Creatine HCl, Buffered, Ethyl Ester, Nitrate and Other Marketed Forms: What Evidence Exists

Form by form

Creatine HCl in more detail

The "38 times" claim comes from a report that creatine HCl was 37.9 times more soluble in water than monohydrate at 25 degrees C. The review points out the two were assessed at different saturation pH values and that the researchers did not directly compare plasma or tissue creatine. [3] Since then, trials have compared the two forms:

• 40 people aged 18-25 trained with weights for 8 weeks, taking HCl or monohydrate (study amount 0.03 g per kg body mass, with one monohydrate group also loading). Both improved strength and muscle size versus placebo, with HCl showing no benefit over monohydrate. [9]
• 40 collegiate male soccer players over 4 weeks of repeated sprint training: all creatine groups beat placebo, and the HCl and ethyl ester groups showed larger gains in jump, sprint and peak power than the monohydrate group. [7] The abstract reports 10 people per group.
• 36 perimenopausal and menopausal women for 8 weeks received HCl at study amounts of 750 or 1,500 mg per day, or a combination with ethyl ester, or placebo. Medium-dose HCl beat placebo on reaction time and measured frontal brain creatine, and all products were well tolerated. [10] There was no monohydrate comparison, and brain creatine is a biomarker, not a clinical outcome.

Mixed results from small trials do not settle the question. See also Creatine monohydrate vs HCl and other forms.

Ethyl ester, buffered and nitrate

• Ethyl ester is a chemically altered creatine and is not creatine itself, according to a review, which also reports that it rapidly degrades to creatinine in stomach acid. [3] In the 7-week trial, in which participants were randomized to placebo, monohydrate or ethyl ester at about 20 g/day for 5 days then about 5 g/day (study amounts), serum creatinine was higher with ethyl ester than with placebo or monohydrate. [6]
• Buffered products add alkaline ingredients; the 2022 review found that neither recommended nor loading-equivalent amounts produced greater changes than monohydrate. [3]
• Nitrate: by molecular weight creatine nitrate contains 67.5% creatine. [3] A 2016 review said the safety of creatine nitrate had been evaluated but still needs further investigation. [11] Proper evidence not found for head-to-head performance trials against monohydrate in the sources we searched.

Content per gram

Theoretical creatine by weight: HCl 78.2%, nitrate 67.5%, citrate 40.6% and malate 49.4%, versus 87.9% for monohydrate. [3] The same weight of product therefore holds different amounts of creatine. See creatine amounts in studies.

Blends and serums

In one marketplace survey of 175 products, 16 forms other than monohydrate were found, and 21.7% were blends of different creatine forms. [12] The review also describes an oral "serum" product sold as 2.5 g of creatine per 5 mL; testing found less than 10 mg of creatine and 69 mg of creatinine per dose. [3]