Potential interactions between creatine supplementation and prescription drugs: a narrative review and evidence-mapping perspective.

BACKGROUND

Creatine is one of the most widely used dietary supplements worldwide and is increasingly consumed by non-athletic populations, including older adults and individuals with chronic metabolic, neurological, and musculoskeletal conditions. Given the high prevalence of prescription drug use in these populations, concomitant use of creatine and medications is common. Several biological pathways suggest potential creatine-drug interactions, particularly related to renal handling and biomarker interpretation; however, the clinical relevance of such interactions remains unclear.

METHODS

A PRISMA-aligned narrative and evidence-mapping review was conducted. PubMed (MEDLINE), Scopus, and the Cochrane Library (CENTRAL) were searched without date restrictions for human studies evaluating oral creatine supplementation in the context of concomitant prescription drug use, pharmacokinetics, or interaction-related safety outcomes. Title and abstract screening was performed using predefined eligibility criteria. In parallel, major drug-drug interaction databases (UpToDate, DDInter, Medscape, DrugBank, Drugs.com, the Merck Manual, and the FDA Drug Development and Drug Interactions resource) were queried to contextualize potential interaction signals.

RESULTS

Database searches identified 270 records, of which 132 unique articles remained after deduplication; none met inclusion criteria for full-text evaluation as human studies directly assessing creatine-drug interactions. Across drug-drug interaction databases, no clinically established creatine-drug interactions of moderate or high severity were identified. Reported interaction signals were uniformly classified as minor or theoretical and were primarily attributed to renal excretion-based mechanisms, without evidence of confirmed adverse clinical outcomes.

CONCLUSIONS

Despite widespread real-world co-use of creatine supplements and prescription medications, no controlled human studies have directly evaluated creatine-drug interactions. Available evidence from creatine-drug interaction resources suggests predominantly low-severity, theoretical interaction signals rather than clinically confirmed interaction risk. However, the absence of documented clinical evidence should not be interpreted as evidence that interactions cannot occur, particularly in high-risk populations. These findings highlight a substantial evidence gap and underscore the need for targeted human studies to inform clinical guidance.