Creatine Monohydrate vs HCl: Solubility and Evidence

Creatine monohydrate is the crystalline form of creatine containing one water molecule, and it is the most studied form in supplements. Creatine HCl (hydrochloride) is a salt that dissolves much better in water; in marketing it is described with phrases such as “the same effect with a lower dose” and “does not upset the stomach.” This page sets side by side what the solubility difference shows, what the only directly comparative measurement in humans found, the ISSN position, and the regulation in Türkiye. For details on all the other forms: creatine monohydrate and other forms.

Differences between creatine monohydrate and HCl

What does the solubility difference show?

Gufford and colleagues compared the aqueous solubility and partition coefficients of six N-methylguanidinium salts of creatine with monohydrate. The solubility of the salts was significantly higher than that of monohydrate; the hydrochloride and mesylate were 38 and 30 times more soluble, respectively. In Caco-2 cell monolayers, the permeability of pyruvate, citrate, and hydrochloride was compared; there was no significant difference from monohydrate for the salts other than citrate. ^[4] This study is a laboratory measurement: it measures solubility and permeability in a cell model; it does not measure absorption in humans, muscle creatine, or digestive tolerance. The introduction of the study says that the low solubility of monohydrate leads to water retention and digestive discomfort; this is a background assumption, not a finding of the study.

There are two separate views on bioavailability. The 2021 review by Antonio and colleagues and the 2011 review by Jäger state that monohydrate is not degraded during normal digestion and that about 99% of what is taken orally is retained in tissue or excreted in urine; the Jäger review also concludes that there is little or no evidence that the newer forms are more effective or safer than monohydrate. ^{[2] [3]} In contrast, in the rat study by Alraddadi and colleagues, the absolute oral bioavailability of monohydrate was measured as 53% at the low dose and 16% at the high dose; the authors interpreted this as monohydrate absorption being incomplete and dose-dependent. The estimated bioavailability values given for HCl in the same study (66% versus 17%) are a model simulation, not a measurement, and two authors of the study are inventors of creatine HCl patents. ^[5] These values measured in animals have not been confirmed in humans.

What the evidence says: performance in humans

The study that directly compares monohydrate with HCl is by Duan and colleagues: 40 male university soccer players were randomly assigned to a monohydrate, creatine ethyl ester, creatine HCl, or placebo group (10 people per group) and performed 4 weeks of repeated sprint training. All groups improved; the groups receiving creatine improved more than placebo in jump, sprint, and peak power. The ethyl ester and HCl groups showed larger gains than the monohydrate group in jump, 20 m sprint, L-run, and peak power; there was no difference between groups in mean power and VO2max. The authors report that the study received no funding and that there was no conflict of interest. ^[6]

The limits of this finding are as follows: the groups had 10 people each; because the same amount of powder (5 g) was given to each group, the amount of creatine actually received was not the same owing to the molar mass difference between the forms; muscle creatine was not measured directly (the authors state that direct metabolic indicators are needed); and the study was conducted in young, male, university soccer players during a 4-week training period. ^[6] The claim of “the same effect with a lower dose” was not tested in this study, because the dose was not reduced. The 2021 review by Antonio and colleagues writes that there was no peer-reviewed publication showing that, at equal amounts, the salts increase creatine storage more than monohydrate; this single small study from 2026 was published after that sentence and needs to be replicated. ^[2] By this site’s criteria, a single RCT is at most grade C.

Price logic and the label

On a label, the form name and the amount of creatine per serving are separate pieces of information. According to Jäger’s table, the creatine content of monohydrate by weight is 87.9%. ^[3] The content of HCl comes out at about 78% from the molecular weights of creatine (131.1 g/mol) and its hydrochloride (167.6 g/mol); the same method gives 87.9% for monohydrate. The arithmetic result: about 12% more powder is needed in HCl for the same gram of creatine (87.9/78.2 ≈ 1.12). Price is therefore compared per gram of creatine, not per gram of powder; a higher price does not indicate a proven advantage. The purity of monohydrate can also vary with the production method: the 2021 review by Antonio and colleagues reports that in some productions made with different starting materials, dicyandiamide reached 5.4% and dihydrotriazine 0.09%, and higher heavy metal levels were detected. ^[2]

Side effects and safety

ISSN 2017 states that the only consistently reported side effect of creatine monohydrate in the literature is weight gain, and that studies lasting up to 5 years in healthy and patient groups showed no health risk. ^[1] The claim that “HCl is easier on the stomach” rests on the solubility rationale, and data comparing digestive tolerance between the two forms by measurement are limited. Kidney, liver, and product safety are covered in a separate guide.

Situation in Türkiye

In the 21/09/2026 version of the Ministry of Agriculture and Forestry’s Restricted Substances List for Food Supplements, “Creatine / Phosphocreatine (together or separately)” appears with chemical synthesis as the source; a maximum of 3 g/day is stated for age 11 and older (publication date 22/01/2016). Tricreatine malate is a separate line (maximum 4 g/day, 16/06/2017). There is no separate line under the name creatine hydrochloride in the list. ^[8] The study protocols reported by ISSN 2017 include 3–5 g/day for maintenance; the value in the list and the protocols used in studies are not the same thing. ^[1] That every food supplement is subject to Ministry of Agriculture and Forestry approval is explained in the creatine guide.

Verdict

The evidence says this: creatine HCl is about 38 times more soluble than monohydrate; this difference has not translated into a permeability difference in a cell model, a measurement of absorption in humans, or a digestive tolerance result. The only RCT in humans comparing directly with monohydrate (40 soccer players, groups of 10, 4 weeks) reported a difference in jump, sprint, and peak power in favor of HCl; muscle creatine was not measured, the same amount of powder was given, and the result has not been replicated. The evidence for monohydrate, in contrast, rests on many studies and the IOC 2018 and ISSN 2017 assessments. Price comparison is done per gram of creatine. This page does not recommend a personal product or amount.