CreGAAtine is a unique creatine proprietary blend that contains creatine precursor – guanidinoacetic acid (GAA) and creatine. It brings magic to your body and brain.
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.
How CreGAAtine works?
GAA as a direct organic precursor of creatine
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. AGAT is present in high amounts in pancreas and kidneys, but is also detected in muscles, brain, heart, lung, spleen, testis and thymus. 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). This simple reaction occurs primarily in liver, but can also take organs that have high level of energy production (skeletal muscles, brain, heart) (1,2). The process of GAA and creatine formation is presented in the Picture 1 below.
The activity of the first mentioned enzyme (AGAT) can be inhibited when creatine is taken exogenously (as a supplement). That means that after a certain period of supplementation with creatine, the enzyme that initiated the production of creatine in our body is stopped and the amount of creatine that our body produces decreases. On the other hand, that does not seem to occur with GAMT when GAA is exogenously applied. This implies that the formation of creatine from GAA is a process that cannot be inhibited when you supplement GAA (1).
Picture 1. Synthesis of GAA and creatine
GAA uses 4 different ways to enter a cell
GAA is a small molecule that can enter cells using four different pathways as opposed to creatine which passes inside a cell using one receptor CT1. GAA uses three different receptors including CT1, taurine receptors, GABA receptors and a process that does not depend on receptors called passive diffusion. This process is illustrated in the Picture 2.
Picture 2. Transport pathways of GAA and creatine, adapted from Ostojić et al (2017) (3)
The advantage of tackling multiple channels via coadministration of creatine and GAA is seen in exhaustive exercise where the demand for energy is higher. When CT1 receptor is saturated (all receptors occupied) with exogenous creatine (taken as a supplement), supplementing GAA may target other transport channels and additionally boost your creatine levels compared to creatine alone (3).
What are the main benefits of using the supplement?
There are 6 main superior effects of CreGAAtine over standard creatine formulations:
CreGAAtine is superior at increasing creatine muscle levels compared to creatine alone
In a randomized control trial that compared coadministration of creatine-monohydrate and GAA with creatine alone, it was shown that the level of creatine increased by 16.9% in the coadministration group compared to an increase by 2% in creatine only group after 4 weeks (4).
Picture 3. Effect of CreGAAtine on muscle creatine
2. CreGAAtine is superior at increasing creatine brain levels compared to creatine alone
The same randomized controlled study also examined creatine brain levels in both groups. CreGAAtine was again superior to creatine alone, reaching 3.9 times higher creatine levels in gray matter and 1.9 times higher creatine levels in white matter compared to sole creatine (4).
Picture 4. Effect of CreGAAtine on brain creatine
3. CreGAAtine does not lead to excess body weight gain probably due to less water retention with CreGAAtine compared to creatine alone
Compared to creatine alone, coadministation of GAA and creatine leads to less weight gain. This property of creatine can sometimes be recognized as a side effect, such as in weight-sensitive sports and in female population. This effect may be due to lower water-bonding capacity of CreGAAtine over creatine alone. GAA is less hydrophyllic molecule than creatine, meaning that GAA molecule ’’likes’’ water less than creatine (4).
4. There are less non-responders to CreGAAtine compared to creatine alone
As creatine receptors in brain and muscles are close to being saturated with endogenous creatine under physiological conditions, the advantage of GAA to use extra transport ways creates a great strategy to overcome limited utilisation of exogenous creatine (5,6). CreGAAtine ensures that there are less non-responders compared to regular creatine (7).
5. CreGAAtine increases strength with a focus on less developed muscle groups.
The combination of GAA and creatine has a great potential due to the possible synergism between the two substances (3). GAA targets muscle groups with lower initial level of strength, which are the muscles of the upper body in the general population. This advantage can be due to easer absorption of GAA by these muscles as the baseline level is initially lower in these muscles (4).
6. CreGAAtine is protected from degradation due to a single-dose packaging in three-layer sachets
CreGAAtine is packed in a single-dose three-layer sachet of a pharmaceutical grade, which allows its comfortable use, but also protects creatine from converting into creatinine (its ineffective form) when exposed to heat and moisture. Regular bulk packages of creatine easily let the moisture come into the package every time you open the package, which in time leads to creatine degradation (8,9).
Side Effects and Safety
There are no known side effects of CreGAAtine. A study that examined the effect of CreGAAtine on plasma homocysteine in healthy men and women over the course of 28 days, found that there was a small increase in plasma homocysteine, but no subjects with homocysteine level above the reference range. Similar case is with creatinine, there was a small increase, but within the reference range (10). CreGAAtine is an Informed Sports certified product, which confirms it is a doping-free supplement.
When and how to take it?
CreGAAtine should be taken twice a day, one sachet in the morning and one sachet in the afternoon. It is best absorbed when you disolve it in a glass of lukewarm water and drink immediately. CreGAAtine should be taken both on your workout and non-workout days. If you take one sachet around your workout, you can take it either before or after it, whatever is more comfortable to you.
The correct dosage of CreGAAtine is 2 sachets a day.
Slika 5. Cregaatine use
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- Ostojic SM. Creatine synthesis in the skeletal muscle: the times they are a-changin’. Am J Physiol Endocrinol Metab. 2021;320(2):E390-E391. doi:10.1152/ajpendo.00645.2020
- Ostojic SM. Co-administration of creatine and guanidinoacetic acid for augmented tissue bioenergetics: A novel approach?. Biomed Pharmacother. 2017;91:238-240. doi:10.1016/j.biopha.2017.04.075
- 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
- 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
- Christie DL. Functional insights into the creatine transporter. Subcell Biochem. 2007;46:99-118. doi:10.1007/978-1-4020-6486-9_6
- Ostojic SM. Short‐term GAA loading: Responders versus nonresponders analysis. Food Science & Nutrition. 2020 Aug;8(8):4446-8.
- 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
- 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
- Ostojic SM, Todorovic N, Stajer V. Effect of Creatine and Guanidinoacetate Supplementation on Plasma Homocysteine in Metabolically Healthy Men and Women. Annals of Nutrition and Metabolism. 2021;77(5):307-8.