Ketone monoester attenuates declines in cognitive performance and oxygen saturation during acute severe hypoxic exposure under resting conditions.
Level 2 - randomized trial
Individual randomized crossover trial
PubMed 39190580 · doi:10.1113/EP091794
What was done
In a single-blind randomized crossover trial, 16 male military personnel (mean age 25.3 years) performed resting cognitive tests across three environmental conditions: baseline room air, normoxia (20 min, 20.9% O2), and severe hypoxia (20 min, simulated 6096 m, 9.7% O2) via a reduced O2 breathing device. Participants ingested either an (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester (KME; 650 mg/kg split dose given 30 min before each exposure) or a taste-matched placebo. Blood (R)-beta-hydroxybutyrate (R-βHB) and glucose concentrations, arterial oxygen saturation (SpO2), and cognitive efficiency on a Defense Automated Neurobehavioral Assessment (DANA) code substitution task were evaluated.
What was found
KME ingestion produced a rapid and sustained rise in blood R-βHB (>4 mM at 30 min post-ingestion; P < 0.001) and lowered blood glucose by ~20 mg/dL (P < 0.01) relative to placebo. During hypoxic exposure, KME attenuated the drop in cognitive efficiency, yielding 6.8 more correct responses per minute compared to placebo (95% CL: 1.0 to 12.6; P = 0.018). KME also mitigated the drop in SpO2 by 6.40% (95% CL: 0.04 to 12.75; P = 0.049), with SpO2 reaching 76.8 ± 6.4% in the KME condition versus 70.4 ± 7.4% with placebo.
Why it matters
This study provides evidence that exogenous ketone monoesters can preserve both peripheral oxygen saturation and cognitive speed/accuracy during acute severe hypoxic stress in humans, suggesting potential utility as a nutritional countermeasure in extreme aviation or high-altitude environments.
Limits
The sample was small (n = 16) and restricted entirely to young, healthy male military personnel, limiting generalizability to females or other age groups. The study was single-blind, tested only a brief 20-minute resting exposure to normobaric hypoxia, and did not evaluate performance during physical exertion or sustained field conditions.
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