Creatine Monohydrate vs HCl: Two Small Trials That Disagree

Two forms of the same molecule, one with a thirty-year literature and one with a solubility argument. The comparative record between them turns out to be two studies of forty people that point in opposite directions. This is research journalism and contains no usage guidance, per our editorial standards.

First, how much comparative evidence is there?

A search of PubMed on 2026-09-11 for creatine together with hydrochloride or HCl, restricted to randomised controlled trials, returns seven records. That number is misleading, and the way it is misleading is worth showing, because it is how a thin literature comes to look adequate.

Four of the seven are trials of unrelated drugs that happen to be hydrochloride salts. The real comparative literature is three papers, and only two of them put hydrochloride and monohydrate in the same experiment.

The two that did, and what they found

Eghbali, Arazi and Suzuki, 2024. Forty participants aged 18–25, randomly divided into four groups of ten, eight weeks of resistance training at 70–85% of one-repetition maximum: hydrochloride at 0.03 g/kg; monohydrate with a five-day loading phase at 0.3 g/kg then 0.03 g/kg; monohydrate without loading at 0.03 g/kg; placebo. Strength, body fat percentage, skeletal muscle mass, muscular cross-sectional area and a panel of hormones were measured before and after.

All three supplement groups beat placebo on strength, arm and thigh cross-sectional area and skeletal muscle mass, and on the hormonal panel. The paper's conclusion on the form question is one clause: both "significantly enhanced the beneficial effects of RT on strength, hypertrophy, and hormonal responses, with Cr-HCl showing no benefit over CrM" (PMID 39545789).

Duan, Wang and Wang, 2026. Forty collegiate male soccer players, four groups of ten, four weeks of repeated sprint training three times a week: monohydrate, ethyl ester, hydrochloride, placebo. Outcomes were countermovement vertical jump, 20-m sprint, an L-run agility test, Wingate anaerobic power and an incremental exercise test.

All the creatine groups beat placebo on physical performance, peak power and fatigue index, with no differences in mean power output or VO₂max. And then the finding that contradicts the 2024 trial: "the Ee and Hcl forms of Cr showed superior gains (p < 0.05) in physical performance and peak power compared to the Mon form" (PMID 42720250).

Why this is not a tie to be broken by preference

Ten people per arm. Four weeks against eight weeks. Sprint-and-jump outcomes against strength-and-cross-sectional-area outcomes. Two different populations, two different training stimuli, two different endpoint families, and one arm of ten in each.

A comparison between two salts of the same molecule, where any real difference is likely to be small, needs far more participants than either study had to detect that difference reliably — and when two underpowered studies disagree, the most probable explanation is that both are noisy rather than that one has found the truth.

There is one asymmetry worth naming, and it favours the null result. Eghbali matched the amounts: the hydrochloride arm and the non-loading monohydrate arm both received 0.03 g/kg of body mass. That is the only place in this literature where the two forms were tested at the same amount rather than each at its own marketed amount, and it found no separation.

The number that dwarfs both trials

In the 2025 analysis of the creatine safety literature, the authors compiled 685 human clinical trials of creatine supplementation covering 12,839 supplemented participants. Of those studies, 95% administered creatine monohydrate, at an average of about 0.166 g/kg/day for a mean of 64.7 days (Antonio, Kreider et al., J Int Soc Sports Nutr 2025, PMID 40198156).

That single figure reframes the whole question. Every effect size quoted for creatine, every safety conclusion, every dose-response observation and every meta-analysis this site has cited — including the small effect sizes in our comparison against the research compounds and the muscle-saturation curves behind the loading phase — is a monohydrate result. The evidence does not belong to creatine as a category. It belongs to one salt of it.

A different form is not thereby inferior. It is untested, which is a different and more honest word, and it is the word that applies to most things sold in this market.

What the solubility argument does and does not establish

Creatine hydrochloride dissolves more readily in water than the monohydrate. That is a real property and nobody disputes it. Two claims are then attached to it: that a smaller amount suffices, and that gastrointestinal complaints are reduced.

Neither has a comparative trial behind it. The 2024 study administered the same amount per kilogram to both arms, so it cannot speak to the first claim. Neither trial reported a comparative gastrointestinal outcome. And the controlled record on creatine's gastrointestinal burden in general — 4.9% of creatine study groups against 4.3% of placebo groups across 685 trials — is not a large signal to reduce.

The honest summary

• The comparative literature is three creatine-form trials, two of which compare the forms head to head.
• Those two disagree, with ten participants per arm each.
• The one comparison that matched the amounts found no advantage for hydrochloride.
• 95% of the entire creatine evidence base used monohydrate, which is why monohydrate is the form with numbers attached to it.
• The other forms are not worse on the evidence. There is not enough evidence for them to be worse on.

The International Society of Sports Nutrition's own 2021 review still lists whether other forms are similar or superior to monohydrate as one of twelve open questions about creatine (PMID 33557850). After three decades and hundreds of trials, that question being open is the finding.

Sources and dates

All PubMed searches run 2026-09-11 via E-utilities.

Figures are reported as the sources state them. Nothing here is a recommendation or an instruction.