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Hepatotoxicity of green tea: an update

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Abstract

Green tea (GT), obtained from the leaves of Camellia sinensis (L.) Kuntze (Fam. Theaceae), is largely used for its potential health benefits such as reduction in risk of cardiovascular diseases and weight loss. Nevertheless, it is suspected to induce liver damage. Present work reviews the hepatic adverse reactions associated with GT-based herbal supplements, published by the end of 2008 to March 2015. A systematic research was carried out on PubMed, MedlinePlus, Scopus and Google Scholar databases, without any language restriction. Moreover, some accessible databases on pharmacovigilance or phytovigilance were consulted. The causality assessment was performed using the CIOMS/RUCAM score. Nineteen cases of hepatotoxicity related to the consumption of herbal products containing GT were identified. The hepatic reactions involved mostly women (16/19); the kind of liver damage was generally classified as hepatocellular (16/19). The causality assessment between consumption of herbal preparation and hepatic reaction resulted as probable in eight cases and as possible in eleven cases. In seven cases, patients used preparations containing only GT, while twelve reactions involved patients who took multicomponent preparations (MC). The reactions induced by GT had a generally long latency (179.1 ± 58.95 days), and the outcome was always resolution, with recovery time of 64.6 ± 17.78 days. On the contrary, liver injury associated with MC had a shorter latency (44.7 ± 13.85 days) and was more serious in four cases that required liver transplantation and, when resolution occurred, the recovery time was longer (118.9 ± 38.79). MC preparations contained numerous other components, many of which are suspected to induce liver damage, so it is difficult to ascribe the toxicity to one specific component, e.g., GT. Present data confirm a certain safety concern with GT, even if the number of hepatic reactions reported is low considering the great extent of use of this supplement. The mechanism of GT hepatotoxicity remains unclear, but factors related to the patient are becoming predominant. A major safety concern exists when GT is associated with other ingredients that can interact between them and with GT, enhancing the risk of liver damage. Patients should be discouraged from using herbal or dietary supplements containing complex mixtures and should be encouraged to use herbal and dietary supplement possibly under supervision of healthcare professionals.

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References

  • Actis GC, Bugianesi E, Ottobrelli A, Rizzetto M (2007) Fatal liver failure following food supplements during chronic treatment with montelukast. Dig Liver Dis 39:953–955. doi:10.1016/j.dld.2006.10.002

    CAS  PubMed  Google Scholar 

  • Amariles P, Angulo N, Agudelo-Agudelo J, Gaviria G (2009) Hepatitis associated with aqueous green tea infusions: a case study. Farm Hosp 33:289–291. doi:10.1016/S1130-6343(09)72471-7

    CAS  PubMed  Google Scholar 

  • Anderson RA (1998) Effects of chromium on body composition and weight loss. Nutr Rev 56:266–270. doi:10.1111/j.1753-4887.1998.tb01763.x

    CAS  PubMed  Google Scholar 

  • Andrade RJ, Lucena MI, Fernández MC, Vega JL, García-Cortés M, Casado M, Guerrero-Sanchez E, Pulido-Fernandez F (2002) Cholestatic hepatitis related to use of irbesartan: a case report and a literature review of angiotensin II antagonist-associated hepatotoxicity. Eur J Gastroenterol Hepatol 14:887–890. doi:10.1097/00042737-200208000-00014

    PubMed  Google Scholar 

  • Arimone Y, Bégaud B, Miremont-Salamé G, Fourrier-Réglat A, Moore N, Molimard M, Haramburu F (2005) Agreement of expert judgment in causality assessment of adverse drug reactions. Eur J Clin Pharmacol 61:169–173. doi:10.1007/s00228-004-0869-2

    PubMed  Google Scholar 

  • Arroyo-Martinez Q, Sáenz MJ, Argüelles Arias F, Acosta MS (2011) Lycium barbarum: a new hepatotoxic “natural” agent? Dig Liver Dis 43:749. doi:10.1016/j.dld.2011.04.010

    PubMed  Google Scholar 

  • Arzenton E, Magro L, Paon V, Capra F, Apostoli P, Guzzo F, Conforti A, Leone R (2014) Acute epatitis caused by green tea infusion: a case report. Adv Pharmacoepidemiol Drug Saf 3:170. doi:10.4172/2167-1052.1000170

    Google Scholar 

  • Bardia A, Nisly NL, Zimmerman MB, Gryzlak BM, Wallace RB (2007) Use of herbs among adults based on evidence-based indications: findings from the National Health Interview Survey. Mayo Clin Proc 82:561–566. doi:10.4065/82.5.561

    PubMed Central  PubMed  Google Scholar 

  • Belfrage B, Malmström R (2008) Several cases of liver affected by Aloe vera. Lakartidningen 105:45

    PubMed  Google Scholar 

  • Benichou C, Danan G, Flahault A (1993) Causality assessment of adverse reactions to drugs–II. An original model for validation of drug causality assessment methods: case reports with positive rechallenge. J Clin Epidemiol 46:1331–1336. doi:10.1016/0895-4356(93)90102-7

