Skip to main content

Advertisement

SpringerLink
Log in

Hepatotoxicity from green tea: a review of the literature and two unpublished cases

  • Review Article
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To review the current literature on suspected green tea-related hepatic reactions and to describe two new cases reported within the framework of the Italian surveillance system of natural health products.

Results

A literature search of publication between 1999 and October 2008 retrieved 34 cases of hepatitis. Histological examination of the liver revealed inflammatory reactions, cholestasis, occasional steatosis, and necrosis. A positive dechallenge was reported in 29 cases. There was one reported death. A positive rechallenge occurred in seven cases (20%). In the two new cases, the causality assessment was judged as “possible” according to the RUCAM score.

Conclusions

Our analysis of the published case reports suggests a causal association between green tea and liver damage. The hepatotoxicity is probably due to (-)-epigallocatechin gallate or its metabolites which, under particular conditions related to the patient’s metabolism, can induce oxidative stress in the liver. In a few cases, toxicity related to concomitant medications could also be involved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bruneton J (1999) Pharmacognosy, phytochemistry, medicinal plants, 2nd edn. Lavoisier Publ, Paris

    Google Scholar 

  2. Dufresne CJ, Farnworth ER (2001) A review of latest research findings on the health promotion properties of tea. J Nutr Biochem 12:404–421

    Article  PubMed  CAS  Google Scholar 

  3. Wolfram S (2007) Effects of green tea and EGCG on cardiovascular and metabolic health. J Am Coll Nutr 26:373S–388S

    PubMed  CAS  Google Scholar 

  4. Shula Y (2007) Tea and cancer chemoprevention: a comprehensive review. Asian Pac J Cancer Prev 8:155–166

    Google Scholar 

  5. Kao YH, Chang HH, Lee MJ, Chen CL (2006) Tea, obesity, and diabetes. Mol Nutr Food Res 50:188–210

    Article  PubMed  CAS  Google Scholar 

  6. Menniti-Ippolito F, Mazzanti G, Santuccio C et al (2008) Surveillance of suspected adverse reactions to natural health products in Italy. Pharmacoepidemiol Drug Saf 17:626–635

    Article  PubMed  Google Scholar 

  7. Ben Yahia M, Mavier P, Metreau JM et al (1993) Chronic active hepatitis and cirrhosis induced by wild germander. Three cases. Gastroenterol Clin Biol 17:959–962

    PubMed  CAS  Google Scholar 

  8. Castot A, Larrey D (1992) Hepatitis observed during a treatment with a drug or tea containing Wild Germander. Evaluation of 26 cases reported to the Regional Centers of Pharmacovigilance. Gastroenterol Clin Biol 16:916–922

    PubMed  CAS  Google Scholar 

  9. Legoux JL, Maitre F, Labarriere D, Gargot D, Festin D, Causse X (1992) Cytolytic hepatitis and wild germander: a new case with reintroduction. Gastroenterol Clin Biol 16:813–815

    PubMed  CAS  Google Scholar 

  10. Danan G, Benichou C (1993) Causality assessment of adverse reactions to drugs–I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 46:1323–1330

    Article  PubMed  CAS  Google Scholar 

  11. Shim M, Saab S (2008) Severe hepatotoxicity due to Hydroxycut: a case report. Dig Dis Sci. doi:10.1007/s10620-008-0353-4

  12. Bjornsson E, Olsson R (2007) Serious adverse liver reactions associated with herbal weight-loss supplements. J Hepatol 47:295–297 author reply 297-298

    Article  PubMed  CAS  Google Scholar 

  13. Federico A, Tiso A, Loguercio C (2007) A case of hepatotoxicity caused by green tea. Free Radic Biol Med 43:474

    Article  PubMed  CAS  Google Scholar 

  14. Molinari M, Watt KD, Kruszyna T et al (2006) Acute liver failure induced by green tea extracts: case report and review of the literature. Liver Transpl 12:1892–1895

    Article  PubMed  Google Scholar 

  15. Javaid A, Bonkovsky HL (2006) Hepatotoxicity due to extracts of Chinese green tea (Camellia sinensis): a growing concern. J Hepatol 45:334–335 author reply 335–336

    Article  PubMed  CAS  Google Scholar 

  16. Martinez-Sierra C, Rendon Unceta P, Martin Herrera L (2006) Acute hepatitis after green tea ingestion. Med Clin (Barc) 127:119

    Article  Google Scholar 

  17. Jimemez-Saenz M, Martinez-Sanchez C (2006) Acute hepatitis associated with the use of green tea infusions. J Hepatol 44:616–617

    Article  CAS  Google Scholar 

  18. Bonkovsky HL (2006) Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med 144:68–71 Erratum in: Ann Intern Med 144:380

    PubMed  Google Scholar 

  19. Mathieu N, Bouallegue L, Mognol P, Vallot T, Soule JC (2005) Hepatic toxicity probably due to X-elles used in phytotherapy. Gastroenterol Clin Biol 29:1188–1189

