Prophylactic caffeine mitigatesimpairments in psychomotor vigilance and mood during graded CO₂exposures in healthy men and women: a randomized crossover trial

Introduction: Elevated inspired carbon dioxide (CO 2 ) is an environmental threat in various occupational settings. The impact of CO 2 dose on behavior including mood and psychomotor vigilance is not understood, and countermeasures to mitigate adverse effects of CO 2 exposure are lacking. Objective: To determine the effect of stepwise increases in inspired CO 2 on psychomotor vigilance and mood, and to examine the efficacy of caffeine supplementation to attenuate the expected decrements. We hypothesized that caffeine administration would reduce the adverse impact of graded CO 2 exposures on psychomotor vigilance and mood. Methods and Results: Participants completed a control trial to characterize the effect of graded CO 2 exposure (sequential 12-minute stages of 0%, 2%, 4%, 6%, and 8% inspired CO 2 , all with 21% oxygen) on mood and psychomotor vigilance during seated rest in 24 individuals (12 men, 12 women). Two minutes into each stage, participants began a 5-minute psychomotor vigilance test (PVT), responding as quickly as possible to randomly timed visual stimuli. Volunteers also completed the Profile of Mood States (POMS 2-A) questionnaire, rating 65 mood-related adjectives on a five-point scale for “How are you feeling right now?”. The POMS 2-A responses are grouped into a composite, total mood disturbance score and 6 subscale scores for tension, depression, anger, vigor, fatigue, and confusion. In the control trial, reaction time on the PVT was slower at 2%, 4%, 6%, and 8% inspired CO 2 compared to 0% inspired CO 2 (main effect of inspired CO 2 p<0.001). Total mood disturbance increased progressively (main effect of inspired CO 2 p≤0.001) beginning at 4% inspired CO 2 . Tension, depression, fatigue, and confusion increased during graded CO 2 exposure (main effects of inspired CO 2 p<0.05), whereas vigor decreased (p<0.05) and anger was unchanged. After completing the control trial, 23 participants (11 men, 12 women) repeated the graded CO 2 exposure 1 hour following either caffeine (400 mg) or placebo supplementation using a randomized, double-blind, crossover design. Caffeine improved reaction time during graded CO 2 exposure (treatment main effect p=0.017). Caffeine in a dose-dependent manner lowered total mood disturbance, fatigue, and confusion during graded CO 2 exposure (treatment main effects p<0.02), whereas vigor was increased by caffeine (p=0.02), and tension, anger, and depression were not significantly altered by caffeine. Conclusion: Our novel findings show that caffeine mitigates impairments in psychomotor vigilance and mood during graded CO 2 exposure. Funded by USAMRDC: author views not representative of the U.S. Army or DoD. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.