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.

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.

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