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Two Patients with Acute Liver Injury Associated with Use of the Herbal Weight-Loss Supplement Hydroxycut

Tyler Stevens, MD; Asif Qadri, MD; and Nizar N. Zein, MD
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From the Cleveland Clinic Foundation, Cleveland, OH 44118.


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Ann Intern Med. 2005;142(6):477-478. doi:10.7326/0003-4819-142-6-200503150-00026
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Comments

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Chromium polynicotinate linked to hepatotoxicity
Posted on March 26, 2005
Philip J Gregory
University of the Pacific
Conflict of Interest: None Declared
Stevens, et al. are correct to point out that it is impossible to tell with certainty which ingredient(s) in Hydroxycut is responsible for hepatotoxicty in these two cases. But one ingredient stands out as the most likely: chromium polynicotinate. This formulation of chromium is bound to molecules of niacin. A previous case report describes acute hepatitis in a patient who took chromium polynicotinate in combination with herbal extracts over a period of 5 months. Symptoms resolved when the product was discontinued (1). Reference: 1. Lanca S, Alves A, Vieira AI, et al. Chromium-induced toxic hepatitis. Eur J Intern Med 2002;13:518-20.

Conflict of Interest:

None declared

Hepatotoxicity associated with green tea extracts
Posted on May 16, 2005
José M Porcel
Arnau de Vilanova University Hospital, 25198 Lleida, Spain
Conflict of Interest: None Declared

TO THE EDITOR: Stevens and colleagues, in their description of two patients with acute liver injury associated with the use of Hydroxycut, stated that no previous cases of hepatotoxicity resulting from any of the ingredients of this herbal weight-loss supplement had been reported (1). However, at least a dozen of cases of toxic hepatitis after the use of hydroalcoholic extracts of green tea (Camellia sinensis), a compound of Hydroxycut, are well recognized in the non-English literature (MEDLINE 1966-2005; key words: Camellia sinensis, hepatitis) (2,3). These observations have led some of such products to be withdrawn from the market in France and Spain. Here, we describe a case of severe hepatotoxicity associated with a dietary supplement containing green tea which is marketed in Spain for weight loss.

A previously healthy 53-year-old woman, presented with 15 days of fatigue, vomiting, low-grade fever, jaundice and right upper abdominal pain. She had taken "Fitofruit grasas acumuladas" (Gerblé, Barcelona, Spain), an herbal medicine sold for losing weight that contains extracts of green tea, for 2 weeks, 1 capsule 3 times per day, one month previously. On examination, jaundice and 4 cm-hepatomegaly were noted. Laboratory analysis revealed a total bilirrubin level of 91.4 mmol/L, aspartate aminotransferase level of 927 U/L, alanine aminotransferase level of 1,259 U/L, alkaline phosphatase level of 187 U/L, and prothrombine time of 12.7 seconds. Additional results of laboratory studies included negative tests for hepatitis A, B and C viruses, Epstein- Barr virus, cytomegalovirus, and antinuclear and antimitochondrial antibodies. Except for hepatomegaly, ultrasonography did not show any hepatic or biliary abnormality. The patient discontinued taking the dietary supplement and five weeks later liver function tests returned to normal.

The mechanism of hepatotoxicity of green tea extracts is unknown. Schmidt and colleagues found that high concentrations of green tea can damage cultured rat hepatocytes, due in part to the constituent epigallocatechin-3-gallate (4). Nevertheless, the low bioavailability of this latter compound in humans makes unlikely that the sporadic cases of liver injury after using hydroalcoholic green tea extracts can be explained by such a mechanism. Probably, most reactions are either idiosyncratic or immunoallergic.

