Dietary Supplements

Effects of six weeks of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function and markers of health in healthy adults.

TL;DR

Dietary supplementation with GAA (2 g/d) and the combination of CrM (10 g/d + GAA 2 g/d) for six weeks improved delayed verbal episodic recognition memory and retrieval speed and some measures of perceived stress, sleep quality, and quality of life, but most cognitive tests were not affected.

Key Findings

GAA supplementation with CrM significantly improved overall reaction time compared to placebo.

  • Significant interaction effects were observed in overall reaction time (p = 0.031), with a mean change of -330 ms (95% CI: -629, -31) compared to PLA.
  • GAA alone tended to improve overall reaction time (-241.8 ms [95% CI: -533, 50], p = 0.10), approaching but not reaching significance.
  • Study design: double-blind, randomized, counterbalanced; 58 healthy active adults (33 females, mean age 35.5 ± 14 years).
  • Supplementation duration was six weeks; GAA dose was 2 × 1 g/d and CrM dose was 2 × 5 g/d.

GAA supplementation with CrM significantly improved YES reaction time compared to placebo.

  • YES reaction time improved by -290 ms (95% CI: -484, -96), p = 0.004 in the GAA + CrM group compared to PLA.
  • Recalled correct reaction time approached significance (-178 ms [95% CI: -374, 21], p = 0.078) compared to PLA.
  • Recalled correct YES also approached significance (7.4% [95% CI: -1, 15.8], p = 0.084) compared to PLA.
  • These findings relate to delayed verbal episodic recognition memory and retrieval speed.

Most cognitive tests showed limited to no effects from GAA supplementation with or without CrM.

  • No significant effects were observed on the Delayed Picture Recognition Task Test, Digit Vigilance Task Test, Corsi Block Task Test, or Stroop Color-Word Task Test.
  • The authors noted 'inconsistencies in the findings' and that 'several differences only approached significance.'
  • The study was characterized as a 'proof-of-concept exploratory clinical trial.'
  • The authors concluded that 'additional research is needed before conclusions can be drawn.'

Participants in the GAA group engaged in significantly more moderate physical activity compared to the placebo group.

  • The amount of time engaged in moderate physical activity was significantly greater (p < 0.05) in the GAA group compared to PLA.
  • This finding was observed after six weeks of supplementation.
  • GAA dose in this group was 2 × 1 g/d with placebo (2 × 5 g/d maltodextrin).

GAA supplementation was associated with reduced perceived stress on specific Perceived Stress Scale items.

  • Participants in the GAA group reported a lower frequency of controlling irritations (p = 0.036).
  • Participants in the GAA group reported a lower frequency of feeling like difficulties are mounting (p = 0.053).
  • These effects were specific to the GAA-only group and were assessed via the Perceived Stress Scale questionnaire.

GAA supplementation was associated with some quality of life improvements, while GAA + CrM was associated with both positive and mixed quality of life changes.

  • Participants in the GAA group reported less frequent feelings of being worn out (p = 0.068) and that their health was excellent (p = 0.092).
  • Participants in the GAA + CrM group reported more frequent limitations when bending, kneeling, or stooping (p = 0.053).
  • GAA + CrM participants more often felt full of life (p = 0.081) and less frequently felt downhearted and depressed (p = 0.066).
  • Several of these differences only approached significance (p > 0.05 to p < 0.10).

Sleep quality assessments showed some positive and potentially undesirable effects in the supplementation groups.

  • The paper reports 'some positive and potentially undesirable effects were observed in sleep quality assessments.'
  • Specific directions of these sleep quality changes were mixed across the supplementation groups.
  • Sleep quality was assessed as part of a battery of questionnaires at baseline and after six weeks.

No clinically meaningful changes were observed in blood markers or self-reported side effects among any of the groups.

  • Participants donated fasting blood samples at baseline and after six weeks of supplementation.
  • No clinically meaningful changes were observed in blood markers across PLA, GAA, and GAA + CrM groups.
  • No clinically meaningful differences in self-reported side effects were observed among groups.
  • This suggests that GAA (2 g/d) with or without CrM (10 g/d) was generally well-tolerated over six weeks in healthy adults.

The study used a three-arm double-blind randomized design with 58 healthy active adults supplemented for six weeks.

  • Participants: 58 healthy and active adults (33 females), mean age 35.5 ± 14 years, mean weight 76.2 ± 14 kg.
  • Three groups: PLA (2 × 6 g/d maltodextrin), GAA (2 × 1 g/d) + PLA (2 × 5 g/d), or GAA (2 × 1 g/d) + CrM (2 × 5 g/d).
  • Data were analyzed using General Linear Model (GLM) multivariate and univariate with repeated measures, mean changes from baseline with 95% confidence intervals, and Chi-squared analysis.
  • Significance threshold was p ≤ 0.05; approaching significance was defined as p > 0.05 to p < 0.10.
  • Clinical trial registration: ISRCTN68542582.

What This Means

This research suggests that taking guanidinoacetic acid (GAA), a compound the body uses to make creatine, either alone or combined with creatine monohydrate (CrM), for six weeks may offer some modest cognitive and well-being benefits in healthy adults. Specifically, people taking GAA combined with creatine showed faster reaction times and improved memory retrieval speed compared to those taking a placebo. People taking GAA alone also tended to be more physically active, reported feeling less stressed, and had some improvements in quality of life measures like feeling less worn out. However, most of the cognitive tests examined — including tests of attention, visual memory, spatial memory, and mental flexibility — showed no significant differences between supplementation groups and placebo. The study enrolled 58 healthy, active adults who were randomly assigned to take either a placebo, GAA alone (2 grams per day), or GAA combined with creatine (12 grams per day total) for six weeks. Blood tests showed no clinically meaningful safety concerns, and participants did not report notable side effects, suggesting the supplements were well tolerated. Some sleep quality findings were mixed, with both positive and potentially undesirable changes observed. This research suggests that GAA supplementation, particularly when combined with creatine, may have some promise for improving certain aspects of memory speed and retrieval, as well as stress and quality of life perceptions. However, the authors emphasize that this was a preliminary exploratory study with several inconsistent findings and results that often only approached statistical significance. They concluded that additional, larger studies are needed before firm conclusions can be drawn about the cognitive benefits of GAA supplementation.

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Citation

Chun J, Babakhani K, Gonzalez D, Dickerson B, Sowinski R, Rasmussen C, et al.. (2026). Effects of six weeks of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function and markers of health in healthy adults.. Journal of the International Society of Sports Nutrition. https://doi.org/10.1080/15502783.2026.2711032