Get Your Personalized Supplement StackSupplement Stack Quiz

Guanidinoacetate

Also known as: GAA, glycocyamine, Guanidinoacetic acid, Guanidinoacetate

Overview

Guanidinoacetate (GAA), also known as glycocyamine, is a naturally occurring amino acid derivative and a crucial intermediate in the body's biosynthesis of creatine. It is primarily synthesized in the kidneys from glycine and arginine. As a direct precursor to creatine, GAA is methylated by S-adenosylmethionine (SAM) to form creatine, a key molecule for cellular energy metabolism, particularly in muscles. Supplementation with GAA is explored as a strategy to increase endogenous creatine levels, potentially enhancing muscle energy, physical performance, and body composition. Beyond its role in creatine synthesis, GAA also influences methylation metabolism and homocysteine regulation, as its conversion to creatine consumes methyl groups. While research on GAA is emerging, with several pilot studies and animal models providing insights, large-scale human randomized controlled trials specifically on GAA supplementation are limited. The current evidence suggests it can increase creatine synthesis and may have sex-specific effects on body composition, but more robust research is needed to fully establish its efficacy and safety profile.

Benefits

Guanidinoacetate (GAA) supplementation primarily aims to increase creatine availability, which is crucial for cellular energy. A pilot study (n=23) indicated that combined GAA and creatine supplementation significantly increased extracellular mass (p=0.009) and potentially intracellular water in males (p=0.049), suggesting a positive impact on body composition. While direct evidence for physical performance enhancement from GAA alone is limited, its role as a creatine precursor implies indirect benefits. GAA also modulates methionine cycle metabolites, potentially reducing hepatic S-adenosylmethionine (SAM) and increasing S-adenosylhomocysteine (SAH), which influences homocysteine metabolism and methylation pathways. It may also stimulate insulin secretion, further impacting methyl group metabolism. The observed body composition changes are statistically significant but come from a small pilot study, limiting generalizability. Sex-specific effects were noted, with males showing different intracellular water responses. Short-term supplementation (7 days) has shown measurable changes, but long-term benefits require further investigation.

How it works

Guanidinoacetate (GAA) functions as a direct precursor to creatine. Its primary mechanism involves methylation by S-adenosylmethionine (SAM) through the enzyme guanidinoacetate N-methyltransferase (GAMT), converting GAA into creatine. This process consumes methyl groups, thereby impacting the methionine cycle and influencing levels of homocysteine. By increasing creatine synthesis, GAA enhances cellular energy metabolism, particularly in muscle tissue. It also interacts with liver methylation pathways, affecting enzymes like cystathionine-β-synthase (CBS) and betaine-homocysteine methyltransferase (BHMT), which are involved in homocysteine metabolism. Additionally, GAA may stimulate insulin secretion, which can further influence methyl group metabolism enzymes. Oral GAA is bioavailable and rapidly converted to creatine in the liver and kidneys, contributing to its systemic effects.

Side effects

Guanidinoacetate (GAA) is generally considered safe at studied doses, but its safety profile is not extensively documented in humans due to limited research. A primary concern is its impact on methylation demand; the conversion of GAA to creatine consumes methyl groups, which can potentially elevate homocysteine levels. Elevated homocysteine is a known cardiovascular risk factor. While some evidence suggests insulin-mediated homocysteine reduction might counterbalance this, caution is advised. Common, uncommon, or rare side effects are not well-documented in human studies, with no significant adverse events reported in small pilot trials. Potential drug interactions exist with medications affecting methylation or homocysteine metabolism, necessitating caution. Contraindications are not clearly defined, but individuals with pre-existing methylation disorders or elevated homocysteine should exercise caution. Specific population considerations include observed sex-specific effects on body composition, and its safety and efficacy in older adults, children, or individuals with specific disease states remain largely unresearched.

Dosage

The optimal dosage for Guanidinoacetate (GAA) is not definitively established due to limited human research. A pilot study that observed effects on body composition used 2 grams of GAA combined with 2 grams of creatine daily for 7 days. The minimum effective dose for GAA alone is not well-established. Animal studies have utilized higher doses (5-10 g/kg), but human dosing requires careful titration due to the potential impact on methylation and homocysteine levels. The maximum safe dose for GAA is currently unknown; high doses may increase methylation demand and homocysteine. Short-term supplementation (7 days) has shown measurable effects, but longer-term duration studies are needed. GAA is typically taken orally and is often combined with creatine for potential synergistic effects. Adequate methyl donors, such as folate and vitamin B12, may be necessary to mitigate potential homocysteine elevation, especially with higher doses or prolonged use.

FAQs

Is GAA supplementation safe?

Preliminary data suggest safety at moderate doses, but due to its impact on methylation, monitoring methylation status and homocysteine levels is advisable, especially with prolonged use.

Does GAA improve muscle performance?

GAA acts as a precursor to creatine, which is known to improve muscle performance. However, direct evidence for performance enhancement from GAA alone is limited, with most benefits observed in combination with creatine.

Can GAA cause elevated homocysteine?

Yes, GAA's conversion to creatine consumes methyl groups, which can increase methylation demand and potentially elevate homocysteine levels. However, insulin effects might counterbalance this in some individuals.

Should GAA be combined with creatine?

Some research suggests that combining GAA with creatine may offer unique or synergistic effects on body composition compared to creatine alone, making it a common approach in studies.

How quickly do effects appear?

In pilot studies, changes in body composition have been observed within one week of supplementation, indicating a relatively rapid onset of some effects.

Research Sources

https://pmc.ncbi.nlm.nih.gov/articles/PMC11493483/ – This pilot randomized controlled crossover trial investigated the effects of creatine and guanidinoacetate (GAA) supplementation on body composition in 23 healthy young adults. The study found that combined creatine+GAA increased extracellular mass compared to creatine alone, with sex-specific effects on intracellular water, suggesting a potential role for GAA in body composition modulation.
https://www.frontiersin.org/journals/animal-science/articles/10.3389/fanim.2022.972868/full – This narrative review, drawing on animal studies, explores how guanidinoacetate (GAA) supplementation impacts methionine cycle metabolites. It highlights that GAA can alter methylation pathways, potentially increasing homocysteine and affecting key methylation enzymes, while also suggesting a possible role in stimulating insulin secretion.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9999677/ – This source is a meta-analysis on creatine supplementation, not directly on GAA. It provides high-quality evidence for creatine's benefits on memory and physical function, serving as indirect context for GAA's role as a creatine precursor, but offers no direct data on GAA itself.
https://academic.oup.com/nutritionreviews/article-pdf/81/4/416/49456949/nuac064.pdf – This source is a systematic review on creatine, not directly on GAA. It provides high-quality evidence for creatine's benefits on physical function, serving as indirect context for GAA's role as a creatine precursor, but offers no direct data on GAA itself.
https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/jpen.2607 – This source is a systematic review on creatine, not directly on GAA. It provides high-quality evidence for creatine's benefits, serving as indirect context for GAA's role as a creatine precursor, but offers no direct data on GAA itself.