    CAS  PubMed  Google Scholar 

  • Bergman J, Schjøtt J (2009) Hepatitis caused by Lotus-f3? Basic Clin Pharmacol Toxicol 104:414–416. doi:10.1111/j.1742-7843.2009.00385.x

    CAS  PubMed  Google Scholar 

  • Boehm K, Borrelli F, Ernst E, Habacher G, Hung SK, Milazzo S, Horneber M (2009) Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Rev 8:CD005004. doi:10.1002/14651858.CD005004.pub2

    Google Scholar 

  • Bottenberg MM, Wall GC, Harvey RL, Habib S (2007) Oral Aloe vera-induced hepatitis. Ann Pharmacother 41:1740–1743. doi:10.1345/aph.1K132

    PubMed  Google Scholar 

  • Bunchorntavakul C, Reddy KR (2013) Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther 37:3–17. doi:10.1111/apt.12109

    CAS  PubMed  Google Scholar 

  • Butt MS, Ahmad RS, Sultan MT, Qayyum MM, Naz A (2015) Green tea and anticancer perspectives: updates from last decade. Crit Rev Food Sci Nutr 55:792–805. doi:10.1080/10408398.2012.680205

    CAS  PubMed  Google Scholar 

  • Cavaliere C, Rea C, Lynch ME, Blumenthal M (2010) Herbal supplement sales rise in all channels in 2009. HerbalGram 86:62–65

    Google Scholar 

  • Cerulli J, Grabe DW, Gauthier I, Malone M, McGoldrick MD (1998) Chromium picolinate toxicity. Ann Pharmacother 32:428–431. doi:10.1345/aph.17327

    CAS  PubMed  Google Scholar 

  • Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J, Drug Induced Liver Injury Network (DILIN) (2008) Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 135: 1924–1934, 1934.e1–1934.e4. doi: 10.1053/j.gastro.2008.09.011

  • Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ (2014) ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 109:950–966. doi:10.1038/ajg.2014.131

    PubMed  Google Scholar 

  • Chang CH, Chang YC, Lee YC, Liu YC, Chuang LM, Lin JW (2015) Severe hepatic injury associated with different statins in patients with chronic liver disease: a nationwide population-based cohort study. J Gastroenterol Hepatol 30:155–162. doi:10.1111/jgh.12657

    CAS  PubMed  Google Scholar 

  • Chauhan B, Kumar G, Kalam N, Ansari SH (2013) Current concepts and prospects of herbal nutraceutical: a review. J Adv Pharm Technol Res 4:4–8. doi:10.4103/2231-4040.107494

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chow HH, Hakim IA, Vining DR, Crowell JA, Ranger-Moore J, Chew WM, Celaya CA, Rodney SR, Hara Y, Alberts DS (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. doi:10.1158/1078-0432.CCR-04-2549

    CAS  PubMed  Google Scholar 

  • Church RJ, Gatti DM, Urban TJ, Long N, Yang X, Shi Q, Eaddy JS, Mosedale M, Ballard S, Churchill GA, Navarro V, Watkins PB, Threadgill DW, Harrill AH (2015) Sensitivity to hepatotoxicity due to epigallocatechin gallate is affected by genetic background in diversity outbred mice. Food Chem Toxicol 76:19–26. doi:10.1016/j.fct.2014.11.008

    CAS  PubMed  Google Scholar 

  • Curciarello J, De Ortúzar S, Borzi S, Bosia D (2008) Severe acute hepatitis associated with intake of Aloe vera tea. Gastroenterol Hepatol 31:436–438. doi:10.1157/13125590

    PubMed  Google Scholar 

  • 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. doi:10.1016/0895-4356(93)90101-6

    CAS  PubMed  Google Scholar 

  • Dela Cruz AC, Patel TT, Maynard E, Shah M, Lee EY, Angulo P (2014) Fulminant liver failure secondary to “Saba appetite control and energy” weight loss supplement. Gastroenterology 146:S-1002. doi:10.1016/S0016-5085(14)63644-1

    Google Scholar 

  • Denison HJ, Jameson KA, Syddall HE, Dennison EM, Cooper C, Sayer AA, Robinson SM (2012) Patterns of dietary supplement use among older men and women in the UK: findings from the Hertfordshire Cohort Study. J Nutr Health Aging 16:307–311. doi:10.1007/s12603-012-0016-1

    CAS  PubMed  Google Scholar 

  • Dias TR, Alves MG, Tomás GD, Socorro S, Silva BM, Oliveira PF (2014) White tea as a promising antioxidant medium additive for sperm storage at room temperature: a comparative study with green tea. J Agric Food Chem 62:608–617. doi:10.1021/jf4049462

    CAS  PubMed  Google Scholar 

  • Dong H, Slain D, Cheng J, Ma W, Liang W (2014) Eighteen cases of liver injury following ingestion of Polygonum multiflorum. Complement Ther Med 22:70–74. doi:10.1016/j.ctim.2013.12.008

