Effect of Ketone Ester Supplementation on Hypoxic Tolerance

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effect of Ketone Ester Supplementation on Hypoxic Tolerance

Conditions
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Ketosis, Hypoxia

Intervention / Treatment
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* Dietary Supplement: Ketone ester
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 1 session with ketone ester supplementation and 1 session with taste and viscosity matched placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketone group<br>Ketone esters will be provided | Dietary Supplement: Ketone ester<br>* 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<br>|
| Placebo Comparator: Placebo group<br>Ketone placebo will be provided | Dietary Supplement: Placebo<br>* Water, 5% sucralose (w/w), octaacetate (1 mM)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Mountain Sickness, Sleep, Cognitive Decline