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Al222
Al222 (25681 pt) 2026-Sep-15 11:52

Creatine: properties, uses, pros, cons, safety

Creatine is a nitrogen-containing organic compound naturally present in the human body and in foods of animal origin, particularly meat and fish. In the body, it participates in the creatine–phosphocreatine system, which contributes to the rapid regeneration of ATP in tissues with high energy demands.

In cosmetics, its documented function is Skin Conditioning. Its dermatological interest is mainly related to its role in cellular energy metabolism and to experimental and clinical studies evaluating its topical application to the skin.

No specific Cosmetics Regulation provisions are identified under Annexes II–VI of the EU Cosmetics Regulation.

Description

Creatine is a glycine derivative containing a guanidino group. In the human body, it is synthesized mainly from:

  • glycine;

  • arginine;

  • methionine.

Once inside cells, it can be phosphorylated by creatine kinase to form phosphocreatine. The creatine/phosphocreatine system functions as a rapidly available energy reserve for ATP regeneration.

This system is particularly important in muscle, but creatine kinases and creatine transporters are also present in human skin.

Cosmetic Creatine should be distinguished from:

  • Creatine Monohydrate, the hydrated form widely used in dietary supplements;

  • Creatinine, a cyclic metabolic and degradation product;

  • Creatine Phosphate;

  • other creatine salts and derivatives.

Manufacturing process

Industrial creatine is generally produced by chemical synthesis rather than extraction from animal tissues.

One of the principal manufacturing routes involves reaction between:

  • sodium or potassium sarcosinate;

  • cyanamide.

The reaction is carried out under controlled pH and temperature conditions and is followed by:

  • crystallization;

  • separation;

  • washing;

  • recrystallization;

  • filtration;

  • drying;

  • purity control.

Depending on the production process, possible impurities may include:

  • creatinine;

  • dicyandiamide;

  • dihydrotriazine derivatives;

  • residual starting materials.

Alternative production routes may produce different impurity profiles.

Synthetic origin does not make the substance biologically different from naturally occurring creatine when the final material is chemically identical and adequately purified.

Identification data and specifications

CharacteristicValueNote
INCI nameCreatinecosmetic ingredient name
Common nameCreatinenaturally occurring nitrogen-containing compound
Chemical nameN-(Aminoiminomethyl)-N-methylglycineglycine derivative
SynonymsN-Amidinosarcosine; Methylguanidoacetic Acidchemical names
Chemical categoryguanidino derivative of glycinesmall polar molecule
Molecular formulaC₄H₉N₃O₂anhydrous creatine
Molecular weight131.13 g/molanhydrous form
CAS57-00-1anhydrous creatine
EC200-306-6European identifier
PubChem CID586chemical identifier
CosIng reference55520cosmetic ingredient reference
Cosmetic functionSkin Conditioningdocumented function
Cosmetics Regulation provisionsno specific provision identifiedno specific Annex II–VI provision

CAS 6020-87-7 refers to Creatine Monohydrate and should not automatically be used for the anhydrous form.

Indicative physicochemical properties

CharacteristicIndicative valueNote
Physical statecrystalline solidat room temperature
Appearancewhite powder/crystalspurified grade
Odorpractically odorlesscharacteristic
Water solubilityapproximately 13.3 g/L at 18 °Cmoderate
Solubility in ethanolvery lowhighly polar substance
Densityapproximately 1.33 g/cm³indicative value
Ionic behaviorpredominantly zwitterionicunder physiological conditions
Volatilitynegligiblepractically non-volatile
Stability in dry formhighwhen properly stored
Stability in solutionloweraffected by pH, temperature, and time
Thermal behaviordecomposes at elevated temperaturedoes not undergo ordinary boiling

Cosmetics

Creatine may be used in:

  • facial creams;

  • serums;

  • anti-aging products;

  • firming products;

  • eye-area creams;

  • after-sun products;

  • body-care formulations;

  • shampoos;

  • scalp lotions;

  • hair-care products.