    PubMed  Google Scholar 

  • Douros A, Kauffmann W, Bronder E, Klimpel A, Garbe E, Kreutz R (2013) Ramipril-induced liver injury: case report and review of the literature. Am J Hypertens 26:1070–1075. doi:10.1093/ajh/hpt090

    CAS  PubMed  Google Scholar 

  • Egras AM, Hamilton WR, Lenz TL, Monaghan MS (2011) An evidence-based review of fat modifying supplemental weight loss products. J Obes. doi:10.1155/2011/297315

    PubMed Central  PubMed  Google Scholar 

  • Ehrenpreis ED, Kulkarni P, Burke C (2013) What gastroenterologists should know about the gray market, herbal remedies, and compounded pharmaceuticals and their regulation by the Food and Drug Administration. Am J Gastroenterol 108:642–646. doi:10.1038/ajg.2012.348

    PubMed  Google Scholar 

  • Elouni B, Ben Salem C, Zamy M, Ganne N, Beaugrand M, Bouraoui K, Biour M (2010) Cytolytic hepatitis possibly related to levonorgestrel/ethinylestradiol oral contraceptive use: 2 case reports. Ann Pharmacother 44:2035–2037. doi:10.1345/aph.1P201

    PubMed  Google Scholar 

  • Ernst E, De Smet PA, Shaw D, Murray V (1998) Traditional remedies and the “test of time”. Eur J Clin Pharmacol 54:99–100. doi:10.1007/s002280050428

    CAS  PubMed  Google Scholar 

  • Fan X, Chen P, Jiang Y, Wang Y, Tan H, Zeng H, Wang Y, Qu A, Gonzalez FJ, Huang M, Bi H (2015) Therapeutic efficacy of Wuzhi tablet (Schisandra sphenanthera extract) on acetaminophen-induced hepatotoxicity through a mechanism distinct from N-acetylcysteine. Drug Metab Dispos 43:317–324. doi:10.1124/dmd.114.062067

    CAS  PubMed  Google Scholar 

  • FDA (2013) DMAA in Dietary Supplements. US Food and Drug Administration. http://www.fda.gov/Food/DietarySupplements/QADietarySupplements/ucm346576.htm. Accessed 5 Mar 2015

  • FDA Warns Consumers to Stop Using Hydroxycut Products. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149575.htm. Accessed 31 Mar 2015

  • Fernández J, Navascués C, Albines G, Franco L, Pipa M, Rodríguez M (2014) Three cases of liver toxicity with a dietary supplement intended to stop hair loss. Rev Esp Enferm Dig 106:552–555

    PubMed  Google Scholar 

  • Fong TL, Klontz KC, Canas-Coto A, Casper SJ, Durazo FA, Davern TJ II, Hayashi P, Lee WM, Seeff LB (2010) Hepatotoxicity due to hydroxycut: a case series. Am J Gastroenterol 105:1561–1566. doi:10.1038/ajg.2010.5

    PubMed  Google Scholar 

  • Foti RS, Dickmann LJ, Davis JA, Greene RJ, Hill JJ, Howard ML, Pearson JT, Rock DA, Tay JC, Wahlstrom JL, Slatter JG (2008) Metabolism and related human risk factors for hepatic damage by usnic acid containing nutritional supplements. Xenobiotica 38:264–280. doi:10.1080/00498250701802514

    CAS  PubMed  Google Scholar 

  • Franco M, Monmany J, Domingo P, Turbau M (2012) Autoimmune hepatitis triggered by consumption of Goji berries. Med Clin 139:320–321. doi:10.1016/j.medcli.2012.02.009

    Google Scholar 

  • Frédérich M, Wauters JN, Tits M, Jason C, de Tullio P, Van der Heyden Y, Fan G, Angenot L (2011) Quality assessment of Polygonum cuspidatum and Polygonum multiflorum by 1H NMR metabolite fingerprinting and profiling analysis. Planta Med 77:81–86. doi:10.1055/s-0030-1250132

    PubMed  Google Scholar 

  • Gad AS, Khadrawy YA, El-Nekeety AA, Mohamed SR, Hassan NS, Abdel-Wahhab MA (2011) Antioxidant activity and hepatoprotective effects of whey protein and Spirulina in rats. Nutrition 27:582–589. doi:10.1016/j.nut.2010.04.002

    CAS  PubMed  Google Scholar 

  • 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. doi:10.1016/j.freeradbiomed.2005.09.014

    CAS  PubMed  Google Scholar 

  • Gallo E, Maggini V, Berardi M, Pugi A, Notaro R, Talini G, Vannozzi G, Bagnoli S, Forte P, Mugelli A, Annese V, Firenzuoli F, Vannacci A (2013) Is green tea a potential trigger for autoimmune hepatitis? Phytomedicine 20:1186–1189. doi:10.1016/j.phymed.2013.07.004

