Creatine primarily targets creatine kinase enzymes, which include the M-type, U-type (mitochondrial), and B-type isoenzymes. It also interacts with sodium- and chloride-dependent creatine transporter 1, which mediates the cellular uptake of creatine, and guanidinoacetate N-methyltransferase, the enzyme responsible for creatine biosynthesis. Creatine binds to creatine kinase to form phosphocreatine, a critical energy storage molecule.

In vitro studies demonstrate that creatine acts as a high-energy reservoir for the rapid regeneration of ATP through the creatine kinase reaction: Cr + ATP ⇌ PCr + ADP. Creatine has been shown to exert anti-inflammatory activity through the inhibition of TNF-α expression. It also exhibits neuroprotective effects in various in vitro models of neurological injury and disease, protecting neurons from oxidative stress and excitotoxicity.

In vivo, supplemental creatine provides an energy-generating action during anaerobic exercise by maintaining ATP levels through the phosphocreatine system. Creatine has also demonstrated neuroprotective and cardioprotective actions in animal models. Approximately 95% of creatine is found in skeletal muscle, with the remainder distributed in the heart, brain, and other tissues. Creatine is excreted as creatinine in the urine.

Creatine is evaluated in cell-free enzymatic assays using purified creatine kinase enzymes. The compound is incubated with creatine kinase, ATP, and creatine, and the formation of phosphocreatine is measured using coupled enzyme assays or spectrophotometric methods. The reaction kinetics, including Vmax and Km values, are determined to characterize creatine’s role as a substrate for creatine kinase.

Creatine is assessed in cell-based assays using muscle cells or neuronal cell lines. Cells are treated with varying concentrations of creatine, and intracellular phosphocreatine and ATP levels are measured using biochemical assays. Cellular energy metabolism and viability under stress conditions, such as oxygen-glucose deprivation or oxidative stress, are evaluated to assess creatine’s protective effects.

Creatine is administered orally or via dietary supplementation in animal models to evaluate its effects on energy metabolism, athletic performance, and neuroprotection. Efficacy is assessed by measuring tissue phosphocreatine and ATP levels, exercise performance, and markers of neuronal injury in models of neurological disease. Pharmacodynamic studies are conducted to evaluate the dose-response relationship and tissue distribution.

Absorption, Distribution and Excretion
In muscles and nerves, most creatine is phosphorylated to phosphocreatine (pCr) by creatine kinase (CK). CK has three isoenzymes: CK-MM (skeletal muscle isoenzyme), CK-BB (brain isoenzyme), and CK-MB (cardiac isoenzyme). Most phosphocreatine in the body is found in skeletal muscle. Creatine is absorbed in the small intestine and enters the portal circulation, where it is transported to the liver. Ingested creatine and creatine synthesized in the liver then enter systemic circulation and are distributed to various tissues, including muscles and nerves, against a 200:1 concentration gradient across cell membranes via a specific creatine transport system. Metabolism/Metabolites In muscle and nerve cells, approximately 60% to 67% of creatine is converted to phosphocreatine by creatine kinase. Approximately 2% of creatine is converted to creatinine. Both creatine and creatinine are excreted by the kidneys.
Half-life: 3 hours

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Biological half-life
3 hours
Creatine is orally bioavailable and is absorbed from the gastrointestinal tract. It is transported to tissues via the creatine transporter SLC6A8. Following its biosynthesis or absorption, creatine is metabolized in tissues to phosphocreatine, which serves as a major energy storage form. Creatine is non-enzymatically converted to creatinine, which is excreted in the urine. It has a molecular weight of 131.13 g/mol.

Toxicity Summary
In muscles, some creatine binds to phosphate to form phosphocreatine. This reaction is catalyzed by creatine kinase to produce phosphocreatine (PCr). Phosphocreatine binds to adenosine diphosphate (ATP), converting it back to adenosine triphosphate (ATP), a vital energy source for cells shortly before oxidative phosphorylation. Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Creatine is a dietary supplement used to increase muscle mass and improve athletic performance. Creatine is a normal component of breast milk, making up about 9% of an infant's daily requirement. Creatine levels in breast milk after exogenous creatine supplementation in humans have not been measured. Creatine is converted to creatinine in both the mother and infant. It may increase serum creatinine levels in infants, potentially affecting assessments of infant kidney function. Some authors have speculated that creatine supplementation in breastfeeding mothers may help prevent creatine deficiency, but no studies have yet validated this hypothesis. Until more data are available, it is best to avoid creatine supplementation unless prescribed by a healthcare professional.
◉ Impact on breastfed infants
No published information found as of the revision date.
◉ Impact on lactation and breast milk
No published information found as of the revision date.
Creatine is generally recognized as safe for nutritional supplementation. It is an endogenous metabolite and is well-tolerated at recommended doses. It has a CAS number of 57-00-1. The compound is for research use and as a nutraceutical, and is not for therapeutic use.

