Skip to main content

Advertisement

SpringerLink
Log in

Catechins in Dietary Supplements and Hepatotoxicity

  • Original Paper
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

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.

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. 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.

    Article  PubMed  CAS  Google Scholar 

  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. Cole MR, Fetrow CW. Adulteration of dietary supplements. Am J Health Syst Pharm. 2003;60:1576–1580.

    PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  5. Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med. 1992;21:334–350.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  14. Jimenez-Saenz M, Martinez-Sanchez MC. Acute hepatitis associated with the use of green tea infusions. J Hepatol. 2006;44:616–617.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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. Seddick M, Lucidarme D, Creusy C, Filoche B. Is exolise hepatotoxic? Gastroenterol Clin Biol. 2001;25:834–835.

    Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  26. Brown JC, Jiang X. Prevalence of antibiotic-resistant bacteria in herbal products. J Food Prot. 2008;71:1486–1490.

    PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Division of Hepatology, Einstein Medical Center, 5401 Old York Road, Suite 505, Philadelphia, PA, 19141, USA

    Victor J. Navarro & Maricruz Vega

  2. Medicine and Research, Carolinas Medical Center, LBP Center, MMP1, suite 600, 1000 Blythe Blvd, Charlotte, NC, 28236, USA

    Herbert L. Bonkovsky

  3. Cannon Research Center, Carolinas Medical Center, 1000 Blythe Blvd., Charlotte, NC, 28203, USA

    Sun-Il Hwang

  4. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, USA

    Huiman Barnhart

  5. National Institute of Diabetes and Digestive and Kidney Diseases, 2 Democracy Plaza, Room 657, MSC 5450, Bethesda, MD, 20892-5450, USA

    Jose Serrano

Authors
  1. Victor J. Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Herbert L. Bonkovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sun-Il Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maricruz Vega
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huiman Barnhart
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jose Serrano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victor J. Navarro.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 25 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Navarro, V.J., Bonkovsky, H.L., Hwang, SI. et al. Catechins in Dietary Supplements and Hepatotoxicity. Dig Dis Sci 58, 2682–2690 (2013). https://doi.org/10.1007/s10620-013-2687-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-013-2687-9

Keywords

Search

Navigation