Toxicology Reports (Jan 2020)
United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts
- Hellen A. Oketch-Rabah,
- Amy L. Roe,
- Cynthia V. Rider,
- Herbert L. Bonkovsky,
- Gabriel I. Giancaspro,
- Victor Navarro,
- Mary F. Paine,
- Joseph M. Betz,
- Robin J. Marles,
- Steven Casper,
- Bill Gurley,
- Scott A. Jordan,
- Kan He,
- Mahendra P. Kapoor,
- Theertham P. Rao,
- Averell H. Sherker,
- Robert J. Fontana,
- Simona Rossi,
- Raj Vuppalanchi,
- Leonard B. Seeff,
- Andrew Stolz,
- Jawad Ahmad,
- Christopher Koh,
- Jose Serrano,
- Tieraona Low Dog,
- Richard Ko
Affiliations
- Hellen A. Oketch-Rabah
- U.S. Pharmacopeial Convention, Rockville, MD, USA; United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA; Corresponding author at: 12601 Twinbrook Pkwy, Rockville, MD, 20852, USA.
- Amy L. Roe
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA; Vice Chair, (USP GTEH EP, 2015-2020 cycle), USA
- Cynthia V. Rider
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Herbert L. Bonkovsky
- U.S. FDA Liaison to the USP GTEH EP (2015-2020 cycle), USA; Section on Gastroenterology & Hepatology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
- Gabriel I. Giancaspro
- U.S. Pharmacopeial Convention, Rockville, MD, USA; United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Victor Navarro
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA; Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Mary F. Paine
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA; Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA
- Joseph M. Betz
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Robin J. Marles
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Steven Casper
- U.S. FDA Liaison to the USP GTEH EP (2015-2020 cycle), USA
- Bill Gurley
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Scott A. Jordan
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Kan He
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Mahendra P. Kapoor
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Theertham P. Rao
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Averell H. Sherker
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA; Liver Diseases Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 6707 Democracy Blvd., Bethesda, MD, USA
- Robert J. Fontana
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA
- Simona Rossi
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Raj Vuppalanchi
- U.S. FDA Liaison to the USP GTEH EP (2015-2020 cycle), USA
- Leonard B. Seeff
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Andrew Stolz
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Jawad Ahmad
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA
- Christopher Koh
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA; Liver Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, 10 Center Drive, Building 10, Rm 9B-16, Bethesda, MD, 20892, USA
- Jose Serrano
- Expert Members of the Drug Induced Liver Injury Network (DILIN), USA; Liver Diseases Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 6707 Democracy Blvd., Bethesda, MD, USA
- Tieraona Low Dog
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA
- Richard Ko
- United States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA; Chair (USP GTEH EP, 2015-2020 cycle), USA
- Journal volume & issue
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Vol. 7
pp. 386 – 402
Abstract
As part of the United States Pharmacopeia’s ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities, but no evidence of their involvement in GTE-induced liver injury was found during this review. GTE catechin profiles vary significantly with manufacturing processes. Animal and human data indicate that repeated oral administration of bolus doses of GTE during fasting significantly increases bioavailability of catechins, specifically EGCG, possibly involving saturation of first-pass elimination mechanisms. Toxicological studies show a hepatocellular pattern of liver injury. Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140 mg to ∼1000 mg/day and substantial inter-individual variability in susceptibility, possibly due to genetic factors. Based on these findings, USP included a cautionary labeling requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: “Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes).”
