Effects of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function

Plain English summary of protocol

Background and study aims
Creatine monohydrate (CrM) supplementation (e.g., 4 x 5 g or 20 g/d for 5-7 days and 3 – 6 g/d for 4-12 weeks) increases muscle creatine and phosphocreatine (Cr) content by 20% - 40%, and brain creatine and phosphocreatine content by 5% - 15%, thereby improving the ability to produce energy during high-demand states. While most studies have evaluated the effects of CrM supplementation on physical exercise performance, several studies have reported that high-dose creatine supplementation can increase brain phosphocreatine content leading to improved cognitive function. Creatine is obtained in gram quantities from meat and fish and is synthesized in the body when dietary availability is low (2 – 4 grams/kg). In over 30 years of research, clinical trials involving creatine monohydrate supplementation have reported no adverse health risks other than a small amount of weight and muscle mass gain (a desired effect). Conversely, several health benefits have been reported throughout the lifespan.

Guanidinoacetic Acid (GAA) is a precursor in the natural synthesis of creatine in muscle, the heart, and particularly in the brain. Since some animals more effectively convert GAA to creatine, GAA has been added to the feed of animals consumed by humans (e.g., chickens, pigs, etc.) as a means of increasing muscle mass at EFSA-approved dosages of 1,200 mg/kg/d. GAA has also been used as a nutrient in human nutrition since the 1950s and is sold as an ingredient for dietary supplements. Since GAA supplementation has been reported to increase energy levels in the brain more effectively than CrM, dietary supplementation with GAA (with and without CrM) may be an effective way to improve cognitive function. For this reason, GAA supplementation has been suggested to be a novel nootropic to improve cognitive function and brain health. However, while there is strong theoretical rationale, the effects of GAA supplementation (with or without CrM supplementation) on cognitive function have not been studied, particularly in active aging populations who may benefit. The purpose of this study is to evaluate the effects of short-term GAA supplementation with and without CrM on markers of cognitive function and health markers.

Who can participate?
We are recruiting up to 100 male and female participants between the ages of 18 and 65 with a goad of completing 60 participants.

What does the study involve?
Each participant will be asked to visit the lab three times over approximately a six week period. Each study visit will last approximately two hours (minus the first study visit or Familiarization which will last approximately one hour). Each visit after the first Familiarization visit will include; anthropometric measures (height and weight), vital signs (HR and BP) measures, blood draw, DXA scan, physical activity questionnaire (IPAQ), quality of life questionnaire (SF-36), profile of mood states questionnaire (POMS), memory complaint questionnaire (MAP-Q), Wechsler memory scale (WMS - VAP1 and VAP2) questionnaire, Mini-Mental State Examination (MMSE), the Leeds sleep evaluation questionnaire, The Cohen's perceived stress scale (PSS), a menstrual status questionnaire (females only), a menopause status questionnaire (females only), COMPASS cognitive test battery, and side-effects assessment.

What are the possible benefits and risks of of participating?
Possible benefits of participating include increased insight into one's health and fitness status (i.e., anthropometric measurements, vital sign measurements, lab values, DXA body composition and bone density values, etc.). Possible risks of participation include complications from the blood draws (i.e., pain, dizziness, nausea, etc.), radiation exposure from the DXA scan (< 1 mRem per scan), side effects of the supplements (i.e., bloating, cramping, diarrhea, etc.), and possible allergic reactions to the supplements.

Where is the study run from?
The study was run from the Exercise & Sport Nutrition Laboratory (ESNL) at Texas A&M University (USA)

When is the study starting and how long is it expected to run for?
The study planning started on November 20, 2023 and was completed on September 20, 2025.

Who is funding the study?
The study is being funded by the WoodNext Foundation (USA)

Who is the main contact?
Dr Richard Kreider, rbkreider@tamu.edu

Contact information

Dr Richard Kreider
Scientific, Principal investigator

675 John Kimbrough Blvd.
#118
College Station
77843-4253
United States of America

ORCID ID	0000-0002-3906-1658
Phone	+1 9794581498
Email	rbkreider@tamu.edu

Mr Christopher Rasmussen
Public

675 John Kimbrough Blvd.
Suite #206
College Station
77843-4253
United States of America

ORCID ID	0009-0005-8941-3067
Phone	+1 9794581741
Email	crasmussen@tamu.edu

Study information

Eligibility

Locations

Countries of recruitment

• United States of America

Study participating centre

Results and Publications

Study outputs

Editorial Notes

11/11/2025: Trial's existence confirmed by Texas A&M University Institutional Review Board (IRB).