Creatine is a derivative of glycine, with a methyl group and an amidine group attached to its nitrogen atom. It has neuroprotective effects, nutritional and health benefits, and is a metabolite in humans and mice, as well as having anti-aging effects. Creatine belongs to the guanidine family and is also a derivative of glycine. It is the conjugate acid of creatine and a tautomer of creatine zwitterions. Creatine is an amino acid derivative found in vertebrate tissues and urine. In muscle tissue, creatine is usually present as phosphocreatine. Creatine is excreted in urine as creatinine. Creatine has been reported to be present in soybeans (Glycine max), citrus fruits (Citrus reticulata), and several other organisms with relevant data. Creatine is an endogenous amino acid derivative produced by vertebrates and is mainly found in muscle cells. Creatine is crucial for energy storage. Creatine phosphorylation produces phosphocreatine, which acts as a phosphate donor in the conversion of ADP to ATP, providing energy for muscle contraction. Dietary creatine supplementation may improve muscle atrophy caused by cancer and other chronic diseases. Creatine is an amino acid found in vertebrate tissues and urine. In muscle tissue, creatine is usually present as phosphocreatine. Creatine is excreted in urine as creatinine. Creatine is part of the cellular energy shuttle system. The high-energy phosphate group of ATP is transferred to creatine to form phosphocreatine, as follows: Cr + ATP <-> PCr + ADP. This reaction is reversibly catalyzed by creatine kinase. In the human body, creatine is mainly synthesized in the liver, utilizing parts of the structure of three different amino acids—arginine, glycine, and methionine. 95% of it is stored in skeletal muscle, with the remainder stored in the brain, heart, and testes. Creatine is an amino acid found in vertebrate tissues and urine. In muscle tissue, creatine is usually present as phosphocreatine. Creatine is excreted in urine as creatinine. Pharmacological Indications: Used for nutritional supplementation and also for treating dietary deficiencies or imbalances. Mechanism of Action: In muscles, some creatine combines with phosphate to form phosphocreatine. This reaction is catalyzed by creatine kinase, ultimately producing phosphocreatine (PCr). Creatinolfosfate binds to adenosine diphosphate (ATP), converting it back to adenosine triphosphate (ATP), a crucial energy source for cells' short-term ATP needs before oxidative phosphorylation. Creatine supplementation may play an energy-generating role during anaerobic exercise and may also have neuroprotective and cardioprotective effects. Creatine, creatine kinase, and Creatinolfosfate constitute a complex cellular energy buffering and transport system, connecting energy-producing and energy-consuming sites in mitochondria. Creatine kinase is a key enzyme involved in cellular energy homeostasis. It reversibly catalyzes the transfer of high-energy phosphate bonds in Creatinolfosfate (PCr) to adenosine diphosphate (ADP) to form adenosine triphosphate (ATP), and catalyzes the transfer of high-energy phosphate bonds in ATP to creatine to form Creatinolfosfate. During strenuous exercise and skeletal muscle contraction, bioenergy metabolism shifts from a pathway dominated by oxidative phosphorylation for ATP production to one dominated by anaerobic glycolysis.
Therapeutic Uses
Creatine and its analogue cyclic creatine can inhibit the growth of various solid tumors in rat cancer models; these tumors express high levels of creatine kinase (CK). Although its mechanism of tumor suppression is not yet clear…

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Drug Warning
Crevicine phosphate inhibits enzymes in the glycolytic pathway, including glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase, and pyruvate kinase.
Safety data are currently lacking, especially regarding long-term use of creatine, its use in children (including adolescents), and in debilitated individuals; therefore, more relevant data are urgently needed. There are reports that long-term use of creatine may have nephrotoxicity. Long-term creatine supplementation should not be recommended under any circumstances; therefore, further research is needed.
Crevicine is contraindicated in patients with renal failure and kidney disease (such as nephrotic syndrome).
Adverse event reports submitted to the U.S. Food and Drug Administration (FDA) include rash, dyspnea, vomiting, diarrhea, nervousness, anxiety, migraine, fatigue, polymyositis, myopathy, seizures, and atrial fibrillation.
There are reports of elevated serum creatinine (a metabolite of creatine and a marker of kidney function) in some patients taking creatine with normal renal function. This effect on kidney function is reversible upon discontinuation of creatine. Creatine is an essential non-protein amino acid derivative found in all animals. It is synthesized by the kidneys, liver, and pancreas using L-arginine, glycine, and L-methionine. After synthesis, creatine is transported to skeletal muscle, heart, brain, and other tissues. Most creatine is metabolized in these tissues to Creatinolfosfate (Creatinolfosfate). Creatinolfosfate is the body's primary energy storage form. Creatine supplementation may play an energy-generating role during anaerobic exercise and may also have neuroprotective and cardioprotective effects.
Creatine is an endogenous metabolite that is also known as methylguanidoacetic acid. It has a molecular formula of C4H9N3O2. The compound was first identified in 1832 by Michel Eugène Chevreul. It is used as a standard for quantitative analysis to study energy metabolic pathways and related diseases. Creatine has no approved therapeutic indications but is widely used as a dietary supplement.

C4H9N3O2

131.14

131.069

57-00-1

586

White to off-white solid powder

1.4±0.1 g/cm3

271.6±42.0 °C at 760 mmHg

~295 °C (dec.)

118.1±27.9 °C

0.0±1.2 mmHg at 25°C

1.552

-1.88

3

3

3

9

134

0

O([H])C(C([H])([H])N(/C(=N/[H])/N([H])[H])C([H])([H])[H])=O

CVSVTCORWBXHQV-UHFFFAOYSA-N

InChI=1S/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9)

2-[carbamimidoyl(methyl)amino]acetic acid

NSC-8752; NSC 8752; Creatine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~6.25 mg/mL (~47.66 mM)

Solubility in Formulation 1: 20 mg/mL (152.51 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)