Many people still wonder whether creatine—a widely used supplement supported by substantial scientific evidence—is truly safe and which available form is most effective. This post addresses the second question, but first, a brief review.
Creatine: What Is It?
Creatine is a nitrogenous amine derivative synthesized from glycine, arginine and methionine. Through a series of reactions in the kidneys, liver, pancreas and certain brain regions, these three amino acids form creatine. Its main function is to regenerate ATP—the currency with which cells pay the energy costs of biological processes—from ADP. Phosphocreatine (PCr) donates its phosphate group to ADP, which contains two phosphates, to form ATP again. Creatine also transports energy-related intermediates from the mitochondria to the cytosol. Approximately 95% of creatine is stored in muscle, with the remainder in tissues such as the heart, brain and testicles. Most muscle creatine is stored as PCr and the rest as Cr. The body degrades around 1 – 2% per day and eliminates it as creatinine. Endogenous synthesis and dietary intake, mainly from meat and fish and from supplements when used, replace this loss.
Creatine Forms: Which Is Most Effective?
Of all studied forms of creatine, creatine monohydrate (CrM) is the most economical and effective. It was the first creatine source marketed as a dietary supplement and remains the most common. It is considered the gold standard for comparing other sources because its bioavailability, stability and low cost are well established, and numerous studies support its effectiveness and safety. As Kreider and colleagues note, no published peer-reviewed studies show that other forms—including effervescent, buffered, citrate, nitrate, serum and ethyl-ester creatine or beverages—produce greater creatine retention than CrM. Studies show less physiological impact from these forms than from monohydrate. Several factors may explain this. Bioavailability is important: it describes how much of a nutrient in a food or supplement reaches the target tissue and is available for metabolic use. Some newer forms do not contain the complete creatine molecule; they retain only part of it or bind other compounds so tightly that digestion may not release the creatine, preventing an increase in blood concentration. A creatine supplement is not necessarily effective simply because blood creatine rises after ingestion. It should increase blood levels, but it must also enter tissue. Studies of new forms must therefore be reviewed carefully before assuming that a large blood increase means the product is working; it may reflect persistence in blood rather than uptake by the target tissue. Many creatine-related compounds also contain less creatine by molecular weight than CrM, requiring more of the source to provide an equivalent amount of released creatine, even assuming those alternatives are truly bioavailable.
One further point: Creapure® creatine monohydrate is manufactured in Germany using water as a solvent, producing 99,9%-pure monohydrate free from contaminants. Other sources, particularly from China, have been found to contain contaminants such as dicyandiamide, dihydrotriazine, dimethyl sulfate, thiourea and creatinine, and/or elevated heavy-metal concentrations including mercury and lead. These can result from different chemical precursors, poorly controlled synthesis, organic solvents and/or less suitable filtration. German-made CrM is therefore the most widely used and is considered the gold standard in clinical trials establishing safety and effectiveness.
Stability is another important characteristic. CrM is quite stable as a powder and shows no signs of degrading to creatinine over years, even at high temperatures. In solution, however, creatine is less stable and degrades to creatinine faster as pH falls—degradation stops at pH < 2,5—and temperature rises. It should therefore be consumed immediately after mixing with an acidic drink or refrigerated to slow degradation and consumed within a couple of days. Some recent studies show high stability, although controlling pH and temperature remains advisable.
“Because of hydrochloric acid, the stomach's low pH causes less than 1% of CrM to degrade, while 99% is absorbed by tissues or excreted in urine after ingestion.”
Solubility is another important aspect. When CrM is added to water, it is not highly soluble and some sediment may remain at the bottom of the glass after the first sip. Do not worry: the creatine remains 100% bioavailable. Add more water and continue drinking. Some recommend warm water, fruit juice or sports drinks with a pH between 2,5 – 4,5, and/or mixing with powdered carbohydrates and/or protein to suspend CrM better, reduce sedimentation and improve muscle uptake. Although acidic drinks improve solubility, over time they could increase degradation to creatinine. If CrM is mixed with an acidic drink, it is best consumed soon afterward to avoid conversion to creatinine in the even more acidic stomach environment.
“The only advantage of taking CrM with an acidic drink is leaving less CrM at the bottom of the glass to swirl and consume in the final sip. Claiming that a particular creatine form is absorbed more effectively than CrM because it is more water-soluble is an unsupported marketing exaggeration.”
Recommended Intake includes the classic protocol: a loading phase lasting 5 – 7 days with approximately 20 g per day, divided into four servings, followed by 3 to 5 g/day for 30 days. This increases blood and muscle creatine and PCr by around 20 – 40%. Low doses of 3 – 6 grams/day for 4 to 12 weeks are also effective. Consuming Cr with carbohydrates or protein appears to promote greater retention. Some studies report that taking CrM with nutrients that improve insulin sensitivity, such as D-pinitol, Russian tarragon or fenugreek extract, improves creatine retention, although additive effects on performance or adaptation are limited or absent. There is also no evidence that micronized versions are more bioavailable.
Performance Effects are seen particularly in high-intensity sports, and creatine also supports training adaptations in adolescents, adults and older people. Its increasingly strong and varied health benefits are no less important. Another post discusses whether creatine monohydrate or any of its forms carries risks. For now, remember that creatine monohydrate is the most studied, economical and effective form, and that Creapure® offers the highest assurances of purity and safety.
Dietary-supplement regulations vary by country: some are based on FDA guidance and others on national expert committees. CrM is available worldwide, although in some countries the amount is limited to 3 – 5 g per serving. Not every marketed creatine form is available in every country. In Australia, Canada, China, Japan, South Korea and Europe, CrM is the only creatine source approved for sale, and it is the only form with approved health claims in Europe, Canada, Japan and South Korea. No alternative form of Cr has shown superior bioavailability, effectiveness or safety compared with CrM. It is striking that many forms, including creatine serum, continue to be marketed despite clear evidence that they are ineffective.
Remember that CrM is the gold standard for comparing creatine forms because it has the strongest safety and effectiveness evidence among those studied.
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Creatine
Author
Fernando Mata (Registration No. AND-01053)
MSc Physiology; MSc Biomedicine; MSc Nutrition; PhD Student
Managing Director of the Center for Advanced Studies in Nutrition
References
Kreider RB, Jäguer R, Purpura M. Bioavailability, efficacy, safety, and regulatory status of creatine and related compound: a critical review. Nutrients. 2022
