Single-arm pilot safety study of creatine hydrochloride in healthy adultsDid a week of creatine hydrochloride change your blood sugar or kidney markers in healthy adults?

medRxiv Published April 18, 2026 Study authors: Wagner, J. C.; Ostojic, S.; Faulkner, W.; Faulkner, M. DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Consider that this small pilot study found no clinically meaningful lab changes with short-term creatine hydrochloride in healthy adults.

This is a single-arm pilot safety study in 11 healthy adults at a single center. The intervention was 750 mg/day creatine hydrochloride for 28 consecutive days, with baseline as the comparator. The primary outcome was short-term laboratory safety and tolerability, with secondary outcomes including lipid parameters, hematologic indices, renal markers, chemistry analytes, fasting glucose, and serum bicarbonate.

The authors found that fasting glucose increased modestly by 8.1 mg/dL prior to multiplicity adjustment but was not statistically significant after FDR correction and remained within reference ranges. Serum bicarbonate decreased slightly by 2.4 mmol/L; this was statistically detectable in parametric analysis but not consistently supported by nonparametric testing, and values remained within physiological limits. For lipid parameters, hematologic indices, renal markers, and most chemistry analytes, no clinically meaningful changes were observed after adjustment for multiple comparisons.

Limitations noted by the authors include the single-center, single-arm, single-blind design; the small sample size (n=11); the study population limited to healthy adults; and the lack of controlled human safety data specific to creatine hydrochloride. The study did not report adverse events, serious adverse events, or discontinuations.

Practice relevance was not reported, and the authors caution against overstatement regarding generalizability to other populations, long-term safety, and efficacy. The evidence is preliminary and from a small pilot study.

Imagine taking a supplement every day for a month and wondering if it quietly changes your body. This small study asked exactly that about creatine hydrochloride. Eleven healthy adults took 750 mg of the supplement daily for 28 days at a single medical center. The goal was simply to see if their blood and urine tests showed any warning signs of trouble.

Most of the blood work stayed within normal limits. Lipid levels, blood cell counts, and kidney markers did not change in a way that mattered. However, fasting glucose did rise by about 8 mg/dL, and serum bicarbonate dropped slightly. Even with these small shifts, all values remained inside the safe ranges doctors use to judge health.

No one in the group stopped taking the pill because of side effects, and no serious problems occurred. But remember, this was a pilot study with only 11 people. It cannot tell us if the drug is safe for sick people, older adults, or for years of use. These results are just a first step, not a final answer.

What this means for you:

Short-term creatine hydrochloride was safe in 11 healthy adults, though small lab changes occurred.

Study Details

Sample sizen = 11

EvidenceLevel 5

PublishedApr 2026

View Original Abstract ↓

Background: Creatine monohydrate (typically 5 to 20 g/day) has a well-established safety profile across diverse populations. Creatine hydrochloride (CR-HCl) is a highly soluble creatine formulation that may allow effective supplementation at substantially lower doses (750 mg to 3 g/day); however, controlled human safety data specific to CRHCl remain limited. Objective: To evaluate the short-term laboratory safety and tolerability of low dose CRHCl supplementation administered for 28 days in healthy adults. Methods: This single center, single arm, singl blind pilot safety study enrolled 11 healthy adults (10 females, 1 male; mean age 44.6 plus/minus 7.2 years). Participants consumed 750 mg/day CRHCl for 28 consecutive days while maintaining their usual diet and physical activity patterns. Fasting blood and urine samples were collected at baseline and Day 28. Laboratory assessments included hematological, lipid, and clinical chemistry biomarkers. Pre and post changes were evaluated using paired parametric and nonparametric tests, baseline-adjusted regression models, bootstrap confidence intervals, and false discovery rate (FDR) correction. Results: All participants completed the intervention. No clinically meaningful changes were observed in lipid parameters, hematologic indices, renal markers, or most chemistry analytes after adjustment for multiple comparisons. Fasting glucose increased modestly (8.1 mg/dL) prior to multiplicity adjustment but was not statistically significant after FDR correction and remained within reference ranges. Serum bicarbonate decreased slightly (2.4 mmol/L); although statistically detectable in parametric analysis, values remained within physiological limits and were not consistently supported by nonparametric testing.

Single-arm pilot safety study of creatine hydrochloride in healthy adultsDid a week of creatine hydrochloride change your blood sugar or kidney markers in healthy adults?

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Single-arm pilot safety study of creatine hydrochloride in healthy adultsDid a week of creatine hydrochloride change your blood sugar or kidney markers in healthy adults?

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