Creatine monohydrate: properties, uses, pros, cons, safety

Creatine monohydrate is the monohydrate form of creatine, a nitrogen-containing compound naturally present in the body and largely stored in skeletal muscle. In the food sector, it is mainly used in supplements for adults who perform high-intensity physical exercise, with the use of the ingredient that must comply with rules of purity, solubility, stability and compliance with grade quality specifications.

Definition

Creatine monohydrate is a single defined compound (not a mixture): creatine associated with one molecule of crystallization water. Functionally, it is linked to the phosphocreatine system involved in rapid ATP (adenosine triphosphate; the primary cellular “energy currency”) resynthesis during short, repeated high-intensity efforts.

Main uses

Industrial use.
Raw material for supplements (powders, tablets, capsules) with attention to: purity, particle size, flowability, contaminant control, and batch-to-batch consistency.

Key constituents

The product consists primarily of creatine monohydrate. In practice, commercial grades differ mainly in impurity profile and quality management: moisture, ash, heavy metals, microbiology, and process-related contaminants (whether and as declared and controlled by the supplier as a function of the market and quality standard).

Nutritional use note and bioactive compounds

It is not a “nutritional” ingredient in the sense of a source of vitamins or minerals, but a bioactive compound with a specific ergogenic role. The EU-recognized benefit relates to improved physical performance in short, repeated, high-intensity exercise, provided a suitable daily intake is achieved. From a formulation standpoint, the objective is to ensure per-serving dose, uniformity, and stability over shelf life.

Energy (calories)

At typical use levels (a few grams per day), the caloric contribution to the finished product is generally negligible and is not an operational priority compared with purity, dose accuracy, and overall quality.

Identification data and specifications

Indicative physico-chemical properties

Functional role and practical mechanism of action

Its functional role is linked to the phosphocreatine system: by increasing intramuscular creatine (and phosphocreatine) availability, it can support rapid ATP resynthesis during intense, repeated activity. Practically, the effect is most relevant for sprint-like efforts or repeated short sets, rather than exclusively long-duration moderate-intensity activity.

Formulation compatibility

In powders and capsules, compatibility is generally favorable; key issues are flowability, blend uniformity, and moisture stability. In ready-to-drink beverages or aqueous shots, the main topics become perceived solubility, sedimentation, and time stability; validation through accelerated testing and real packaging is essential. Flavors, acidifiers, and the overall matrix can influence stability in solution and sensory acceptance.

Use guidelines

Operationally, formulations are often designed to deliver a daily dose consistent with directions for use and any authorized claims. In market practice, a daily maintenance dose of a few grams is common and, in some protocols, an initial higher-dose phase may be used; correct management requires clear labeling, controlled portioning, and attention to gastrointestinal tolerability.

Quality, grades, and specifications

Supplier qualification is central. Typical controls include: assay/purity, impurity profile, moisture, particle size, heavy metals, microbiology, and compliance with food-safety standards. Adoption of GMP (good manufacturing practice; benefit: reduces variability and contamination) and HACCP (hazard analysis and critical control points; benefit: identifies and controls food-safety risks via critical control points) is a practical indicator of a robust supply chain.

Safety, regulatory, and environment

Safety should be assessed on the finished product considering daily dose, use conditions, and target population. In the EU, an authorized claim exists related to physical performance, usable only under specific conditions (daily dose and adult target population performing high-intensity exercise).

Allergen.
It is not typically classified as an allergen.

Contraindications 
Use caution in case of kidney disease or conditions requiring monitoring of renal function; in such cases, medical advice before use is appropriate. Practical undesirable effects can include gastrointestinal discomfort and body-weight changes related to intracellular water retention, more likely with high doses or suboptimal intake patterns. During pregnancy/breastfeeding and in pediatric populations, use should be approached cautiously and guided by a qualified professional.

Formulation troubleshooting

Sedimentation in beverages.
Action: optimize particle size, dispersion, and mixing process; consider “shake-and-drink” formats; validate with real shelf-life testing.

Powder caking.
Action: control moisture, use barrier packaging, optimize flowability, and manage storage conditions.

Poor sensory acceptance.
Action: rebalance flavor/sweeteners, evaluate delivery form (capsules vs powder), and manage solution concentration appropriately.

