Evidence map›Paper›PMID 32140423›Full record

ReviewToxicology reports2020

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 and 16 more

Registry-linked trialOpen access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Toxicology reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05195918 (Dose Ranging Study of Oral Epigallocatechin-3-gallate), which is not on this map. Cited by 65 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 4 pooled it
19.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05195918 phase1completednot on this mapstarted 2023, after this paper: background citation

Dose Ranging Study of Oral Epigallocatechin-3-gallate (EGCG) Given Daily for 12 Weeks to Patients With Idiopathic Pulmonary Fibrosis (IPF) Evaluating Safety, PK Interactions With Standard of Care Drugs, and Biomarkers of Drug Effect

TypeinterventionalSponsorHal ChapmanRan2023 to 2026Enrolled50ConditionsIdiopathic Pulmonary FibrosisArmsEGCG 300 mg + Nintedanib, EGCG 300 mg + Pirfenidone, Placebo 2 capsules + Nintedanib or Pirfenidone, EGCG 600 mg + Nintedanib, EGCG 600 mg + Pirfenidone
3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 4 syntheses or guidelines pooled it, 156 citations in OpenAlex.

  1. Pooled it
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  13. Article
  14. Challenges in herbal-induced liver injury identification and prevention.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  15. Green Tea: Current Knowledge and Issues.Foods (Basel, Switzerland) · 2025
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 5 institutions in 1 country.

Hellen A Oketch-RabahU.S. Pharmacopeial Convention, Rockville, MD, USA.
Amy L RoeUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Cynthia V RiderUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Herbert L BonkovskyU.S. FDA Liaison to the USP GTEH EP (2015-2020 cycle).
Gabriel I GiancasproU.S. Pharmacopeial Convention, Rockville, MD, USA.
Victor NavarroUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Mary F PaineUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Joseph M BetzUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Robin J MarlesUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Steven CasperU.S. FDA Liaison to the USP GTEH EP (2015-2020 cycle).
Bill GurleyUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Scott A JordanUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Kan HeUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Mahendra P KapoorUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Theertham P RaoUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Averell H SherkerExpert Members of the Drug Induced Liver Injury Network (DILIN), USA.
Robert J FontanaExpert Members of the Drug Induced Liver Injury Network (DILIN), USA.
Simona RossiExpert Members of the Drug Induced Liver Injury Network (DILIN), USA.
Raj VuppalanchiU.S. FDA Liaison to the USP GTEH EP (2015-2020 cycle).
Leonard B SeeffExpert Members of the Drug Induced Liver Injury Network (DILIN), USA.
Andrew StolzExpert Members of the Drug Induced Liver Injury Network (DILIN), USA.
Jawad AhmadExpert Members of the Drug Induced Liver Injury Network (DILIN), USA.
Christopher KohExpert Members of the Drug Induced Liver Injury Network (DILIN), USA.
Jose SerranoExpert Members of the Drug Induced Liver Injury Network (DILIN), USA.
Tieraona Low DogUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
Richard KoUnited States Pharmacopeia Green Tea Hepatotoxicity Expert Panel (USP GTEH EP, 2015-2020 cycle), Rockville, MD, USA.
United States Pharmacopeial Convention · USUnited States Food and Drug Administration · USNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health · USUniversity of Michigan–Ann Arbor · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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: "

Indexed as

ADME, Absorption, distribution, metabolism, and excretionALP, alkaline phosphataseALT, alanine aminotransferaseAST, aspartate aminotransferaseAUC, area under the curveBw, body weightCAM, causality assessment methodCamellia sinensisC, CatechinCG, (+)‐catechin‐3‐gallateCIH, Concanavalin A-induced hepatitisCMC, chemistry, manufacturing, and controlsCOMT, catechol‐O‐methyltransferaseConA, Concanavalin ADietary supplementsDILI, drug‐induced liver injuryDILIN, Drug‐Induced Liver Injury NetworkDO, Diversity OutbredDSAE, JS3 USP Dietary Supplements Admission Evaluations Joint Standard-Setting SubcommitteeDS, Dietary SupplementEC, (–)‐epicatechinECG, (‐)‐epicatechin‐3‐gallateEFSA, European Food Safety AuthorityEGC, (–)‐epigallocatechinEGCG, (–)‐epigallocatechin‐3‐gallateFDA, United States Food and Drug AdministrationGC, (+)‐gallocatechinGCG, (–)‐gallocatechin‐3‐gallateGreen teaGreen tea extractGTE, green tea extractGT(E), green tea or green tea extractGTEH, EP Green Tea Extract Hepatotoxicity Expert PanelGT, green teaHDS, herbal dietary supplementHepatotoxicityHPMC, Hydroxypropyl methylcelluloseLD50, lethal dose, medianLFT(s), liver function test(s)Liver injuryLT(s), Liver test(s)MGTT, Minnesota Green Tea TrialMIDS, multi-ingredient dietary supplementMRL, maximum residue limitNAA, N-acetyl aspartateNIDDK, National Institute of Diabetes and Digestive and Kidney DiseasesNIH, National Institutes of HealthNOAEL, no observed adverse effect levelNTP, National Toxicology ProgramOSM, online supplementary materialPAs, Pyrrolizidine AlkaloidsPD-1, Programmed death domain-1PDGTE, powdered decaffeinated green tea extractPK/PD, pharmacokinetics and pharmacodynamicsRUCAM, Roussel Uclaf Causality Assessment MethodSIDS, single-ingredient dietary supplementTGF-beta, Transforming growth factor betaUSP, United States Pharmacopeiaγ-GT, Gamma-glutamyl transferase

Identifiers

PMID32140423
PMCPMC7044683
OpenAlexW3006339909

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.