Intermittent exogenous ketosis does not reduce acute mountain sickness during early terrestrial high-altitude acclimatization

PURPOSE: Intermittent exogenous ketosis via ketone monoester (KE) ingestion has been shown to enhance physiological responses and reduce acute mountain sickness (AMS) symptoms during acute normobaric hypoxia. Its effects during early acclimatization to terrestrial high-altitude, however, remain unclear. METHODS: Thirty-four participants were randomised to an intermittent exogenous ketosis (IEK, n=17) or placebo (PLA, n=17) group and underwent a near sea level trial (295 m) without supplementation, followed by a four-day sojourn at 3375 m during which they received regular KE (IEK) or placebo (PLA) supplements. AMS symptoms, hematological markers, and resting ventilatory, cardiovascular, and cerebral tissue oxygenation responses were assessed each day upon waking, at midday, and before sleep throughout the exposure. RESULTS: KE consistently elevated circulating β-hydroxybutyrate post-ingestion (P<0.001), confirming intermittent exogenous ketosis in the IEK group. AMS incidence peaked at 25-35% after 8 h, however incidence and symptom severity were similar in IEK vs. PLA across the altitude exposure (P≥0.822). KE ingestion induced (keto)acidosis, resulting in augmented ventilatory response in IEK (P≤0.037), but failed to mitigate hypoxia-induced blood and cerebral deoxygenation relative to PLA (P≥0.234). KE ingestion increased daytime cardiac output and lowered morning blood pressure in IEK (P≤0.031), while it did not affect autonomic, eryrthropoietic, or redox responses compared to PLA (P≥0.099). CONCLUSION: Although KE alters some physiological responses, it does not seem to importantly modulate AMS incidence and severity during early terrestrial altitude acclimatization.