liver damage has increased [5,6]. In April 2003, theSpanish Agency of Medicine and Health Products with-drew the over the counter medicine Exolise� from themarket. This contained an ethanolic extract of greentea, and was the cause of four cases of hepatotoxicityin Spain [7] and nine in France [8]. In none of the Her-balife� products containing green tea is the type of ex-tract or the amount of active substances specified. Onthe other hand, several authors [9–11] have reportedcases of acute hepatitis associated with the consumptionof Aloe vera tablets or capsules. Aloe vera is the maincomponent of the drink Herbal Aloe sold by Herbalife�.

We do not believe that the hepatotoxicity of the Her-balife� products is confined to three countries alone.The lower use in some areas, the underreporting of ad-verse reactions, and the lower ability to detect or reportinformation in the international scientific media couldbe the reasons for explaining this lack of informationfrom other countries. For some time, Latin Americanand Spanish health professionals have been discussingthe safety of Herbalife� products and similar com-pounds on internet forums.

Schoepfer et al. [2] and Stickel [3] consider that thehepatotoxicity associated with Herbalife� products doesnot seem to be a threat to public health and have sug-gested an incidence lower than that of the non-steroidalanti-inflammatory drugs. In our opinion, the evaluationof this safety problem is impossible because we have noprecise consumption data nor isolated active substancesof established efficacy. Perhaps the hepatotoxicity we arespeaking about is of low incidence and affects patientswith genetic susceptibility or other risk factors. How-ever, the growing consumption of products promotedas ‘‘natural”, without defined composition, quality con-trol and demonstrated activity and safety is a real healthproblem that should be kept under control. Today weare speaking only about the products of the Herbalife�

brand, but tomorrow we may be speaking about otherproducts or other brands.

References

[1] Elinav E, Pinsker G, Safadi R, Pappo O, Bromberg M, Anis E, et al.Association between consumption of Herbalife� nutritionalsupplements and acute hepatotoxicity. J Hepatol 2007;47:514–520.

[2] Schoepfer AM, Engel A, Fattinger K, Marbet UA, Criblez D,Reichen J, et al. Herbal does not mean innocuous: ten cases ofsevere hepatotoxicity associated with dietary supplements fromHerbalife� products. J Hepatol 2007;47:521–526.

[3] Stickel F. Slimming at all costs: Herbalife�-induced liver injury. JHepatol 2007;47:444–446.

[4] Duque JM, Ferreiro J, Salgueiro E, Manso G. Hepatotoxicityassociated with the consumption of herbal slimming products.Med Clin (Barc) 2007;128:238–239.

[5] Bonkovsky HL. Hepatotoxicity associated with supplementscontaining Chinese green tea (Camellia sinensis). Ann InternMed 2006;144:68–71.

[6] Jimenez-Saenz M, Martınez-Sanchez MC. Acute hepatitis associ-ated with the use of green tea infusions. J Hepatol 2006;44:616–617.

[7] Pedros C, Cereza G, Garcıa N, Laporte JR. Hepatotoxicidad porextracto etanolico seco de Camellia sinensis. Med Clin (Barc)2003;121:598–599.

[8] Vial T, Bernard G, Lewden B, Dumortier J, Descotes J. Hepatiteaigue imputable a l’Exolise� (Camellia sinensis). GastroenterolClin Biol 2003;27:1166–1167.

[9] Rabe C, Musch A, Schirmacher P, Kruis W, Hoffmann R. Acutehepatitis induced by an aloe vera preparation: a case report.World J Gastroenterol 2005;11:303–304.

[10] Kanat O, Ozet A, Ataergin S. Aloe vera-induced acute toxichepatitis in a healthy young man. Eur J Inter Med 2006;17:589.

[11] Bottenberg MM, Wall GC, Harvey RL, Habib S. Oral aloe vera-induced hepatitis. Ann Pharmacother 2007;41:1740–1743.

Gloria MansoLaureano Lopez-Rivas

Jose Marıa DuqueEsther Salgueiro

Pharmacovigilance Centre of Asturias – Medicine,

Julian Claveria 6, Oviedo 33006, Spain

Tel.: +34985103546; fax: +34985103551 (G. Manso)

E-mail address: gmanso@uniovi.es (G. Manso)

doi:10.1016/j.jhep.2008.05.007

More reports of potential hepatotoxicity of Herbalife products: Reply

To the Editor:

The Letter to the Editor by Manso and colleaguesfrom Spain [1] reiterates the deep concern recently raised[2–4] regarding the potential hepatotoxicity of one ormore HerbalifeTM products. This report adds 4 morepatients to the already described 22 patients from twocountries, who developed a variable degree of liverinjury in association with the intake of HerbalifeTM

products.