    CAS  PubMed  Google Scholar 

  • Garcia-Alvarez A, Egan B, de Klein S, Dima L, Maggi FM, Isoniemi M, Ribas-Barba L, Raats MM, Meissner EM, Bade M, Bruno F, Salmenhaara M, Milà-Villarroel R, Knaze V, Hodgkins C, Marculescu A, Uusitalo L, Restani P, Serra-Majem L (2014) Usage of plant food supplements across six European countries: findings from the PlantLIBRA Consumer Survey. PLoS One 9:e92265. doi:10.1371/journal.pone.0092265

    PubMed Central  PubMed  Google Scholar 

  • Ghabril M, Bonkovsky HL, Kum C, Davern T, Hayashi PH, Kleiner DE, Serrano J, Rochon J, Fontana RJ, Bonacini M, US Drug-Induced Liver Injury Network (2013) Liver injury from tumor necrosis factor-α antagonists: analysis of thirty-four cases. Clin Gastroenterol Hepatol 11(558–564):e3. doi:10.1016/j.cgh.2012.12.025

    PubMed  Google Scholar 

  • Gloro R, Hourmand-Ollivier I, Mosquet B, Mosquet L, Rousselot P, Salamé E, Piquet MA, Dao T (2005) Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea. Eur J Gastroenterol Hepatol 17:1135–1137. doi:10.1097/00042737-200510000-00021

    PubMed  Google Scholar 

  • Graziadei IW, Joseph JJ, Wiesner RH, Therneau TM, Batts KP, Porayko MK (1998) Increased risk of chronic liver failure in adults with heterozygous alpha1-antitrypsin deficiency. Hepatol 28:1058–1063. doi:10.1002/hep.510280421

    CAS  Google Scholar 

  • Grube B, Chong PW, Lau KZ, Orzechowski HD (2013) A natural fiber complex reduces body weight in the overweight and obese: a double-blind, randomized, placebo-controlled study. Obesity 21:58–64. doi:10.1002/oby.20244

    CAS  PubMed Central  PubMed  Google Scholar 

  • Guo L, Shi Q, Fang JL, Mei N, Ali AA, Lewis SM, Leakey JE, Frankos VH (2008) Review of usnic acid and Usnea barbata toxicity. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 26:317–338. doi:10.1080/10590500802533392

    CAS  PubMed  Google Scholar 

  • Gürgen S, Yücel A, Karakuş A, Ceçen D, Ozen G, Koçtürk S (2014) Usage of whey protein may cause liver damage via inflammatory and apoptotic responses. Hum Exp Toxicol. doi:10.1177/0960327114556787

    PubMed  Google Scholar 

  • Haimowitz S, Hsieh J, Shcherba M, Averbukh Y (2015) Liver failure after hydroxycut™ use in a patient with undiagnosed hereditary coproporphyria. J Gen Intern Med. doi:10.1007/s11606-014-3153-x

    PubMed  Google Scholar 

  • Hayashi PH, Barnhart HX, Fontana RJ, Chalasani N, Davern TJ, Talwalkar JA, Reddy KR, Stolz AA, Hoofnagle JH, Rockey DC (2014) Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the Drug-Induced Liver Injury Network (DILIN). Liver Int. doi:10.1111/liv.12540

    PubMed  Google Scholar 

  • Huang L, Zhao H, Huang B, Zheng C, Peng W, Qin L (2011) Acanthopanax senticosus: review of botany, chemistry and pharmacology. Pharmazie 66:83–97. doi:10.1691/ph.2011.0744

    CAS  PubMed  Google Scholar 

  • Inno A, Basso M, Vecchio FM, Marsico VA, Cerchiaro E, D’Argento E, Bagalà C, Barone C (2011) Anastrozole-related acute hepatitis with autoimmune features: a case report. BMC Gastroenterol 11:32. doi:10.1186/1471-230X-11-32

    PubMed Central  PubMed  Google Scholar 

  • Isbrucker 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. doi:10.1691/ph.2011.0744

    CAS  PubMed  Google Scholar 

  • Jiménez-Encarnación E, Ríos G, Muñoz-Mirabal A, Vilá LM (2012) Euforia-induced acute hepatitis in a patient with scleroderma. BMJ Case Rep. doi:10.1136/bcr-2012-006907

    PubMed  Google Scholar 

  • 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. doi:10.1002/lt.21127

    PubMed  Google Scholar 

  • Jodoin J, Demeule M, Beliveau R (2002) Inhibition of the multidrug resistance P-glycoprotein activity by green tea polyphenols. Biochim Biophys Acta 1542:149–159. doi:10.1016/S0167-4889(01)00175-6

    CAS  PubMed  Google Scholar 

  • Kågedal K, Bironaite D, Ollinger K (1999) Anthraquinone cytotoxicity and apoptosis in primary cultures of rat hepatocytes. Free Radic Res 31:419–428. doi:10.1080/10715769900300981

