Acute liver injury following Garcinia cambogia weight-loss supplementation: case series and literature review

Abstract

Herbal weight-loss supplements are sold as self-medication products, and are often used under the misconception that their natural origin guarantees their safety. Food supplements are not required to provide any benefit/risk profile evaluation before marketing; however, possible risks associated with use of herbal extracts in food supplements are becoming more and more documented in the literature. Some herbs are listed as the leading cause of herb-induced liver injury, with a severe or potentially lethal clinical course, and unpredictable herb–drug interactions. Garcinia cambogia (GC) extract and GC-containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we present four cases of acute liver failure in women taking GC extract for weight loss, and a literature review of clinical evidences about hepatic toxicity in patients taking dietary supplements containing GC extract.

This is a preview of subscription content, log in to check access.

Fig. 1

References

  1. 1.

    10 facts on obesity. http://www.who.int/features/factfiles/obesity/en/. Accessed 07 May 2018

  2. 2.

    Skeie G, Braaten T, Hjartaker A, Lentjes M, Amiano P, Jakszyn P et al (2009) Use of dietary supplements in the European prospective investigation into cancer and nutrition calibration study. Eur J Clin Nutr 63(Suppl 4):S226–S238

    Article  PubMed  CAS  Google Scholar 

  3. 3.

    Dietz B, Bolton JL (2007) Botanical dietary supplements gone bad. Chem Res Toxicol 20:586–590

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. 4.

    Pittler MH, Schmidt K, Ernst E (2005) Adverse events of herbal food supplements for body weight reduction: systematic review. Obes Rev 6:93–111

    Article  PubMed  CAS  Google Scholar 

  5. 5.

    Bray GA (2008) Are non-prescription medications needed for weight control? Obesity 16:509–514

    Article  PubMed  Google Scholar 

  6. 6.

    Pajor EM, Oenema A, Eggers SM, de Vries H (2017) Exploring beliefs about dietary supplement use: focus group discussions with Dutch adults. Public Health Nutr 20:2694–2705

    Article  PubMed  Google Scholar 

  7. 7.

    Garcia-Cortes M, Robles-Diaz M, Ortega-Alonso A, Medina-Caliz I, Andrade RJ (2016) Hepatotoxicity by dietary supplements: a Tabular listing and clinical characteristics. Int J Mol Sci 17:537

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. 8.

    Fassina P, Scherer Adami F, Terezinha Zani V, Kasper Machado IC, Garavaglia J, Quevedo Grave MT et al (2015) The effect of Garcinia cambogia as coadjuvant in the weight loss process. Nutr Hosp 32:2400–2408

    PubMed  Google Scholar 

  9. 9.

    Semwal RB, Semwal DK, Vermaak I, Viljoen A (2015) A comprehensive scientific overview of Garcinia cambogia. Fitoterapia 102:134–148

    Article  PubMed  CAS  Google Scholar 

  10. 10.

    Onakpoya I, Hung SK, Perry R, Wider B, Ernst E (2011) The use of garcinia extract (Hydroxycitric Acid) as a weight loss supplement: a systematic review and meta-analysis of randomised clinical trials. J Obes 2011:509038

    Article  PubMed  Google Scholar 

  11. 11.

    Ohia SE, Opere CA, LeDay AM, Bagchi M, Bagchi D, Stohs SJ (2002) Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). Mol Cell Biochem 238:89–103

    Article  PubMed  CAS  Google Scholar 

  12. 12.

    Mazzanti G, Moro PA, Raschi E, Da Cas R, Menniti-Ippolito F (2017) Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system. Br J Clin Pharmacol 83:894–908

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. 13.

    Actis GC, Bugianesi E, Ottobrelli A, Rizzetto M (2007) Fatal liver failure following food supplements during chronic treatment with montelukast. Digestive Liv Dis 39:953–955

    Article  CAS  Google Scholar 

  14. 14.

    Teschke R, Wolff A, Frenzel C, Schwarzenboeck A, Schulze J, Eickhoff A (2014) Drug and herb induced liver injury: council for international organizations of medical sciences scale for causality assessment. World J Hepatol 6:17–32

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Allen SF, Godley RW, Evron JM, Heider A, Nicklas JM, Thomas MP (2014) Acute necrotizing eosinophilic myocarditis in a patient taking Garcinia cambogia extract successfully treated with high-dose corticosteroids. Can J Cardiol 30(1732):e13–e15

    Google Scholar 

  16. 16.

