Safety assessment of the dietary supplement OxyELITE™ Pro (New Formula) in inbred and outbred mouse strains

•Dietary supplement OxyELITE Pro - New Formula (OEP-NF) was linked to severe liver injuries in the United States.•Hepatotoxicity of OEP-NF was assessed in outbred (CD-1) and inbred (B6C3F1) mouse strains.•OEP-NF produced histological, biochemical and molecular alterations that are characteristic to liver injury.•OEP-NF-induced weight loss was transitory, followed by body weight gain in all experimental groups.•These findings bolster concerns for the safety and efficacy of OEP-NF, and similar products, in humans.

Herbal dietary supplements have gained wide acceptance as alternatives to conventional therapeutic agents despite concerns regarding their efficacy and safety. In 2013, a spate of severe liver injuries across the United States was linked to the dietary supplement OxyELITE Pro-New Formula (OEP-NF), a multi-ingredient product marketed for weight loss and exercise performance enhancement. The principal goal of this study was to assess the hepatotoxic potential of OEP-NF in outbred and inbred mouse models. In an acute toxicity study, significant mortality was observed after administering 10X and 3X mouse-equivalent doses (MED) of OEP-NF, respectively. Increases in liver/body weight ratio, ALT and AST were observed in female B6C3F1 mice after gavaging 2X and 1.5X MED of OEP-NF. Similar findings were observed in a 90-day feeding study. These alterations were paralleled by altered expression of gene- and microRNA-signatures of hepatotoxicity, including Cd36, Nqo1, Aldoa, Txnrd1, Scd1 and Ccng1, as well as miR-192, miR-193a and miR-125b and were most pronounced in female B6C3F1 mice. Body weight loss, observed at week 1, was followed by weight gain throughout the feeding studies. These findings bolster safety and efficacy concerns for OEP-NF, and argue strongly for implementation of pre-market toxicity studies within the dietary supplement industry.