Exogenous ketosis does not alter oxygenation, oxygen uptake kinetics or whole-body efficiency during submaximal exercise in early high-altitude acclimatization

Exogenous ketosis, induced via ketone monoester (KE) ingestion, has been shown to attenuate hypoxia-induced blood, muscle and brain deoxygenation, and augment oxygen uptake (V̇O 2 ) under acute normobaric hypoxia. However, its effects on exercise responses during early acclimatization at terrestrial high-altitude remain unexplored. Thirty-four healthy, active adults completed four exercise sessions: one near sea-level and then once per day during a three-day altitude sojourn (3375 m), with regular KE or placebo ingestion. Pulmonary gas-exchange, minute ventilation, cardiac output, pulse oxygen saturation, skeletal muscle tissue saturation index (TSI), and brain TSI, were measured during moderate- and heavy-intensity exercise. KE ingestion induced ketosis at the start of each exercise session (group×time interaction P<0.001). However, compared with placebo, KE resulted in a comparable (group×time interaction P=0.501) high-altitude-induced slowing of the primary phase time constant of V̇O 2 kinetics during heavy-intensity exercise (time effect P<0.001). Moreover, both groups exhibited similar (all group×time interactions P>0.123) hypoxia-related decreases in gas-exchange and increases in minute ventilation, accompanied by reductions in pulse oxygen saturation and brain TSI during both moderate- and heavy-intensity exercise across the three days (all time effects P<0.015). Notably, KE ingestion increased cardiac output during moderate-intensity exercise on the first altitude day (group×time interaction P=0.042). Whole-body energy efficiency was preserved across time at 3375 m (time effect P=0.060) in both groups (group×time interaction P=0.084). These data indicate that intermittent exogenous ketosis does not attenuate altitude-induced alternations in V̇O 2 kinetics or tissue oxygenation, nor improves whole-body efficiency, during moderate- or heavy-intensity exercise across three days at 3375 m.