Which specific supplement ingredients have documented links to hepatotoxicity and how common are these events?
Executive summary
A broad body of clinical case reports and surveillance studies links specific supplement ingredients — notably anabolic steroids, green tea extract, and multi-ingredient nutritional supplements (MINS) — to clinically significant liver injury, while many other botanicals carry smaller but documented risks (e.g., Garcinia cambogia, kava, black cohosh, pyrrolizidine-alkaloid–containing herbs, usnic acid, vitamin A, kratom) [1] [2] [3] [4]. The true frequency of supplement-associated hepatotoxicity is uncertain and likely undercounted, but observational data show herbal and dietary supplements (HDS) now comprise a substantial and growing share of drug-induced liver injury (DILI) cases in multiple countries and that millions of U.S. adults use products containing ingredients that have been implicated in liver damage [5] [6] [7].
1. The ingredients most consistently implicated in published cases
Three groups dominate published series: androgenic anabolic steroids (often in bodybuilding products), green tea extracts (Camellia sinensis), and multi-ingredient nutritional supplements (MINS) such as Hydroxycut, OxyELITE Pro and other proprietary weight‑loss or “wellness” blends; these are repeatedly named in clinical reviews and the Drug‑Induced Liver Injury Network (DILIN) literature as leading culprits [1] [2] [8]. Other botanicals and compounds with documented case reports include Garcinia cambogia, kava, black cohosh, pyrrolizidine-alkaloid–containing herbs (eg, Gynura/Tusanqi, Senecio species), usnic acid, high‑dose vitamin A, ma huang/ephedra and stimulants such as 1,3‑DMAA, while emerging concerns have been raised for kratom, ashwagandha, turmeric/curcumin preparations, and red yeast rice in surveillance studies [2] [3] [4] [9] [7].
2. How common are these events — population exposure versus detected injury
Population surveys estimate that about 5% of U.S. adults used at least one of six botanicals identified as potentially hepatotoxic in the prior 30 days — extrapolated to roughly 15 million Americans — and the specific six studied included turmeric/curcumin, green tea extract, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha [9] [7] [10]. In clinical series, HDS account for a large and rising share of DILI cases: U.S. data report HDS‑related injury increased from ~7% of DILI cases in 2004–05 to ~20% by 2013–14, and recent analyses put HDS at roughly 16–20% of DILI in prospective registries [5] [1]. However, absolute incidence rates (cases per user‑years) are poorly defined because reporting is passive, products are heterogeneous, and surveillance systems miss many events [6] [2].
3. Why attribution is difficult and why counts are conservative
Most implicated products are complex blends, labels are frequently inaccurate, and adulteration or contamination (pharmacologic drugs, microbes, or undeclared plant alkaloids) has been repeatedly documented, all of which confound causal attribution [11] [10] [6]. Regulators in many countries do not require pre‑market safety testing for HDS, so post‑market case series and registries — which suffer from underreporting and varying diagnostic rigor — form the evidence base [8] [6]. Some reviews emphasize that for certain herbs (eg, black cohosh) large pooled datasets show very low overt liver‑injury incidence, underscoring variability in risk estimates and the importance of high‑quality studies [4].
4. Clinical severity, notable outbreaks and contested cases
Severity ranges from transient enzyme elevations to fulminant hepatic failure requiring transplantation; high‑profile outbreaks include OxyELITE Pro and Hydroxycut episodes that produced hospitalizations, transplants and deaths before product reformulation or market withdrawal [1] [2] [12]. Industry pushback and contested causality have occurred (for example, Herbalife disputes), and investigations have sometimes identified contaminants or undeclared compounds as the likely toxin rather than the named herbal ingredient, illustrating both corporate and investigational agendas that can cloud interpretation [11] [12].
5. Practical interpretation: risk is real but individualized; uncertainty persists
The literature supports clear, reproducible links between certain ingredients and hepatotoxicity (anabolic steroids, green tea extract, several MINS, and specific botanicals with pyrrolizidine alkaloids), while many other associations rest on smaller case series or surveillance signals [1] [2] [4]. Use prevalence is high, recognized DILI attribution to HDS is rising, and under‑ascertainment, variable product content, and multi‑ingredient formulations mean measured rates underestimate true harm; clinicians and consumers should treat implicated ingredients with caution and consult registries such as LiverTox for ingredient‑specific summaries [13] [6] [5].