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Completed

NCT Number: NCT06032156

Ketone Dose and Cerebral Blood Flow Study

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.

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Key information

Age range

18 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Low Dose β-OHB

Dietary Supplement

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.

High Dose β-OHB

Dietary Supplement

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.

Placebo

Other

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.

Primary outcomes

  1. Resting cerebral blood flow (CBF)

    Time frame: 2-hour

    Measured via duplex ultrasound of the extra-cranial arteries (internal carotid and vertebral arteries).

Secondary outcomes

  1. Cognitive Function

    Time frame: 2-hour

    The MST (Mnemonic Similarity Task) will be used to assess hippocampal-dependent memory and pattern separation.

  2. Plasma beta-hydroxybutyrate area under the curve

    Time frame: 2-hour

    Venous blood samples will be obtained via intravenous catheter

  3. Brain-derived neurotrophic factor (BDNF)

    Time frame: 2-hour, then following completion of submaximal exercise bout

    Serum and plasma BDNF measured in venous blood samples will be obtained via intravenous catheter

  4. Oxygen uptake (VO2)

    Time frame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)

    Breath-by-breath analysis performed via metabolic cart

  5. End-tidal CO2

    Time frame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)

    Breath-by-breath analysis performed via PowerLab Gas Analyzer (AD Instruments)

  6. Mean arterial pressure (MAP)

    Time frame: 2-hour

    Automated blood pressure cuff measurement of brachial artery pressure in mmHg.

Sponsors and collaborators

Lead sponsor

McMaster University

Other

Registry information

Official study title

The Acute Effects of a High Versus Low Dose of a Ketone Monoester Supplement on Cerebral Blood Flow and Cognition

Acronym: kCBF

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Sep 11, 2023
Registry last updated
Feb 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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