    PubMed  Google Scholar 

  • Kanat O, Ozet A, Ataergin S (2006) Aloe vera-induced acute toxic hepatitis in a healthy young man. Eur J Intern Med. 17:589. doi:10.1016/j.ejim.2006.04.017

    PubMed  Google Scholar 

  • Kaswala D, Shah S, Patel N, Raisoni S, Swaminathan S (2014) Hydroxycut-induced liver toxicity. Ann Med Health Sci Res 4:143–145. doi:10.4103/2141-9248.126627

    PubMed Central  PubMed  Google Scholar 

  • Keske MA, Ng HL, Premilovac D, Rattigan S, Kim JA, Munir K, Yang P, Quon MJ (2015) Vascular and metabolic actions of the green tea polyphenol epigallocatechin gallate. Curr Med Chem 22:59–69. doi:10.2174/0929867321666141012174553

    CAS  PubMed  Google Scholar 

  • Kim YJ, Choi MS, Park YB, Kim SR, Lee MK, Jung UJ (2013) Garcinia cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation. World J Gastroenterol 19:4689–4701. doi:10.3748/wjg.v19.i29.4689

    PubMed Central  PubMed  Google Scholar 

  • Koncic MZ, Tomczyk M (2013) New insights into dietary supplements used in sport: active substances, pharmacological and side effects. Curr Drug Targets 4:1079–1092. doi:10.2174/1389450111314090016

    Google Scholar 

  • Lacey R, Evans A (2014) An unusual cause of jaundice in a patient with breast cancer. BMJ Case Rep. doi:10.1136/bcr-2014-205764

    Google Scholar 

  • Lambert JD, Kennett MJ, Sang S, Reuhl KR, Ju J, Yang CS (2010) Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. Food Chem Toxicol 48:409–416. doi:10.1016/j.fct.2009.10.030

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lança S, Alves A, Vieira AI, Barata J, de Freitas J, de Carvalho A (2002) Chromium-induced toxic hepatitis. Eur J Intern Med 13:518–520. doi:10.1016/S0953-6205(02)00164-4

    PubMed  Google Scholar 

  • Lee J, Lee MS, Nam KW (2014) Acute toxic hepatitis caused by an Aloe vera preparation in a young patient: a case report with a literature review. Korean J Gastroenterol 64:54–58. doi:10.4166/kjg.2014.64.1.54

    PubMed  Google Scholar 

  • Lei X, Chen J, Ren J, Li Y, Zhai J, Mu W, Zhang L, Zheng W, Tian G, Shang H (2015) Liver damage associated with polygonum multiflorum thunb: a systematic review of case reports and case series. Evid Based Complement Altern Med. doi:10.1155/2015/459749

    Google Scholar 

  • Licata A, Macaluso FS, Craxì A (2013) Herbal hepatotoxicity: a hidden epidemic. Intern Emerg Med 8:13–22. doi:10.1007/s11739-012-0777-x

    PubMed  Google Scholar 

  • López-Cepero Andrada JM, Lerma Castilla S, Fernández Olvera MD, Amaya Vidal A (2007) Hepatotoxicity caused by a Noni (Morinda citrifolia) preparation. Rev Esp Enferm Dig 99:179–181

    PubMed  Google Scholar 

  • Lorenzo-Almorós A, Polo-Sabau J, Barrio-Dorado MD, Ruggiero García M (2015) Acute liver injury induced by green tea extracts. Gastroenterol Hepatol 38:44–45. doi:10.1016/j.gastrohep.2014.07.004

    PubMed  Google Scholar 

  • Mazzanti G, Menniti-Ippolito F, Moro PA, Cassetti F, Raschetti R, Santuccio C, Mastrangelo S (2009) Hepatotoxicity from green tea: a review of the literature and two unpublished cases. Eur J Clin Pharmacol 65:331–341. doi:10.1007/s00228-008-0610-7

    PubMed  Google Scholar 

  • Mc Donnell WM, Bhattacharya R, Halldorson JB (2009) Fulminant hepatic failure after use of the herbal weight-loss supplement Exilis. Ann Intern Med 151:673–674. doi:10.7326/0003-4819-151-9-200911030-00021

    Google Scholar 

  • Menniti-Ippolito F, Mazzanti G, Vitalone A, Firenzuoli F, Santuccio C (2008) Surveillance of suspected adverse reactions to natural health products: the case of propolis. Drug Saf 31:419–423. doi:10.2165/00002018-200831050-00007

    PubMed  Google Scholar 

  • Millonig G, Stadlmann S, Vogel W (2005) Herbal hepatotoxicity: acute hepatitis caused by a Noni preparation (Morinda citrifolia). Eur J Gastroenterol Hepatol 17:445–447

    PubMed  Google Scholar 

  • Moreira CT, Oliveira AL, Comar JF, Peralta RM, Bracht A (2013) Harmful effects of usnic acid on hepatic metabolism. Chem Biol Interact 203:502–511. doi:10.1016/j.cbi.2013.02.001

