Abstract
Herbal and dietary supplements (HDS) have been used for health-related purposes since more than 5000 years, and their application is firmly anchored in all societies worldwide. Over last decades, a remarkable renaissance in the use of HDS can be noticed in affluent societies for manifold reasons. HDS are forms of complementary and alternative medicines commonly used to prevent or treat diseases, or simply as a health tonic. Another growing indication for HDS is their alleged benefit for weight loss or to increase physical fitness. Access is easy via internet and mail-order pharmacies, and their turnover reaches billions of dollars in the USA and Europe alone. However, HDS are generally not categorized as drugs and thus less strictly regulated in most countries. As a result, scientific evidence proving their beneficial effects is mostly lacking, although some HDS may have purported benefits. However, the majority lacks such proof of value, and their use is predominantly based on belief and hope. In addition to missing scientific evidence supporting their use, HDS are typically prone to batch-to-batch variability in composition and concentration, contamination, and purposeful adulteration. Moreover, numerous examples of preparations emerged which have been linked to significant liver injury. These include single ingredients, such as kava, germander, and several Chinese herbals. Other HDS products associated with liver toxicity consist of multiple, often ill-defined ingredients, such as Hydroxycut and Herbalife. Affirmative diagnostic tests are not available, and the assessment of liver injury ascribed to HDS depends on a thorough and proactive medical history, careful exclusion of other causes, and a search for available reports on similar events linked to the intake of the suspected preparation or ingredients contained therein.
Similar content being viewed by others
References
Agarwal R, Wang ZY, Bik DP, Mukhtar H (1991) Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450-mediated monooxygenase activity in rat epidermal and hepatic microsomes. Drug Metab Dispos 19:620–624
Aithal GP, Rawlins MD, Day CP (2000) Clinical diagnostic scale: a useful tool in the evaluation of suspected hepatotoxic adverse drug reactions. J Hepatol 33:949–952
Alaerts G, Pieters S, Logie H et al (2014) Exploration and classification of chromatographic fingerprints as additional tool for identification and quality control of several Artemisia species. J Pharm Biomed Anal 95:34–46
Anderson IB, Mullen WH, Meeker JE, Khojasteh-Bakht SC, Oishi S, Nelson SD, Blanc PD (1996) Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med 124:726–734
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
Bakerink JA, Gospe SM, Dimand RJ, Eldridge MW (1996) Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics 98:944–947
Benninger J, Schneider HT, Schuppan D, Kirchner T, Hahn EG (1999) Acute hepatitis induced by greater celandine (Chelidonium majus). Gastroenterology 117:1234–1237
Beuers U, Spengler U, Pape G (1992) Hepatitis after chronic abuse of senna. Lancet 337:372–373
Bouziri A, Hamdi A, Menif K, Ben Jaballah N (2010) Hepatorenal injury induced by cutaneous application of Atractylis gummifera L. Clin Toxicol (Phila) 48:752–754
Bras G, Jeliffe DB, Stuart KL (1954) Veno-occlusive disease of the liver with non-portal type of cirrhosis occurring in Jamaica. Arch Pathol 57:285
Brinkhaus B, Lindner M, Schuppan D, Hahn EG (2000) Chemical, pharmacological and clinical profile of the East Asian plant Centella asiatica. Phytomedicine 7:427–448
But PP, Tomlinson B, Lee KL (1996) Hepatitis related to the Chinese medicine Shou-wu-pian manufactured from Polygonum multiflorum. Vet Hum Toxicol 38:280–282
Cárdenas A, Restrepo JC, Sierra F et al (2006) Acute hepatitis due to Shen-Min, a herbal product derived from Polygonum multiflorum. J Clin Gastroenterol 40:629–632
