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Digestive Diseases and Sciences

, Volume 58, Issue 9, pp 2682–2690 | Cite as

Catechins in Dietary Supplements and Hepatotoxicity

  • Victor J. NavarroEmail author
  • Herbert L. Bonkovsky
  • Sun-Il Hwang
  • Maricruz Vega
  • Huiman Barnhart
  • Jose Serrano
Original Paper

Abstract

Background

Many herbal dietary supplements (HDS) contain green tea extract (GTE) and its component catechins, although their presence may not always be indicated on the product label.

Purpose

Because GTE and catechins have been implicated in human hepatotoxicity in several case reports, our objective was to determine whether catechins were present in HDS that were implicated in hepatotoxicity, even if not identified among the labeled ingredients, and whether these compounds could be associated with liver injury.

Methods

We assayed 97 HDS implicated in human hepatotoxicity for catechins.

Results

We found that 29 of 73 HDS (39.7 %) that did not identify GTE or any of its component catechins on their label contained catechins. Among patients with confirmed hepatotoxicity, there was no statistically significant association between the presence of catechin or the dose consumed and liver injury causality score, severity, or pattern of liver injury. Catechin levels tended to be highest in products used for weight loss, although catechin concentrations were low in most products.

Conclusions

Many HDS commonly contain catechins that are implicated in hepatotoxicity, although their presence may not be indicated on the product label. Although our results did not establish an association between GTE or catechins with hepatotoxicity, they highlight some of the many complexities and uncertainties that surround the attribution of drug-induced liver injury (DILI) to HDS.

Keywords

Green tea extract Hepatotoxin Contamination EGCG Hepatocellular jaundice 

Notes

Acknowledgments

This study was supported by the NIDDK, NIH. See website for a complete list of DILIN funding sources, DILIN sites, investigators, co-investigators, coordinators, and staff https://dilin.dcri.duke.edu/publications-1.

Conflict of interest

Victor J. Navarro, MD—Rottapharm/Madaus, consultant, research support. Herbert L. Bonkovsky, MD—Lundbeck S/A, consulting; Lundbeck S/A: speaking and teaching; Merck: grant/research support; Clinuvel, Inc: consulting; Clinuvel, Inc: grant/research support; Vertex: grant/research support; Amer Porphyria Foundation: advisory committees or review panels; Iron Disorders Institute: advisory committees or review panels; Iron Disorders Institute: board membership; Sun-Il Hwang, PhD; Maricruz Vega, MPH; Huiman Barnhart, PhD; and Jose Serrano, MD, PhD—no conflicts of interest.

Supplementary material

10620_2013_2687_MOESM1_ESM.doc (25 kb)
Supplementary material 1 (DOC 25 kb)