    Joseph DJM, Levine M (2014) Stress induced cardiomyopathy after ingestion of Garcinia cambogia. Clin Toxicol 52:739–740

    Google Scholar 

  17. 17.

    Lopez AM, Kornegay J, Hendrickson RG (2014) Serotonin toxicity associated with Garcinia cambogia over-the-counter supplement. J Med Toxicol 10:399–401

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Roche B, Chenoweth JA, Radke JB, Poppenga RH, Sutter ME (2014) Hypoglycemia associated with Garcinia Cambogia ingestion. Clin Toxicol 52:736

    Google Scholar 

  19. 19.

    Sikka G, Gupta A, Bachan M, Khan Z (2016) “Uber-trim” causes immune thrombocytopenic purpura: a life threatening case report. Chest 150:392A

    Article  Google Scholar 

  20. 20.

    Bystrak T, Cervera-Hernandez ME, Reddy N, King Z, Bratberg J (2017) Garcinia Cambogia, diabetic ketoacidosis, and pancreatitis. R I Med J 100:48–50

    Google Scholar 

  21. 21.

    Sidhu RLS, Khehra L (2016) Garcinia cambogia: a link between the “miracle” weight loss pill and acute pancreatitis. Am J Gastroenterol 111:S560–S561

    Google Scholar 

  22. 22.

    Dehoney S, Wellein M (2009) Rhabdomyolysis associated with the nutritional supplement Hydroxycut. Am J Health Syst Pharm 66:142–148

    Article  PubMed  CAS  Google Scholar 

  23. 23.

    Hines EQDTE, Melville LD, Su MK (2015) Severe rhabdomyolysis associated with Garcinia cambogia. Clin Toxicol 53:746–747

    Google Scholar 

  24. 24.

    Mansi IA, Huang J (2004) Rhabdomyolysis in response to weight-loss herbal medicine. Am J Med Sci 327:356–357

    Article  PubMed  Google Scholar 

  25. 25.

    Cotovio G, Oliveira-Maia AJ (2017) Hypomania induced by a Garcinia cambogia supplement. Aust N Z J Psychiatry 51:641–642

    Article  PubMed  Google Scholar 

  26. 26.

    Narasimha A, Shetty PH, Nanjundaswamy MH, Viswanath B, Bada Math S (2013) Hydroxycut—dietary supplements for weight loss: can they induce mania? Aust N Z J Psychiatry 47:1205–1206

    Article  PubMed  Google Scholar 

  27. 27.

    Nguyen DC, Timmer TK, Davison BC, McGrane IR (2017) Possible Garcinia cambogia-induced mania with psychosis: a case report. J Pharm Pract 1:897190017734728

    Google Scholar 

  28. 28.

    Wong MK, Darvishzadeh A, Maler NA, Bota RG (2016) Five supplements and multiple psychotic symptoms: a case report. Prim Care Companion CNS Disord. https://doi.org/10.4088/PCC.15br01856

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Hendrickson BP, Shaikh N, Occhiogrosso M, Penzner JB (2016) Mania induced by Garcinia cambogia: a case series. Prim Care Companion CNS Disord. https://doi.org/10.4088/PCC.15l01890

    PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Chen GC, Ramanathan VS, Law D, Funchain P, Chen GC, French S et al (2010) Acute liver injury induced by weight-loss herbal supplements. World J Hepatol 2:410–415

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Corey R, Werner KT, Singer A, Moss A, Smith M, Noelting J et al (2016) Acute liver failure associated with Garcinia cambogia use. Ann Hepatol 15:123–126

    Article  PubMed  Google Scholar 

  32. 32.

    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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. 33.

    Elinav E, Pinsker G, Safadi R, Pappo O, Bromberg M, Anis E et al (2007) Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity. J Hepatol 47:514–520

    Article  PubMed  CAS  Google Scholar 

  34. 34.

    Fong TL, Klontz KC, Canas-Coto A, Casper SJ, Durazo FA, Davern TJ 2nd et al (2010) Hepatotoxicity due to hydroxycut: a case series. Am J Gastroenterol 105:1561–1566

    Article  PubMed  Google Scholar 

  35. 35.

    Jones FJ, Andrews AH (2007) Acute liver injury associated with the herbal supplement hydroxycut in a soldier deployed to Iraq. Am J Gastroenterol 102:2357–2358

    Article  PubMed  Google Scholar 

  36. 36.