Centers for Disease Control and Prevention (2003) Hepatic toxicity possibly associated with kava-containing products—United States, Germany, and Switzerland. JAMA 289:36–37
Centers for Disease Control and Prevention (2013) (CDC). Notes from the field: acute hepatitis and liver failure following the use of a dietary supplement intended for weight loss or muscle building—May–October 2013. MMWR Morb Mortal Wkly Rep 62:817–819
Cerda C, Bruguera M, Parés A (2013) Hepatotoxicity associated with glucosamine and chondroitin sulfate in patients with chronic liver disease. World J Gastroenterol 19:5381–5384
Chalasani N, Fontana RJ, Bonkovsky HL et al (2008) Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 135:1924–1934
Chang J (1999) Scientific evaluation of traditional Chinese medicine under DSHEA: a conundrum. Dietary Supplement Health and Education Act. J Altern Complement Med 5:181–189
Chao S, Anders M, Turbay M, Olaiz E, Mc Cormack L, Mastai R (2008) Toxic hepatitis by consumption Herbalife products a case report. Acta Gastroenterol Latinoam 38:274–277
Chitturi S, Farrell GC (2008) Hepatotoxic slimming aids and other herbal hepatotoxins. J Gastroenterol Hepatol 23:366–373
Christl SU, Seifert A, Seeler D (2009) Toxic hepatitis after consumption of traditional kava preparation. J Travel Med 16:55–56
Crijns AP, de Smet PA, van den Heuvel M, Schot BW, Haagsma EB (2002) Acute hepatitis after use of a herbal preparation with greater celandine (Chelidonium majus). Ned Tijdschr Geneeskd 146:124–128
Dantuluri S, North-Lewis P, Karthik SV (2011) Gotu Kola induced hepatotoxicity in a child—need for caution with alternative remedies. Dig Liver Dis 43:500
Dara L, Hewett J, Lim JK (2008) Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol 14:6999–7004
Davies LP, Drew CA, Duffield P, Johnston GA, Jamieson DD (1992) Kavapyrones and resin: studies on GABAA, GABAB and benzodiazepine binding sites in rodent brain. Pharmacol Toxicol 71:120–126
Deconinck E, Custers D, De Beer JO (2015) Identification of (antioxidative) plants in herbal pharmaceutical preparations and dietary supplements. Methods Mol Biol 1208:181–199
DeLeve LD, McCuskey RS, Wang X et al (1999) Characterization of a reproducible rat model of hepatic veno-occlusive disease. Hepatology 29:1779–1791
DeLeve LD, Shulman HM, McDonald GB (2002) Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Semin Liver Dis 22:27–42
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
Duque JM, Ferreiro J, Salgueiro E, Manso G (2007) Hepatotoxicity associated with the consumption of herbal slimming products. Med Clin (Barc) 128:238–239
Durazo FA, Lassman C, Han SB et al (2004) Fulminant liver failure due to usnic acid for weight loss. Am J Gastroenterol 99:950–952
Eardley S, Bishop FL, Prescott P et al (2012) A systematic literature review of complementary and alternative medicine prevalence in EU. Forsch Komplementmed 19(Suppl 2):18–28
Efferth T, Kaina B (2011) Toxicities by herbal medicines with emphasis to traditional Chinese medicine. Curr Drug Metab 12:989–996
Eisenberg DM, Kessler RC, Foster C et al (1993) Unconventional medicine in the United States: prevalence, costs, and patterns of use. NEJM 328:246–252
Eisenberg DM, Davis RB, Ettner SL et al (1998) Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national study. JAMA 280:1569–1575
El Sherrif Y, Potts JR, Howard MR et al (2013) Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1/ABCB11 mutations? Liver Int 33:1266–1270
Elinav E, Pinsker G, Safadi R et al (2007) Association between consumption of Herbalife® nutritional supplements and acute hepatotoxicity. J Hepatol 47:514–520
Erlinger S (1997) Drug-induced cholestasis. J Hepatol 26(Suppl 1):1–4
