10620_2008_353_54_2-web 406.408

Severe Hepatotoxicity Due to Hydroxycut: A Case Report Received: 13 April 2008 / Accepted: 15 May 2008 / Published online: 26 July 2008Ó Springer Science+Business Media, LLC 2008 31–103 U/l), total bilirubin of 18.1 mg/dl (normal 0.2–1.1mg/dl), conjugated bilirubin of 9.0 (normal 0.0–0.2 mg/dl), A 28-year-old male was transferred to our institution with 3 albumin level of 4 g/dl (normal 3.7–5.1 g/dl), prothrombin weeks of fatigue, dyspnea on exertion, jaundice, and dark time of 12.8 s (normal 9.2–10.6 s), normal complete blood urine. In an effort to lose weight, he had been taking Hy- count, normal electrolyte panel, and normal estimated droxycut, two tablets, two to three times per day (which is glomerular filtration rate. Aminotransferase levels and within the manufacturer’s suggested dosing), from 3 prothrombin time began to decline immediately after months prior to admission up until the development of admission and bilirubin peaked on hospital day 2 at 22.4 symptoms. Additionally, for soreness associated with his mg/dl. Acetaminophen level was undetectable. Tests for aerobic exercise program, he took an over-the-counter viral hepatitis were negative. Ferritin was markedly ele- pain-reliever containing acetaminophen 250 mg, aspirin vated at 9519 ng/ml (normal 10–210 ng/ml). HFE 250 mg, and caffeine 65 mg, four tablets per day for the 10 genotyping was negative for H63D or C282Y mutations.
days leading up to the development of his symptoms. He Antinuclear antibody titer was 1:40 (normal, \1:40), was not a heavy drinker of ethanol, drinking 2–3 beers per smooth muscle antibody titer was 1:20 (normal, \1:20), week. Physical examination was unremarkable and without liver kidney microsomal antibody was negative, and solu- stigmata of chronic liver disease. Laboratory analysis ble liver antigen antibody was negative. Serum copper revealed a serum aspartate aminotransferase of 1049 U/l level was 96 mcg/dl (normal 70–140 mcg/dl) and cerulo- (normal range 7–36 U/l), alanine aminotransferase of 2272 plasmin was 31 mg/dl (normal 18–54 mg/dl). Twenty-four (normal 4–45 U/l), alkaline phosphatase of 152 U/l (normal hour urine copper level was 290 mcg/dl (normal 3–50 mcg/dl). Slit-lamp examination for Kaiser-Fleischer rings wasequivocal. Abdominal ultrasound with Doppler and com- Recent reports have identified an association between hepatotoxicity puted tomography (CT) scan with intravenous contrast and the weight loss supplement Hydroxycut (MuscleTech, were both normal. The patient’s liver function tests con- Mississauga, Ontario, Canada). Here we report a case of severe tinued to improve and he was discharged on hospital day 9.
hepatotoxicity associated with Hydroxycut and summarize thepublished data identifying an association between the herbal compounds in Hydroxycut and hepatotoxicity.
Though the markedly elevated 24-h urine copper level and Division of Digestive Diseases, David Geffen School slit-lamp examination equivocal for Kaiser-Fleischer rings of Medicine at UCLA, 1629 Veteran Avenue, Apt. 5, suggested the possibility of underlying Wilson disease, the Los Angeles, CA 90024, USAe-mail: [email protected] normal serum copper and ceruloplasmin levels, lack ofunderlying cirrhosis, lack of supportive family history, lack of concomitant neurological or psychiatric disturbance, and UCLA Department of Medicine, Division of Digestive Diseases, lack of hemolysis all argued against this diagnosis. In the Box 957302, 200 Medical Plaza Suite 214, Los Angeles,CA 90095-7302, USA end, it was felt that the patient’s elevated urinary copper level was due to his marked cholestasis and that his pre- predominant polyphenol or catechin within this extract, epigallocatechin-2-gallate (EGCG), may be the causative agent ]. An in vitro study suggested that high concen- This is the third reported case of hepatotoxicity associ- trations of EGCG were cytotoxic to rat liver cells [ ated with Hydroxycut. The first case demonstrated a However, this manuscript concluded that the oral bio- predominantly hepatocellular injury pattern on liver func- availability of EGCG in green tea extracts was probably tion tests with peak alanine aminotransferase 3962 U/l that too low to produce serum levels approaching the levels that resolved after 4 weeks, while the other demonstrated a were cytotoxic to the rat liver cells. Because of this, it has predominantly cholestatic pattern of injury (confirmed on been further proposed that the hepatotoxicity associated liver biopsy) that resolved after 2 months In both cases, with green tea extract may be an idiosyncratic and/or the patients were taking three tablets three times per day.
