Guanidinoacetic Acid
Also known as: GAA, Guanidinoacetate
Randomised trials and pharmacokinetic studies in healthy adults and clinical populations show that oral GAA raises plasma and tissue creatine in a dose-dependent manner; some trials report improved muscular strength and work capacity but no consistent reduction in subjective fatigue in chronic fatigue syndrome. Pharmacokinetics are nonlinear and systemic exposure increases more than proportionally with dose.
Last reviewed: 2026-10-14 · 4 indexed studies
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Overview
Guanidinoacetic acid (GAA) is the biosynthetic precursor of creatine and is marketed as an oral supplement to raise tissue creatine. Human trials show that multi-week doses (around 2.4–3 g/day) increase muscle and some brain regional creatine levels and may improve certain performance metrics, while effects on clinical fatigue outcomes have been inconsistent.
Mechanism & Function
Mechanism of Action
GAA is converted enzymatically to creatine in the body; supplementation increases substrate availability for creatine synthesis, thereby raising creatine concentrations in muscle and some brain regions.
Physiological Role
Precursor in endogenous creatine biosynthesis; influences cellular energy buffering by increasing creatine/phosphocreatine pools.
Primary Pathways
Performance / Health Relevance
By increasing creatine availability in muscle and some brain regions, GAA may augment high-energy phosphate buffering and support short-term work capacity and strength in some populations.
Evidence Review
Practical Use & Dosage
- Minimum Effective Dose
- 1.2 g (single-dose PK effects observed); 2.4 g/day produced tissue creatine increases in trials
- Optimal Range
- Approximately 2.4–3 g/day for multi-week loading (as used in trials demonstrating tissue creatine rise and some performance gains)
- Upper / Caution Level
- Not established from provided abstracts
- Timing
- Oral, daily dosing in divided or single doses as per trials (studies used once-daily dosing)
- Best Format
- Oral powder or capsules
- Bioavailability
- Single-dose pharmacokinetics are nonlinear with greater-than-dose-proportional increases in systemic exposure across 1.2–4.8 g.
- Absorption Considerations
- Oral GAA rapidly increases plasma GAA and raises plasma creatine within hours; tissue creatine increases occur over weeks.
Safety & Interactions
Side Effects
- •Nausea
- •Insomnia
- •Other mild to moderate adverse events reported in some trials
Contraindications
- Not established in provided abstracts
Drug Interactions
- •No specific interactions reported in provided abstracts
Who Should Avoid
- •People with urea cycle disorders or known metabolic disorders involving arginine/guanidino compounds (not directly studied here)
- •Pregnant or breastfeeding women (no data in provided abstracts)
Monitoring
Monitor for adverse effects; clinical monitoring and specialist input advised in people with known inborn errors of metabolism.
Frequently Asked Questions
Auto-generated from indexed evidence — dosage, safety, interactions, and more.
When is Guanidinoacetic Acid typically used or indicated?
Guanidinoacetic Acid is most commonly used for: Increase tissue creatine stores, Support exercise performance / work capacity, Investigational use for fatigue syndromes. Precursor in endogenous creatine biosynthesis; influences cellular energy buffering by increasing creatine/phosphocreatine pools.
How does Guanidinoacetic Acid work?
GAA is converted enzymatically to creatine in the body; supplementation increases substrate availability for creatine synthesis, thereby raising creatine concentrations in muscle and some brain regions.
What is the recommended dose of Guanidinoacetic Acid?
The optimal range is Approximately 2.4–3 g/day for multi-week loading (as used in trials demonstrating tissue creatine rise and some performance gains). with a minimum effective dose of 1.2 g (single-dose PK effects observed); 2.4 g/day produced tissue creatine increases in trials. Best taken: Oral, daily dosing in divided or single doses as per trials (studies used once-daily dosing). Upper / caution level: Not established from provided abstracts.
What are the side effects of Guanidinoacetic Acid?
Reported side effects include: Nausea; Insomnia; and Other mild to moderate adverse events reported in some trials. Monitoring: Monitor for adverse effects; clinical monitoring and specialist input advised in people with known inborn errors of metabolism.
Does Guanidinoacetic Acid interact with medications?
Known or theoretical interactions: No specific interactions reported in provided abstracts. Always check with a clinician before combining with prescription medication.
Who should avoid Guanidinoacetic Acid?
Guanidinoacetic Acid is generally not recommended for: People with urea cycle disorders or known metabolic disorders involving arginine/guanidino compounds (not directly studied here); Pregnant or breastfeeding women (no data in provided abstracts); and Not established in provided abstracts.
How strong is the evidence for Guanidinoacetic Acid?
Evidence level: Moderate (overall score 57/100), based on 4 indexed studies on SuppIndex.
Research & References (4)
Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review.
Systematic review of dietary supplements for fatigue in ME/CFS identified some studies (including GAA) that reported reductions in fatigue but noted small sample sizes and high risk of bias.
Guanidinoacetic acid loading for improved location-specific brain creatine.
Secondary analysis of a trial in 19 healthy men given 3 g/day GAA for 4 weeks showed increases in total creatine in several brain regions with variable responder rates by region.
Single-dose oral guanidinoacetic acid exhibits dose-dependent pharmacokinetics in healthy volunteers.
Randomised, placebo-controlled single-dose PK study in 48 young adults comparing 1.2, 2.4 and 4.8 g oral GAA showed dose-dependent and nonlinear pharmacokinetics and dose-related rises in plasma creatine.
Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome.
Double-blind, crossover RCT in 21 women with chronic fatigue syndrome given 2.4 g/day GAA or placebo for 3 months showed increased muscle creatine and improvements in strength and aerobic power but no effect on general fatigue or musculoskeletal soreness.
Related Ingredients
Other top-rated ingredients in Ergogenic Compounds.
Creatine Monohydrate
94/100A naturally occurring nitrogenous organic acid that facilitates recycling of adenosine triphosphate (ATP) in muscle and brain tissue via the phosphocreatine shuttle.
Maltodextrin
78/100Short-chain α-1,4 linked glucose polymer that is rapidly hydrolysed by brush-border maltase to glucose; near-equivalent glycaemic response to glucose but lower osmolality at concentration.
Cyclic Dextrin (HBCD)
72/100Produced via cyclic-glucanotransferase action on amylopectin, HBCD forms cluster-like macromolecules ~160 kDa that solubilise at low osmolality (≈4 mOsm/L) and clear the stomach faster than maltodextrin or glucose polymers.
Research Overview
Moderate EvidenceCite this ingredient
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Stable URL
https://thesuppindex.com/ingredients/guanidinoacetic-acid
SuppIndex. (2026). Guanidinoacetic Acid: Evidence summary, dosage and clinical studies. Retrieved October 16, 2026, from https://thesuppindex.com/ingredients/guanidinoacetic-acid
Based on 4 indexed studies · Evidence level: Moderate.
Goal Ratings
Stack Compatibility
Mechanistically compatible with creatine supplementation (both raise creatine), but effects and safety of combined use were not addressed in the provided abstracts.