Ernst E, Hung SK (2011) Great expectations: what do patients using complementary and alternative medicine hope for? Patient 4:89–101
Estes JD, Stolpman D, Olyaei A et al (2003) High prevalence of potentially hepatotoxic herbal supplement use in patients with fulminant hepatic failure. Arch Surg 138:852–858
Fau D, Lekehal M, Farrell G et al (1997) Diterpenoids from germander, an herbal medicine, induce apoptosis in isolated rat hepatocytes. Gastroenterology 113:1334–1346
Favreau JT, Ryu ML, Braunstein G et al (2002) Severe hepatotoxicity associated with the dietary supplement LipoKinetix. Ann Intern Med 136:590–595
Foley S, Butlin E, Shields W, Lacey B (2014) Experience with OxyELITE pro and acute liver injury in active duty service members. Dig Dis Sci 59:3117–3121
Fong T, Klontz KC, Canas-Coto A et al (2010) Hepatotoxicity due to Hydroxycut: a case series. Am J Gastroenterol 105:1561–1566
Fu PP, Chiang HM, Xia Q et al (2009) Quality assurance and safety of herbal dietary supplements. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 27:91–119
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
García-Cortés M, Borraz Y, Lucena MI et al (2008) Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry. Rev Esp Enferm Dig 100:688–695
Georgiou M, Sianidou L, Hatzis T, Papadatos J, Koutselinis A (1988) Hepatotoxicity due to Atractylis gummifera-L. J Toxicol Clin Toxicol 26:487–493
Goodarzi M, Russell PJ, Vander Heyden Y (2013) Similarity analyses of chromatographic herbal fingerprints: a review. Anal Chim Acta 804:16–28
Gordon WP, Huitric AC, Seth CL, McClanahan RH, Nelson SD (1987) The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab Dispos 15:589–594
Gori L, Galluzzi P, Mascherini V et al (2011) Two contemporary cases of hepatitis associated with Teucrium chamaedrys L. decoction use: case reports and review of literature. Basic Clin Pharmacol Toxicol 109:521–526
Hamid S, Rojter S, Vierling J (1997) Protracted cholestatic hepatitis after the use of prostata. Ann Intern Med 127:169
Hamouda C, Hédhili A, Ben Salah N, Zhioua M, Amamou M (2004) A review of acute poisoning from Atractylis gummifera L. Vet Hum Toxicol 46:144–146
Han D, Matsumaru K, Rettori D, Kaplowitz N (2004) Usnic acid-induced necrosis of cultured mouse hepatocytes: inhibition of mitochondrial function and oxidative stress. Biochem Pharmacol 67:439–451
Hardeman E, Van Overbeke L, Ilegems S, Ferrante M (2008) Acute hepatitis induced by greater celandine (Chelidonium majus). Acta Gastroenterol Belg 71:281–282
Horowitz RS, Feldhaus K, Dart RC, Stermitz FR, Beck JJ (1996) The clinical spectrum of Jin Bu Huan toxicity. Arch Intern Med 156:899–903
http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2012/01/WC500120714.pdf. Accessed Dec 22 2014
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm172824.htm. Accessed Dec 22 2014
http://www.fda.gov/Safety/recalls/ucm145164.htm. Accessed Nov 27 2014
http://livertox.nih.gov/. Accessed Dec 22 2014
Ishak KG (1981) Hepatic lesions caused by anabolic and contraceptive steroids. Semin Liver Dis 1:116–128
Jang JS, Seo EG, Han C et al (2008) Four cases of toxic liver injury associated with Dictamnus dasycarpus. Korean J Hepatol 14:206–212
Jhoo J-W, Freeman JP, Heinze TM et al (2006) In vitro cytotoxocity of nonpolar constituents from different parts of kava plant (Piper methysticum). J Agric Food Chem 54:3157–3162
Jin X, Zheng RH, Li YM (2008) Green tea consumption and liver disease: a systematic review. Liver Int 28:990–996
Johannsson M, Ormarsdottir S, Olafsson S (2010) Hepatotoxicity associated with the use of Herbalife. Laeknabladid 96:167–172
Jones FP, Andrews AH (2007) Acute liver injury associated with the herbal supplement Hydroxycut in a soldier deployed to Iraq. Am J Gastroenterol 102:2357
Jorge OA, Jorge AD (2005) Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 97:115–124
