Effects of Short-Term Creatine Nitrate Plus Creatinine Intake on Creatine Pharmacokinetics and Safety Biomarkers in Healthy Adults

Abstract

Background: A blend of creatine nitrate and creatinine has demonstrated promising bioavailability; however, prior studies have not thoroughly examined its pharmacokinetics and safety profiles, particularly its impact on kidney stress indicators, such as serum cystatin C. Objective: This study aimed to assess the effects of varying doses of creatine nitrate-creatinine intervention on pharmacokinetics and safety in healthy humans. Methods: Ten young adults (mean age 26.1 ± 5.0 years; 5 females) volunteered for this double-blind, crossover, randomized controlled trial. The participants were randomly assigned to receive either a low-dose creatine nitrate-creatinine mixture (CN-CRN-Low; 1.5 g of creatine nitrate and 1.5 g of creatinine), a high-dose creatine nitrate-creatinine mixture (CN-CRN-High; 3 g of creatine nitrate and 3 g of creatinine), or 1.5 g of creatine nitrate (CONTROL) in both a single-dose pharmacokinetics experiment, and a 14-day safety trial. Results: Both CN-CRN-Low and CN-CRN-High interventions displayed increased volume of distribution and total clearance compared to the CONTROL intervention (P < 0.05) in a single-dose pharmacokinetics experiment. Additionally, the CN-CRN-High intervention showed significantly higher creatine maximum serum concentrations compared to the other interventions (P < 0.05). Serum cystatin C levels remained unchanged across all interventions (P = 0.65), with no participants experiencing abnormal cystatin C concentrations or major changes in other safety biomarkers. Conclusion: The present study demonstrates dose-specific utilization of creatine nitrate-creatinine intervention, with the mixture induced no kidney damage. Further studies are needed to explore the potential functional and performance benefits of creatine nitrate-creatinine supplementation in diverse clinical and athletic cohorts.