Dietary supplements containing Garcinia cambogia extract, alone or in conjunction with green tea may cause clinically similar severe liver injury, an analysis of the Drug-Induced Liver Injury Network shows.
Garcinia cambogia, either alone or with green tea is very commonly promoted for weight loss. However, sporadic cases of liver failure from Garcinia cambogia have been reported, but its role in liver injury is controversial.
Among more than 1,400 cases of documented drug-induced liver injury from 2004 to 2018, there were 22 cases related to G. cambogia supplements with or without green tea; of these, 91% required hospitalisation for hepatocellular liver injury with jaundice, one patient needed a transplant, and two died, according to Dr Victor Navarro of the Einstein Healthcare Network in Philadelphia, and colleagues, published in Clinical Gastroenterology and Hepatology.
The immune-mediated allele HLA-B*35X01 was more frequently detected among patients with liver injuries from supplements containing G. cambogia alone (60%), compared with control groups of those with injuries from other types of dietary supplements or conventional drugs.
"Although the allele frequency was lower than what was reported recently with green tea-associated liver injury (72-90% depending on causality score), the hepatocellular pattern of enzyme elevations and moderate to a severe course with jaundice raises the possibility that G. cambogia liver injury is immune-mediated [and] occurring in predisposed individuals," Navarro and co-authors wrote. "However, this association needs to be confirmed."
Compared with liver injuries from green tea-infused supplements, those attributable to G. cambogia alone did not differ in clinical or histological features, or biochemical testing, the authors noted, nor were there differences in patient demographics. Navarro's group noted that G. cambogia is often marketed with green tea, and that perhaps the two "are additive or synergistic in their adverse effects in genetically susceptible individuals".
"Before starting any supplement, I encourage my patients to discuss the product with me so we can discuss the safety and possibly consider alternative strategies," said Dr Michelle T Long, of Boston Medical Centre, who was not involved in this study. “Some individuals experienced liver injury 12 months after taking the Garcinia cambogia or HCA [hydroxycitric acid]-containing supplement, which highlights the need for patients to keep careful track of any products they use, even over a long timeframe," she told MedPage Today.
"G. cambogia was used primarily by young women, mostly white and Hispanic, who were overweight but not obese," the authors said. "Unless the clinician actively pursues questions during clinical history-taking, G. cambogia as the implicated agent for liver injury could be easily missed. This situation emphasises the need for clinicians to inquire about [herbal and dietary supplements] use in all cases of acute hepatitis."
Long added that clinicians should ask patients about supplements they are no longer taking as well, if there is suspicion for drug-induced liver injury.
Garcinia cambogia, or Malabar tamarind, is a fruit native to parts of India and Southeast Asia. The rind contains HCA, which has been marketed as a natural weight-loss product, among other beneficial claims. Use of the extract in dietary supplements has been linked with liver injury.
For their study, the researchers evaluated 1,418 participants from the Drug-Induced Liver Injury Network, an NIH consortium study of medical centres, who were enrolled from 2004 to 2018 and had "probable, highly likely, or definite drug-induced liver injury". Patients were included if their liver injury was sustained within six months of enrollment and confirmed by blood tests.
Among the 22 cases of liver injury due to G. cambogia, the product was consumed alone in five cases, and was combined with green tea in 16 cases and with another herbal supplement, ashwagandha, in one case. Control groups involved patients with liver injury from green tea supplements (n=57; excluding G. cambogia), from other non-anabolic steroid supplements (n=103; excluding G. cambogia and green tea), or from conventional drugs (n=1,143).
Median age in the G. cambogia group was 35 (range 17-54), more than half were female, most were overweight, 64% identified as white, and 41% identified as Hispanic. Follow-up occurred at six months. Median onset from taking G. cambogia to liver injury was 51 days.
Rash or fever also occurred among three of the G. cambogia patients. Seven patients had severe liver injury, 13 had moderate injury, and two cases were fatal. Two of the 19 surviving patients sustained chronic drug- induced liver injury.
Study limitations included the inability to chemically test all supplements, the authors acknowledged. They also noted that G. cambogia has a long latency period, up to a year, which "might falsely reassure patients and the clinicians treating these patients about G. cambogia as an implicated agent”.
Study details
Garcinia Cambogia, Either Alone or in Combination with Green Tea Causes Moderate to Severe Liver Injury
Raj Vuppalanchi, Herbert L. Bonkovsky, Jawad Ahmad, Huiman Barnhart, Francisco Durazo, Robert J. Fontana, Jiezhun Gu, Ikhlas Khan, David E. Kleiner, Christopher Koh, Don C. Rockey, Elizabeth J. Phillips, Yi-Ju Li, Jose Serrano, Andrew Stolz, Hans L. Tillmann, Leonard B. Seeff, Jay H. Hoofnagle, Victor J. Navarro
Published in Clinical Gastroenterology & Hepatology 13 August 2021
ABSTRACT
Background
Garcinia cambogia, either alone or with green tea, is commonly promoted for weight loss. Sporadic cases of liver failure from G. cambogia have been reported, but its role in liver injury is controversial.
Methods
Among 1418 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2018, we identified 22 cases (adjudicated with high confidence) of liver injury from G. cambogia either alone (n=5) or in combination with green tea (n=16) or Ashwagandha (n=1). Control groups consisted of 57 patients with liver injury from herbal and dietary supplements (HDS) containing green tea without G. cambogia and 103 patients from other HDS.
Results
Patients who took G. cambogia were between 17 to 54 years, with liver injury arising 13 to 223 days (median = 51) after the start. One patient died, one required liver transplantation, and 91% were hospitalised. The liver injury was hepatocellular with jaundice. Although the peak values of aminotransferases were significantly higher (2001 ± 1386 U/L) in G. cambogia group (p <0.018), the median time for improvement in total bilirubin (TB) was significantly lower compared to the control groups (10 vs. 17 and 13 days, p = 0.03). The presence of HLA-B*35:01 allele was significantly higher in the G. cambogia containing HDS (55%) compared to patients due to other HDS (19%) (p = 0.002) and those with acute liver injury from conventional drugs (12%) (p = 2.55×10-6).
Conclusions
The liver injury caused by G. cambogia and green tea is clinically indistinguishable. The possible association with HLA-B*35:01 allele suggests an immune-mediated mechanism of injury.
Medpage Today article – Herbal Weight-Loss Supplement Tied to Severe Liver Damage (Open access)
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