Its cosmetic interest is supported by the presence of the creatine kinase system in skin cells and by evidence that topically applied creatine can become available to cutaneous cells.

Cellular energy metabolism and oxidative stress

Studies on keratinocytes and epidermal systems have indicated that creatine can:

  • support the creatine kinase system;

  • contribute to mitochondrial function;

  • help maintain cellular energy availability;

  • reduce some consequences of oxidative stress;

  • increase cellular resistance to experimentally induced UV-related damage.

These findings provide a plausible rationale for its use in cosmetics designed for skin exposed to environmental stress.

Creatine is not a UV filter and cannot replace an authorized sunscreen ingredient.

Collagen, wrinkles and firmness

Topical research has also investigated effects related to skin structure and aging.

In dermal fibroblast models, creatine has been associated with increased collagen-related activity and procollagen synthesis.

In a study involving 43 men, a formulation containing creatine, guarana, and glycerol, applied for six weeks, produced improvements in parameters including:

  • cheek sagging;

  • crow's feet;

  • under-eye wrinkles.

Other studies using formulations containing creatine and folic acid have reported improvements in skin firmness and parameters related to collagen metabolism.

These results are encouraging, but many of the formulations were multicomponent systems, so the entire clinical effect cannot be quantitatively attributed to creatine alone.

Overall, however, the topical evidence is more substantial than for many cosmetic ingredients whose anti-aging positioning relies exclusively on in vitro results.

Hair

Creatine is also used in hair and scalp products.

Multicomponent formulations containing creatine have been investigated in relation to hair loss, but such studies generally do not allow the specific contribution of creatine to be isolated.

A long-standing hypothesis suggested that oral creatine supplementation might increase DHT and thereby promote hair loss.

A randomized controlled study published in 2025 using 5 g/day of creatine monohydrate for 12 weeks found no significant differences from placebo in:

  • DHT;

  • DHT/testosterone ratio;

  • hair density;

  • follicular unit count;

  • overall hair thickness.

Current evidence therefore does not support the claim that creatine itself causes hair loss.

Food and dietary supplements

Creatine occurs naturally mainly in:

  • meat;

  • fish;

  • other animal tissues.

In dietary supplements, the most widely studied form is Creatine Monohydrate.

In the European Union, specific health claims are authorized.

For adults performing high-intensity exercise, the authorized claim states:

“Creatine increases physical performance in successive bursts of short-term, high-intensity exercise.”

The beneficial effect is obtained with a daily intake of 3 g of creatine.

For adults over 55 years of age who regularly perform resistance exercise, an authorized claim also relates to improvement of the effect of resistance training on muscle strength, under defined exercise conditions and with 3 g/day.

By contrast, a 2024 EFSA assessment concluded that a sufficient cause-and-effect relationship had not been established between creatine supplementation and a general improvement in cognitive function. Creatine should therefore not be presented in the EU as having a broadly authorized cognitive benefit.

Pros

  • It is a physiological substance naturally present in the human body.

  • The creatine/phosphocreatine mechanism is well characterized.

  • Specific topical skin data are available.

  • Cellular studies support effects on energy metabolism and oxidative stress.

  • Clinical studies exist on cosmetic formulations containing creatine.

  • It is compatible with aqueous formulations within its solubility limits.

  • It has low volatility and low bioaccumulation potential.

  • Synthetic manufacture allows a high degree of standardization and purity.

Cons

  • Stability in solution is lower than in the dry state.

  • Unfavorable pH, temperature, and storage conditions can promote formation of creatinine.

  • Water solubility is limited compared with some other small hydrophilic ingredients.

  • Many cosmetic studies use creatine together with other active ingredients.

  • Anti-aging and collagen claims should remain proportional to the available evidence.

  • It is not a sunscreen filter.

