Randomized controlled trial2026Open access

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

Chun J, Babakhani K, Gonzalez DE, Dickerson B, Sowinski RJ, Rasmussen CJ, Kreider RB

Journal of the International Society of Sports Nutrition · 0 citations

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Author industry ties

Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.

How it was studied

Design
Randomized controlled trial (indexed by PubMed)
Studied in
People
Main outcome
Health markers and function

Who paid for it

Funding
Possibly industry funded
Nonprofit
WoodNext Foundation
Authors
At least one author declares a financial tie to industry

Based on 1 listed funder(s) and full-text disclosure statement.

Publication

Published
2026-09-12 · J Int Soc Sports Nutr · vol. 23 · issue sup1 · p. 2711032
Publisher
Springer Science+Business Media
Cited
0 citations · more than 81% of similar papers · 0.0× the field average
References
170 works
Access
Open access (journal) · CC-BY-NC
Research areas
Muscle metabolism and nutrition · Nutrition and Health in Aging · Biochemical effects in animals
Keywords
Creatine, Cognition, Univariate analysis, Multivariate analysis, Univariate, Analysis of variance, Clinical nutrition, Confidence interval
MeSH
humans, creatine, glycine, double-blind method, affect, cognition, reaction time, dietary supplements, adult, middle aged, female, male, young adult, biomarkers, sleep quality

7 authors

  • Jisun Chun
  • Khatereh Babakhani
  • Drew Edward Gonzalez
  • Broderick Dickerson
  • Ryan J. Sowinski
  • Chris J. Rasmussen

Abstract

Background

Guanidinoacetic acid (GAA) supplementation has been reported to increase brain creatine content more effectively than creatine monohydrate (CrM). However, the effects on cognitive function are unclear.

Purpose

The purpose of this proof-of-concept exploratory clinical trial was to determine whether GAA supplementation with and without CrM affects cognitive function and/or markers of health.

Methods

In a double-blind, randomized, and counterbalanced manner, 58 healthy and active adults (33 females, 35.5 ± 14 years, 76.2 ± 14 kg) ingested a PLA (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) for six weeks. The participants donated fasting blood samples and completed a battery of tests and questionnaires assessing various aspects of function, mood, stress, sleep quality, and markers of health at baseline and after six weeks of supplementation. Data were analyzed using General Linear Model (GLM) multivariate and univariate with repeated measures, and mean changes from baseline with 95% confidence intervals, and Chi-squared analysis, and considered significant when the probability of error was 0.05 or less, and approaching significance (p > 0.05-p < 0.10).

Results

GAA supplementation tended to improve overall reaction time (-241.8 ms [-533, 50], p = 0.10) while significant interaction effects were observed in overall reaction time (p = 0.031-330 ms [-629, -31]) and YES reaction time (-290 ms [-484, -96], p = 0.004) while recalled correct reaction time (-178 ms [-374, 21], p = 0.078) and recalled correct YES (7.4 % [-1, 15.8], p = 0.084) approached significance compared to PLA. Limited to no 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 amount of time engaged in moderate physical activity was significantly greater (p p = 0.036), and feeling like difficulties are mounting (p = 0.053) on the Perceived Stress Scale. Some positive and potentially undesirable effects were observed in sleep quality assessments. The quality of life assessment revealed that 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) while those in the GAA + CrM group reported more frequent limitations when bending, kneeling, or stooping (p = 0.053), more often feeling full of life (p = 0.081), and less frequency in feeling downhearted and depressed (p = 0.066). No clinically meaningful changes were observed in blood markers or self-reported side effects among the groups.

Conclusion

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. However, most cognitive tests were not affected, particularly when comparing the GAA to the PLA group; there were some inconsistencies in the findings, and several differences only approached significance. Additional research is needed before conclusions can be drawn. Clinical trial registration: ISRCTN68542582.

Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC).

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