References

  1. 1.
    Qato DM, Alexander GC, Conti RM, Johnson M, Schumm P, Lindau ST. Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States. JAMA. 2008;300:2867–2878.PubMedCrossRefGoogle Scholar
  2. 2.
    US Food and Drug Administration. Dietary Supplements. Aug 2005. Available at http://www.fda.gov/food/dietarysupplements/default.htm. Accessed September 1, 2011.
  3. 3.
    Cole MR, Fetrow CW. Adulteration of dietary supplements. Am J Health Syst Pharm. 2003;60:1576–1580.PubMedGoogle Scholar
  4. 4.
    Adachi M, Saito H, Kobayashi H, et al. Hepatic injury in 12 patients taking the herbal weight loss aids Chaso or Onshido. Ann Intern Med. 2003;139:488–492.PubMedCrossRefGoogle Scholar
  5. 5.
    Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med. 1992;21:334–350.PubMedCrossRefGoogle Scholar
  6. 6.
    Isbrucker RA, Bausch J, Edwards JA, Wolz E. Safety studies on epigallocatechingallate (EGCG) preparations. Part 1: genotoxicity. Food Chem Toxicol. 2006;44:626–635.PubMedCrossRefGoogle Scholar
  7. 7.
    Isbrucker RA, Edwards JA, Wolz E, Davidovich A, Bausch J. Safety studies on epigallocatechingallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies. Food Chem Toxicol. 2006;44:636–650.PubMedCrossRefGoogle Scholar
  8. 8.
    Isbrucker RA, Edwards JA, Wolz E, Davidovich A, Bausch J. Safety studies on epigallocatechingallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. Food Chem Toxicol. 2006;44:651–661.PubMedCrossRefGoogle Scholar
  9. 9.
    Galati G, Lin A, Sultan AM, O’Brien PJ. Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic Biol Med. 2006;40:570–580.PubMedCrossRefGoogle Scholar
  10. 10.
    Takami S, Imai T, Hasumura M, Cho YM, Onose J, Hirose M. Evaluation of toxicity of green tea catechins with 90-day dietary administration to F344 rats. Food Chem Toxicol. 2008;46:2224–2229.PubMedCrossRefGoogle Scholar
  11. 11.
    Ullmann U, Haller J, Decourt JP, Girault N, Girault J, Richard-Caudron AS. A single ascending dose study of epigallocatechingallate in healthy volunteers. J Int Med Res. 2003;31:88–101.PubMedCrossRefGoogle Scholar
  12. 12.
    Pisters KM, Newman RA, Coldman B, et al. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol. 2001;19:1830–1838.PubMedGoogle Scholar
  13. 13.
    Gloro R, Hourmand-Ollivier I, Mosquet B, et al. Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea. Eur J Gastroenterol Hepatol. 2005;17:1135–1137.PubMedCrossRefGoogle Scholar
  14. 14.
    Jimenez-Saenz M, Martinez-Sanchez MC. Acute hepatitis associated with the use of green tea infusions. J Hepatol. 2006;44:616–617.PubMedCrossRefGoogle Scholar
  15. 15.
    Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med. 2006;144:68–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Molinari M, Watt KD, Kruszyna T, et al. Acute liver failure induced by green tea extracts: case report and review of the literature. Liver Transpl. 2006;12:1892–1895.PubMedCrossRefGoogle Scholar
  17. 17.
    Javaid A, Bonkovsky HL. Hepatotoxicity due to extracts of Chinese green tea (Camellia sinensis): a growing concern. J Hepatol. 2006;45:334–335.PubMedCrossRefGoogle Scholar
  18. 18.
    Chalasani N, et al. Causes, clinical features, and outcomes from a prospective study of drug induced liver injury in the United States. Gastroenterology. 2008;135:1924–1934.PubMedCrossRefGoogle Scholar
  19. 19.
    Fontana RJ, Watkins PB, Bonkovsky HL, et al. Drug-induced liver injury network (DILIN) prospective study: rationale, design and conduct. Drug Saf. 2009;32:55–68.PubMedCrossRefGoogle Scholar
  20. 20.
    Vega M, Vuppalanchi R, Bonkovsky H, et al. The US drug induced liver injury network: establishment of an herbal and dietary supplements (HDS) repository. Hepatology. 2011;54:528A (Abstract 341).Google Scholar
  21. 21.
    Hwang SI, Lee YY, Park JO, et al. Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method. Clin Chim Acta. 2011;412:2241–2247.PubMedCrossRefGoogle Scholar
  22. 22.
    US Food and Drug Administration. Warning on Hydroxycut Products. May 1, 2009. Available at http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm152152.htm. Accessed September 1, 2011.
  23. 23.
    Seddick M, Lucidarme D, Creusy C, Filoche B. Is exolise hepatotoxic? Gastroenterol Clin Biol. 2001;25:834–835.Google Scholar
  24. 24.
    Sarma DN, Barrett ML, Chavez ML, et al. Safety of green tea extracts: a systematic review by the US Pharmacopeia. Drug Saf. 2008;31:469–484.PubMedCrossRefGoogle Scholar
  25. 25.
    Lambert JD, Kennett MJ, Sang S, Reuhl KR, Ju J, Yang CS. Hepatotoxicity of high oral dose (−)-epigallocatechin-3-gallate in mice. Food Chem Toxicol. 2010;48:409–416.PubMedCrossRefGoogle Scholar
  26. 26.
    Brown JC, Jiang X. Prevalence of antibiotic-resistant bacteria in herbal products. J Food Prot. 2008;71:1486–1490.PubMedGoogle Scholar
  27. 27.
    Stickel F, Droz S, Patsenker E, Bogli-Stuber K, Aebi B, Leib SL. Severe hepatotoxicity following ingestion of Herbalife nutritional supplements contaminated with Bacillus subtilis. J Hepatol. 2009;50:111–117.PubMedCrossRefGoogle Scholar
  28. 28.
    Demeule M, Michaud-Levesque J, Annabi B, et al. Green tea catechin as novel antitumor and antiangiogenic. Curr Med Chem-Anti-Cancer Agents. 2002;2:441–463.CrossRefGoogle Scholar
  29. 29.
    Ciesek S, von Hahn T, Colpitts CC, et al. The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry. Hepatology. 2011;54:1947–1955.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Victor J. Navarro
    • 1
    Email author
  • Herbert L. Bonkovsky
    • 2
  • Sun-Il Hwang
    • 3
  • Maricruz Vega
    • 1
  • Huiman Barnhart
    • 4
  • Jose Serrano
    • 5
  1. 1.Division of HepatologyEinstein Medical CenterPhiladelphiaUSA
  2. 2.Medicine and ResearchCarolinas Medical Center, LBP CenterCharlotteUSA
  3. 3.Cannon Research CenterCarolinas Medical CenterCharlotteUSA
  4. 4.Department of Biostatistics and Bioinformatics, Duke University Medical CenterDuke Clinical Research InstituteDurhamUSA
  5. 5.National Institute of Diabetes and Digestive and Kidney DiseasesBethesdaUSA

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