Science behind CreGAAtine
Even though there are various Creatine preparations under numerous brand names, there is no firm evidence of superiority of one formulation over the other.
Case in point, the existing study has shown that the muscle Creatine content does not alter significantly when comparing Creatine Monohydrate and Creatine Ethyl Ester (1).
A comprehensive review concluded that, despite the marketing claims, the advantage of the varying Creatine forms over Creatine-Monohydrate regarding their safety and efficacy profiles is not substantiated (2).
To learn more about Guanidinoacetic Acid (GAA), you can read some of the 200+ GAA research studies here.
CreGAAtine is a novel scientifically proven dietary supplement, made of Creatine and Guanidinoacetic Acid (GAA), which is a natural organic compound that acts as a direct precursor of Creatine.
GAA is synthesised in a catalytic reaction from L-arginine and glycine, via an enzyme called Larginine-glycine amidinotransferase (AGAT). In the reaction, an amidino group is transferred from L-arginine to glycine forming GAA and ornithine.
The following transformation of GAA to Creatine is catalysed by Sadenosyl-L-methionine: N-guanidinoacetate methyltransferase (GAMT), where the amidino group is methylated, thereby forming Creatine. Both enzymes are found in high amounts throughout the pancreas and liver.
While AGAT is also highly expressed in the kidneys, the level of GAMT is low (3). Even though AGAT located in the liver was found to be repressed by Creatine, it does not seem to occur with GAMT, which may imply that the conversion of GAA to Creatine cannot be repressed when GAA is exogenously applied (4).
Furthermore, other tissues with high energy output, such as the brain, musculoskeletal and myocardium systems, were also found to be additional places where GAA-Creatine conversion occurs (5,6).
According to Daly’s research, it seems that GAMT activity is high enough to synthesise the sufficient amount of Creatine in the musculoskeletal tissue as well (3,5).
CreGAAtine boosts muscle and brain bioenergetics with superior
Creatine Monohydrate administration over 4 weeks increases muscle Creatine of about 2%, while CreGAAtine™ leads to a 16.9% increase of Creatine inside the musculoskeletal system, which is a relative rise of 8.5 times (7).
A randomized double-blind superiority trial compared the effect of the administration of GAA-Creatine preparation to standard Creatine over 4 weeks.
The results showed that the combination yields a significantly greater change from baseline in Creatine levels in vastus medialis muscle, a part of the quadriceps muscle group (7).
A study that investigated the effect of 2g GAA and 2g Creatine in elderly (>65 years) showed an even higher increase.
Specifically, the provision of the coadministration of GAA and Creatine led to a 32% increase from the baseline level after 8 weeks (8).
CreGAAtine increases Creatine levels in the Brain.
CreGAAtine™ is an advanced preparation compared to other Creatine formulas, as it results in enhanced Creatine levels in the brain. Specifically, the Creatine-GAA combination leads to a 3.9 times higher Creatine level in the brain's grey matter and 1.9 times higher concentration in the brain's white matter, compared to Creatine alone (7).
The augmented Creatine-increasing effect in brain tissue may be explained by the multiple modes of transport pathways of GAA, and the synergistic effect between GAA and Creatine. Even though Creatine receptors are most probably saturated with Creatine upon their coadministration, GAA can enter the cells via other protein carriers and in that manner provide an additional Creatine rise inside the cell (9).
While GAA effectively targets the cerebellum, white matter and grey matter, its effect on the thalamus is lacking (10,11). On the other hand, Creatine itself reaches on the thalamus, but has a limited effect on white matter in contrast to GAA (12). In elderly people (>65 years), the increase in Creatine content in the brain after 8 weeks of Creatine-GAA supplementation (2g of each per day) leads to a 26% increase from baseline results in specific brain compartments (8).
CreGAAtine has 4 ways to enter the Cell.
Creatine has only one known way of entering the cell, which over time, the cell becomes saturated with continuous Creatine supplementation, resulting in a lower capacity to transport Creatine into the cell (9).
CreGAAtine™ not only uses the regular Creatine receptors, but also utilises 3 additional pathways in order to enter the cell, including GABA and Taurine receptors, and even passive diffusion which does not require any protein carrier (13,14). Once it enters the cell, GAA turns into Creatine in a GAMT-controlled catalytic reaction and increases intracellular Creatine levels.
Moreover, CreGAAtine ensures the desired boost as there are less non-responders in contrast to regular Creatine (15). As Creatine receptors in the brain and muscles are close to being saturated with endogenous Creatine under physiological conditions (13,16), the advantage of GAA to utilise additional transport systems creates an effective strategy to overcome limited exogenous Creatine utilisation and meet advanced energetical needs in an exhaustive work-out session.
