Novel creatine formulation exhibits similar serum creatine concentrations and pharmacokinetics to creatine monohydrate in healthy adults

Background Creatine monohydrate (CrM) is the most widely studied creatine form, demonstrating robust efficacy, bioavailability, and safety. With creatine growing in popularity, alternative formulations of creatine have been developed to target solubility and to optimize absorption pharmacokinetics (PK), as well as to reduce gastrointestinal (GI) intolerability. The purpose of the current study was to evaluate the acute effects of a novel creatine monohydrate (OptiCreatineTM; CrO) compared to CrM on serum creatine PK and GI tolerability in healthy adults.Methods Healthy, recreationally active adults (age: 22 ± 3 years; males n = 8, females n = 9) consumed a single 5-gram dose of CrM or CrO across two separate visits following an overnight fast, in a randomized, double-blind, crossover design. Venous blood samples were collected at baseline and 30, 60, 90, 120, 180, 240, and 300 mins post-ingestion of their assigned treatment to assess serum creatine concentrations. PK parameters including peak concentration (Cmax), time to peak (Tmax), absorption rate constant (ka), elimination rate constant (kel; h−1), and area under the curve (AUC₀–T) were derived using nonlinear regression modeling. GI symptoms were assessed using validated questionnaires.Results There was no difference in serum creatine concentrations between CrM or CrO across all participants (p = 0.707), males (p = 0.318), or females (p = 0.996) at any time point. Serum creatine increased over time regardless of treatment (p < 0.0001). No differences were observed between CrM and CrO for Cmax (mean difference ± standard deviation (MD ± SD): 7.66 ± 50.37μM; p = 0.82), Tmax (MD ± SD: −0.04 ± 0.13 h; p = 0.54), ka (MD ± SD: −0.15 ± 0.45 h−1; p = 0.51), kel (MD ± SD: 0.01 ± 0.03 h−1; p = 0.61), or AUC₀–T (MD ± SD: 22.09 ± 160.57 μM·h; p = 0.74), with no sex × treatment interactions (p ≥ 0.05). Descriptive evaluation showed similar GI symptom profiles between conditions, with low frequency and minimal severity reported across both treatments.Conclusions A single 5-gram dose of CrO produced similar serum creatine and PK characteristics to CrM in healthy adults. These findings support CrO as a viable delivery option, with no significant differences in acute pharmacokinetic profiles or GI tolerability compared to CrM.