    CAS  PubMed  Google Scholar 

  • Mrzljak A, Kosuta I, Skrtic A, Kanizaj TF, Vrhovac R (2013) Drug-induced liver injury associated with Noni (Morinda citrifolia) juice and phenobarbital. Case Rep Gastroenterol 7:19–24. doi:10.1159/000343651

    PubMed Central  PubMed  Google Scholar 

  • Neff GW, Reddy KR, Durazo FA, Meyer D, Marrero R, Kaplowitz N (2004) Severe hepatotoxicity associated with the use of weight loss diet supplements containing ma huang or usnic acid. J Hepatol 41:1062–1064. doi:10.1016/j.jhep.2004.06.028

    PubMed  Google Scholar 

  • Nortadas R, Barata J (2012) Fulminant hepatitis during self-medication with conjugated linoleic acid. Ann Hepatol 11:265–267

    PubMed  Google Scholar 

  • Patel SS, Beer S, Kearney DL, Phillips G, Carter BA (2013) Green tea extract: a potential cause of acute liver failure. World J Gastroenterol 19:5174–5177. doi:10.3748/wjg.v19.i31.5174

    PubMed Central  PubMed  Google Scholar 

  • Perdices EV, Medina-Cáliz I, Hernando S, Ortega A, Martín-Ocaña F, Navarro JM, Peláez G, Castiella A, Hallal H, Romero-Gómez M, González-Jiménez A, Robles-Díaz M, Lucena MI, Andrade RJ (2014) Hepatotoxicity associated with statin use: analysis of the cases included in the Spanish Hepatotoxicity Registry. Rev Esp Enferm Dig 106:246–254

    CAS  PubMed  Google Scholar 

  • Pillukat MH, Bester C, Hensel A, Lechtenberg M, Petereit F, Beckebaum S, Müller KM, Schmidt HH (2014) Concentrated green tea extract induces severe acute hepatitis in a 63-year-old woman—a case report with pharmaceutical analysis. J Ethnopharmacol 155:165–170. doi:10.1016/j.jep.2014.05.015

    PubMed  Google Scholar 

  • Powers SK, Jackson MJ (2008) Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 88(4):1243–1276. doi:10.1152/physrev.00031.2007

    CAS  PubMed Central  PubMed  Google Scholar 

  • Radha Krishna Y, Mittal V, Grewal P, Fiel MI, Schiano T (2011) Acute liver failure caused by ‘fat burners’ and dietary supplements: a case report and literature review. Can J Gastroenterol 25:157–160

    PubMed Central  Google Scholar 

  • Ramos R, Mascarenhas J, Duarte P, Vicente C, Casteleiro C (2009) Conjugated linoleic acid-induced toxic hepatitis: first case report. Dig Dis Sci 54:1141–1143. doi:10.1007/s10620-008-0461-1

    PubMed  Google Scholar 

  • RELIS database (2007) CLA, Lotus-f3 og hepatitt. RELIS Vest. http://relis.arnett.no/Utredning_Ekstern.aspx?Relis=3&S=4390&R=X. Accessed 11 Mar 2015

  • Rietjens IM, Boersma MG, Haan Ld, Spenkelink B, Awad HM, Cnubben NH, van Zanden JJ, Hv Woude, Alink GM, Koeman JH (2002) The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids. Environ Toxicol Pharmacol 11(3–4):321–333

    CAS  PubMed  Google Scholar 

  • Rietveld A, Wiseman S (2003) Antioxidant effects of tea: evidence from human clinical trials. J Nutr 133:3285S–3292S

    CAS  PubMed  Google Scholar 

  • Rohde J, Jacobsen C, Kromann-Andersen H (2011) Toxic hepatitis triggered by green tea. Ugeskr Laeger 173:205–206

    PubMed  Google Scholar 

  • Rossi S, Navarro VJ (2014) Herbs and liver injury: a clinical perspective. Clin Gastroenterol Hepatol 12:1069–1076. doi:10.1016/j.cgh.2013.07.030

    PubMed  Google Scholar 

  • Sanchez W, Maple JT, Burgart LJ, Kamath PS (2006) Severe hepatotoxicity associated with use of a dietary supplement containing usnic acid. Mayo Clin Proc 81:541–544. doi:10.4065/81.4.541

    PubMed  Google Scholar 

  • Sarma DN, Barrett ML, Chavez ML, Gardiner P, Ko R, Mahady GB, Marles RJ, Pellicore LS, Giancaspro GI, Low Dog T (2008) Safety of green tea extracts: a systematic review by the US Pharmacopeia. Drug Saf 31:469–484. doi:10.2165/00002018-200831060-00003

    PubMed  Google Scholar 

  • Schönthal AH (2011) Adverse effects of concentrated green tea extracts. Mol Nutr Food Res 55:874–885. doi:10.1002/mnfr.201000644

    PubMed  Google Scholar 

  • Seeff LB, Bonkovsky HL, Navarro VJ, Wang G (2014) Herbal products and the liver: a review of adverse effects and mechanisms. Gastroenterology. doi:10.1053/j.gastro.2014.12.004