    Kothadia JPRR, Olivera-Martinez M (2016) Hepatoxicity associated with Garcinia cambogia used as a weight loss supplement. Am J Gastroenterol 111:S881

    Google Scholar 

  37. 37.

    Lunsford KE, Bodzin AS, Reino DC, Wang HL, Busuttil RW (2016) Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation. World J Gastroenterol 22:10071–10076

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    McDonnell WM, Bhattacharya R, Halldorson JB (2009) Fulminant hepatic failure after use of the herbal weight-loss supplement exilis. Ann Intern Med 151:673–674

    Article  PubMed  Google Scholar 

  39. 39.

    Melendez-Rosado J, Snipelisky D, Matcha G, Stancampiano F (2015) Acute hepatitis induced by pure Garcinia cambogia. J Clin Gastroenterol 49:449–450

    Article  PubMed  Google Scholar 

  40. 40.

    Schoepfer AM, Engel A, Fattinger K, Marbet UA, Criblez D, Reichen J et al (2007) Herbal does not mean innocuous: ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife products. J Hepatol 47:521–526

    Article  PubMed  CAS  Google Scholar 

  41. 41.

    Shim M, Saab S (2009) Severe hepatotoxicity due to Hydroxycut: a case report. Dig Dis Sci 54:406–408

    Article  PubMed  Google Scholar 

  42. 42.

    Smith RJ, Bertilone C, Robertson AG (2016) Fulminant liver failure and transplantation after use of dietary supplements. Med J Aust 204:30–32

    Article  PubMed  Google Scholar 

  43. 43.

    Stevens T, Qadri A, Zein NN (2005) Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med 142:477–478

    Article  PubMed  Google Scholar 

  44. 44.

    Stickel F, Droz S, Patsenker E, Bogli-Stuber K, Aebi B, Leib SL (2009) Severe hepatotoxicity following ingestion of Herbalife nutritional supplements contaminated with Bacillus subtilis. J Hepatol 50:111–117

    Article  PubMed  CAS  Google Scholar 

  45. 45.

    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

    Article  PubMed  Google Scholar 

  46. 46.

    The use of the WHO-UMC system for standardised case causality assessment. https://www.who-umc.org/media/2768/standardised-case-causality-assessment.pdf. Accessed 07 May 2018

  47. 47.

    Fontana RJ, Watkins PB, Bonkovsky HL, Chalasani N, Davern T, Serrano J et al (2009) Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Saf 32:55–68

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. 48.

    Hayamizu K, Hirakawa H, Oikawa D, Nakanishi T, Takagi T, Tachibana T et al (2003) Effect of Garcinia cambogia extract on serum leptin and insulin in mice. Fitoterapia 74:267–273

    Article  PubMed  CAS  Google Scholar 

  49. 49.

    Amin KA, Kamel HH, Abd Eltawab MA (2011) The relation of high fat diet, metabolic disturbances and brain oxidative dysfunction: modulation by hydroxy citric acid. Lipids Health Dis 10:74

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. 50.

    Oluyemi KA, Omotuyi IO, Jimoh OR, Adesanya OA, Saalu CL, Josiah SJ (2007) Erythropoietic and anti-obesity effects of Garcinia cambogia (bitter kola) in Wistar rats. Biotechnol Appl Biochem 46:69–72

    Article  PubMed  CAS  Google Scholar 

  51. 51.

    Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C (1998) Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA 280:1596–1600

    Article  PubMed  CAS  Google Scholar 

  52. 52.

    Cheng IS, Huang SW, Lu HC, Wu CL, Chu YC, Lee SD et al (2012) Oral hydroxycitrate supplementation enhances glycogen synthesis in exercised human skeletal muscle. Br J Nutr 107:1048–1055

    Article  PubMed  CAS  Google Scholar 

  53. 53.

    Amin KA, Kamel HH, Abd Eltawab MA (2011) Protective effect of Garcinia against renal oxidative stress and biomarkers induced by high fat and sucrose diet. Lipids health Dis 10:6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. 54.

    Marquez F, Babio N, Bullo M, Salas-Salvado J (2012) Evaluation of the safety and efficacy of hydroxycitric acid or Garcinia cambogia extracts in humans. Crit Rev Food Sci Nutr 52:585–594

    Article  PubMed  Google Scholar 

  55. 55.

