assess hippocampal-dependent memory and pattern separation.
Time frame: 2-hour
Plasma beta-hydroxybutyrate area under the curve
Venous blood samples will be obtained via intravenous catheter
Time frame: 2-hour
Brain-derived neurotrophic factor (BDNF)
Serum and plasma BDNF measured in venous blood samples will be obtained via intravenous catheter
Time frame: 2-hour, then following completion of submaximal exercise bout
Oxygen uptake (VO2)
Breath-by-breath analysis performed via metabolic cart
Time frame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
End-tidal CO2
Breath-by-breath analysis performed via PowerLab Gas Analyzer (AD Instruments)
Time frame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
Mean arterial pressure (MAP)
Automated blood pressure cuff measurement of brachial artery pressure in mmHg.
Time frame: 2-hour
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