Hepatotoxicity due to herbal dietary supplements: Past, present and the future

Dietary supplements (DS) constitute a widely used group of products comprising vitamin, mineral, and botanical extract formulations. DS of botanical or herbal origins (HDS) comprise nearly 30% of all DS and are presented on the market either as single plant extracts or multi-extract-containing products. Despite generally safe toxicological profiles of most products currently present on the market, rising cases of liver injury caused by HDS – mostly by multi-ingredient and adulterated products – are of particular concern. Here we discuss the most prominent historical cases of HDS-induced hepatotoxicty – from Ephedra to Hydroxycut and OxyELITE Pro-NF, as well as products with suspected hepatotoxicity that are either currently on or are entering the market. We further provide discussion on overcoming the existing challenges with HDS-linked hepatotoxicity by introduction of advanced in silico, in vitro, in vivo, and microphysiological system approaches to address the matter of safety of those products before they reach the market. •Herbal dietary supplement hepatotoxicity is on the rise.•Most prominent historical cases – Ephedra, Hydroxycut, and OxyELITE-Pro – are discussed.•A number of emerging products on the market are suspected to be hepatotoxic.•Advanced in silico, in vitro, in vivo, and microphysiological systems may aid in pre-market safety assessment.