hypersensitivity-type reaction or that an undetected com- The manufacturer’s list of active ingredients in Hy- pound contaminating the extract may be the causative droxycut is shown in Table [Of the ingredients listed, extracts of Garcinia cambogia, Gymnema sylvestre, and Finally, we cannot rule out an interaction between the green tea (Camellia sinensis) have been associated with compounds in Hydroxycut and the acetaminophen the patient cases of severe hepatotoxicity. In the one case associated was taking concomitantly. Although we found no studies with Garcinia cambogia and Gymnema sylvestre, the patient directly investigating this possibility, one might speculate had taken a 7-day course of two dietary weight-loss sup- that one or more of the compounds in Hydroxycut could plements, one of which contained both Garcinia cambogia induce or stimulate the CYP2E1 cytochrome system, lead to and Gymnema sylvestre, the week prior to becoming jaun- diced This particular case progressed to fulminant (NAPQI), and thus accentuate acetaminophen-induced hepatic failure and death. The authors speculated that a hepatotoxicity, much like chronic ethanol consumption.
synergistic interaction between the weight-loss supplements Caution should be exercised by consumers using the and chronic use of a leukotriene antagonist inhibitor, a class weight-loss supplement Hydroxycut. There is evidence that of medicine that has been associated with severe hepato- extracts of Garcinia cambogia, Gymnema sylvestre, and toxicity, resulted in her fulminant and ultimately fatal green tea (Camellia sinensis) contained in Hydroxycut may be associated with severe and even fatal hepatotoxicity.
There have been at least 11 case reports associating green tea extract (Camellia sinensis extract) with severe hepatotoxicity In all cases, except two whichrequired liver transplantation there was eventual 1. Stevens T, Qadri A, Zin NN (2005) Two patients with acute liver recovery after cessation of the supplement containing the injury associated with use of the herbal weight-loss supplement extract. In one case there was some suggestion of Hydroxycut. Ann Intern Med 142(6):477–478 causation, as the patient rechallenged herself with the same supplement and again presented with severe hepatotoxicity.
3. Actis GC, Bugianesi E, Ottobrelli A, Rizzetto M (2007) Fatal The mechanism of the potential toxicity of green tea liver failure following food supplements during chronic treatment extract is unclear. There has been speculation that the 4. Bonkovsky HL (2005) Hepatotoxicity associated with supple- ments containing Chinese green tea (Camellia sinensis). Ann 5. Porcel JM, Bielsa S, Madronero AB (2005) Hepatotoxicity associated with green tea extracts [electronic letter]. Accessed at 6. Garcia-Moran S, Saez-Royuela F, Gento E, Lopez Morante A, Arias L (2004) Acute hepatitis associated with Camellia thea and Orthosiphon stamineus ingestion. Gastroenterol Hepatol 27:559–560. 7. Thiolet C, Mennecier D, Bredin C, Moulin O, Rimlinger H, Ni- zou C et al (2002) Acute cytolysis induced by Chinese tea.
Oolong tea extract (as Camellia sinensis) 8. Vial T, Bernard G, Lewden B, Dumortier J, Descotes J (2003) Acute hepatitis due to exolise, a Camellia sinensis-derived drug.
Other ingredients: hydroxypropyl cellulose, microcrystalline cellulose, polyvinlypyrrolidone, croscarmellose sodium, vegetable 9. Gloro R, Hourmand-Ollivier I, Mosquet B, Mosquet L, Rousselot stearine, magnesium stearate, coating, silica, acesulfame- P, Salame´ E et al (2005) Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea. Eur J Gastroenterol 13. Molinari M, Watt KD, Kruszyna T, Nelson R, Walsh M, Huang WY et al (2006) Acute liver failure induced by green tea extracts: 10. Abu el Wafa Y, Benavente Ferna´ndez A, Talavera Fabuel A, case report and review of the literature. Liver Transpl 12:1892– Pe´rez Ramos MA, Ramos-Clemente JI (2005) Acute hepatitis induced by Camellia sinensis (green tea). Med Intern 22(6):298 14. Schmidt M, Schmitz HJ, Baumgart A, Gue´don D, Netsch MI, 11. Duen˜as Sadornil C, Fabregas Puigtio´ S, Dura´ndez R (2005) Kreuter MH et al (2005) Toxicity of green tea extracts and their Hepatotoxicity due to Camelia sinensis. Med Clin (Barc) constituents in rat hepatocytes in primary culture. Food Chem 12. Pedros C, Cereza G, Garcia N, Laporte JR (2003) Liver toxicity of Camellia sinensis dried etanolic extract. Med Clin (Barc)121:598–599. doi:

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