Ketone Dose and Cerebral Blood Flow Study

NCT06032156 | Completed

• 1 other identifier: kCBF
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebrovascular Function; Cognition

Keywords

Cerebral Blood Flow; Cognition; Beta-hydroxybutyrate (β-OHB)

Outcome Measures

Primary Outcomes (1)

• Resting cerebral blood flow (CBF)

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

  2-hour

Secondary Outcomes (6)

• Cognitive Function

  2-hour

• Plasma beta-hydroxybutyrate area under the curve

  2-hour

• Brain-derived neurotrophic factor (BDNF)

  2-hour, then following completion of submaximal exercise bout

• Oxygen uptake (VO2)

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

• End-tidal CO2

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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Single dose of a taste-matched calorie-free placebo

Other: Placebo

High Dose β-OHB

EXPERIMENTAL

Single dose of a ketone monoester (\[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight)

Dietary Supplement: High Dose β-OHB

Low Dose β-OHB

EXPERIMENTAL

Single dose of a ketone monoester (\[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight)

Dietary Supplement: Low Dose β-OHB

Interventions

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.

Low Dose β-OHB

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.

High Dose β-OHB

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- Between the ages of 18 and 35

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Location

Study Officials

• Jeremy J Walsh, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: September 11, 2023
• Study Start: November 8, 2023
• Primary Completion: May 30, 2024
• Study Completion: August 30, 2024
• Last Updated: February 13, 2026

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 12 months and ending 36 months following article publication.
• Access Criteria: Anyone who wishes to access the data.

Locations

CA (1)