Jung KA, Min HJ, Yoo SS et al (2011) Drug-induced liver injury: twenty five cases of acute hepatitis following ingestion of Polygonum multiflorum Thunb. Gut Liver 5:493–499
Jussofie A, Schmiz A, Hiemke C (1994) Kavapyrone enriched extract from piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacol 116:469–474
Kafrouni MI, Anders RA, Verma S (2007) Hepatotoxicity associated with dietary supplements containing anabolic steroids. Clin Gastro Hepatol 5:809–812
Kakar F, Akbarian Z, Leslie T et al (2010) An outbreak of hepatic veno-occlusive disease in Western Afghanistan associate with exposure to wheat flour contaminated with pyrrolizidine alkaloids. J Toxicol 2010:313280
Kane JA, Kane SP, Jain S (1995) Hepatitis induced by traditional Chinese herbs; possible toxic components. Gut 36:146–147
Kassler WJ, Blanc P, Greenblatt R (1991) The use of medicinal herbs by human immunodeficiency virus-infected patients. Arch Intern Med 151:2281–2288
Kauma H, Koskela R, Mäkisalo H, Autio-Harmainen H, Lehtola J, Höckerstedt K (2004) Toxic acute hepatitis and hepatic fibrosis after consumption of chaparral tablets. Scand J Gastroenterol 39:1168–1171
Kouzi SA, McMurty RJ, Nelson SD (1994) Hepatotoxicity of germander (Teucrium chamedrys L.) and one of its constituent neoclerodane diterpenes, teucrin A in the mouse. Chem Res Toxicol 7:850–856
Krishnan PV, Feng ZZ, Gordon SC (2009) Prolonged intrahepatic cholestasis and renal failure secondary to anabolic steroid-enriched dietary supplements. J Clin Gastroenterol 43:672–675
Laird AR, Ramchandani N, deGoma EM, Avula B, Khan IA, Gesundheit N (2008) Acute hepatitis associated with the use of an herbal supplement (Polygonum multiflorum) mimicking iron-overload syndrome. J Clin Gastroenterol 42:861–862
Larrey D, Vial T, Pauwels A et al (1992) Hepatitis after Germander (Teucrium chamaedrys) adminstration: another instance of herbal medicine hepatotoxicity. Ann Intern Med 117:129–132
Leach MJ, Moore V (2012) Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev 12(9):CD007244
Lekehal M, Pessayre D, Lereau JM, Moulis C, Fourasté I, Fau D (1996) Hepatotoxicity of the herbal medicine, germander. Metabolic activation of its furano diterpenoids by cytochrome P450 3A depletes cytoskeleton-associated protein thiols and forms plasma membrane blebs in rat hepatocytes. Hepatology 24:212–218
Levitsky J, Alli TA, Wisecarver J, Sorrell MF (2005) Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 50:538–539
Lim TY, Considine A, Quaglia A, Shawcross DL (2013) Subacute liver failure secondary to black cohosh leading to liver transplantation. BMJ Case Rep 2013
Lin TJ, Tsai MS, Chiou NM, Deng JF, Chiu NY (2002) Hepatotoxicity caused by Breynia officinalis. Vet Hum Toxicol 44:87–88
Lin TJ, Su CC, Lan CK, Jiang DD, Tsai JL, Tsai MS (2003) Acute poisonings with Breynia officinalis—an outbreak of hepatotoxicity. J Toxicol Clin Toxicol 41:591–594
Lin BR, Yu CJ, Chen WC et al (2009) Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling. J Biomed Sci 16:35
Lin G, Wang JY, Li N et al (2011) Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum. J Hepatol 54:666–673
Loeper J, Descatoire V, Letteron P et al (1994) Hepatotoxicity of germander in mice. Gastroenterology 106:464–472
Lüde S, Török M, Dieterle S et al (2007) Hepatic effects of Cimicifuga racemosa extract in vivo and in vitro. Cell Mol Life Sci 64:2848–2857
Ma KF, Zhang XG, Jia HY (2014) CYP1A2 polymorphism in Chinese patients with acute liver injury induced by Polygonum multiflorum. Genet Mol Res 13:5637–5643
Mahady GB, Low Dog T, Barrett ML, Chavez ML, Gardiner P, Ko R, Marles RJ, Pellicore LS, Giancaspro GI, Sarma DN (2008) United States pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause 15:628–638
