Analysis of 386 alternative medicinal products implicated in liver injury reveal clinically relevant associations with potentially hepatotoxic botanicals, pharmaceutical adulteration, heavy metal contamination, and undisclosed animal content.

BACKGROUND

Complementary and alternative medicine (CAM)-related hepatotoxicity is a growing global concern. We utilized multi-modal analysis to characterize CAM product safety and identify predictors of severe liver injury.

METHODS

This retrospective study analyzed 386 CAM products from 91 consecutive patients (mean 4.2 products/patient) presenting with CAM-related adverse events at a tertiary center in South India (2021-2023). Product-level analyses characterize the CAM supply chain while patient-level analyses inform clinical outcome associations. Investigations included ingredient documentation, heavy metal quantification, and GC-MS compound profiling.

RESULTS

The mean patient age was 48.2 years (75.8% male). ACLF occurred in 39.6% of all patients (36/91) and 41.9% of those with hepatic adverse events (36/86), with associated mortality of 38.9% (14/36) compared to 10.9% (6/55) in non-ACLF presentations (OR 5.20, P = 0.004). Heavy metals exceeded WHO limits in many products: mercury (34%), cadmium (25%), arsenic (21%), and lead (14%). Cadmium exposure exceeding WHO limits showed a strong association with ACLF (75.9% vs 22.6%, P<0.001, FDR q<0.001). The association with mortality did not reach statistical significance after correction for multiple comparisons (34.5% vs 16.1%, uncorrected P = 0.061, FDR q=0.24). Undeclared pharmaceutical adulteration (at least one adulterant found in 27.7% of products; exposure to at least one adulterated product in 46.2% of patients) and animal-derived content (31.3%) were prevalent. Notably, unlabeled product consumption significantly predicted mortality (P = 0.025).

CONCLUSION

CAM-associated liver injury frequently manifests as ACLF with high mortality, driven by pervasive heavy metal contamination and adulteration. Unlabeled product exposure is a strong mortality predictor, highlighting the urgent need for mandatory product surveillance.