Altitude-related hypoxia decreases human functional capacity, especially during exercise. Even with prolonged acclimatization, the physiological adaptations are insufficient to preserve exercise capacity, especially at higher altitudes completely. Consequently, there has been an ongoing search for various interventions to mitigate the negative effects of hypoxia on human performance and functional capacity. Interestingly, early data in rodents and humans indicate that intermittent exogenous ketosis (IEK) by ketone ester intake improves hypoxic tolerance, i.e.by facilitating muscular and neuronal energy homeostasis and reducing oxidative stress. Furthermore, there is evidence to indicate that hypoxia elevates the contribution of ketone bodies to adenosine-triphosphate (ATP) generation, substituting glucose and becoming a priority fuel for the brain. Nevertheless, it is reasonable to postulate that ketone bodies might also facilitate long-term acclimation to hypoxia by upregulation of both hypoxia-inducible factor-1α and stimulation of erythropoietin production. The present project aims to comprehensively investigate the effects of intermittent exogenous ketosis on physiological, cognitive, and functional responses to acute and sub-acute exposure to altitude/hypoxia during rest, exercise, and sleep in healthy adults. Specifically, we aim to elucidate 1) the effects of acute exogenous ketosis during submaximal and maximal intensity exercise in hypoxia, 2) the effects of exogenous ketosis on sleep architecture and quality in hypoxia, and 3) the effects of exogenous ketosis on hypoxic tolerance and sub-acute high-altitude adaptation. For this purpose, a placebo-controlled clinical trial (CT) in hypobaric hypoxia (real high altitude) corresponding to 3375 m a.s.l. (Rifugio Torino, Courmayeur, Italy) will be performed with healthy individuals to investigate both the functional effects of the tested interventions and elucidate the exact physiological, cellular, and molecular mechanisms involved in acute and chronic adaptation to hypoxia. The generated output will not only provide novel insight into the role of ketone bodies under hypoxic conditions but will also be of applied value for mountaineers and athletes competing at altitude as well as for multiple clinical diseases associated with hypoxia.
Age range
18 Years – 35 Years
Sex
ALL
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Cerebrovascular reactivity to carbon dioxide (CO2)
Timeframe: On Day 1 at sea level (in normoxia). On Day 2 (36 hours after) of exposure to hypobaric hypoxia.
Cognitive function
Timeframe: On Day 1 at sea-level (in normoxia). On Day 0 and Day 2 (4 hours and 48 hours) after exposure to hypobaric hypoxia, respectively.
Acute Mountain Sickness (AMS)
Timeframe: Every day at 9.00 p.m. (before sleep) and at 6.15 a.m. (upon waking) in normoxia and hypobaric hypoxia, respectively.
Change in lung function estimating forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1).
Timeframe: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Change in lung function estimating peak expiratory flow (PEF).
Timeframe: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Change in lung function
Timeframe: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Heart rate response to exercise
Timeframe: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Respiratory response to exercise
Timeframe: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Changes in muscular oxygenation during exercise
Timeframe: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Changes in cerebral oxygenation during exercise
Timeframe: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Changes in the rate of muscular oxygen consumption (mV#O2)
Timeframe: Every day before each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Duration of different sleep stages
Timeframe: Throughout the entire duration of the night, up to 8 hours after individual bedtime (between 10 p.m. and 6 a.m.). On Day 0 in normoxia. On Day 0 and Day 2 in hypobaric hypoxia.
Changes in oxidative stress markers in the blood
Timeframe: Blood samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Change in salivary cortisol concentration
Timeframe: Saliva samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Change in hydration status
Timeframe: Urine samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Baroreflex sensitivity
Timeframe: Within 24 h hours after exposure to normoxia and hypobaric hypoxia, respectively
Change in nocturnal oxygen saturation
Timeframe: Throughout the entire duration of the night, up to 8 hours after individual bedtime (between 10 p.m. and 6 a.m.). On Day 0 in normoxia. On Day 0 and Day 2 in hypobaric hypoxia.
Absolute amount of nocturnal urinary catecholamine excretion
Timeframe: From 10 p.m. to 6 a.m. on Day 0 in normoxia and Day 0, Day 1 and Day 2 in hypobaric hypoxia.