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

Abstract

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.

Keywords: Botanicals; Dietary supplements; Hepatotoxicity; Microphysiological system; Phytochemicals; Safety assessment.

Fig. 1.

Selection of an appropriate model is the pillar of successful research. A 4-months old NZO/HltJ female mouse, weighing in at 93 g, the embodiment of a diet-independent obesity and fatty liver disease. This is an excellent model to investigate the efficacy and safety of products targeted for weight management, performance enhancement, and treatment of fatty liver disease.

Fig. 2.

Hepatocytes and sinusoidal endothelium in a two-cell liver-on-chip model. Primary human hepatocytes were seeded in one channel of an organ-on-chip system and human liver sinusoidal endothelial cells were seeded in the other. (A) Hepatocytes. (B) Sinusoidal endothelial cells. Dashes outline one representative cell in each channel. 400× magnification.