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

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. This study aimed to assess the effects of varying doses of creatine nitrate-creatinine intervention on pharmacokinetics and safety in healthy humans. 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. 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. 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.