References

1.Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement Hydroxycut. Ann Inter Med. 2005;142:477-8. [PMID: 15767636]

2.Vial T, Bernard G, Lewden B, Dumortier J, Descotes J. Hépatite aigue imputable à l´Exoliseâ (Camellia sinensis). Gastroenterol Clin Biol. 2003;27:1166-7. [PMID: 14770123]

3.Pedrós C, Cereza G, García N, Laporte JR. Hepatotoxicidad por extracto etanólico seco de Camellia sinensis. Med Clin (Barc). 2003;121:598-9. [PMID: 14622530]

4. Schmidt M, Schmitz HJ, Baumgart A, Guedon D, Netsch MI, Kreuter MH, et al. Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture. Food Chem Toxicol. 2005;43:307-14. [PMID: 15621343]

Conflict of Interest:

None declared

Hepatotoxicity in patients may have been the result of alternative factors
Posted on November 2, 2005
Debasis Bagchi
Creighton University Medical Center
Conflict of Interest: None Declared

Rebuttal to the "Letter to the Editor: Two patients with acute liver injury associated with use of the herbal weight-loss supplement Hydroxycut" T. Stevens, A. Qadri and N.N. Zein, Annals of Internal Medicine 142 (6):477-478, 2005

We conducted a thorough search of the medical literature and were unable to locate a single prior report or case of hepatoxicity associated with the ingredients used in Hydroxycut. The present report appears to be based on two isolated incidents. Thus, the induction of hepatotoxicity in these two patients may have been the result of factors unrelated to the ingestion of Hydroxycut. Importantly, the authors stated that "evidence for the efficacy of Garcinia cambogia in promoting weight loss is not compelling" [Ref. Lenz and Hamilton, J. Am. Pharm. Assoc. (Wash DC) 44: 59 -67 (2004)]. While the evidence for efficacy of some forms of Garcinia cambogia may be questionable, the form used in Hydroxycut is not. The active compound in Garcinia cambogia is (-)-hydroxycitric acid (HCA), typically available in dietary supplements as a relatively insoluble calcium salt at ineffective dosages. The form used in Hydroxycut is a highly soluble and bioavailable calcium/potassium salt of HCA called Super Citrimax. Extensive in vitro, in vivo and human clinical trials have demonstrated that efficacious doses of Super Citrimax are highly effective and completely safe to take (1-11). Recent studies have demonstrated the ability of Super Citrimax to boost serotonin levels and activity in the body, reduce appetite, increase fat oxidation, improve blood lipids and decrease body weight 3-times greater than diet and exercise alone following eight weeks of supplementation. Extensive toxicology studies have been performed as well. We encourage the authors to review these publications, whereby they may draw a different conclusion.

1. S.E. Ohia, S.O. Awe, A.M. LeDay, C.A. Opere and D. Bagchi. Effect of hydroxycitric acid on serotonin release from isolated rat brain cortex. Res. Commun. Mol. Pathol. Pharmacol. 109: 210-216 (2001).

2. Y.C. Loe, N. Bergeron, N. Rodriguez and J.M. Schwarz. Gas chromatography/mass spectrometry method to quantify blood hydroxycitrate concentration. Anal. Biochem. 292:148-154 (2001).

3. S.E. Ohia, C.A. Opere, A.M. LeDay, M. Bagchi, D. Bagchi and S.J. Stohs. Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). Mol. Cell. Biochem. 238: 89-103 (2002).

4. N. Talpur, B.W. Echard, T. Yasmin, D. Bagchi and H.G. Preuss. Effects of niacin-bound chromium, maitake mushroom fraction SX and (-)- hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats. Mol. Cell. Biochem. 252: 369-377 (2003).

5. M. Shara, S.E. Ohia, T. Yasmin, A. Zardetto-Smith, A. Kincaid, M. Bagchi, A. Chatterjee, D. Bagchi and S.J. Stohs. Dose- and time-dependent effects of a novel (-)-hydroxycitric acid extract on hepatic and testicular lipid peroxidation, DNA fragmentation and histopathological data over a period of 90 days in rats. Mol. Cell. Biochem. 254: 339-346 (2003).

6. H.G. Preuss, D. Bagchi, M. Bagchi, C.V. Sanyasi Rao, S. Satyanarayana and D.K. Dey. Efficacy of a novel, natural extract of (-)- hydroxycitric acid (HCA-SX) and a combination of HCA-SX, niacin-bound chromium and Gymnema sylvestre extract in weight management in human volunteers. Nutrition Research 24: 45-58 (2004).

7. H.G. Preuss, D. Bagchi, M. Bagchi, C.V. Sanyasi Rao, D.K. Dey and S. Satyanarayana. Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss. Diabetes, Obesity and Metabolism 6: 171-180 (2004).

