BACKGROUND: During hypoxia an operators cognitive performance may decline. This decline is linked to altered brain metabolism, resulting in decreased adenosine triphosphate (ATP) production. Ketone bodies are an alternative substrate to glucose for brain metabolic requirements; previous studies have shown that the presence of elevated ketone bodies in the blood maintains brain ATP levels and reduces cerebral glycolysis during hypoxia. Thus, ketones may be a strategy to mitigate cognitive decline in hypoxia. Ketone ester (KE) consumption allows rapid elevation of blood ketone levels; therefore, we investigated the effects of consuming a KE drink on cognitive performance during hypoxia. Here, we report results of a pilot study.METHODS: There were 11 subjects who completed a cognitive performance test battery under conditions of normoxia and hypoxia following consumption of a KE drink and a placebo control drink.RESULTS: Significant hypoxia effects (O₂ saturation minimum was found to range between 63 and 88 in subjects) were found for blink duration (Ph2 0.665) and blink rate (Ph2 0.626), indicating that the hypoxia condition was associated with longer blink durations and lower blink rates. Significant hypoxia effects were likewise observed for a code substitution task (Ph2 0.487), indicating that performance on the task was significantly disrupted by the hypoxia stressor. KE consumption had a significant effect on blink duration (Ph2 0.270) and the code substitution task (Ph2 0.309).DISCUSSION: These finding suggest that some effects of acute hypoxia can be mitigated by nutritional ketosis.Coleman K, Phillips J, Sciarini M, Stubbs B, Jackson O, Kernagis D. A metabolic intervention for improving human cognitive performance during hypoxia. Aerosp Med Hum Perform. 2021; 92(7):556562.