Biomarkers of Creatine Metabolism in Humans: From Plasma to Saliva and Beyond

The literature on creatine biomarkers in various bodily fluids remains limited. The purpose of this review is to explore the available data regarding the presence of molecules considered biomarkers of creatine metabolism—namely creatine, guanidinoacetate, and creatinine—across different bodily fluids and matrices. In addition to providing reference values for each biofluid, the paper reports concentrations of these biomarkers in different pathologies. The impairment of creatine metabolism is most extensively studied in creatine deficiency syndromes, which are characterized by genetic deficiencies in either the enzymes involved in creatine biosynthesis or creatine transport. However, other conditions may also influence creatine metabolism to some extent. Our paper also focuses on the transport pathways of these metabolites from their originating tissues to various bodily fluids, typically mediated by the creatine transporter (SLC6A8), with evidence suggesting the involvement of other transporters as well. Gas and liquid chromatography have replaced traditional methods for the analytical detection of biomarkers of creatine metabolism and are now commonly used for this purpose. The paper also discusses the differences and variations between these analytical methods.