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 (V̇o2) 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 3 day altitude sojourn (3,375 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 V̇o2 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 3 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 3,375 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 V̇o2 kinetics or tissue oxygenation, nor improves whole-body efficiency, during moderate- or heavy-intensity exercise across 3 days at 3,375 m.NEW & NOTEWORTHY This study demonstrates that intermittent exogenous ketosis does not alter the high-altitude slowing of the primary phase of V̇o2 kinetics during the transition to heavy-intensity exercise, nor does it change ventilatory, gas exchange, blood or tissue oxygenation responses, or whole-body efficiency across 3 days at 3,375 m. However, preexercise ketone monoester ingestion increased cardiac output during moderate-intensity exercise on arrival to 3,375 m and after 24 h, but this did not translate to broader physiological benefits.