Myostatin inhibitor, Myogenic promotor | Steroid like gains from Creatine precursor Guanidinoacetic acid (GAA)

[LVZZO]

Potential cognitive enhancer?
I know some people that take 15g creatine instead of the usual 5 because it’s good for the brain or something

Likely the more effective than of high dose creatine

trials suggest that supplementing with GAA (often combined with creatine) can significantly increase tissue creatine levels (by ~16.9% vs. ~2.0% with creatine alone)

 

[mvp2v1]

I have been gatekeeping this and decided to release it to the wider audience, hopefully it will have a big impact with some people trying it out and posting results.

I will be very brief with the explanation.
(summary)

Guanidinoacetic acid(GAA)

Guanidinoacetic acid(GAA) Description: White crystalline powder,slightly soluble in water Purity: 98%min by HPLC Indication: Guanidinoacetic acid (GAA; also known as Glycocyamine or guanidinoacetate or 2-guanidinoacetic acid) is a nutritional feed additive classified as “amino acid,their...

www.phiphar.com

Basically, GAA is approved for animal feed to improve weight gain and more importantly lean mass gains.
The main benefit is that will ~8x the creatine levels compared to creatine
The main downsides are some increase need for methylation so you can supplement with betain for example

Spoiler

While guanidinoacetic acid (GAA) supplementation can enhance muscle creatine levels and improve exercise performance, it's important to be aware of potential downsides:


1. Increased Methylation Demand and Homocysteine Levels


GAA conversion to creatine requires methylation, utilizing methyl groups from compounds like S-adenosylmethionine. Elevated GAA intake can increase the body's methylation demand, potentially leading to higher homocysteine levels—a risk factor for cardiovascular diseases. However, some studies have reported that GAA supplementation did not significantly raise homocysteine levels in healthy adults. citeturn0search1


2. Gastrointestinal Discomfort


Some individuals have reported transient nausea during the initial weeks of GAA supplementation. In a post-marketing surveillance study, 5.3% of participants experienced such symptoms, though none discontinued use due to these effects. citeturn0search1


3. Potential Neurotoxic and Pro-Oxidant Effects


Animal studies have indicated that excessive GAA accumulation may have neurotoxic and pro-oxidant effects. While these findings are not yet confirmed in humans, they suggest caution with high-dose GAA supplementation. citeturn0search0


4. Impact on Liver Enzymes


Some research has noted changes in liver enzyme levels following GAA supplementation. For instance, a study reported a 13.6% increase in alkaline phosphatase levels after GAA intervention, though other clinical enzymes remained unaffected. citeturn0search4


5. Increased Methyl Group Requirements


GAA supplementation may elevate the body's demand for methyl groups, which could affect overall methyl group utilization and related metabolic processes. citeturn0search7


Conclusion


While GAA supplementation offers potential benefits for muscle performance, it's essential to consider these potential downsides. Consulting with a healthcare professional before starting GAA supplementation is advisable to ensure it aligns with individual health needs and to monitor for any adverse effects.

And more importantly it's hard to source, you have to go for animal feed or from more expensive lab stuff
https://cymitquimica.com/products/10-F450285/352-97-6/2-guanidinoacetic-acid/

You can now start to see some products including, namely CreGAAtine

https://www.cregaatine.com/cregaatine-creatine-differences/

or this one
iherb.com/pr/aurora-nutrascience-active-liposomal-creatine-plus-gaa-r-ala-10-packets-0-63-oz-18-g-each/146504

I prompted ChatGPT to resume the mechanism and expected gains
But I think it understates the potential gains

Spoiler

Both guanidinoacetic acid (GAA) and creatine work by boosting the energy available to muscle cells, but they do so via slightly different routes that can lead to enhanced muscle growth when paired with resistance training.


GAA’s Mechanism and Muscle Growth
GAA is the immediate precursor to creatine. In the body, it’s synthesized from glycine and arginine in the kidney and then converted in the liver (using a methyl group from S‑adenosyl‑L‑methionine) into creatine—the key molecule stored in muscle as phosphocreatine. Phosphocreatine rapidly regenerates adenosine triphosphate (ATP) during high-intensity exercise. This extra ATP helps you push through harder training sessions and recover faster, which over time results in greater muscle hypertrophy. In effect, by boosting creatine synthesis, GAA indirectly improves the anabolic stimulus your muscles receive.


