Acute creatine–guanidinoacetate supplementation improves regional brain oxygenation following sleep deprivation: A randomized controlled trial

Background: Sleep deprivation impairs cognitive performance and may alter regional cerebral oxygenation. Nutritional strategies that preserve brain oxygenation could help mitigate these adverse effects. Aim: To compare the acute effects of creatine–guanidinoacetate (GAA), molecular hydrogen inhalation, caffeine, and placebo on regional brain oxygenation and attention-related performance following sleep deprivation. Methods: Twenty-two healthy young adults completed a 24-hour sleep deprivation protocol and were randomly assigned to receive creatine–GAA, molecular hydrogen inhalation, caffeine, or placebo. Brain oxygenation was assessed using functional near-infrared spectroscopy over the frontal, temporal, and occipital cortices during a modified attention network test. Alertness, executive control, orienting, reaction time, and accuracy were also evaluated. Summary: Creatine–GAA significantly increased frontal oxygen saturation (50.8% ± 4.1% to 61.0% ± 5.9%, P  = 0.01; Cohen's d  = 2.00) and temporal oxygen saturation (63.1% ± 4.8% to 70.2% ± 2.6%, P  = 0.01; Cohen's d  = 1.83). Significant time-by-treatment interactions were observed for frontal oxygen saturation ( P  = 0.043; ηp ²  = 0.331), temporal oxygen saturation ( P  = 0.021; ηp ²  = 0.428), and occipital total hemoglobin ( P  = 0.022; ηp ²  = 0.405). No significant between-group differences were observed in attention-related outcomes. Acute creatine–GAA supplementation improved regional brain oxygenation following sleep deprivation, particularly in the frontal and temporal cortices, without measurable improvements in attention-related performance. These preliminary findings support further investigation of creatine-based nutritional strategies in larger randomized controlled trials.