Ketone monoester ingestion and cognitive and physical performance during exercise-heat stress

Sustaining cognitive and physical performance under extreme environmental conditions is critical for special operation forces (SOF). Hyperthermia negatively impacts cognitive function due to reductions in cerebral blood flow, substrate availability, thermal tolerance, and increased cardiovascular strain. While ketone monoester have demonstrated beneficial effects on cognition, their efficacy during exercise-heat stress remains unexplored.

Seventeen endurance-trained males (age = 23.8 ± 5.2 y; VO₂max = 58.6 ± 3.2 ml·kg^-1·min^-1) completed a randomized, double-blind, counterbalanced, crossover study. Participants ingested 4 mg·kg^-1 caffeine combined with either a ketone monoester (KET; (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate) or an energy-matched carbohydrate control (CHO; Cluster Dextrin™). Each experimental visit consisted of 90 minutes of loaded treadmill exercise in the heat (34 °C, 45% RH) followed by a high-intensity time-to-exhaustion (TTE) test. Cognitive performance (1-back, 2-back, Dynavision reaction time [RT], object hit and avoid [OHA]), blood metabolites, average heart rate, and core body temperature (CBT) were assessed before, during, and after exercise and analyzed using linear mixed-model ANCOVA. TTE duration and maximal heart rate during TTE were analyzed using paired-samples t tests.

For cognitive performance, KET demonstrated significantly greater 1-back total accuracy (+2.8%, p = 0.001) and target accuracy (8.9%, p < 0.001) relative to CHO across all timepoints, Additionally, KET increased overall target discrimination (d': + 0.3, p = 0.001) irrespective of task condition and timepoint. For 2-back, no overall between-condition differences were observed in total or target accuracy across time points, although task difficulty remained higher than 1-back performance overall. No between-condition differences were observed for RT or OHA outcomes. For blood metabolites, KET significantly increased circulating BHB concentrations relative to CHO at mid- and post-exercise (+1.7 and + 3.5 mmol·L^-1, respectively; both p < 0.001) and reduced blood glucose by 14.7 and 27.6 mg·dL^-1 at the same time points (p = 0.002 and p < 0.001, respectively). For average heart rate, there was a main effect of time, with heart rate lower during the first 45-minutes exercise bout than the second (-7.7 beats·min^-1, p = 0.01), but no effect of condition (p = 0.453). CBT increased over time in both conditions (p < 0.001) but did not differ between KET and CHO (p = 0.065). TTE duration was significantly longer following KET than CHO (8.9 ± 4.6 vs 7.0 ± 2.1 min; p = 0.04), whereas maximal heart rate during TTE did not differ between conditions (p = 0.112).

Ketone monoester ingestion combined with caffeine improved select aspects of working memory and resulted in a significantly longer time-to-exhaustion compared with carbohydrate control following prolonged, loaded exercise in the heat. However, these effects were not universal across all cognitive outcomes, as no between-condition differences were observed for 2-back, RT, or OHA. Notably, despite performance differences, average heart rate, maximal heart rate during TTE, and core temperature did not differ. Together, these findings suggest that ketone monoester and caffeine co-ingestion may support specific cognitive and physical aspects of performance during sustained exercise-heat stress without altering cardiovascular or thermal strain.