  • Raw-material quality depends strongly on control of synthesis-related impurities.

Safety and regulation

The general safety profile of creatine is well characterized because of its physiological presence and extensive nutritional use.

No specific SCCS or CIR assessment dedicated exclusively to cosmetic Creatine has been identified that establishes a universal maximum concentration.

Nevertheless, there are no major indications that properly purified and correctly formulated creatine presents a particular cosmetic safety concern at normal use levels.

Stability and creatinine formation

One of the principal technical issues is spontaneous conversion of creatine into creatinine through intramolecular cyclization.

Degradation is promoted especially by:

  • prolonged storage in solution;

  • certain acidic conditions;

  • elevated temperatures.

For liquid cosmetic formulations, long-term stability should therefore be tested rather than relying only on the initial creatine assay.

EU Cosmetics Regulation provisions

No specific:

Cosmetics Regulation provisions

are identified for Creatine under Annexes II–VI of Regulation (EC) No 1223/2009.

The usual safety assessment of the finished cosmetic product remains necessary.

Raw-material control

For professional evaluation, it is advisable to obtain:

  • updated SDS;

  • Certificate of Analysis (COA);

  • technical data sheet;

  • creatine assay;

  • confirmation of anhydrous or monohydrate form;

  • water content;

  • creatinine;

  • dicyandiamide;

  • dihydrotriazines;

  • thiourea where relevant to the manufacturing route;

  • residual sarcosine;

  • residual cyanamide;

  • metals;

  • pH;

  • microbiological specifications where relevant;

  • stability data;

  • storage conditions.

For liquid cosmetic products, it is also useful to measure the remaining creatine content after stability testing, because initially pure material may gradually degrade during the commercial life of the product.

Environment

Creatine is a small polar molecule naturally present in living organisms.

Its environmental characteristics include:

  • very low volatility;

  • low tendency to bioaccumulate;

  • high mobility in water;

  • potential biodegradation in biological systems and wastewater treatment.

The environmental profile of the commercial ingredient therefore depends mainly on the industrial synthesis and purification process, including:

  • energy consumption;

  • production of precursors;

  • reagent management;

  • treatment of process water;

  • control of by-products.

Conclusion

Creatine is a physiological compound involved in the cellular creatine–phosphocreatine energy system and is used in cosmetics as a Skin Conditioning ingredient.

Compared with many cosmetic ingredients marketed as cellular “energy boosters,” it has a well-defined biological rationale and topical studies showing interesting effects on cellular energy metabolism, oxidative stress and, in specific formulations, skin firmness and wrinkles.

No specific Cosmetics Regulation provisions are identified for the ingredient.

Creatine can be considered a generally favorable cosmetic ingredient with an interesting level of supporting evidence, with particular attention to purity, chemical form, creatinine and other synthesis impurities, solubility, pH, processing temperature, and stability in the finished product.

References_________________________________________________________________________

Forbes SC, Cordingley DM, Cornish SM, Gualano B, Roschel H, Ostojic SM, Rawson ES, Roy BD, Prokopidis K, Giannos P, Candow DG. Effects of Creatine Supplementation on Brain Function and Health. Nutrients. 2022 Feb 22;14(5):921. doi: 10.3390/nu14050921. 

Abstract. While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.

Butts J, Jacobs B, Silvis M. Creatine Use in Sports. Sports Health. 2018 Jan/Feb;10(1):31-34. doi: 10.1177/1941738117737248. 

