Ketone Monoester, With and Without Caffeine, Prevents Mental Fatigue and Preserves Cognitive Performance

Roca, GM, Barker, GA, and Waldman, HS. Ketone monoester, with and without caffeine, prevents mental fatigue and preserves cognitive performance. J Strength Cond Res XX(X): 000–000, 2026—This study examined the effects of acute ingestion of a ketone monoester (KME), with and without caffeine (KME + CAF), on cognitive performance after mental fatigue (MF). In a double-blind, randomized crossover design, 25 healthy adults (20 men, 5 women) completed 3 trials (KME + CAF, KME, placebo [PLA]) involving a battery of cognitive tests (task-switching [TS], Stroop Test [ST]) before and after a 20-minute MF time load dual back (TLDB) protocol. Subjective fatigue and workload were assessed alongside capillary blood β-hydroxybutyrate (βHB) and glucose. Mental fatigue induction was confirmed by a ∼100% increase in perceived fatigue and impaired TLDB reaction time in PLA. Both KME conditions elevated βHB to ∼1.5 mM, confirming nutritional ketosis. Compared with PLA, KME + CAF produced the largest improvements in TS (Δ reaction time: −97 ms; d = −0.97) and ST (Δ reaction time: −61 ms; d = −0.61), whereas KME alone primarily prevented the decline observed in the PLA condition. Time load dual back reaction time was faster for KME + CAF and KME vs. PLA ( p < 0.05), with no differences between ketone conditions. Subjective workload and fatigue did not differ by supplement, and gastrointestinal symptoms were mild. These findings suggest that acute KME ingestion preserves cognitive flexibility and selective attention under MF, with additive benefits when combined with CAF. These findings highlight the potential of KME + CAF as a strategy to sustain executive function during cognitively demanding tasks in athletic and tactical settings.