Effect of Ketone Ester Supplementation on Sleep and Recovery in Hypoxia

Study Overview
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Brief Summary
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This study specifically aims to elucidate the effects of IEK on sleep and recuperation in hypoxia, after training in normoxia. These conditions are in line with the widely applied live-high train-low strategy. Moreover, blood and tissue oxygenation status, as well as cerebral blood flow and cognitive function will be assessed.

Detailed Description
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During training stages in order to prepare for an important event, sleep and recuperation are almost equally important as the appropriate training strategy. This training strategy often consists of living-high (sleeping at -stimulated- altitude) and training low (training at sea level). A decreased oxygen availability, also known as hypoxia, however often disrupts sleep quality and thus compromises the overall training efficiency. Ketones are recently found to improve sleep quality, thus potentially playing a pivotal role in altitude training. Therefore, the investigators want to evaluate the effects of ketones on sleep in hypoxia, after training in normoxia. Moreover, the effect on a performance test, during a simulated 30 min time trial on the next morning, will be investigated. During this protocol, cerebral blood flow will be assessed, as well as ventilation, blood and tissue oxygen status, heart rate variability, and cognitive function.

Official Title
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Effect of Ketone Ester Supplementation on Sleep and Recovery in Hypoxia

Conditions
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Ketosis, Hypoxia, Sleep

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained prior to any experimental procedures Males between 18 and 35 years old Recreational or competitive cyclists performing regular cycling training sessions with an average training volume of more than 6 hours per week Good health status confirmed by a medical screening Body Mass Index (BMI) between 18 and 25 Normal sleep pattern as assessed by the Pittsburgh Sleep Quality Index Moderate sleep chronotype (extreme morning and evening chronotypes will be excluded), assessed by the Horne and Östberg questionnaire Exclusion Criteria: Any kind of injury/pathology that is a contra-indication for hypoxic exposure and/or to perform high-intensity exercise, evaluated by a sport medical screening Intake of any medication or nutritional supplement that is known to affect exercise, performance or sleep. Intake will be assessed during recruitment and the sport medical screening. 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 the last 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 Pre-existing, diagnosed psychiatric conditions or diagnosed anxiety Excessive daytime sleepiness as assessed by the Epworth scale Depression or anxiety as assessed by the Beck Depression Inventory and Beck Anxiety Inventory. Only a score in the range of 'normal ups and downs' (score 1-10) for depression or 'minimal anxiety' (score 0-7) for anxiety are tolerated. History of addiction or excessive caffeine/alcohol consumption assessed by a questionnaire 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 both training and sleep in normoxia, supplemented with placebo (NPL) 1 session with training in normoxia, sleep in hypoxia, supplemented with placebo (HPL) 1 session with training in normoxia, sleep in hypoxia, supplemented with ketones (HKE)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normoxia - placebo<br>Both training and sleep in normoxia, supplemented with placebo | Dietary Supplement: Placebo<br>* Water, 5% collagen(w/w), octoacetate (1 mM)<br>|
| Experimental: Hypoxia - placebo<br>Training in normoxia and sleep in hypoxia, supplemented with placebo | Dietary Supplement: Placebo<br>* Water, 5% collagen(w/w), octoacetate (1 mM)<br>|
| Experimental: Hypoxia - ketones<br>Training in normoxia and sleep in hypoxia, supplemented with ketones | Dietary Supplement: Ketone ester<br>* A total of 75g ketone ester supplementation will be administered in 3 bouts of 25g in order to establish intermittent exogenous ketosis: twice immediately after training, and one 30 minutes before sleep. The ketone ester used is (R)-3-hydroxybutyl (R)-3-hydroxybutyrate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of different sleep stages | Measured using polysomnography | Throughout the entire duration of the night, up to 9 hours after individual bedtime | 
| Exercise performance | Measured as the average power output (W) during a 30 minutes time trial | 30 minutes on the second morning of the protocol | 
| Change in nocturnal oxygen saturation | Measured using pulse oximetry | Throughout the entire duration of the night, up to 9 hours after individual bedtime | 
| Absolute amount of nocturnal urinary catecholamine excretion | Measured using ELISA of collected nocturnal urine | Subjects empty bladder before sleep and urine will be collected throughout the entire duration of the night, up to 9 hours after individual bedtime and in the morning immediately after waking up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Ketones, Living-high Training-low