Systematic review of harm from case reports and clinical trials of the oral use of arctostaphylos uva-ursi, turnera diffusa and achillea millefolium

Aim To quantify and assess adverse events reported in the literature from the oral ingestion by humans of Arctostaphylos uva-ursi, Turnera diffusa and Achillea millefolium. Method A systematic literature search for human case reports and clinical trials reporting adverse events from the oral ingestion of A. uva-ursi, T. diffusa and A. millefolium was conducted. Case reports were evaluated for quality using the Quality of Case Reports of Adverse Events instrument, and for causality using the WHO-UMC instrument. Clinical trials were evaluated for adherence to the CONSORT Extensions for Herbal Medicinal Interventions and Harms. Results Two case reports and 15 clinical trials were included for analysis. One case report and two clinical trials reported adverse events for A. millefolium, one case report and no clinical trials reported adverse events for A. uva-ursi, and no case reports and one clinical trial reported adverse events for T. diffusa. Quality and causality assessment of case reports varied, and low adherence to CONSORT Extensions for Herbal Medicinal Interventions and Harms was observed in clinical trials. Conclusion There appears to be very limited evidence of harm in humans from the oral ingestion of A. uva-ursi, A. millefolium and T. diffusa. The quality of reporting of both case reports and clinical trials involving herbal medicines needs to be improved to better understand the complex issue of herbal safety.