The dataset was obtained as part of the research project “Intermittent Exogenous Ketosis (IEK) at High Altitude” (ClinicalTrials.gov: NCT06097754). Within this project, healthy, recreationally active adults underwent a series of assessments performed during rest, sleep, and exercise. The initial trials were performed at near sea level (295 m; Faculty of Sport, University of Ljubljana, Slovenia) without supplementation, in order to establish a true baseline. Approximately six weeks later, the corresponding high altitude trials were carried out during a four-day sojourn at 3375 m (3375 m; Refugio Torino hut, Mont Blanc massif, Aosta Valley, Italy), where participants intermittently ingested either ketone ester (KE) supplements (IEK group; n = 17) or a placebo (PLA group; n = 17).
Previous research has shown that exogenous ketosis, induced via KE ingestion can increase blood, skeletal muscle, and brain tissues oxygenation, as well as augment oxygen uptake both at rest and during exercise upon acute simulated high altitude exposures (Poffe et al., 2021; Stalmans et al., 2024; Stalmans, Tominec, Lauriks, et al., 2025; Stalmans, Tominec, Robberechts, et al., 2025). However, these investigations have been almost exclusively limited to acute, short-term laboratory exposures to normobaric hypoxia (≤15 h). Although these experimental settings allow for precise control of environmental and physiological variables, they may not adequately reflect the complex responses observed in more ecologically valid high altitude environments. Therefore, the present study aimed to extend existing evidence to terrestrial high altitude conditions by examining the integrated ventilatory, cardiovascular, muscular, cerebral, and whole-body efficiency responses to intermittent exogenous ketosis during moderate- and heavy-intensity exercise in the early phase of acclimatization to terrestrial high altitude. Specifically, the objective was to assess exercise responses across three days at 3375 m, with outcomes evaluated both during the on-transition phase (exercise onset) and upon the (end-exercise) attainment of steady state.
The study, entitled “Effects of Intermittent Exogenous Ketosis on Physiological Responses During Moderate- and Heavy-Intensity Exercise Across Three Days at 3375 m”, employed a randomized parallel-groups, placebo-controlled design involving 34 participants (28 males, 6 females). Participants were allocated to either the IEK group (n = 17; 3 females) or the PLA group (n = 17; 3 females) based on a true randomisation. Each participant completed four exercise sessions: one near sea level (without supplementation) and three during the high altitude sojourn (1 ± 1 h, 25 ± 1 h, and 49 ± 1 h post-arrival at high haltitude), while intermittently ingesting either KE (IEK group; comulative dose of 250 g, 3.54 ± 0.51 g/kg body mass; ~1750 kcal) or placebo (PLA group; comulative dose of 250 g, 3.65 ± 0.53 g/kg body mass; ~0 kcal) supplements, 30 min before exercise sessions (at ~0.5, ~24.5, and ~48.5 h), as well as before various resting measurements (~2.5, ~17.5, ~29.5, ~41.5, and ~43.5 h) and consistently prior to sleep (~7.5 and ~31.5 h post-arrival at high altitude).
Exercise bouts in the moderate-intensity domain consisted of a 3 min rest period, followed by 2 min of unloaded cycling at 0 W, and then 3 × 6 min intervals of cycling at the prescribed constant workload, each interspread with 6 min of cycling at 0 W. Exercise bouts in the heavy-intensity domain began with a 3 min rest period, followed by 2 min of cycling at 0 W, and then a single 8 min interval of cycling at the prescribed constant workload. The exercise intensities for the constant workload exercise bouts were determined using the results of the incremental cycling test performed during the preliminary testing session at sea level. The moderate-intensity exercise prescriptions were determined based on the power output corresponding to 80% of the V̇O2 at gas exchange threshold. The heavy-intensity exercise prescriptions were defined according to the power output corresponding to V̇O2 at 50% of delta between the gas exchange threshold and respiratory compensation point. Given the known high altitude-related decrease in V̇O2peak, the power output prescriptions for the high altitude trial were adjusted accordingly (MacInnis et al., 2015). Specifically, the percentage decrease in V̇O2peak at an altitude of 3375 m was individually determined for each participant, with reductions ranging from -14% to -28%. These individualized reductions were then applied to the power output prescriptions for the moderate- and heavy-intensity exercise bouts. This adjustment ensured similar relative intensities in both trials, accounting for participants’ theoretical altitude-specific V̇O2peak reduction
In addition, during exercise sessions, comprehensive physiological measurements were obtained, including ventilation, pulmonary gas exchange, cardiac hemodynamics, as well as blood, skeletal muscle and brain oxygenation, assessed using a metabolic cart (Quark CPET, COSMED, Rome, Italy), transthoracic impedance cardiography (Physioflow Enduro, Manatec Biomedical, Paris, France), earlobe oximetry (Nonin Xpod oximeter, Plymouth, MN, United States), and near-infrared spectroscopy (PortaLite MKII, Artinis Medical Systems, Elst, the Netherlands), respectively. Additionally, capillary blood samples were drawn from the left earlobe at rest ~30 min after supplement ingestion to determine β-hydroxybutyrate concentrations (GlucoMen Areo 2K-meter, A. Menarini Diagnostics, Florence, Italy). The collected data were further used to model V̇O2 kinetics and calculate primary kinetic parameters during transitions from baseline to exercise at moderate and heavy intensities.
KE ingestion consistently induced ketosis at the start of exercise sessions at high altitude (IEK vs. PLA: ~2.5 vs. ~0.3 mM, all P < 0.001). However, compared to the PLA group, the IEK group exhibited comparable high altitude-induced alternations (all P < 0.045) in V̇O2 kinetics (P > 0.085), pulmonary gas exchange (P > 0.123), minute ventilation (P > 0.147), pulse oxygen saturation (P > 0.302), brain (P > 0.282) and muscle TSI (P > 0.602), as well as whole-body efficiency (P > 0.060) during both moderate- and/or heavy-intensity exercise across three days at 3375 m. Notably, KE ingestion increased cardiac output during moderate-intensity exercise at both 1 ± 1 h and 25 ± 1 h post-arrival at 3375 m.
Collectively, however, these findings do not support intermittent exogenous ketosis as an effective strategy for enhancing V̇O2 kinetics- and oxygenation-related physiological responses, or improving whole-body efficiency during moderate- or heavy-intensity exercise in the early stages of acclimatization to high altitude.
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