CreGAAtine vs. Creatine – similarities and differences

What is Creatine?

Creatine (from Greek kreas, flesh) holds a special place among sport supplements, as it is one of the most studied ergogenic aids on the market with a long tradition of use (discovered in 1927). Creatine is a substance that is naturally produced in our body from three amino acids – arginine, glycine, and methionine.

In our body, creatine can bind a high-energy phosphate group (Pi) forming phosphocreatine (Pcr) (or creatine phosphate (CP)) with help of an enzyme called creatine kinase (CK). This way, Pcr serves as a reserve of high-energy phosphates in skeletal muscles, brain, and heart. Pcr can rapidly donate phosphate groups to regenerate the levels of adenosine triphosphate (ATP), the energy currency of the cell, which is quickly depleted during the short periods of intense workout (Picture 1). In this reaction, Pcr is degraded to creatine and phosphate group which is then bound to adenosine diphosphate, thus creating ATP. Phosphocreatine system is the fastest energy system in our body, as it can synthesize the pool of ATP faster than cell respiration. It is a crucial energy system for a high-intensity workout, as it will be used for the first 10 to 12 seconds of intense exercise (1).

Picture 1. Phosphocreatine energy system

What is & CreGAAtine?

CreGAAtine is a novel dietary supplement intended for use in sports and fitness. It is a unique formulation that came to the market after years of research led by one of the top 10 creatine experts in the world, Prof. Sergej Ostojić. The proprietary formulation has reached the sport supplements shelves in 2021 thanks to cooperation of Carnomed and Applied Bioenergetics Lab.

CreGAAtine is a dietary supplement that contains creatine (creatine monohydrate) and its direct precursor – guanidinoacetic acid (GAA). GAA is an organic compound that is synthesized in a reaction from two amino acids – L-arginine and glycine, regulated by an enzyme called L-arginine-glycine amidinotransferase (AGAT). In this chemical reaction, two amino acids bind together, forming GAA and a by-product ornithine. In the next step, one methyl group is added to GAA forming creatine with help of an enzyme S-adenosyl-L-methionine:N-guanidinoacetate methyltrasferase (GAMT) (Picture 2).

Slika 2. Picture 2. Guanidinoacetic acid (GAA) as a precursor of creatine

Difference between CreGAAtine & Creatine

There are 6 main differences between CreGAAtine and regular creatine formulations:

    • CreGAAtine is superior at increasing creatine muscle levels compared to creatine alone
    • CreGAAtine is superior at increasing creatine brain levels compared to creatine alone
    • CreGAAtine does not lead to excess body weight gain, probably due to less water retention with CreGAAtine compared to creatine alone
    • There are less non-responders to CreGAAtine compared to creatine alone
    • CreGAAtine increases strength with a focus on less developed muscle groups.
    • CreGAAtine is protected from degradation due to a single-dose packaging in three-layer sachets

To read more about each of these points, please refer to our blog post ’’CreGAAtine – What it is, how it works and the correct dosage’’

Molecular formulae

The molecular formulae of GAA and creatine in their synthetic pathway are shown in Picture 3. The process starts from two amino acids, L-arginine and glycine, that form GAA and ornithine. In the next step, GAA binds one methyl group and forms creatine.

Picture 3. Molecular formulae of GAA and creatine

Significance

The significance of CreGAAtine lies in its superiority over creatine in:

