Ketone monoester intake affects the ventilatory response to O2 and CO2 in healthy individuals at high altitude.

Introduction. Both cerebral blood flow (CBF) and ventilation (V̇E) respond to systemic O2 and CO2 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 V̇E and CBF at terrestrial altitude, as well as their reactivity to O2 and CO2 (V̇ER 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, V̇ER and CVR were calculated as respectively V̇E or MCAv per [end-tidal CO2 pressure (PETCO2)] while breathing ambient air (i.e., baseline stage), 3% or 6% hyperoxic CO2, 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 CO2 partial pressure, and bicarbonate concentrations. KE induced hyperventilation and reduced V̇ER, mostly originating from the baseline-to-3%-CO2 transition. KE did not affect MCAv or CVR. Conclusions. The effect of KE on V̇ER presumably resulted from hyperventilation while breathing ambient air, rather than reflecting altered V̇ER to O2 and CO2, but the underlying mechanisms remain uncertain. Despite acid-base dysregulations with KE intake, cerebrovascular outcomes remained unaltered.