CreGAAtine helps weak muscles get Stronger. It works like creatine for muscle growth
CreGAAtine targets the weaker muscle groups as well, and increases their strength by 20% compared to
A study on 48 athletes, both men and women, demonstrated that this novel dietary agent and Creatine precursor significantly improves both upper and lower body muscle endurance (16).
The combination of GAA and Creatine is of particular interest due to the possible synergism between the two substances (8).
GAA was shown to target the muscle groups with lower levels of strength, which are muscles of the upper body in the general population.
The facilitation of the GAA absorption by the exercise-naive tissues may be explained by their tendency to better to absorb GAA, as the GAA levels are initially lower in these compartments (7).
CreGAAtine reduces Creatine-driven side effects.
Creatine tends to increase total body weight by water retention, giving your muscles a balloon-like appearance. A study that examined two different Creatine formulations demonstrated that the Creatine-Monohydrate intake results in the largest incline in total and intracellular body water when compared to placebo and Creatine Ethyl Ester.
Creatine Ethyl Ester led to the highest increase in extracellular water in comparison to the two other groups (18). The optimised formulation in CreGAAtine was created to make you stronger and to help you to build your lean muscles tissue without excess body weight gain. In a randomised, double-blind trial, the
GAA-Creatine arm was shown to result in a lower weight gain and more favourable outcomes in upper body muscular strength (7).
CreGAAtine is easily taken.
With the use of bulk packaging, Creatine products tend to lose their potency by up to 50% over time, as Creatine easily soaks up water through humidity. The single-dose packaging of CreGAAtine not only ensures optimal bioavailability and stability, but also gives you the convenience of taking your single doses with you (19). Creatine is a hygroscopic substance, which indicates that Creatine powder tends to absorb moisture from the ambient air (20).
As a consequence, over time Creatine turns to its inactive form, Creatinine, which does not have an ergogenic effect as Creatine (21). Contrarily, GAA is a highly stable substance as its content does not vary more than 5%, even after 15 months of storage. It implies warranted delivery of GAA and ensures its Creatine-boosting and performance-enhancing effect (17,22,23).
CreGAAtine comes in an innovative package, a pharmaceutical grade triplex foil sachet, which was designed to provide the maximum protection from moisture and to prevent Creatine degradation. The CreGAAtine powder inside the sachet remains intact which is reflected in its fine granulation once the sachet is opened.
No known safety concerns.
In a randomized double-blind controlled trial examining the GAA-Creatine formulation, no side effects were reported. Total plasma homocysteine levels remained in the physiological range, as well as the tissue choline levels (7).
A study published in Annals of Nutrition and Metabolism analysed the effect of GAA-Creatine coadministration in eight healthy young adults, with normal homocysteine levels over a two-month period.
The study concluded that the supplementation may lead to a mild rise in homocysteine, but it does not induce hyperhomocysteinemia (levels above 14 µmol/l).
This effect is probably observed due to supplemented Creatine, which prevents endogenous homocysteine production in Creatine synthesis pathways (24).
Administration of sole GAA appears to be safe in terms of GAA brain accumulation, and DNA methylation following its intake (25,26).
Trust your product - it’s important to know that many Creatine-based supplements in the market contain some contaminants, which surely implies their low quality (27).
CreGAAtine has been certified by Informed Sport, which guarantees that each batch we release to the market is free of banned substances .
Do Not Risk It - Be the sporting professional you strive to be with CreGAAtine.
1. Spillane, M., Schoch, R., Cooke, M., Harvey, T., Greenwood, M., Kreider, R., & Willoughby, D. S. (2009). The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. Journal of the International Society of Sports Nutrition, 6, 6. https://doi.org/10.1186/1550-2783-6-6
2. Jäger, R., Purpura, M., Shao, A. et al. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. Amino Acids 40, 1369–1383 (2011). https://doi.org/10.1007/s00726-011-0874-6
3. Wyss, M., & Kaddurah-Daouk, R. (2000). Creatine and creatinine metabolism. Physiological reviews.
4. Walker, J. B. (1979). Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol, 50, 177-242.
5. Daly, M. M. (1985). Guanidinoacetate methyltransferase activity in tissues and cultured cells. Archives of biochemistry and biophysics, 236(2), 576-584.
6. Ostojic, S.M., 2021. Creatine synthesis in the skeletal muscle: the times they are a-changin’. American Journal of Physiology-Endocrinology and Metabolism, 320(2), pp.E390-E391.
7. Semeredi, S., Stajer, V., Ostojic, J., Vranes, M., & Ostojic, S. M. (2019). Guanidinoacetic acid with creatine compared with creatine alone for tissue creatine content, hyperhomocysteinemia, and exercise performance: A randomized, double-blind superiority trial. Nutrition (Burbank, Los Angeles County, Calif.), 57, 162–166. https:// doi.org/10.1016/j.nut.2018.04.009
8. Seper, V., Korovljev, D., Todorovic, N., Stajer, V., Ostojic, J., Nesic, N. and Ostojic, S.M., 2021. GuanidinoacetateCreatine Supplementation Improves Functional Performance and Muscle and Brain Bioenergetics in the Elderly: A Pilot Study. Annals of Nutrition and Metabolism, 77(4), pp.244-247.