Conclusion

Creatine monohydrate is a functional ingredient for supplements, mainly positioned to support performance in short, repeated, high-intensity exercise. Robust industrial use requires strict quality control, management of solubility and stability (especially in liquids), correct regulatory framing of claims, and directions for use consistent with dose and target population.

Mini-glossary

ATP. Adenosine triphosphate; the main molecule involved in cellular energy transfer (note: creatine support is more relevant for short, intense efforts).
GMP. Good manufacturing practice; benefit: reduces variability and contamination through controlled manufacturing practices.
HACCP. Hazard analysis and critical control points; benefit: systematic prevention and control of food-safety hazards via critical control points.

References__________________________________________________________________________

de Guingand DL, Palmer KR, Snow RJ, Davies-Tuck ML, Ellery SJ. Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis. Nutrients. 2020 Jun 15;12(6):1780. doi: 10.3390/nu12061780. 

Abstract. Creatine Monohydrate (CrM) is a dietary supplement routinely used as an ergogenic aid for sport and training, and as a potential therapeutic aid to augment different disease processes. Despite its increased use in recent years, studies reporting potential adverse outcomes of CrM have been mostly derived from male or mixed sex populations. A systematic search was conducted, which included female participants on CrM, where adverse outcomes were reported, with meta-analysis performed where appropriate. Six hundred and fifty-six studies were identified where creatine supplementation was the primary intervention; fifty-eight were female only studies (9%). Twenty-nine studies monitored for adverse outcomes, with 951 participants. There were no deaths or serious adverse outcomes reported. There were no significant differences in total adverse events, (risk ratio (RR) 1.24 (95% CI 0.51, 2.98)), gastrointestinal events, (RR 1.09 (95% CI 0.53, 2.24)), or weight gain, (mean difference (MD) 1.24 kg pre-intervention, (95% CI -0.34, 2.82)) to 1.37 kg post-intervention (95% CI -0.50, 3.23)), in CrM supplemented females, when stratified by dosing regimen and subject to meta-analysis. No statistically significant difference was reported in measures of renal or hepatic function. In conclusion, mortality and serious adverse events are not associated with CrM supplementation in females. Nor does the use of creatine supplementation increase the risk of total adverse outcomes, weight gain or renal and hepatic complications in females. However, all future studies of creatine supplementation in females should consider surveillance and comprehensive reporting of adverse outcomes to better inform participants and health professionals involved in future trials.

Shao A, Hathcock JN. Risk assessment for creatine monohydrate. Regul Toxicol Pharmacol. 2006 Aug;45(3):242-51. doi: 10.1016/j.yrtph.2006.05.005.

Abstract. Creatine monohydrate (creatine) has become an increasingly popular ingredient in dietary supplements, especially sports nutrition products. A large body of human and animal research suggests that creatine does have a consistent ergogenic effect, particularly with exercises or activities requiring high intensity short bursts of energy. Human data are primarily derived from three types of studies: acute studies, involving high doses (20 g/d) with short duration (< or = 1 week), chronic studies involving lower doses (3-5 g/d) and longer duration (1 year), or a combination of both. Systematic evaluation of the research designs and data do not provide a basis for risk assessment and the usual safe Upper Level of Intake (UL) derived from it unless the newer methods described as the Observed Safe Level (OSL) or Highest Observed Intake (HOI) are utilized. The OSL risk assessment method indicates that the evidence of safety is strong at intakes up to 5 g/d for chronic supplementation, and this level is identified as the OSL. Although much higher levels have been tested under acute conditions without adverse effects and may be safe, the data for intakes above 5 g/d are not sufficient for a confident conclusion of long-term safety.

Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Med. 2000 Sep;30(3):155-70. doi: 10.2165/00007256-200030030-00002. 

Abstract. The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects in healthy individuals. Nevertheless, idiosyncratic effects may occur when large amounts of an exogenous substance containing an amino group are consumed, with the consequent increased load on the liver and kidneys. Regular monitoring is compulsory to avoid any abnormal reactions during oral creatine supplementation.

Candow DG, Chilibeck PD, Forbes SC, Fairman CM, Gualano B, Roschel H. Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty and Cachexia. Bone. 2022 Sep;162:116467. doi: 10.1016/j.bone.2022.116467.

Candow DG, Moriarty T. Effects of Creatine Monohydrate Supplementation on Muscle, Bone and Brain- Hope or Hype for Older Adults? Curr Osteoporos Rep. 2024 Nov 1;23(1):1. doi: 10.1007/s11914-024-00895-x.