The Effect of Acute Ketone Monoester Supplementation on Glucose Oxidation During Exercise (KETONE)

The Effect of Acute Ketone Monoester Supplementation on Glucose Oxidation During Exercise Performed With High Rates of Carbohydrate Ingestion in Trained Cyclists

The purpose of this study is to examine the effect of exogenous ketone body supplementation on carbohydrate metabolism during exercise. In a randomized, crossover, and double-blind study, 20 endurance trained adult males and females aged 18-50 years, will ingest carbohydrates with either a ketone monoester supplement before and throughout a 3-hour exercise session or carbohydrates with a flavour-matched ketone-free placebo. The main aim of this study is to compare the exogenous carbohydrate oxidation rates during exercise between the ketone monoester and placebo conditions.

Study Overview

• Status: Recruiting
• Conditions: Exercise Metabolism
• Intervention / Treatment: Dietary supplement: CHO+KETONE; Dietary supplement: CHO+PLACEBO

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luc van Loon, PhD; Phone Number: 0031 43 388 1743; Email: l.vanloon@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Recruiting
      • Maastricht University Medical Center+
      • Contact: LJC van Loon, Professor; Phone Number: 0031433881397; Email: L.vanLoon@maastrichtuniversity.nl
      • Sub-Investigator: Philippe Pinckaers, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-50 years of age
• Trained cyclist/triathlete (VO2peak > 55 ml/kg/min for males and >48 ml/mg/min for females)
• Healthy as per medical history and investigator's/physician's judgement
• Having given written informed consent

Exclusion Criteria:

• Use of medication that could impact study outcomes and/or interfere with the expected mechanism of action of ketone supplements (e.g. Chronic use of gastric acid suppressing medication, statins, corticosteroids)
• Smoking
• Diagnosed acute or chronic medical conditions that, in the opinion of the investigator, could impact study outcomes (e.g. Diabetes mellitus)
• Diagnosed musculoskeletal disorders
• Adhering to a carbohydrate restrictive diet
• Participation in another study at the same time
• Blood donation in the 2 months before the first experimental trial
• Plasma donation in the 2 weeks before the first experimental trial
• Males: VO2peak <55 ml/min/kg body mass
• Females: VO2peak <48 ml/min/kg body mass
• Females: pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CHO+KETONE; Interventional drink with glucose + ketone monoester	Dietary supplement: CHO+KETONE; Sports drink containing glucose and ketone mono-esters
Placebo Comparator: CHO+PLACEBO; Placebo drink with glucose + placebo	Dietary supplement: CHO+PLACEBO; Sports drink containing glucose and placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exogenous carbohydrate oxidation rate	Exogenous carbohydrate oxidation rate during exercise measured by 13C enrichment in breath. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endogenous carbohydrate disappearance rate	Endogenous carbohydrate disappearance rate during exercise measured by stable isotope tracer methodology. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise
Exogenous carbohydrate disappearance rate	Exogenous carbohydrate disappearance rate during exercise measured by stable isotope tracer methodology. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise
Total carbohydrate disappearance rate	Total carbohydrate disappearance rate during exercise measured by stable isotope tracer methodology. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise
Exogenous carbohydrate appearance rate	Exogenous carbohydrate appearance rate during exercise measured by stable isotope tracer methodology. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise
Endogenous carbohydrate appearance rate	Endogenous carbohydrate appearance rate during exercise measured by stable isotope tracer methodology. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise
Total carbohydrate appearance rate	Total carbohydrate appearance rate during exercise measured by stable isotope tracer methodology. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise
Plasma glucose enrichments during exercise	Plasma glucose enrichments during exercise measured by stable isotope tracer methodology. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total carbohydrate oxidation	Total carbohydrate oxidation during exercise, measured indirectly by using traditional stoichiometric calculations of carbohydrate oxidation. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise
Blood parameters	Plasma glucose, insulin, glycerol, free fatty acids, and ketone body concentrations (including area under the curve) following drink ingestion. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise
Exercise economy during cycling	Exercise economy during the exercise trial. CHO+KETONE vs CHO+PLACEBO condition, will be determined based on the amount of work performed during cycling (workload), and the amount of energy expenditure as measured by indirect calorimetry.	Acute:during 3 hours of exercise
Exercise heart rate	Heart rate during exercise. CHO+KETONE vs CHO+PLACEBO condition	Acute:during 3 hours of exercise

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 24, 2024

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: METC 23-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be made available upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No