Ketone monoester attenuates oxygen desaturation during weighted ruck exercise under acute hypoxic exposure but does not impact cognitive performance.
Level 2 - randomized trial
Randomized crossover trial in humans
PubMed 39190570 · doi:10.1113/EP091789
What was done
In a single-blind randomized crossover study, 16 males underwent cognitive assessments before and during acute normobaric hypoxia (simulated altitude of 4,572 m, 11.8% O2) combined with moderate exercise (two 20-minute weighted ruck bouts with ~22 kg at 3.2 km/h on a 10% incline). Participants consumed either an (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester (573 mg/kg) or a calorie- and taste-matched placebo (~50 g maltodextrin), both co-ingested with 40 g of dextrose prior to hypoxia exposure. Measured outcomes included blood R-βHB concentrations, oxygen saturation, and cognitive tests (Defense Automated Neurobehavioral Assessment code substitution, Stroop color and word test, and a shooting simulation).
What was found
Ketone monoester ingestion rapidly increased and sustained R-βHB concentrations above 3 mM (P < 0.001). Ketone monoester attenuated the decline in blood oxygen saturation during hypoxic exposure by 2.4% to 4.2% compared with placebo (P < 0.05). However, cognitive performance on the DANA code substitution task, Stroop task, and shooting simulation did not differ significantly between ketone monoester and placebo trials before or during hypoxic exposure.
Why it matters
Exogenous ketosis can modestly preserve peripheral oxygen saturation during acute severe hypoxic stress and loaded physical exertion, though this physiological benefit did not confer short-term cognitive or marksmanship advantages.
Limits
The study evaluated a small sample of 16 participants, limited strictly to males. It examined acute, short-duration normobaric hypoxia, leaving effects during chronic hypobaric altitude exposure untested. The study was single-blinded rather than double-blinded.
Cited by
- partial Administration of exogenous ketones without dietary changes improves cognitive retention during acute hypoxic exposure at altitudes between 15,000 and 20,000 feet.
- context 1,3-butanediol-based exogenous ketones elevate blood hydrogen ions, increase blood oxygen saturation (SpO2), and improve cognitive function in acute hypoxia.