Green Tea Extract as a Safe and Effective Dietary Supplement: Lessons Learned from Mice

Abstract Objectives Green tea extracts (GTEs) are common ingredients among dietary supplements marketed for weight loss and weight management. However, GTEs and their various catechin polyphenols have also been linked to a number of hepatotoxicity cases. Methods The purpose of this study was to investigate, using various mouse models, the hepato- and cardiotoxic potential of a well-characterized GTE; its ability to promote weight loss; and its effect on the gut microbiome. Results Gavaging GTE over a range of 1X–10X mouse equivalent doses (MED) for up to 2 weeks did not elicit significant histomorphological, physiological, biochemical or molecular alterations in the livers of lean B6C3F1 mice. Similarly, no evidence of hepato- or cardiotoxicity was noted when GTE was administered to obese NZO/HlLtJ mice for 8 weeks, either alone or in combination with caffeine (CAF) and/or exercise (EX). Eight weeks of GTE administration in combination with CAF resulted in significant body weight reduction in obese mice, which was further enhanced by EX. Furthermore, GTE/CAF combinations partially mitigated obesity-associated small and large droplet steatosis and decreased both portal and lobular inflammation, demonstrating hepatoprotective capabilities. Administration of GTE at MEDs comparable to those consumed by humans resulted in significant modulation of gut microflora, with increases in beneficial Akkermansia spp. among lean mouse phenotypes being most pronounced. This favorable change in the gut microbiome may provide a mechanistic link to weight loss management. Conclusions Results of this study demonstrate that appropriate doses of caffeinated GTE can serve as a useful adjunct in weight management strategies. Furthermore, clinically relevant doses of GTE/CAF combinations did not produce hepato- or cardiotoxicity, but rather show significant potential to promote liver health by reversing early signs of non-alcoholic fatty liver disease and hepatosteatosis. Funding Sources NIGMS 1P20 GM109005.