Creatine with guanidinoacetic acid improves prefrontal brain oxygenation before, during, and after a cognitive task: A randomized controlled pilot trial

Background: Preliminary studies suggest that creatine and guanidinoacetic acid (GAA) may function as moderate vasodilators, enhancing tissue oxygen saturation. However, the potential effects of this combination on brain oxygenation in humans remain unknown. Aim: The primary objective of this randomized controlled pilot trial was to assess cerebral blood oxygenation indices following a 7-day administration of a mixture containing creatine and GAA in healthy adults. Methods: Nineteen apparently healthy young adults (mean age 21.2 ± 0.4 years; 9 females) were randomly assigned to receive either a mixture (consisting of 2 g of creatine and 2 g of GAA) or a placebo in a crossover design. Oxygen saturation (SpO2) and hemoglobin index (tHb) in the prefrontal cortex were assessed at rest (REST), during meditation that focused on mindful breathing (MED), during a three-component cognitive task (TASK), and during a post-task recovery (REC) before and after 7 days of supplementation. Results: Two-way ANOVA with repeated measures revealed statistically significant differences (treatment vs. time interaction) between interventions for SpO2 during the REST (F = 5.733, P = 0.028), MED (F = 5.897, P = 0.026), and REC phases (F = 6.715, P = 0.018), indicating that the creatine-GAA mixture was more effective than placebo in enhancing oxygen saturation in the prefrontal brain both before, during, and after a cognitive task. Conclusion: These promising findings are of considerable interest for nutritional neuroscience but require validation through well-designed longitudinal trials with larger sample sizes. The study is registered at ClinicalTrials.gov (NCT06371651).