Effects of intermittent exogenous ketosis on acute mountain sickness and underlying physiological responses during early high-altitude acclimatizationTominec, Domen (Avtor) Stalmans, Myrthe (Avtor) Narang, Benjamin J. (Avtor) Pialoux, Vincent (Avtor) Millet, Grégoire P. (Avtor) Poffé, Chiel (Avtor) Debevec, Tadej (Avtor) acute mountain sicknessaltitude acclimatizationhypoxiaketonesThe dataset was collected within the Intermittent Exogenous Ketosis (IEK) at High Altitude project (ClinicalTrials.gov: NCT06097754), which investigated the effects of ketone ester (KE) supplementation during early acclimatization to terrestrial high altitude. Healthy recreationally active adults completed comprehensive physiological assessments at sea level (295 m; Faculty of Sport, University of Ljubljana, Slovenia) and during a four-day sojourn at 3375 m (Refugio Torino, Mont Blanc massif, Italy). Following baseline testing, participants were randomly assigned in a parallel-group, placebo-controlled design to receive either intermittent KE supplementation (IEK group; n = 17) or placebo (PLA group; n = 17). KE or placebo was administered repeatedly before exercise, resting measurements, and consistently before sleep throughout the altitude sojourn. Previous studies demonstrated that KE ingestion can augment physiological responses and attenuate acute mountain sickness (AMS) symptoms during simulated normobaric hypoxia. However, evidence from prolonged terrestrial high-altitude exposure remained limited. The present study therefore examined whether intermittent exogenous ketosis modifies AMS development and integrated ventilatory, cardiovascular, cerebral, muscular, autonomic, erythropoietic, and redox responses during early acclimatization at high-altitude. The protocol included repeated assessments of AMS incidence and severity, cardiorespiratory function, systemic blood oxygenation, gas exchange, cerebral and skeletal muscle oxygenation, cardiac output, acid–base balance, blood gases, and circulating biomarkers. AMS incidence and severity were evaluated using the 2018 Lake Louise Acute Mountain Sickness Score at sea level and multiple time points during altitude sojourn. Morning measurements included heart rate, heart rate variability, pulse oximetry, and blood pressure, while daytime assessments involved ventilatory and cardiovascular measurements during seated rest on a cycle ergometer. Capillary and venous blood samples were analyzed for acid–base status, blood gases, hemoglobin concentration, growth differentiation factor 15 (GDF15), erythropoietin (EPO), advanced oxidation protein products (AOPP), and superoxide dismutase (SOD) activity. KE supplementation consistently elevated circulating β-hydroxybutyrate concentrations, confirming intermittent exogenous ketosis in the IEK group. Although AMS incidence peaked within the first hours of altitude sojourn, no differences in AMS incidence or symptom severity were observed between IEK and PLA groups. KE ingestion induced mild ketoacidosis and enhanced ventilatory responses to hypoxia, while also increasing daytime cardiac output and reducing morning blood pressure. However, KE supplementation did not improve systemic or tissue oxygenation and had no significant effects on autonomic, erythropoietic, or redox responses compared with placebo. Overall, the findings indicate that intermittent KE supplementation during a four-day terrestrial high-altitude sojourn effectively induces exogenous ketosis and modifies selected ventilatory, cardiovascular, and acid–base responses, but does not attenuate AMS development or improve oxygenation during early acclimatization. The results further suggest that physiological effects of KE supplementation may be system- and time-dependent, warranting further investigation during longer and more diverse high-altitude exposures.20262026-05-13 14:16:01Neznano182484sl