9. Ostojic, S.M., 2017. Co-administration of creatine and guanidinoacetic acid for augmented tissue bioenergetics: A novel approach?. Biomedicine & Pharmacotherapy, 91, pp.238-240.
10. Ostojic, S.M., 2020. Guanidinoacetic acid loading for improved location-specific brain creatine. Clinical Nutrition.
11. Ostojic, S.M., Ostojic, J., Drid, P. and Vranes, M., 2016. Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men. Applied Physiology, Nutrition, and Metabolism, 41(9), pp.1005-1007.
12. Dechent, P., Pouwels, P.J.W., Wilken, B., Hanefeld, F. and Frahm, J., 1999. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 277(3), pp.R698-R704.
13. Tachikawa, M., Kasai, Y., Yokoyama, R., Fujinawa, J., Ganapathy, V., Terasaki, T. and Hosoya, K.I., 2009. The blood–brain barrier transport and cerebral distribution of guanidinoacetate in rats: involvement of creatine and taurine transporters. Journal of neurochemistry, 111(2), pp.499-509.
14. Tachikawa, M., Ikeda, S., Fujinawa, J., Hirose, S., Akanuma, S.I. and Hosoya, K.I., 2012. γ-Aminobutyric acid transporter 2 mediates the hepatic uptake of guanidinoacetate, the creatine biosynthetic precursor, in rats. PloS one, 7(2), p.e32557.
15. Ostojic, S.M., 2020. Short‐term GAA loading: Responders versus nonresponders analysis. Food Science & Nutrition, 8(8), pp.4446-4448.
16. Christie DL. Functional insights into the creatine transporter. Subcell Biochem. 2007;46:99-118. doi: 10.1007/978-1-4020-6486-9_6. PMID: 18652074.
17. Ostojic, S.M., Stojanovic, M.D. and Hoffman, J.R., 2015. Six-week oral guanidinoacetic acid administration improves muscular performance in healthy volunteers. Journal of Investigative Medicine, 63(8), pp.942-946. Watch a short video explainer.
18. Spillane, M., Schoch, R., Cooke, M., Harvey, T., Greenwood, M., Kreider, R. and Willoughby, D.S., 2009. The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. Journal of the International Society of Sports Nutrition, 6(1), p.6.
19. Van der Poel, A.F., Braun, U., Hendriks, W.H. and Bosch, G., 2019. Stability of creatine monohydrate and guanidinoacetic acid during manufacture (retorting and extrusion) and storage of dog foods. Journal of animal physiology and animal nutrition, 103(4), pp.1242-1250.
20. Sakata, Y., Shiraishi, S. and Otsuka, M., 2004. Effect of pulverization on hydration kinetic behaviors of creatine anhydrate powders. Colloids and Surfaces B: Biointerfaces, 39(4), pp.187-193.
21. Uzzan, M., Nechrebeki, J., Zhou, P. and Labuza, T.P., 2009. Effect of water activity and temperature on the stability of creatine during storage. Drug development and industrial pharmacy, 35(8), pp.1003-1008.
22. Van der Poel, A.F., Braun, U., Hendriks, W.H. and Bosch, G., 2019. Stability of creatine monohydrate and guanidinoacetic acid during manufacture (retorting and extrusion) and storage of dog foods. Journal of animal physiology and animal nutrition, 103(4), pp.1242-1250.
23. Ostojic, S.M., Niess, B., Stojanovic, M. and Obrenovic, M., 2013. Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans. International journal of medical sciences, 10(2), p.141.
24. Ostojic, S.M., Todorovic, N. and Stajer, V., 2021. Effect of Creatine and Guanidinoacetate Supplementation on Plasma Homocysteine in Metabolically Healthy Men and Women. Annals of Nutrition and Metabolism, 77(5), pp.307-308.
25. Ostojic, S.M. and Ostojic, J., 2018. Dietary guanidinoacetic acid does not accumulate in the brain of healthy men. European journal of nutrition, 57(8), pp.3003-3005.
26. Ostojic, S.M., Mojsin, M., Drid, P. and Vranes, M., 2018. Does Dietary Provision of Guanidinoacetic Acid Induce Global DNA Hypomethylation in Healthy Men and Women?. Lifestyle genomics, 11(1), pp.16-18. 27. Moret, S., Prevarin, A. and Tubaro, F., 2011. Levels of creatine, organic contaminants and heavy metals in creatine dietary supplements. Food chemistry, 126(3), pp.1232-1238.