What ingredients in over‑the‑counter weight‑loss supplements are most commonly linked to liver injury?
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Executive summary
Over‑the‑counter weight‑loss supplements most commonly linked to clinically significant liver injury include green tea extract (GTE, especially EGCG), Garcinia cambogia (hydroxycitric acid), usnic acid, Ephedra/ma huang, and several other botanicals such as kava, black cohosh, germander and chaparral; multi‑ingredient “fat burner” products and contamination with undeclared pharmaceuticals further complicate attribution [1] [2] [3] [4] [5]. The pattern is largely idiosyncratic—sometimes immune‑mediated, sometimes mitochondrial/oxidative stress‑related—and is amplified by high concentrations, ingredient interactions, and weak regulatory oversight of supplements [1] [2] [5] [4].
1. Green tea extract: a repeatedly implicated suspect with a complex story
Concentrated green tea extracts (GTE), rich in catechins such as epigallocatechin gallate (EGCG), have been implicated in dozens of case reports and case series of acute hepatocellular injury and even liver failure requiring transplantation, with at least 50 published reports linking GTE to clinically apparent hepatitis since 2006 and product withdrawals in Europe after clusters of cases [1] [2] [6]. Toxicology suggests high doses of EGCG cause mitochondrial injury and oxidative stress in animals, but human reactions often appear idiosyncratic and may involve genetic susceptibility—an association with HLA‑B*35:01 has been reported in GTE‑related liver injury—so dose alone does not fully explain risk [1] [7].
2. Garcinia cambogia and related weight‑loss extracts: repeated signals in case reports
Garcinia cambogia, whose active principle is hydroxycitric acid, has been repeatedly reported in association with clinically significant liver injury across regions and registries, and in vitro and epidemiologic work suggests combined use with other weight‑loss agents (for example GTE) may increase hepatotoxic potential, though isolating causation is often difficult because products are multi‑ingredient [8] [9] [7].
3. Usnic acid, Ephedra (ma huang) and other historical “fat burners” that cause direct toxicity
Usnic acid—an herbal mitochondrial uncoupler once promoted in fat burners—has been directly linked to fulminant hepatic failure and transplant cases, while Ephedra/ma huang (ephedra alkaloids) was tied to hepatic as well as cardiovascular harms and led to regulatory bans in some jurisdictions; both illustrate single‑ingredient products with clear toxicity signals [3] [2].
4. A broader list of suspect botanicals and promoting factors
Additional botanicals reported in the literature with links to liver injury include kava, black cohosh, germander (Teucrium chamaedrys), chaparral (Larrea tridentata), guggul, turmeric/curcumin formulations (noting enhanced absorption with piperine may raise risk), red yeast rice and conjugated linoleic acid (CLA), and case counts across registries implicate weight‑loss and multi‑ingredient products frequently in women and bodybuilding products in men [4] [2] [8] [9] [6].
5. Why attribution is hard — multi‑ingredient products, contamination, and regulatory gaps
Many implicated products are blends marketed as “fat burners,” making it difficult to identify the causative molecule; undeclared pharmaceutical adulterants or contaminants have been documented and may explain heterogeneity of injury patterns, and FDA oversight differs from that for drugs so post‑market detection and product withdrawals (rather than pre‑market proof of safety) are the norm [10] [1] [2] [11].
6. Mechanisms, susceptibility and the limits of evidence
Reported mechanisms range from idiosyncratic immune reactions (suggested by HLA associations) to direct mitochondrial toxicity and oxidative stress from agents like EGCG or usnic acid, and genetic factors, co‑medications, fasting, and dose/formulation (extract method, bioavailability enhancers like piperine) all modify risk; importantly, randomized trials rarely capture these rare but severe events, so evidence comes mainly from case reports, registries and mechanistic studies [1] [7] [8] [6].
7. Takeaway for clinicians and policymakers
Clinical series and surveillance data consistently point to green tea extract, Garcinia cambogia, usnic acid, Ephedra/ma huang and a set of other botanicals as the most frequent suspects in supplement‑related liver injury, with multi‑ingredient products and undeclared components complicating causal inference; meaningful mitigation will require better pre‑market ingredient verification, mandatory product listing and stronger post‑market surveillance as recommended by experts and sources such as LiverTox and international reviews [1] [11] [6].