Ketone monoester intake affects the ventilatory response to O 2 and CO 2 in healthy individuals at high altitude

Introduction. Both cerebral blood flow (CBF) and ventilation (V̇ E ) respond to systemic O 2 and CO 2 levels. Ketone ester (KE) ingestion elicits hyperventilation, thereby increasing blood oxygenation in hypoxia while reducing blood buffering capacity and inducing hypocapnia-mediated CBF reductions. We aimed to characterize the impact of KE on V̇ E and CBF at terrestrial altitude, as well as their reactivity to O 2 and CO 2 (V̇ E R and CVR, respectively). Methods. Thirty-four participants performed a double-blind, placebo-controlled study consisting of a normoxic and a hypobaric hypoxic session. The latter was performed after 20 h at terrestrial altitude (3,375 m). While no supplements were provided at sea level, the altitude session involved regular ingestion of KE or placebo drinks. Middle cerebral artery velocity (MCAv) was measured using transcranial Doppler ultrasonography. Using a steady-state protocol, V̇ E R and CVR were calculated as respectively ΔV̇ E or ΔMCAv per Δ[end-tidal CO 2 pressure (P ET CO 2 )] while breathing ambient air ( i.e., baseline stage), 3% or 6% hyperoxic CO 2 , or during hyperventilation-induced hypocapnia. Blood acid-base balance was evaluated from an arterialized capillary blood sample. Results. KE intake increased blood [β-hydroxybutyrate] and reduced blood pH, arterial CO 2 partial pressure, and bicarbonate concentrations. KE induced hyperventilation and reduced V̇ E R, mostly originating from the baseline-to-3%-CO 2 transition. KE did not affect MCAv or CVR. Conclusions. The effect of KE on V̇ E R presumably resulted from hyperventilation while breathing ambient air, rather than reflecting altered V̇ E R to O 2 and CO 2 , but the underlying mechanisms remain uncertain. Despite acid-base dysregulations with KE intake, cerebrovascular outcomes remained unaltered.