    PubMed  Google Scholar 

  • Sharma T, Wong L, Tsai N, Wong RD (2010) Hydroxycut(®) (herbal weight loss supplement) induced hepatotoxicity: a case report and review of literature. Hawaii Med J 69:188–190

    PubMed Central  PubMed  Google Scholar 

  • Shiyovich A, Sztarkier I, Nesher L (2010) Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus. Am J Med Sci 340:514–517. doi:10.1097/MAJ.0b013e3181f41168

    PubMed  Google Scholar 

  • Silano V, Coppens P, Larrañaga-Guetaria A, Minghetti P, Roth-Ehrang R (2011) Regulations applicable to plant food supplements and related products in the European Union. Food Funct 2:710–719. doi:10.1039/c1fo10105f

    CAS  PubMed  Google Scholar 

  • Snyder FJ, Dundas ML, Kirkpatrick C, Neill KS (2009) Use and safety perceptions regarding herbal supplements: a study of older persons in southeast Idaho. J Nutr Elder 28:81–95. doi:10.1080/01639360802634043

    PubMed  Google Scholar 

  • Stadlbauer V, Fickert P, Lackner C, Schmerlaib J, Krisper P, Trauner M, Stauber RE (2005) Hepatotoxicity of NONI juice: report of two cases. World J Gastroenterol 11:4758–4760

    PubMed  Google Scholar 

  • Stadlbauer V, Weiss S, Payer F, Stauber RE (2008) Herbal does not at all mean innocuous: the sixth case of hepatotoxicity associated with Morinda citrifolia (Noni). Am J Gastroenterol 103:2406–2407. doi:10.1111/j.1572-0241.2008.02010_8.x

    PubMed  Google Scholar 

  • Stickel F, Kessebohm K, Weimann R, Seitz HK (2011) Review of liver injury associated with dietary supplements. Liver Int 31:595–605. doi:10.1111/j.1478-3231.2010.02439.x

    CAS  PubMed  Google Scholar 

  • Tenore GC, Daglia M, Ciampaglia R, Novellino E (2015) Exploring the nutraceutical potential of polyphenols from black, green and white tea infusions—an overview. Curr Pharm Biotechnol 16:264–271. doi:10.2174/1389201016666150118133604

    Google Scholar 

  • Teschke R, Schwarzenboeck A, Hennermann KH (2008) Causality assessment in hepatotoxicity by drugs and dietary supplements. Br J Clin Pharmacol 66:758–766. doi:10.1111/j.1365-2125.2008.03264.x

    PubMed Central  PubMed  Google Scholar 

  • Teschke R, Zhang L, Melzer L, Schulze J, Eickhoff A (2014) Green tea extract and the risk of drug-induced liver injury. Expert Opin Drug Metab Toxicol 10:1663–1676. doi:10.1517/17425255.2014.971011

    CAS  PubMed  Google Scholar 

  • Ullmann U, Haller J, Decourt JP, Girault N, Girault J, Richard-Caudron AS, Pineau B, Weber P (2003) A single ascending dose study of epigallocatechin gallate in healthy volunteers. J Int Med Res 31:88–101

    CAS  PubMed  Google Scholar 

  • Update on the USP Green Tea Extract Monograph. http://www.usp.org/usp-nf/notices/retired-compendial-notices/update-usp-green-tea-extract-monograph. Accessed 31 Mar 2015

  • Urban TJ, Daly AK, Aithal GP (2014) Genetic basis of drug-induced liver injury: present and future. Semin Liver Dis 34:123–133. doi:10.1055/s-0034-1375954

    CAS  PubMed  Google Scholar 

  • US National Library of Medicine—NIH http://www.nlm.nih.gov/medlineplus/healthtopics.html. Accessed 16 Feb 2015 (bisogna indicare il documento consultato)

  • Vanstraelen S, Rahier J, Geubel AP (2008) Jaundice as a misadventure of a green tea (Camellia sinensis) lover: a case report. Acta Gastroenterol Belg 71:409–412

    PubMed  Google Scholar 

  • Verhelst X, Burvenich P, Van Sassenbroeck D, Gabriel C, Lootens M, Baert D (2009) Acute hepatitis after treatment for hair loss with oral green tea extracts (Camellia sinensis). Acta Gastroenterol Belg 72:262–264

    CAS  PubMed  Google Scholar 

  • Vilella AL, Limsuwat C, Williams DR, Seifert CF (2013) Cholestatic jaundice as a result of combination designer supplement ingestion. Ann Pharmacother 47:e33. doi:10.1345/aph.1R405

    PubMed  Google Scholar 

  • Villalta D, Imbastaro T, Di Giovanni S, Lauriti C, Gabini M, Turi MC, Bizzaro N (2012) Diagnostic accuracy and predictive value of extended autoantibody profile in systemic sclerosis. Autoimmun Rev 12:114–120. doi:10.1016/j.autrev.2012.07.005

