Ketone monoester attenuates declines in cognitive performance and oxygen saturation during acute severe hypoxic exposure under resting conditions

Abstract Exogenous ketone supplements are a potential augmentation strategy for cognitive resilience during acute hypoxic exposure due to their capacity to attenuate the decline in oxygen (O2) availability, and by providing an alternative substrate for cerebral metabolism. Utilizing a single‐blind randomized crossover design, 16 male military personnel (age, 25.3 ± 2.4 year, body mass, 86.2 ± 9.3 kg) performed tests of cognitive performance at rest in three environments: room air (baseline), normoxia (20 min; 0 m; 20.9% O2) and hypoxia (20 min; 6096 m, 9.7% O2) using a reduced O2 breathing device (ROBD). (R)‐3‐Hydroxybutyl (R)‐3‐hydroxybutyrate (R‐BD R‐βHB) ketone monoester (KME; 650 mg/kg, split dose given at 30 min prior to each exposure) or taste‐matched placebo (PLA) was ingested prior to normoxia and hypoxic exposure. Blood R‐βHB and glucose concentrations, cognitive performance and O2 saturation (SpO2) were collected throughout. KME ingestion increased blood R‐βHB concentration, which was rapid and sustained (>4 mM 30 min post; P