Manso G, López-Rivas L, Salgueiro ME et al (2011) Continuous reporting of new cases in Spain supports the relationship between Herbalife® products and liver injury. Pharmacoepidemiol Drug Saf 20:1080–1087
Maria VAJ, Victorino RMM (1997) Development and validation of a clinical scale for the diagnosis of drug-induced hepatitis. Hepatology 26:664–669
Marignani M, Gallina S, Di Fonzo M et al (2010) Use and safety perception of herbal remedies in patients with liver/biliary tract disorders: an Italian study. J Clin Gastroenterol 44(Suppl 1):S54–S57
Mattei A, Rucay P, Samuel D (1995) Liver transplantation for severe acute liver failure after herbal medicine (Teucrium polium) administration. J Hepatol 22:597
Mazzanti G, Battinelli L, Daniele C et al (2004) New case of acute hepatitis following the consumption of Shou Wu Pian, a Chinese herbal product derived from Polygonum multiflorum. Ann Intern Med 140:W30
McRae CA, Agarwal K, Mutimer D, Bassendine MF (2002) Hepatitis associated with Chinese herbs. Eur J Gastroenterol Hepatol 14:559–562
Mei N, Guo L, Fu PP, Fuscoe JC, Luan Y, Chen T (2010) Metabolism, genotoxicity, and carcinogenicity of comfrey. J Toxicol Environ Health B Crit Rev 13:509–526
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
Moro PA, Cassetti F, Giugliano G et al (2009) Hepatitis from Greater celandine (Chelidonium majus L.): review of literature and report of a new case. J Ethnopharmacol 124:328–332
Mouaffak Y, Boutbaoucht M, Ejlaidi A, Toufiki R, Younous S (2013) Fatal poisoning by Atractylis gummifera L.: a case report. Arch Pediatr 20:496–498
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
Nadir A, Agrawal S, King PD, Marshall JB (1996) Acute hepatitis associated with the use of a Chinese herbal product, Ma-Huang. Am J Gastrol 91:1436–1438
Nadir A, Reddy D, Van Thiel DH (2000) Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity. Am J Gastroenterol 95:3634–3637
Navarro VJ, Barnhart H, Bonkovsky HL et al (2014) Liver injury from herbals and dietary supplements in the US Drug Induced Liver Injury Network. Hepatology 60:1399–1408
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
Ng V, Tran TT, Sundaram V (2014) An unexpected cause of an infiltrative liver mass. Gastroenterology 147:e12–e13
Panis B, Wong DR, Hooymans PM et al (2005) Recurrent toxic hepatitis in a Caucasian girl related to the use of Shou-Wu-Pian, a Chinese herbal preparation. J Pediatr Gastroenterol Nutr 41:256–258
Park GJ, Mann SP, Ngu MC (2001) Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum. J Gastroenterol Hepatol 16:115–117
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
Piciotto A, Campo N, Brizzolara R et al (1998) Chronic hepatitis induced by Jin Bu Huan. J Hepatol 28:165–167
Pierard S, Coche JC, Lanthier P et al (2009) Severe hepatitis associated with the use of black cohosh: a report of two cases and an advice for caution. Eur J Gastroenterol Hepatol 21:941–945
Pittler MH, Ernst E (2000) Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 20:84–89
Poon WT, Chau TL, Lai CK et al (2008) Hepatitis induced by Teucrium viscidum. Clin Toxicol (Phila) 46:819–822
Popat A, Shear NH, Malkiewicz I et al (2001) The toxicity of Callilepis laureola, a South African traditional herbal medicine. Clin Biochem 34:229–236
Popat A, Shear NH, Malkiewicz I, Thomson S, Neuman MG (2002) Mechanism of Impila (Callilepis laureola)-induced cytotoxicity in Hep G2 cells. Clin Biochem 35:57–64
Posadzki P, Watson LK, Alotaibi A, Ernst E (2013) Prevalence of use of complementary and alternative medicine (CAM) by patients/consumers in the UK: systematic review of surveys. Clin Med 13:126–131
Prakash AS, Pereira TN, Reilly PE, Seawright AA (1999) Pyrrolizidine alkaloids in human diet. Mutat Res 443:53–67
Regev A (2014) Drug-induced liver injury and drug development: industry perspective. Semin Liver Dis 34:227–239
