A systematic review and quality assessment of case reports of adverse events for borage (Borago officinalis), coltsfoot (Tussilago farfara) and comfrey (Symphytum officinale)

Symphytum officinale (comfrey), Tussilago farfara (coltsfoot) and Borago officinalis (borage) have long histories of therapeutic use, but their safety has been questioned due to the presence of unsaturated pyrrolizidine alkaloids (PAs). The evidence base underlying these concerns relies in part on case reports. This systematic review assesses these case reports for their reliability to inform this debate. Method: Study selection was restricted to case reports describing possible pyrrolizidine alkaloid related harm and ingestion of comfrey, coltsfoot or borage. An extensive search of academic databases was conducted. Papers meeting the criteria were critically appraised. Results: The search resulted in 11 appropriate case reports, none of which involved borage. Nine reports were assessed for causality and indicated some degree of association between the material ingested and the adverse event. Lack of unequivocal identification of the species ingested compromised attribution and was a significant source of uncertainty. Three levels of identity confusions were found; misidentification or substitution at the level of the whole herb; omission of appropriate botanical identification and attribution of a specific PA to either comfrey or coltsfoot when it is a constituent found in other plants of established toxicity. Conclusion: These cases are an unreliable body of evidence on which to draw conclusions about the safety of the oral consumption of Symphytum officinale and Tussilago farfara. Toxicological studies based on oral ingestion of phytochemically-complex preparations of these herbs may be the most accurate methodology for assessing clinical risk.