    CAS  PubMed  Google Scholar 

  • Vitalone A, Menniti-Ippolito F, Moro PA, Firenzuoli F, Raschetti R, Mazzanti G (2011) Suspected adverse reactions associated with herbal products used for weight loss: a case series reported to the Italian National Institute of Health. Eur J Clin Pharmacol 67:215–224. doi:10.1007/s00228-010-0981-4

    PubMed  Google Scholar 

  • Vitalone A, Menniti-Ippolito F, Raschetti R, Renda F, Tartaglia L, Mazzanti G (2012) Surveillance of suspected adverse reactions to herbal products used as laxatives. Eur J Clin Pharmacol 8:231–238. doi:10.1007/s00228-011-1128-y

    Google Scholar 

  • Waldman W, Piotrowicz G, Sein Anand J (2013) Hepatoxic effect of a noni juice consumption—a case report. Przegl Lek 70:690–692

    PubMed  Google Scholar 

  • Wang L, Zhang X, Liu J, Shen L, Li Z (2014) Tea consumption and lung cancer risk: a meta-analysis of case–control and cohort studies. Nutrition 30:1122–1127. doi:10.1016/j.nut.2014.02.023

    CAS  PubMed  Google Scholar 

  • Weinstein DH, Twaddell WS, Raufman JP, Philosophe B, Mindikoglu AL (2012) SlimQuick™-associated hepatotoxicity in a woman with alpha-1 antitrypsin heterozygosity. World J Hepatol 4:154–157. doi:10.4254/wjh.v4.i4.154

    PubMed Central  PubMed  Google Scholar 

  • West BJ, Deng S (2011) Ingredients other than noni may be culprits in acute hepatotoxicity in 14-year-old boy. J Pediatr Gastroenterol Nutr 53:469–470. doi:10.1097/MPG.0b013e31822b77e2

    PubMed  Google Scholar 

  • Whitsett M, Halegoua-De Marzio D, Rossi S (2014) SlimQuick™-associated hepatotoxicity resulting in fulminant liver failure and orthotopic liver transplantation. ACG Case Rep J 1:220–222

    PubMed Central  PubMed  Google Scholar 

  • Whitt KN, Ward SC, Deniz K, Liu L, Odin JA, Qin L (2008) Cholestatic liver injury associated with whey protein and creatine supplements. Semin Liver Dis 28:226–231. doi:10.1055/s-2008-1073122

    CAS  PubMed  Google Scholar 

  • Wierzejska R (2014) Tea and health—a review of the current state of knowledge. Przegl Epidemiol 68(501–6):595–599

    Google Scholar 

  • Wu KM, Yao J, Boring D (2001) Green tea extract-induced lethal toxicity in fasted but not in nonfasted dogs. Int J Toxicol 30:19–20. doi:10.1177/1091581810387445

    Google Scholar 

  • Wu QJ, Dong QH, Sun WJ, Huang Y, Wang QQ, Zhou WL (2014) Discrimination of Chinese teas with different fermentation degrees by stepwise linear discriminant analysis (S-LDA) of the chemical compounds. J Agric Food Chem 62:9336–9344. doi:10.1021/jf5025483

    CAS  PubMed  Google Scholar 

  • Yang HN, Kim DJ, Kim YM, Kim BH, Sohn KM, Choi MJ, Choi YH (2010) Aloe-induced toxic hepatitis. J Korean Med Sci 25:492–495. doi:10.3346/jkms.2010.25.3.492

    PubMed Central  PubMed  Google Scholar 

  • Yu EL, Sivagnanam M, Ellis L, Huang JS (2011) Acute hepatotoxicity after ingestion of Morinda citrifolia (Noni Berry) juice in a 14-year-old boy. J Pediatr Gastroenterol Nutr 52:222–224. doi:10.1097/MPG.0b013e3181eb69f0

    PubMed  Google Scholar 

  • Yuce B, Gulberg V, Diebold J, Gerbes AL (2006) Hepatitis induced by Noni juice from Morinda citrifolia: a rare cause of hepatotoxicity or the tip of the iceberg? Digestion 73:167–170

    CAS  PubMed  Google Scholar 

  • Zhou S, Lim LY, Chowbay B (2004) Herbal modulation of P-glycoprotein. Drug Metab Rev 36:57–104. doi:10.1081/DMR-120028427

    CAS  PubMed  Google Scholar 

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Acknowledgments

A. Di Sotto and A. Vitalone were supported by “Enrico and Enrica Sovena Foundation” Rome, Italy. We thank Dr. Patrizia Parisi and Dr. Silvia Di Giacomo for their assistance in retrieving some articles.

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The authors declare that they have no conflict of interest.

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Correspondence to Gabriela Mazzanti.

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Antonella Di Sotto and Annabella Vitalone have contributed equally to this article.

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Mazzanti, G., Di Sotto, A. & Vitalone, A. Hepatotoxicity of green tea: an update. Arch Toxicol 89, 1175–1191 (2015). https://doi.org/10.1007/s00204-015-1521-x

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