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.

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References
10 facts on obesity. http://www.who.int/features/factfiles/obesity/en/. Accessed 07 May 2018
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
Dietz B, Bolton JL (2007) Botanical dietary supplements gone bad. Chem Res Toxicol 20:586–590
Pittler MH, Schmidt K, Ernst E (2005) Adverse events of herbal food supplements for body weight reduction: systematic review. Obes Rev 6:93–111
Bray GA (2008) Are non-prescription medications needed for weight control? Obesity 16:509–514
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
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
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
Semwal RB, Semwal DK, Vermaak I, Viljoen A (2015) A comprehensive scientific overview of Garcinia cambogia. Fitoterapia 102:134–148
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
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
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
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
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
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
Joseph DJM, Levine M (2014) Stress induced cardiomyopathy after ingestion of Garcinia cambogia. Clin Toxicol 52:739–740
Lopez AM, Kornegay J, Hendrickson RG (2014) Serotonin toxicity associated with Garcinia cambogia over-the-counter supplement. J Med Toxicol 10:399–401
Roche B, Chenoweth JA, Radke JB, Poppenga RH, Sutter ME (2014) Hypoglycemia associated with Garcinia Cambogia ingestion. Clin Toxicol 52:736
Sikka G, Gupta A, Bachan M, Khan Z (2016) “Uber-trim” causes immune thrombocytopenic purpura: a life threatening case report. Chest 150:392A
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
Sidhu RLS, Khehra L (2016) Garcinia cambogia: a link between the “miracle” weight loss pill and acute pancreatitis. Am J Gastroenterol 111:S560–S561
Dehoney S, Wellein M (2009) Rhabdomyolysis associated with the nutritional supplement Hydroxycut. Am J Health Syst Pharm 66:142–148
Hines EQDTE, Melville LD, Su MK (2015) Severe rhabdomyolysis associated with Garcinia cambogia. Clin Toxicol 53:746–747
Mansi IA, Huang J (2004) Rhabdomyolysis in response to weight-loss herbal medicine. Am J Med Sci 327:356–357
Cotovio G, Oliveira-Maia AJ (2017) Hypomania induced by a Garcinia cambogia supplement. Aust N Z J Psychiatry 51:641–642
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
Nguyen DC, Timmer TK, Davison BC, McGrane IR (2017) Possible Garcinia cambogia-induced mania with psychosis: a case report. J Pharm Pract 1:897190017734728
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
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
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
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
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
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
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
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
Kothadia JPRR, Olivera-Martinez M (2016) Hepatoxicity associated with Garcinia cambogia used as a weight loss supplement. Am J Gastroenterol 111:S881
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
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
Melendez-Rosado J, Snipelisky D, Matcha G, Stancampiano F (2015) Acute hepatitis induced by pure Garcinia cambogia. J Clin Gastroenterol 49:449–450
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
Shim M, Saab S (2009) Severe hepatotoxicity due to Hydroxycut: a case report. Dig Dis Sci 54:406–408
Smith RJ, Bertilone C, Robertson AG (2016) Fulminant liver failure and transplantation after use of dietary supplements. Med J Aust 204:30–32
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
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
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
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
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
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
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
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
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
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
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
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
Cavalieri ML, D’Agostino D (2017) Drug-, herb- and dietary supplement-induced liver injury. Archivos argentinos de Pediatria 115:e397–e403
Frenzel C, Teschke R (2016) Herbal hepatotoxicity: clinical characteristics and listing compilation. Int J Mol Sci. https://doi.org/10.3390/ijms17050588
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
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
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
Dickinson A, MacKay D (2014) Health habits and other characteristics of dietary supplement users: a review. Nutr J 13:14
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
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
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
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
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
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
Wong AL, Chan TY (2003) Interaction between warfarin and the herbal product quilinggao. Ann Pharmacother 37:836–838
Lee NJ, Fermo JD (2006) Warfarin and royal jelly interaction. Pharmacotherapy 26:583–586
Kennedy J (2005) Herb and supplement use in the US adult population. Clin Ther 27:1847–1858
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
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
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
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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
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DOI: https://doi.org/10.1007/s11739-018-1880-4