Abstract. Context: The use of creatine as a dietary supplement has become increasingly popular over the past several decades. Despite the popularity of creatine, questions remain with regard to dosing, effects on sports performance, and safety. Evidence acquisition: PubMed was searched for articles published between 1980 and January 2017 using the terms creatine, creatine supplementation, sports performance, and dietary supplements. An additional Google search was performed to capture National Collegiate Athletic Association-specific creatine usage data and US dietary supplement and creatine sales. Study design: Clinical review. Level of evidence: Level 4. Results: Short-term use of creatine is considered safe and without significant adverse effects, althoug caution should be advised as the number of long-term studies is limited. Suggested dosing is variable, with many different regimens showing benefits. The safety of creatine supplementation has not been studied in children and adolescents. Currently, the scientific literature best supports creatine supplementation for increased performance in short-duration, maximal-intensity resistance training. Conclusion: While creatine appears to be safe and effective for particular settings, whether creatine supplementation leads to improved performance on the field of play remains unknown.

Antonio J, Candow DG, Forbes SC, Gualano B, Jagim AR, Kreider RB, Rawson ES, Smith-Ryan AE, VanDusseldorp TA, Willoughby DS, Ziegenfuss TN. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? J Int Soc Sports Nutr. 2021 Feb 8;18(1):13. doi: 10.1186/s12970-021-00412-w.

Abstract. Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine 'loading-phase' required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.

Kreider RB, Stout JR. Creatine in Health and Disease. Nutrients. 2021 Jan 29;13(2):447. doi: 10.3390/nu13020447.

Abstract. Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine's role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan.

Ostojic SM. Creatine and multiple sclerosis. Nutr Neurosci. 2022 May;25(5):912-919. doi: 10.1080/1028415X.2020.1819108.

Abstract. Multiple sclerosis (MS) is a complex and debilitating neurodegenerative disease, with unknown cause(s), unpredictable prognosis, and rather limited treatment options. MS is often accompanied by various metabolic disturbances, with impaired creatine metabolism may play a role in its pathogenesis and the clinical course of the disease. This review summarizes human trials describing alterations in creatine levels in the nervous system and other tissues during MS, affects how certain medications for MS affect brain creatine concentrations, and discusses a possible demand for exogenous creatine as an adjunct therapeutic agent in the management of MS. Creatine metabolism seems to be dysfunctional in MS, indicating a low metabolic state of the brain and other relevant organs in this unpredictable demyelinating disease. A disease-driven brain creatine deficit could be seen as a distinctive pathological facet of severe MS that might be approached with targeted therapies in aim to restore creatine homeostasis.

Smith-Ryan AE, DelBiondo GM, Brown AF, Kleiner SM, Tran NT, Ellery SJ. Creatine in women's health: bridging the gap from menstruation through pregnancy to menopause. J Int Soc Sports Nutr. 2025 Dec;22(1):2502094. doi: 10.1080/15502783.2025.2502094.

Abstract. Background: Creatine supplementation in women has gained attention for its potential benefits beyond muscle growth, including reproductive health, cognitive health and aging. Women exhibit distinct physiological differences from men, influenced by hormonal fluctuations during pre-menopause, pregnancy, and menopause, and these factors should be considered for their influence on creatine metabolism. Objective: This review aims to provide a historical evaluation of creatine supplementation in women, its potential applications across female-specific life stages, recent research highlights, and targets for future research. The review also considers the impact of hormonal changes on creatine metabolism and effectiveness as a dietary supplementation. Methods: This is a narrative overview of historical and recent research evaluating the effects of creatine in women. Results: Early studies demonstrated the benefits of creatine on exercise performance in women, though they often overlooked menstrual cycle variability. Recent research has begun to account for these hormonal fluctuations, enhancing the understanding of creatine's applications. Creatine supplementation has shown positive effects on muscle strength, exercise performance, and body composition, particularly when combined with resistance training. Additionally, creatine may improve mood and cognitive function, potentially alleviating symptoms of depression. Emerging evidence suggests creatine's benefits during pregnancy and post-menopause, though data on perimenopausal women remains limited. Conclusion: Creatine supplementation presents a promising strategy for enhancing various aspects of women's health across the lifespan. Future research should focus on optimizing dosing strategies, understanding long-term health implications, and exploring creatine's effects during pregnancy and perimenopause.