Two of the Spanish patients developed quite severehepatitis with jaundice and 3/4 recovered after stoppingintake of the products. Although the information pro-vided is not complete, causality may be established inat least two cases as probable and in the remainingtwo cases as possible, based on the same criteria as re-ported in Ref. [2–4].The development of hepatitis intwo sisters, one of whom has or progressed to chronichepatitis, is an important observation which may shed

290 Letters to the Editor / Journal of Hepatology 49 (2008) 288–294

further light on the potential mechanism of hepatotoxic-ity in these sisters. Although it cannot be established forcertain if autoimmunity or a pharmaco-genetic prepon-derance is the driving force behind these events, the reac-tive hepatitis in the two sisters suggests a commonmechanism. Dr. Manso et al. raise the possibility thatgreen tea or aloe vera ingredients, previously reportedto induce hepatotoxicity may also be the cause in theSpanish group of patients. However, these ingredientswere not taken uniformly by all the reported patientsfrom Israel and Switzerland, and therefore a detailed listof all the ingredients including the chemical compositionis required as stated in the two original reports. In Spainas well as in Israel and Switzerland, it was not possibleto establish the true incidence of hepatotoxicity amongHerbalifeTM users since the number of consumers andtheir demographic characteristics are only partiallyknown. A rough calculation suggested an incidence of25–30 cases per 100,000 HerbalifeTM products among Is-raeli consumers. We agree with the colleagues fromSpain that the true incidence may be higher since liverinjury may remain occult and asymptomatic as is wellknown by practising hepatologists. Thus, it is importantto draw the attention of the Journals readers to reportsof similar cases.

References

[1] Manso G, Lopez-Rivas L, Duque JM, Salgueiro E. Spanish reportsof hepatotoxicity associated with herbalife� products. J Hepatol2008;48:290–291.

[2] Elinav E, Pinsker G, Safadi R, Pappo O, Bromberg M, Anis E,et al. Association between consumption of Herbalife� nutri-tional supplements and acute hepatotoxicity. J Hepatol2007;47:514–520.

[3] Schoepfer AM, Engel A, Fattinger K, Marbet UA, Criblez D,Reichen J, et al. Herbal does not mean innocuous: ten cases ofsevere hepatotoxicity associated with dietary supplements fromHerbalife� products. J Hepatol 2007;47:521–526.

[4] Stickel F. Slimming at all costs: Herbalife�-induced liver injury. JHepatol 2007;47:444–446.

Daniel ShouvalEran Elinav

Hadassah-Hebrew University Medical Center,

P.O. Box 12000, Jerusalem 91120, Israel

Tel.: +972 2 6777 337; fax: +972 2 6420 338(D. Shouval)

E-mail address: shouval@cc.huji.ac.il (D. Shouval)

doi:10.1016/j.jhep.2008.05.006

Herbalife nutritional products and liver injury revisited

To the Editor:

Recently, two reports of 12 and 10 cases of idio-pathic liver disease from Israel [1] and Switzerland[2], respectively, appeared in the same issue of thisjournal alleging in the articles and in an accompanyingeditorial that these cases were caused by the consump-tion of Herbalife products. In fact, the two papers [1,2]concluded unequivocally that causation was certain insome cases. Despite the authors’ strong assertion thata cause and effect relationship between Herbalife prod-uct use and liver injury exists, an objective review ofthe facts raises serious doubt whether such a conclu-sion can be drawn. In Israel [1], the observed liverabnormalities resolved in eleven of the twelve cases re-ported. The remaining patient succumbed to complica-tions of liver transplantation and despite the fact thatthis patient also had evidence of hepatitis B infection,sole attribution of the liver injury to Herbalife productswas made. Another patient had stage I primary biliarycirrhosis and other patients consumed a variety of sub-stances or had other co-morbid diseases that couldhave caused or contributed to the liver disease ob-served. In Switzerland [2], a total of 10 evaluable case

reports with similar characteristics were documentedover seven years.

Taken at face value, these few cases represent an ex-tremely low incidence of suspected liver injury amongthe millions of Herbalife consumers worldwide (5.5 mil-lion consumers in 2004 alone). In 2004 more than40,000,000 servings from 29 different products were dis-tributed to approximately 37,000 Israeli consumers. Asimilar number of servings from 26 different productswere distributed to approximately 80,000 Swiss consum-ers. In the 5 combined cases where causation wasassessed as ‘‘certain” due to a reported combination ofpositive dechallenge and rechallenge, the case detailsremain unclear. As an example, 4 of these patientsdescribed between 3 and 17 different and specific Herba-life products previously consumed prior to dechallenge,and in the remaining patient no specific Herbalife prod-uct in either the reported dechallenge or rechallengecould be identified. Equally concerning is the fact thatthere is no mention of which of the initially reportedproducts were subsequently consumed by any of the pa-tients that allegedly led to the recurrence of symptoms.Even if all 4 patients consumed the exact same 3–17

Letters to the Editor / Journal of Hepatology 49 (2008) 288–294 291