    • After 28 days of CreGAAtine consumption, it leads to 8.5 times higher levels of creatine in skeletal muscles compared to creatine alone. This effect is probably due to 4 ’’doors’’ which CreGAAtine uses to enter a cell, in contrast to 1 door with regular creatine (2).
    • Of the total energy produced in our body, brain uses 20% of it. There is a specific form of creatine kinase in our brain (BB-CK) which indicates that creatine system is highly relevant for energy production in brain (3). Different studies show that creatine can improve memory and intelligence after its oral consumption (4). CreGAAtine use of the course of 4 weeks results in 3.9 higher increase of creatine level in brain grey matter and 1.9 higher increase in brain white matter in contrast to creatine alone (2).
    • CreGAAtine supplementation results in 20% more strength after 4 weeks when compared to sole creatine. Particularly, it seems that CreGAAtine targets less developed muscle groups and thus helps weaker muscles get stronger. It may be that less developed muscles better absorb GAA, as these muscles have lower initial GAA and creatine levels (2).
    • There are less non-responders to CreGAAtine in comparison to creatine alone (5). When creatine transporters get saturated, GAA may utilise additional pathways to enter a cell and overcome the issue of limited utilisation of creatine supplements (6,7).
    • Compared to creatine alone, administation of GAA and creatine leads to less weight gain. Excess weight gain with regular creatine supplements can be recognized as an undesirable effect, such as in weight-sensitive sports, female population, etc. This property of CreGAAtine may be due to lower water-bonding capacity of CreGAAtine over creatine alone. GAA is a less hydrophillic molecule than creatine, meaning that GAA molecule ’’likes’’ water less than creatine (2).
    • CreGAAtine is protected from degradation as it is packed in single-dose sachets. This kind of packaging ensures that creatine does not convert to its inactive form (creatinine) which can easily happened when creatine is packed in bulk jars (8,9).

Side Effects

So far, there are no known side effects of CreGAAtine. Even though GAA component can require more methyl groups for its metabolism and in non-recommended high doses, it leads to an increase in homocysteine, this effect is prevented by adding creatine, which is itself a methyl donor. A study on young men and women showed that when GAA and creatine are used as a mixture over 4 weeks, it does not lead to hyperhomocysteinemia (homocysteine levels above the reference range in blood) (10) .

Main Purpose

CreGAAtine is a sport supplement, ideal for both men and women. Its main effect reflects in increased stores of creatine in our muscles, which provides more energy for intense workout. More energy in our system provides greater workout capacity and better performance results.

Final Verdict

CreGAAtine is a scientifically-revolutionized creatine-based sport supplement. If you want to energize your body, push your limits during the workout days and give a try to innovative formula, then CreGAAtine is an ideal supplement for you.

References:

    1. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107-1213. doi:10.1152/physrev.2000.80.3.1107
    2. Semeredi S, Stajer V, Ostojic J, Vranes M, Ostojic SM. Guanidinoacetic acid with creatine compared with creatine alone for tissue creatine content, hyperhomocysteinemia, and exercise performance: A randomized, double-blind superiority trial. Nutrition. 2019;57:162-166. doi:10.1016/j.nut.2018.04.009
    3. Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Exp Gerontol. 2018;108:166-173. doi:10.1016/j.exger.2018.04.013
    4. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J. 1992 Jan 1;281 ( Pt 1)(Pt 1):21-40. doi: 10.1042/bj2810021. PMID: 1731757; PMCID: PMC1130636.
    5. Ostojic SM. Short‐term GAA loading: Responders versus nonresponders analysis. Food Science & Nutrition. 2020 Aug;8(8):4446-8.
    6. Tachikawa M, Kasai Y, Yokoyama R, et al. The blood-brain barrier transport and cerebral distribution of guanidinoacetate in rats: involvement of creatine and taurine transporters. J Neurochem. 2009;111(2):499-509. doi:10.1111/j.1471-4159.2009.06332.x
    7. Christie DL. Functional insights into the creatine transporter. Subcell Biochem. 2007;46:99-118. doi:10.1007/978-1-4020-6486-9_6
    8. Sakata Y, Shiraishi S, Otsuka M. Effect of pulverization on hydration kinetic behaviors of creatine anhydrate powders. Colloids Surf B Biointerfaces. 2004;39(4):187-193. doi:10.1016/j.colsurfb.2004.07.016
    9. Uzzan M, Nechrebeki J, Zhou P, Labuza TP. Effect of water activity and temperature on the stability of creatine during storage. Drug Dev Ind Pharm. 2009;35(8):1003-1008. doi:10.1080/03639040902755197
    10. Ostojic, Sergej M., Nikola Todorovic, and Valdemar Stajer. “Effect of Creatine and Guanidinoacetate Supplementation on Plasma Homocysteine in Metabolically Healthy Men and Women.” Annals of Nutrition and Metabolism 77.5 (2021): 307-308.

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