    Cavalieri ML, D’Agostino D (2017) Drug-, herb- and dietary supplement-induced liver injury. Archivos argentinos de Pediatria 115:e397–e403

    PubMed  Google Scholar 

  56. 56.

    Frenzel C, Teschke R (2016) Herbal hepatotoxicity: clinical characteristics and listing compilation. Int J Mol Sci. https://doi.org/10.3390/ijms17050588

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Asghar M, Monjok E, Kouamou G, Ohia SE, Bagchi D, Lokhandwala MF (2007) Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats. Mol Cell Biochem 304:93–99

    Article  PubMed  CAS  Google Scholar 

  58. 58.

    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

    Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Sanchez-Valle V, Chavez-Tapia NC, Uribe M, Mendez-Sanchez N (2012) Role of oxidative stress and molecular changes in liver fibrosis: a review. Curr Med Chem 19:4850–4860

    Article  PubMed  CAS  Google Scholar 

  60. 60.

    Dickinson A, MacKay D (2014) Health habits and other characteristics of dietary supplement users: a review. Nutr J 13:14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. 61.

    Gallo E, Maggini V, Berardi M, Pugi A, Notaro R, Talini G et al (2013) Is green tea a potential trigger for autoimmune hepatitis? Phytomedicine 20:1186–1189

    Article  PubMed  CAS  Google Scholar 

  62. 62.

    Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M et al (2017) Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study. Gastroenterology 152:1078–1089

    Article  PubMed  CAS  Google Scholar 

  63. 63.

    Krupa R, Czarny P, Wigner P, Wozny J, Jablkowski M, Kordek R et al (2017) The relationship between single-nucleotide polymorphisms, the expression of DNA damage response genes, and hepatocellular carcinoma in a polish population. DNA Cell Biol 36:693–708

    Article  PubMed  CAS  Google Scholar 

  64. 64.

    Brewer CT, Chen T (2017) Hepatotoxicity of herbal supplements mediated by modulation of cytochrome P450. Int J Mol Sci. https://doi.org/10.3390/ijms18112353

    PubMed  PubMed Central  Article  Google Scholar 

  65. 65.

    Awortwe C, Makiwane M, Reuter H, Muller C, Louw J, Rosenkranz B (2018) Critical evaluation of causality assessment of herb-drug interactions in patients. Br J Clin Pharmacol 84(4):679–693

    Article  PubMed  Google Scholar 

  66. 66.

    Prasad GV, Wong T, Meliton G, Bhaloo S (2002) Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient. Transplantation 74:1200–1201

    Article  PubMed  Google Scholar 

  67. 67.

    Wong AL, Chan TY (2003) Interaction between warfarin and the herbal product quilinggao. Ann Pharmacother 37:836–838

    Article  PubMed  Google Scholar 

  68. 68.

    Lee NJ, Fermo JD (2006) Warfarin and royal jelly interaction. Pharmacotherapy 26:583–586

    Article  PubMed  Google Scholar 

  69. 69.

    Kennedy J (2005) Herb and supplement use in the US adult population. Clin Ther 27:1847–1858

    Article  PubMed  Google Scholar 

  70. 70.

    Thazhath SS, Wu T, Bound MJ, Checklin HL, Standfield S, Jones KL et al (2016) Effects of intraduodenal hydroxycitrate on glucose absorption, incretin release, and glycemia in response to intraduodenal glucose infusion in health and type 2 diabetes: a randomised controlled trial. Nutrition 32:553–559

    Article  PubMed  CAS  Google Scholar 

  71. 71.

    Al-Kuraishy HM, Al-Gareeb AI (2016) Effect of orlistat alone or in combination with Garcinia cambogia on visceral adiposity index in obese patients. J Intercult Ethnopharmacol 5:408–414

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. 72.

    Vasques CA, Schneider R, Klein-Junior LC, Falavigna A, Piazza I, Rossetto S (2014) Hypolipemic effect of Garcinia cambogia in obese women. Phytother Res 28:887–891

    Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Giada Crescioli.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

None.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 120 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Crescioli, G., Lombardi, N., Bettiol, A. et al. Acute liver injury following Garcinia cambogia weight-loss supplementation: case series and literature review. Intern Emerg Med 13, 857–872 (2018). https://doi.org/10.1007/s11739-018-1880-4

Download citation

Keywords

  • Adverse events
  • Dietary supplements
  • Garcinia cambogia
  • Herb-induced liver injury
  • Hydroxycitric acid
  • Liver transplantation
  • Weight-loss supplements