Post-marketing safety profile and potential aspirin interaction of Serenoa repens extract: A real-world study using FAERS and network toxicology

Saw palmetto (Serenoa repens) extract (SPE) originated from Native American traditional medicine and is now globally consumed for benign prostatic hyperplasia. Despite its popularity, its real-world safety profile regarding rare events and potential interactions remains incompletely characterized.

To evaluate post-marketing safety signals of SPE using the FDA Adverse Event Reporting System (FAERS) database and preliminarily explore molecular targets related to SPE-aspirin interactions.

FAERS reports (2004-2025) listing SPE as a suspect drug were analyzed. Disproportionality analyses (reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM), and Bayesian Confidence Propagation Neural Network (BCPNN)) were performed to identify safety signals. Logistic regression assessed factors associated with the reporting of haemorrhage and mortality. Network toxicology investigated molecular targets linking SPE, aspirin, and haemorrhage.

Among 634 reports, hepatobiliary and blood/lymphatic disorders emerged as significant signals. Frequent adverse events included pruritus, cholestasis, confusion, and eosinophilia. Multivariate analysis indicated that age ≥75 and concomitant aspirin were associated with significantly elevated reporting odds for haemorrhage (OR 3.89; 2.28) and fatal outcomes (OR 2.87; 7.26). Network analysis revealed 46 shared targets enriched in clinically relevant pathways, particularly arachidonic acid metabolism and platelet activation, suggesting a potential pharmacological overlap affecting haemostasis.

Real-world data demonstrate significant disproportionate reporting of hepatobiliary and hematological events with SPE. The increased reporting frequency of haemorrhage and fatal outcomes in elderly aspirin users warrants clinical vigilance. These findings, alongside the potential targets identified in silico, suggest that concurrent use in high-risk populations requires careful monitoring.