ORIGINAL RESEARCH article
Front. Gastroenterol.
Sec. Hepatology
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
Cyriac Abby Philips
Tharun Tom Oommen
Arif Hussain Theruvath
Aryalakshmi Sreemohan
Ambily Baby
Rizwan Ahamed
Ajit Tharakan
Philip Augustine
Rajagiri Hospital, Kochi, India
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Abstract
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 analysed 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, unlabelled 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. Unlabelled product exposure is a strong mortality predictor, highlighting the urgent need for mandatory product surveillance.
Summary
Keywords
ACLF, ALF, Ayurveda, AYUSH, Herbal and dietary supplements, Homeopathy
Received
10 January 2026
Accepted
20 February 2026
Copyright
© 2026 Philips, Tom Oommen, Hussain Theruvath, Sreemohan, Baby, Ahamed, Tharakan and Augustine. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Cyriac Abby Philips
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