Robinson O, Want E, Coen M et al (2014) Hirmi valley liver disease: a disease associated with exposure to pyrrolizidine alkaloids and DDT. J Hepatol 60:96–102
Rochon J, Protiva P, Seeff LB et al (2008) Drug-induced Liver Injury Network (DILIN): reliability of the Roussel Uclaf causality assessment method for assessing causality in drug-induced liver injury. Hepatology 48:1175–1182
Roytman MM, Pörzgen P, Lee CL et al (2014) Outbreak of severe hepatitis linked to weight-loss supplement OxyELITE Pro. Am J Gastroenterol 109:1296–1298
Russmann S, Lauterburg BH, Helbling A (2001) Kava hepatotoxicity. Ann Intern Med 135:68–69
Russmann S, Barguil Y, Cabalion P et al (2003) Hepatic injury due to traditional aqueous extracts of kava root in New Caledonia. Eur J Gastroenterol Hepatol 15:1033–1036
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
Sarma DN, Barrett ML, Chavez ML et al (2008) Safety of green tea extracts. A systematic review by the US pharmacopeia. Drug Saf 31:469–484
Savvidou S, Goulis J, Giavazis I, Patsiaoura K, Hytiroglou P, Arvanitakis C (2007) Herb-induced hepatitis by Teucrium polium L.: report of two cases and review of the literature. Eur J Gastroenterol Hepatol 19:507–511
Schoepfer AM, Engel A, Fattinger K et al (2007) Herbal does not mean innocuous: 10 cases of severe hepatotoxicity associated with dietary supplements from Herbalife® products. J Hepatol 47:521–526
Schwingel PA, Cotrim HP, Salles BR et al (2011) Anabolic-androgenic steroids: a possible new risk factor of toxicant-associated fatty liver disease. Liver Int 31:348–353
Seeff LB, Bonkovsky HL, Navarro VJ, Wang G (2014) Herbals and the liver—a review of adverse effects and mechanisms. Gastroenterology. doi:10.1053/j.gastro.2014.12.004
Shah NL, Zacharias I, Khettry U, Afdhal N, Gordon FD (2008) Methasteron-associated cholestatic liver injury: clinicopathologic findings in 5 cases. Clin Gastro Hepatol 6:255–258
Sheikh NM, Philen RM, Love LA (1997) Chaparral-associated Hepatotoxicity. Arch Intern Med 157:913–919
Shim M, Saab S (2009) Severe hepatotoxicity due to Hydroxycut: a case report. Dig Dis Sci 54:406–408
Sorrentino L, Capasso A, Schmidt M (2006) Safety of ethanolic kava extract: results of a study of chronic toxicity in rats. Phytomedicine 13:542–549
Soyuncu S, Cete Y, Nokay AE (2008) Portal vein thrombosis related to Cassia angustifolia. Clin Toxicol (Phila) 46:774–777
Sperl W, Stuppner H, Gassner I, Judmaier W, Dietze O, Vogel W (1995) Reversible hepatic veno-occlusive disease in an infant after consumption of pyrrolizidine-containing herbal tea. Eur J Pediatr 154:112–116
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
Steven T, Qadri A, Zein NN (2005) Two patients with acute liver injury associated with the use of the herbal weight-loss supplement Hydroxycut. Ann Intern Med 142:477–478
Stewart MJ, Steenkamp V, van der Merwe S, Zuckerman M, Crowther NJ (2002) The cytotoxic effects of a traditional Zulu remedy, impila (Callilepis laureola). Hum Exp Toxicol 21:643–647
Stickel F, Pöschl G, Seitz HK et al (2003a) Acute hepatitis induced by Greater Celandine (Chelidonium majus). Scand J Gastroenterol 38:565–568
Stickel F, Baumüller HM, Seitz KH et al (2003b) Hepatitis induced by Kava-Kava (Piper methysticum rhizoma). J Hepatol 39:62–67
Stickel F, Droz S, Patsenker E, Boegli-Studer K, Aebi B, Leib SL (2009) Severe hepatotoxicity following ingestion of Herbalife® nutritional supplements contaminated with Bacillus subtilis. J Hepatol 50:111–117
Stickel F, Kessebohm K, Weimann R, Seitz HK (2011) Review of liver injury associated with dietary supplements. Liver Int 31:595–605
Stillman AE, Huxtable RJ, Consroe P, Kohnen P, Smith S (1977) Hepatic veno-occlusive disease due to pyrrolizidine (Senecio) poisoning in Arizona. Gastroenterology 73:349–352
