Short-Term Safety of Low-Dose Creatine Hydrochloride: A 28-Day Single-Arm Pilot Study

BackgroundCreatine monohydrate (typically 5-20 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 - 3 g/day); however, controlled human safety data specific to CR-HCl remain limited. ObjectiveTo evaluate the short-term laboratory safety and tolerability of low-dose CR-HCl supplementation administered for 28 days in healthy adults. MethodsThis single-center, single-arm, single-blind pilot safety study enrolled 11 healthy adults (10 females, 1 male; mean age 44.6 {+/-} 7.2 years). Participants consumed 750 mg/day CR-HCl 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-post changes were evaluated using paired parametric and nonparametric tests, baseline-adjusted regression models, bootstrap confidence intervals, and false discovery rate (FDR) correction. ResultsAll 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. ConclusionsSupplementation with 750 mg/day CR-HCl for 28 days was well tolerated and was not associated with clinically meaningful alterations in routine laboratory biomarkers. These preliminary findings support the short-term tolerability of low-dose CR-HCl and provide a basis for larger randomized, placebo-controlled studies to further evaluate its safety profile.