Evidence on Lean Muscle Gains
In one randomized, double-blind crossover trial comparing a creatine–GAA mixture with creatine alone, supplementation with the combined formula (providing about 3 g GAA plus 3 g creatine daily) produced a significantly greater rise in tissue creatine levels. For example, muscle creatine content increased by roughly 16.9% with the GAA–creatine combination, compared with only about 2.0% when using creatine alone citeturn4search0.
This enhanced creatine loading translated into performance improvements—for instance, greater bench press strength. In terms of body composition, one study noted that over a similar training period (typically 6–12 weeks), individuals using the creatine–GAA mixture gained about 1.6 kg of weight (which included lean muscle) compared to around 0.7 kg in those taking creatine alone citeturn4search0. Although these weight differences include some water retention, they suggest that the improved energy bioavailability from GAA can allow for a higher quality training stimulus and, consequently, more pronounced muscle growth.


For context, conventional creatine supplementation alone is well documented to produce an extra 1–2 kg (2–4 pounds) of lean muscle mass over a 12‑week resistance training program in young adults citeturn4news12. The creatine–GAA combination appears to augment this effect further by ensuring even higher tissue creatine levels, which enables harder, more productive training sessions without the direct androgenic (steroid-like) activity seen with anabolic steroids. In other words, the “steroid-like” gains reported with GAA result not from hormonal effects but from optimized energy metabolism and the resulting training adaptations.

In Summary

Spoiler

• GAA Boosts Creatine Synthesis: By acting as a precursor, GAA increases muscle phosphocreatine stores, thereby enhancing ATP regeneration during intense exercise.
• Enhanced Training Leads to Greater Muscle Growth: With more energy available, you can train at higher intensities, promoting superior muscle hypertrophy. Studies have shown that a creatine–GAA combination can yield approximately 1–2 kg more lean mass over a training period than creatine alone.
• Comparison with Regular Creatine: While creatine monohydrate alone typically results in a 1–2 kg lean mass gain over 12 weeks, trials suggest that supplementing with GAA (often combined with creatine) can significantly increase tissue creatine levels (by ~16.9% vs. ~2.0% with creatine alone) and improve strength outcomes, translating into enhanced muscle growth citeturn4search0.

Thus, at the “right” dose—typically around 2–3 g of GAA per day combined with an equivalent creatine dose—the improved muscle bioenergetics can lead to notably greater lean muscle gains compared with creatine supplementation alone, all without the direct hormonal actions of anabolic steroids.

After 60 days
Here is a 50% increase in muscle area with GAA in pig loin
Fat thickness is also reduced by 30%
View attachment 3482827

It seems to works as a myostatin inhibitor and myogenic promotor.
Amazingly it isn't known in bodybuilding.
View attachment 3482850
Study:

https://onlinelibrary.wiley.com/doi/10.1111/jpn.13351

Human equivalent dose in the study seems low, but math seems correct at a first glance
It's less than 1g/day

Spoiler

To calculate the human equivalent dose (HED) of the 0.06% GAA dose used in finishing pigs, we use the standard allometric scaling method:

Step 1: Extract the Pig Dosage​

• The study used 0.06% GAA in feed, meaning 0.06 g per 100 g of feed.
• Assuming an average daily feed intake (ADFI) of ~2.81 kg for pigs receiving 0.06% GAA (from Table 3), the daily GAA intake would be:2.81 kg×0.06100=1.686 g GAA/day2.81 \text{ kg} \times \frac{0.06}{100} = 1.686 \text{ g GAA/day}
• The average pig weight was around 81–130 kg, with a midpoint of 105 kg.

Step 2: Convert to Human Equivalent Dose (HED)​

Allometric dose conversion is based on body surface area scaling using the formula:

HED(mg/kg)=Animal dose(mg/kg)×(Animal KmHuman Km)HED (\text{mg/kg}) = \text{Animal dose} (\text{mg/kg}) \times \left(\frac{\text{Animal Km}}{\text{Human Km}}\right)
Using standard Km factors (body surface area correction):

• Pig Km = 24
• Human Km = 37

Calculate the pig's dose in mg/kg:

1686 mg105 kg=16.06 mg/kg\frac{1686 \text{ mg}}{105 \text{ kg}} = 16.06 \text{ mg/kg}
Convert to human equivalent dose:

16.06×(2437)=10.4 mg/kg16.06 \times \left(\frac{24}{37}\right) = 10.4 \text{ mg/kg}

Step 3: Convert to a Total Human Dose​

For a 70 kg human:

10.4×70=728 mg GAA/day≈0.73g/day10.4 \times 70 = \mathbf{728 \text{ mg GAA/day} \approx 0.73 g/day}

Conclusion​

• The human equivalent dose of 0.06% dietary GAA in pigs is about 0.73 g/day for a 70 kg adult.
• This dose is within the commonly used range of 2–3 g/day in human supplementation studies.
• For higher body weight individuals, doses would be slightly higher (e.g., ~1 g/day for a 100 kg person).

