Review of black cohosh-induced toxicity and adverse clinical effects

Black cohosh (Actaea racemosa L) has been utilized for centuries by Native Americans as a traditional herbal medicine. The rhizome and root extract from black cohosh (BCE) is one of the most popular herbal dietary supplements worldwide. Due to its claimed estrogen-like effects, contemporary uses of black cohosh products are primarily for alleviating menopausal and perimenopausal symptoms. However, recent studies indicate that BCE is not only ineffective for menopausal therapy, but also induces genotoxicity through an aneugenic mode of action (MoA). Adverse effects induced by BCE have been reported in humans, with many case studies documenting outcomes ranging from mild reactions to acute liver damage and even death. Consequently, concerns about the safety of BCE have emerged. There are more than 100 chemical constituents in black cohosh products, including triterpene glycosides (>40 chemicals), polyphenols (>20 chemicals), and nitrogenous compounds (>70 chemicals). Therefore, commercially available BCE products can differ markedly in composition, leading to the potential for variable bioactivities among these complex commercial products. This review presents the latest information on the toxicological effects of BCE from both in vivo and in vitro experiments and summarizes the adverse effects of BCE in human clinical trials.