8. M. Shara, S.E. Ohio, R.E. Schmidt, T. Yasmin, A. Zardetto-Smith, A. Kincaid, M. Bagchi, A. Chatterjee, D. Bagchi and S.J. Stohs. Physico- chemical properties of a novel (-)-hydroxycitric acid extract and its effect on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological changes over a period of 90 days. Mol. Cell. Biochem. 260: 171-186 (2004).

9. S. Roy, C. Rink, S. Khanna, C. Phillips, D. Bagchi, M. Bagchi and C.K. Sen. Body weight and abdominal fat gene expression profile in response to a novel hydroxycitric acid based dietary supplement. Gene Expression 11(5/6): 251-262 (2004).

10. M.G. Soni, G.A. Burdock, H.G. Preuss, S.J. Stohs, S.E. Ohia and D. Bagchi. Safety assessment of (-)-hydroxycitric acid and Super CitriMax, a novel calcium/potassium salt. Food Chem. Toxicol. 42: 1513-1529 (2004).

11. B.W. Downs, M. Bagchi, G.V. Subbaraju, M.A. Shara, H.G. Preuss and D. Bagchi, Bioefficacy of a novel calcium-potassium salt of (-)- hydroxycitric acid. Mutation Res. (in press).

Best Regards,

Debasis Bagchi, Ph.D., FACN, CNS, MAIChE

Professor, Department of Pharmacy Sciences, Creighton University Medical Center, 2500 California Plaza, Omaha, NE 68178 Senior Vice President, Research and Development, InterHealth Nutraceuticals, 5451 Industrial Way Benicia, CA 94510

Harry G. Preuss, MD

Department of Physiology, Medicine & Pathology, Georgetown University Medical Center, 4000 Reservoir Road NW, Washington, DC 20057

Conflict of Interest:

None declared

Re: Hepatotoxicity in patients may have been the result of alternative factors
Posted on January 15, 2009
Ano L Lobb
Independent Public Health Consultant
Conflict of Interest: None Declared

Dr. Bagchi's rapid response fails to disclose a major conflict of interest in regards to Hydroxycut, the weight loss supplement that Stevens et al. discuss (1). As Senior Vice President for Research and Development at InterHealth Nutraceuticals both currently and at the time of his response (2), Dr. Bagchi could easily be perceived as having a serious conflict of interest in regards to this discussion. At the very least, this conflict warrants disclosure in the area provided within this forum. According to their own website, InterHealth is the owner and marketer of the product he mentions, Super CitriMax (3). This product also contains G.cambogia and is an ingredient in numerous weight loss supplements, including Hydroxycut (4). Clearly the implication that Hydroxycut may be hepatoxic, and that G. cambogia is one of its ingredients, could have possible financial implications for both InterHealth and Dr. Bagchi. Further, 4 additional case reports linking hepatoxicty to Hydroxycut have been published (5, 6, 7), and G. cambogia is implicated as a possible hepatoxic agent (7), strengthening the concerns first raised by Stevens et al.

References

1. Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement Hydroxycut. Ann Inter Med. 2005;142:477-8. [PMID: 15767636]

2. http://www.interhealthusa.com/About/Leadership-Team.aspx, accessed January 15, 2009

3. http://www.interhealthusa.com/About/Company-History.aspx, accessed January 15, 2009

4. http://www.interhealthusa.com/Ingredients/Super-CitriMax.aspx, accessed January 15, 2009

5. Shim M, Saab S. Severe hepatoxicity due to hydroxycut: A case report. Dig Dis Sci 2008; [Epub ahead of print] [PMID: 18661239 DOI: 10.1007/s10620-008-0353-4]

6. Jones FJ, Andrews AH. Acute liver injury associated with the herbal supplement hydroxycut in a soldier deployed to Iraq. Am J Gastroenterol 2007; 102(10): 2357-2358 [PMID: 17897352]

7. Dara L, Hewett J, Lim JK. Hydroxycut hepatoxicity: A case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol 2008; 14(45): 6999-7004 [PMID: 19058338 DOI:http://dxdoi.org/10.3748/wjg.14.6999]

Conflict of Interest:

None declared

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