    PubMed  Google Scholar 

  20. Gloro R, Hourmand-Ollivier I, Mosquet B et al (2005) Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea. Eur J Gastroenterol Hepatol 17:1135–1137

    Article  PubMed  Google Scholar 

  21. Abu el Wafa Y, Benavente Fernandez A, Talavera Fabuel A, Perez Ramos MA, Ramos-Clemente JI (2005) Acute hepatitis induced by Camellia sinensis (green tea). An Med Interna 22:298

    PubMed  CAS  Google Scholar 

  22. Stevens T, Qadri A, Zein NN (2005) Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med 142:477–478

    PubMed  Google Scholar 

  23. Porcel JM, Beilsa S, Madroñero AB (2005) Hepatotoxicity associated with green tea extracts (electronic letters). Available online at http://www.annals.org/cgi/eletters/142/6/477#1669

  24. Garcia-Moran S, Saez-Royuela F, Gento E, Lopez Morante A, Arias L (2004) Acute hepatitis associated with Camellia tea and Orthosiphon stamineus ingestion. Gastroenterol Hepatol 27:559–560

    Article  PubMed  CAS  Google Scholar 

  25. Lau G, Lo DS, Yao YJ, Leong HT, Chan CL, Chu SS (2004) A fatal case of hepatic failure possibly induced by nitrosofenfluramine: a case report. Med Sci Law 44:252–263

    PubMed  Google Scholar 

  26. Dueñas Sadornil C, Fabregas Puigtio S, Durandez R (2004) Hepatotoxicity due to Camelia sinensis. Med Clin (Barc) 122:677–678

    Article  Google Scholar 

  27. Peyrin-Biroulet L, Petitpain N, Kalt P et al (2004) Probable hepatoxicity from epigallocatecol gallate used for phytotherapy. Gastroenterol Clin Biol 28:404–406

    Article  PubMed  Google Scholar 

  28. Vial T, Bernard G, Lewden B, Dumortier J, Descotes J (2003) Acute hepatitis due to Exolise, a Camellia sinensis-derived drug. Gastroenterol Clin Biol 27:1166–1167

    PubMed  Google Scholar 

  29. Pedros C, Cereza G, Garcia N, Laporte JR (2003) Liver toxicity of Camellia sinensis dried etanolic extract. Med Clin (Barc) 121:598–599

    Article  Google Scholar 

  30. Bajaj J, Knox JF, Komorowski R, Saeian K (2003) The irony of herbal hepatitis: Ma-Huang-induced hepatotoxicity associated with compound heterozygosity for hereditary hemochromatosis. Dig Dis Sci 48:1925–1928

    Article  PubMed  Google Scholar 

  31. Kanda T, Yokosuka O, Tada M et al (2003a) N-nitroso-fenfluramine hepatotoxicity resembling chronic hepatitis. J Gastroenterol Hepatol 18:999–1000

    Article  PubMed  Google Scholar 

  32. Kanda T, Yokosuka O, Okada O, Suzuki Y, Saisho H (2003b) Severe hepatotoxicity associated with Chinese diet product ‘Onshidou-Genbi-Kounou’. J Gastroenterol Hepatol 18:354–355

    Article  PubMed  Google Scholar 

  33. Thiolet C, Mennecier D, Bredin C et al (2002) Acute cytolysis induced by Chinese tea. Gastroenterol Clin Biol 26:939–940

    PubMed  Google Scholar 

  34. Seddik M, Lucidarme D, Creusy C, Filoche B (2001) Is Exolise hepatotoxic? Gastroenterol Clin Biol 25:834–835

    PubMed  CAS  Google Scholar 

  35. Gavilan JC, Bermudez FJ, Salgado F, Pena D (1999) Phytotherapy and hepatitis. Rev Clin Esp 199:693–694

    PubMed  CAS  Google Scholar 

  36. Aithal GP, Day CP (2007) Nonsteroidal anti-inflammatory drug-induced hepatotoxicity. Clin Liver Dis 11:563–575

    Article  PubMed  Google Scholar 

  37. Gomez-Lechon MJ, Ponsoda X, O’Connor E, Donato T, Jover R, Castell JV (2003) Diclofenac induces apoptosis in hepatocytes. Toxicol In Vitro 17:675–680

    Article  PubMed  CAS  Google Scholar 

  38. Larson AM (2007) Acetaminophen hepatotoxicity. Clin Liver Dis 11:525–548

    Article  PubMed  Google Scholar 

  39. Magnin G, de Meeus JB, Sarfati R, Chaouchi O, Paillat A (1996) Hepatic cytolysis caused by tocolytic treatment using micronized natural progesterone. Presse Med 25:102–105

    PubMed  CAS  Google Scholar 

  40. Altintas E, Oguz D, Kacar S, Ozderin Y, Sezgin O, Zengin NI (2004) Dydrogesterone-induced hepatitis and autoimmune haemolytic anemia. Turk J Gastroenterol 15:49–52

