Effect of Ketone Ester Supplementation on Hypoxic Tolerance

This WP specifically aims to elucidate the effects of IEK on hypoxic tolerance and the development and severity of AMS symptoms, blood and tissue oxygenation status, as well as sleep quality during an episode of acute exposure to severe hypoxia.

Study Overview

• Status: Completed
• Conditions: Hypoxia; Ketosis
• Intervention / Treatment: Dietary supplement: Ketone ester; Dietary supplement: Placebo

Detailed Description

Acute altitude exposure impairs exercise tolerance and performance, decreases the rate of maximal oxygen uptake (V̇O2max), cognitive function and sleep quality, and often also induces symptoms of acute mountain sickness (AMS). Previous studies have clearly indicated that ketone bodies exert a neuroprotective effect under hypoxic-ischemic conditions as well as improve hypoxic tolerance in rodents. In support of these earlier observations, recent pilot experiments in young volunteers in our laboratory provide proof of concept that IEK can attenuate oxygen desaturation during exercise in hypoxia. Therefore, given that impaired exercise tolerance in hypoxia is primarily due to impaired oxidative energy production in active tissues (brain and muscle), we hypothesize that IEK can increase blood and tissue (muscle and brain) oxygenation status in hypoxia and thereby enhance global hypoxic tolerance, as well as improve exercise tolerance and endurance exercise performance.

• Study Type: Interventional
• Enrollment (Actual): 16
• 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: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males or females between 18 and 35 years old
• Body Mass Index (BMI) between 18 and 25
• Physically fit and regularly involved in physical activity (2-5 exercise sessions of > 30min per week)
• Good health status confirmed by a medical screening
• Non smoking
• Normal sleep pattern as assessed by the Pittsburgh Sleep Quality Index (PSQI, appendix 2)

Exclusion Criteria:

• Any kind of injury/pathology that is a contra-indication for hypoxic exposure and/or to perform high-intensity exercise
• Intake of any medication or nutritional supplement that is known to affect exercise, performance or sleep
• Intake of analgesics, anti-inflammatory agents, or supplementary anti-oxidants, from 2 weeks prior to the start of the study.
• Recent residence or training under hypoxia; more than 7 days exposure to altitude > 1500m during a period of 3 months preceding the study.
• Night-shifts or travel across time zones in the month preceding the study
• Blood donation within 3 months prior to the start of the study
• Smoking
• More than 3 alcoholic beverages per day
• Involvement in elite athletic training at a semi-professional or professional level
• Any other argument to believe that the subject is unlikely to successfully complete the full study protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketone group; Ketone esters will be provided	Dietary supplement: Ketone ester; A total of 240g ketone ester supplementation will be provided in one of the 28h experimental sessions in order to establish intermittent exogenous ketosis. Sucralose (5% w/w) is added to the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
Placebo Comparator: Placebo group; Ketone placebo will be provided	Dietary supplement: Placebo; Water, 5% sucralose (w/w), octaacetate (1 mM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in incidence of acute mountain sickness symptoms	Scored by Lake Louise Scoring system	Hour 0 - Hour 4 - Hour 10 - Hour 24 - Hour 28
Change in oxygenation status of brain, blood, muscle	Measured by NIRS, pulse oximetry, blood samples	Hour 1 - Hour 4 - Hour 10 - Hour 24 - Hour 28
Change in cerebral blood flow	Measured using duplex ultrasound	Hour 1 - Hour 4 - Hour 10 - Hour 24 - Hour 28
Time in hypoxia	Total time that subjects were able to comply to the experimental protocol and supplementation protocol	From start of hypoxic exposure until subjects are too sick to comply to (supplementation) protocol or until end of protocol, up to 29 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep quality	Measured using polysomnography	Throughout the entire duration of the night, up to 9 hours after individual bedtime

Collaborators and Investigators

• Sponsor: KU Leuven
• Investigators: Principal Investigator: Chiel Poffé, Dr., KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Actual): December 20, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: October 14, 2022
• First Submitted That Met QC Criteria: October 18, 2022
• First Posted (Actual): October 20, 2022

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Sleep; Cognitive Decline; Acute Mountain Sickness
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia
• Other Study ID Numbers: S66320

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No