Strader DB, Bacon BR, Lindsay KL et al (2002) Use of complementary and alternative medicine in patients with liver disease. Am J Gastroenterol 97:2391–2397
Sullivan JB Jr, Rumack BH, Thomas H Jr, Peterson RG, Bryson P (1979) Pennyroyal oil poisoning and hepatotoxicity. J Am Med Assoc 242:2873–2874
Tandon BN, Tandon RK, Tandon HD, Narndranathan M, Joshi YK (1976) An epidemic of veno-occlusive disease of liver in Central India. Lancet 2:271–272
Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A (2012) Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int 32:1543–1556
Thomassen D, Slattery JT, Nelson SD (1990) Menthofuran-dependent and independent aspects of pulegone hepatotoxicity: roles of glutathione. J Pharmacol Exp Ther 253:567–572
Thomassen D, Knebel N, Slattery J, McClanahan RH, Nelson SD (1992) Reactive intermediates in the oxidation of menthofuran by cytochromes P-450. Chem Res Toxicol 5:123–130
Vanderperren B, Rizzo M, Angenot L, Haufroid V, Jadoul M, Hantson P (2005) Acute liver failure with renal impairment related to the abuse of senna anthraquinone glycosides. Ann Pharmacother 39:1353–1357
Vigano M, Lampertico P, Colombo M (2008) Acute hepatitis following assumption of a herbal remedy. Eur J Gastroenterol Hepatol 20:364–365
Vlietinck A, Pieters L, Apers S (2009) Legal requirements for the quality of herbal substances and herbal preparations for the manufacturing of herbal medicinal products in the European Union. Planta Med 75:683–688
von Felden J, Montani M, Kessebohm K, Stickel F (2013) Drug-induced acute liver injury mimicking autoimmune hepatitis after intake of dietary supplements containing glucosamine and chondroitin sulfate. Int J Clin Pharmacol Ther 51:219–223
Waldman W, Piotrowicz G, Sein Anand J (2013) Hepatoxic effect of a noni juice consumption–a case report. Przegl Lek 70:690–692
Watson AR, Coovadia HM, Bhoola KD (1979) The clinical syndrome of Impila (Callilepis laureola) poisoning in children. S Afr Med J 55:290–292
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
Whiting PW, Clouston A, Kerlin P (2002) Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 177:440–443
Wilmot FC, Robertson GW (1920) Senecio disease or cirrhosis of the liver due to senecio poisoning. Lancet II:828–829
Woolf GM, Petrovic LM, Roiter SE et al (1994) Acute hepatitis associated with the Chinese herbal product Jin Bu Huan. Ann Intern Med 10:729–735
Yellapu RK, Mittal V, Grewal P, Fiel M, 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
Yoshida EM, McLean CA, Cheng ES et al (1996) Chinese herbal medicine, fulminant hepatitis and liver transplantation. Am J Gastroenterol 12:2647–2648
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
Zhao P, Wang C, Liu W, Wang F (2014) Acute liver failure associated with traditional Chinese medicine: report of 30 cases from seven tertiary hospitals in China. Crit Care Med 42:e296–e299
Zhong Z, Froh M, Lehnert M et al (2003) Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced liver fibrosis in rats. Am J Physiol Gastrointest Liver Physiol 285:G1004–G1013
Zhou Y, Yang L, Liao Z, He X, Zhou Y, Guo H (2013) Epidemiology of drug-induced liver injury in China: a systematic analysis of the Chinese literature including 21,789 patients. Eur J Gastroenterol Hepatol 25:825–829
Zhou H, Wang YX, Lou HY, Xu XJ, Zhang MM (2014) Hepatic sinusoidal obstruction syndrome caused by herbal medicine: CT and MRI features. Korean J Radiol 15:218–225
Zhu X, Kruhlak NL (2014) Construction and analysis of a human hepatotoxicity database suitable for QSAR modeling using post-market safety data. Toxicology 321:62–72
Conflict of interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stickel, F., Shouval, D. Hepatotoxicity of herbal and dietary supplements: an update. Arch Toxicol 89, 851–865 (2015). https://doi.org/10.1007/s00204-015-1471-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-015-1471-3