    PubMed  Google Scholar 

  41. Yuen YP, Lai CK, Poon WT, Ng SW, Chan AY, Mak TW (2007) Adulteration of over-the-counter slimming products with pharmaceutical analogue—an emerging threat. Hong Kong Med J 13:216–220

    PubMed  CAS  Google Scholar 

  42. Bun SS, Bun H, Guédon D, Rosier C, Ollivier E (2006) Effect of green tea extracts on liver functions in Wistar rats. Food Chem Toxicol 44:1108–1113

    Article  PubMed  CAS  Google Scholar 

  43. Chow HH, Hakim IA, Vining DR et al (2006) Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer Epidemiol Biomarkers Prev 15:2473–2476

    Article  PubMed  CAS  Google Scholar 

  44. Donovan JL, Chavin KD, Devane CL et al (2004) Green tea (Camellia sinensis) extract does not alter cytochrome P450 3A4 or 2D6 activity in healty volunteers. Drug Metab Dispos 32:906–908

    Article  PubMed  CAS  Google Scholar 

  45. Jimenez-Saenz M, Martinez-Sanchez C (2007) Green tea extracts and acute liver failure: the need for caution in their use and diagnostic assessment. Liver Transpl 13:1067

    Article  PubMed  Google Scholar 

  46. Goodin MG, Bray BJ, Rosengreen RJ (2006) Sex- and strain-dependent effects of epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) in the mouse. Food Chem Toxicol 44:1496–1504

    Article  PubMed  CAS  Google Scholar 

  47. Nakagawa K, Okuda S, Miyazawa T (1997) Dose-dependent incorporation of tea catechins, (-)-epigallocatechin-3-gallate and (-)-epigallocatechin into human plasma. Biosci Biotechnol Biochem 61:1981–1985

    Article  PubMed  CAS  Google Scholar 

  48. Isbruker RA, Edwards JA, Wolz E, Davidovich A, Bausch J (2006) Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies. Food Chem Toxicol 44:636–650

    Article  CAS  Google Scholar 

  49. Chow HH, Hakim IA, Vining DR et al (2005) Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals. Clin Cancer Res 11:4627–4633

    Article  PubMed  CAS  Google Scholar 

  50. Ullmann U, Haller J, Decourt JP et al (2003) A single ascending dose study of epigallocatechin gallate in healthy volunteers. J Int Med Res 31:88–101

    PubMed  CAS  Google Scholar 

  51. Lambert JD, Lee MJ, Lu H et al (2003) Epigallocatechin-3-gallate is absorbed but extensively glucuronidated following oral administration to mice. J Nutr 133:4172–4177

    PubMed  CAS  Google Scholar 

  52. Takami S, Imai T, Hasumura M, Cho YM, Onose J, Hirose M (2008) Evaluation of toxicity of green tea catechins with 90-day dietary administration to F344 rats. Food Chem Toxicol 46:2224–2229

    Article  PubMed  CAS  Google Scholar 

  53. Galati G, Lin A, Sultan AM, O’Brien PJ (2006) Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic Biol Med 40:570–580

    Article  PubMed  CAS  Google Scholar 

  54. Schmidt M, Schmitz HJ, Baumgart A et al (2005) Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture. Food Chem Toxicol 43:307–314

    Article  PubMed  CAS  Google Scholar 

  55. Sang S, Hou Z, Lambert JD, Yang CS (2005) Redox properties of tea polyphenols and related biological activities. Antioxid Redox Signal 7:1704–1714

    Article  PubMed  CAS  Google Scholar 

  56. Sang S, Lambert JD, Hong J et al (2005) Synthesis and structure identification of thiol conjugates of (-)-epigallocatechin gallate and their urinary levels in mice. Chem Res Toxicol 18:1762–1769

    Article  PubMed  CAS  Google Scholar 

  57. Lambert JD, Sang S, Yang CS (2007) Possible controversy over dietary polyphenols: benefits vs risks. Chem Res Toxicol 20:583–585

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Sapienza, University of Rome, P.le Aldo Moro, 5, 00185, Rome, Italy

    Gabriela Mazzanti & Sabina Mastrangelo

  2. National Center for Epidemiology, National Institute of Health, Rome, Italy

    Francesca Menniti-Ippolito & Roberto Raschetti

  3. Poison Control Center, Niguarda Ca’ Granda Hospital, Milan, Italy

    Paola Angela Moro & Federica Cassetti

  4. Pharmacovigilance Unit, Italian Medicines Agency, Rome, Italy

    Carmela Santuccio

Authors
  1. Gabriela Mazzanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Menniti-Ippolito
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paola Angela Moro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Federica Cassetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberto Raschetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carmela Santuccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sabina Mastrangelo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriela Mazzanti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mazzanti, G., Menniti-Ippolito, F., Moro, P.A. et al. Hepatotoxicity from green tea: a review of the literature and two unpublished cases. Eur J Clin Pharmacol 65, 331–341 (2009). https://doi.org/10.1007/s00228-008-0610-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-008-0610-7

Keywords

Search

Navigation