The Effects of Exogenous Ketosis on Ultra-endurance Recovery and Performance

Exploring the Role of Intermittent Exogenous Ketosis on Physical and Mental Fatigue During Ultra-endurance Performance

The study aims to investigate the effects of post-exercise and pre-sleep ketosis via oral ketone ester supplementation on physical and mental recovery during a multi-day cycling stage race.

Study Overview

• Status: Completed
• Conditions: Endurance Cycling Performance; Exogenous Ketosis; Fatigue, Mental; Fatigue; Muscle, Heart
• Intervention / Treatment: Dietary supplement: Placebo Supplement; Dietary supplement: Ketone ester supplement

Detailed Description

Ultra-endurance events are becoming increasing popular. Participation in the multi-day events adds a lot of physical and mental strain on the body, while the athletes are still required to perform. Without appropriate recovery the athletes are at increased risk of overreaching, injury, or illness.

Therefore, the purpose of the study is to create a better understanding of the exercise fatigue experienced during ultra-endurance performance and the role intermittent exogenous ketosis (IEK) plays in reducing the amount of fatigue to maintain performance during multi-day racing and lower the risk of injury and illness.

Participants will first compete in a 8-day simulated stage race performed on taxc trainers and then we will conduct a field study during the Absa Cape Epic a 8-day mountain bike stage race. Immediately following each stage and 30-mins before bed the participants will consume either a ketone ester and taste-match placebo drink. During the race the following variables will be measured; hydration status, weight change, activity readiness, and nutrition intake. Cognitive function will be assessed on day 2, 4 and 8 of racing. One day before and one day after the race the participants will report to the lab to assess basal metabolic rate, stress via questionnaires, appetite, cognitive function, muscle biopsies, venous blood samples, mechanical efficiency and 30-min Time Trial.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • KU Leuven

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• have been cycling consistently for at least 1 year before entry into the study
• have been cycling for a minimum of 7 hours per week for the 6 months leading up to the study
• additional for the field study: valid entry to the 2025 edition of the Absa Cape Epic
• non-smoker

Exclusion Criteria:

• Do not follow a ketogenic diet or low-carbohydrate diet
• Have any metabolic or auto-immune disease that will influence their metabolism
• Take medication or supplements that is known to affect ketone supplement metabolism
• suffering from a recurring injury or illness from which they have not fully recovered that is a contr-indication to perform high-intensity exercise
• Unable to finish each stage
• Women: if they are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; Intervention: 8-day multistage mountain bike race/simulation Dietary intervention: placebo supplement (oral supplement containing: 16.4 grams of medium chained triglycerides, 1mM of sucrose octaacetate and water)	Dietary supplement: Placebo Supplement; Placebo supplement: Oral supplement containing: 16.4 grams of medium chained triglycerides, 1mM or sucrose octaacetate and water
Experimental: Experimental group; Intervention: 8-day multistage mountain bike race/simulation Dietary intervention: ketone ester supplement (25 grams of pure R-(3)-hydroxybutyl-(R)-3-hydroxybutyrate ketone monoester drink)	Dietary supplement: Ketone ester supplement; Ketone ester supplement Oral supplement containing: 25 grams of pure (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate ketone monoester drink

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle soreness	Visual analog scale (0-10) How sore does you leg muscles feel? The VAS was used as a subjective measure of muscle soreness	During the intervention
Physical stress	RESTQ-76 sport questionnaire was used to assess the stress-recovery balance	pre-intervention and 1 day after the intervention
Hydration status	Before every stage, the participants provided a urine sample in a cup. A urine-specific refractometer (Atago) was used to determine their hydration status	Baseline, During the intervention and 1 day after the intervention
Cognitive function: reaction time	CANTAB test battery reaction time test was used to determine reaction time in milliseconds.	Pre-intervention, day 2, 4 and 8 of the intervention
Cognitive function: rapid visual processing	CANTAB test battery rapid visual processing test was used to assess their susceptibility to false alarms	Pre-intervention, day 2, 4 and 8 of the intervention
Cognitive function: swm	CANTAB spatial working memory test was used to access executive function; the main outcome measure used was the number of errors	Pre-intervention, day 2, 4 and 8 of the intervention
Sleep Duration	Fitbit inspire 3 was used to measure sleep duration (hours:minutes:seconds)	1 week prior to racing and during the race
Sleep: REM	The Fitbit Inspire 3 was used to measure the total duration of rapid eye motion (REM)sleep during each night for the duration of the study. The REM sleep phase will be analysed in minutes	1 week prior to racing and during the race
Sleep: Non-REM	The Fitbit Inspire 3 will be used to determine the NON-REM sleep phase for each night in minutes	1 week prior to racing and during the race
Sleep: WASO	The FITBIT inspire 3 will be used to measure wake after sleep onset in minutes for each night	1 week prior to racing and during the race

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical efficiency	Mechanical efficiency will be determined during three constant load (100 watts, 150 watts, and 200 watts) cycling bouts of 5 minutes on a calibrated ergometer (Avantronic Cyclus II). Throughout the test, gas exchange will continuously be measured using calibrated metabolic analyzer with a face mask (Cortex, Metalyzer IIIb). VO2 and VCO2 data of the final minute of each workload will be used to calculate gross efficiency (%).	pre-intervention and 1 day after the intervention
Time trial performance	The participants will perform a 30-minute time trial. The average power output (watts) achieved will be used as the outcome measure.	pre-intervention and 1 day after the intervention
Appetite	Appetite will be assessed with a Likert visual analog scale (0-10) using the following four questions: "How hungry do you feel?" "How full do you feel?" "How satisfied do you feel?" "How much do you think you could eat now?"	pre-intervention, during the intervention, 1 day after the intervention
Macronutrient intake	Participants will complete a food diary using the Mijnetemeter application on their phone. Total fat, protein and carbohydrate intake will be determined in grams for each day.	baseline, during the intervention
Total energy intake	Participants will complete a food diary, using the Mijnetemeter application on their phones. total energy intake (kilojoules) will be calculated for each day.	baseline, during the intervention
Racing intensity	hear rate zones during racing	during each stage
Body weight change	Body mass was measured using a SECA, model 813 electrical scale, before and after each stage as a secondary method to assess hydration status. Body mass was measured to the nearest 0.1 kilogram	During the intervention

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: University of Stellenbosch
• Investigators: Principal Investigator: Chiel Poffé, KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): March 27, 2025
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: October 4, 2024
• First Submitted That Met QC Criteria: May 1, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: cycling; mental fatigue; ultra-endurance; physiological strain
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Fatigue; Mental Fatigue
• Other Study ID Numbers: S68178

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