The effects of two days of intermittent exogenous ketosis at high altitude on baroreflex sensitivity and ventilation under hypoxic and hypercapnic conditions.

Abstract

High-altitude (HA) exposure induces an integrated physiological response to mitigate hypoxemia. Exogenous ketosis at simulated HA was previously shown to accentuate sympathetic activation, and attenuate pulse oxygen saturation (SpO₂) decreases through hyperventilation. The aim of this study was to extend these findings by investigating the effects of intermittent exogenous ketosis (IEK) across two days at terrestrial HA (3375 m) on baroreflex, heart rate variability, and hypoxic/hypercapnic ventilatory responses. 34 healthy active adults completed neutral, hypoxic, and hypercapnic (0.03 FiCO₂) exposures, each comprising six minutes of seated rest, once at sea level (SL) and once after two days at HA. Across the two days, participants intermittently ingested either ketone monoester supplements (IEK) or placebo (PLA). During each exposure, blood pressure, ventilation, SpO₂, and end-tidal CO2 pressure (P_ETCO₂) were continuously recorded, and arterialized capillary blood gas content was measured in the final 30 s. Baroreflex sensitivity and time-domain metrics of heart rate variability were reduced at HA (p = 0.006-0.043), but unaffected by group (p = 0.288-0.525). However, ventilation at HA under all three conditions was significantly higher in IEK compared to PLA (all p < 0.001). In hypoxia, this induced a higher SpO₂ (p = 0.038) and capillary O₂ pressure (p = 0.003). In hypercapnia, this induced a lower P_ETCO₂ and capillary CO₂ tension (both p < 0.001). These results extend previous findings, suggesting that IEK enhances ventilation at terrestrial HA and after two days of exposure, with this effect being independent from baroreflex sensitivity or heart rate variability changes.