The interesting part:

Edit: Don't take this supplement, it does not seem safe at all. You may develop a serious condition from it.
The methylation of guanidinoacetate to form creatine consumes more methyl groups than all other methylation reactions combined. Therefore, we examined the effects of increased or decreased methyl demand by these physiological substrates on plasma homocysteine by feeding rats guanidinoacetate- or creatine-supplemented diets for 2 wk. Plasma homocysteine was significantly increased (~50%) in rats maintained on guanidinoacetate-supplemented diets, whereas rats maintained on creatine-supplemented diets exhibited a significantly lower (~25%) plasma homocysteine level.
https://pubmed.ncbi.nlm.nih.gov/11595668/
In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration.
https://www.medsci.org/v10p0141.htm
Elevated homocysteine levels have been implicated in the development of Down’s syndrome, Parkinson’s disease, Alzheimer's disease, stroke, dementia, coronary heart disease, vascular disease, anemias, renal disease and hepatic disease.
You may damage your cognition irreparably.
We found 111 pertinent articles. There were 24 cohort studies, 18 randomized trials, 21 case-control studies, and 48 cross-sectional studies. This review reveals a positive trend between cognitive decline and increased plasma Hcy concentrations in general population and in patients with cognitive impairments. Results from the meta-analyses also confirm this trend. Treatment with vitamin supplementation fails to show a reduction in cognitive decline.
https://pubmed.ncbi.nlm.nih.gov/27531233/
GAA seems to be neurotoxic when accumulates in the brain of experimental animals and patients with inherited 335 disorders of creatine metabolism [28,29], with subjects experience dystonic symptoms, seizures and convulsions.
https://zero.sci-hub.do/5388/df53fc082bbd20ef455f99d98da2bfff/ostojic2016.pdf
Higher GAA levels were associated with an unfavorable cardiometabolic risk profile (higher insulin, higher total homocysteine, and higher body fat percentage).
https://www.mdpi.com/2072-6643/10/1/87

We need to find a way to directly buy NAA.

 

[Seong Gi-Hun]

I was about to comment about this, seems you beat me to it. Animal studies have shown neurotoxic effects

 

[LVZZO]

@mvp2v1 For increased methylation demand you can take tmg, homocysteine increase is also a result of methylation demand and 50% higher is not that much, both can be managed with tmg and a multivitamin with folate and b12
Regarding toxicity it's a matter of dosage, 60mg/kg or 4.2g/70kg increased N-acetylaspartate levels

Dietary guanidinoacetic acid increases brain creatine levels in healthy men - PubMed

Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative...

pubmed.ncbi.nlm.nih.gov

Objective: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention.
Methods: Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA for the first 4 wk of the intervention; afterward GAA dosage was titrated ≤60 mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity.
Results: Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P < 0.05). Thalamus creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P < 0.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention.
Conclusions: Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease.
Keywords: Cerebellum; Creatine synthesis; Gray matter; MR spectroscopy; Side effects; White matter.

What are these side effects compared to sarms and steroids.
GAA is proven and approved for human consumption, all you need is to supplement with some cheap otc supplemens.
The hard part is to source GAA.

 

[LVZZO]

@mvp2v1 For increased methylation demand you can take tmg, homocysteine increase is also a result of methylation demand and 50% higher is not that much, both can be managed with tmg and a multivitamin with folate and b12
Regarding toxicity it's a matter of dosage, 60mg/kg or 4.2g/70kg increased N-acetylaspartate levels

Dietary guanidinoacetic acid increases brain creatine levels in healthy men - PubMed

Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative...

pubmed.ncbi.nlm.nih.gov

What are these side effects compared to sarms and steroids.
GAA is proven and approved for human consumption, all you need is to supplement with some cheap otc supplemens.
The hard part is to source GAA.

Also you probably need to supplement SAMe and or methionine, it has specific functions aside from general methyl donation

This is the protocol from the first link in the OP actually,

Using the ratios (6/4/2), per 3g GAA
3g GAA
2g Betaine
1g Methionine