The protective effect of chemical and natural compounds against amiodarone induced toxicity: A systematic review.
Current evidence does not support the routine use of any protective adjuncts with amiodarone, including L-Carnitine, due to a lack of clinical trials.
Where it sits
this study against the rest of the l-carnitine (levocarnitine) corpusSummary and findings
This systematic review evaluated interventions to prevent or mitigate amiodarone-induced toxicity, focusing on various compounds including L-Carnitine. The review included thirty-five reports, primarily preclinical, with only one observational human study identified. No randomized clinical trials were found, and the evidence did not establish clinical effectiveness for any protective adjuncts.
Abstract
<h4>Objectives</h4>Amiodarone remains an important antiarrhythmic drug, but cumulative exposure can cause pulmonary, hepatic, renal, thyroid, and reproductive toxicity. This systematic review critically compares interventions tested to prevent or attenuate amiodarone-induced injury, evaluates evidence strength and replication, and integrates the implicated molecular pathways.<h4>Methods</h4>PubMed, MEDLINE, Scopus, and Web of Science were searched from inception to July 2025 for English-language in vitro, animal, and human studies of protective interventions against amiodarone toxicity. Animal studies were evaluated using SYRCLE; in vitro studies using an adapted OHAT framework; and the human observational study using the applicable JBI checklist. Because of substantial heterogeneity, findings were synthesized narratively by organ, mechanism, replication, and translational readiness. Database-specific search strategies are reported in Supplementary Table S1. Disagreements were resolved by consensus; agreement was not quantified.<h4>Key findings</h4>Thirty-five reports were included. The evidence was overwhelmingly preclinical; only one observational human report was identified and no randomized clinical trial was found. Pulmonary models predominated. Vitamin E had the broadest replication, while curcumin, silymarin, l-carnitine, and grape-seed preparations were evaluated in more than one report or complementary model. Protection converged on attenuation of lipid peroxidation and inflammatory signaling, preservation of endogenous antioxidants and mitochondrial function, and suppression of apoptosis or TGF-β/Smad-associated fibrosis. Most studies had unclear risk of selection or performance bias.<h4>Conclusion</h4>Current evidence establishes biological plausibility but not clinical effectiveness. No protective adjunct can presently be recommended for routine use with amiodarone. Independent replication, clinically relevant exposure schedules, pharmacokinetic-interaction testing, and rigorously designed human studies are required.
Background
Amiodarone is an important antiarrhythmic drug, but its cumulative use can lead to various toxicities. Previous studies have suggested potential protective interventions against these toxicities, but the strength and applicability of such evidence remain unclear. This systematic review aims to critically compare and synthesize the available literature on interventions tested against amiodarone-induced injury.
Methods
The review searched databases including PubMed, MEDLINE, Scopus, and Web of Science for studies published until July 2025. It included in vitro, animal, and human studies evaluating protective interventions against amiodarone toxicity. The evaluation frameworks varied by study type, with animal studies assessed using SYRCLE and human studies using the JBI checklist.
Results
The review identified thirty-five reports, with only one being an observational human study. The majority of evidence was preclinical, and no randomized clinical trials were found. Vitamin E was noted for its broad replication across studies, while L-Carnitine appeared in multiple reports.
Interpretation
The findings indicate that while there is biological plausibility for the protective effects of certain compounds, including L-Carnitine, the lack of robust clinical evidence limits their application in practice. The small number of human studies and the predominance of preclinical data raise concerns about the clinical relevance of the findings. Further rigorous human studies are necessary to confirm any protective effects.
Key findings
- Thirty-five reports included, with only one observational human study identified.
- Evidence overwhelmingly preclinical; no randomized clinical trial found.
- Vitamin E had the broadest replication among protective interventions.
- L-Carnitine evaluated in more than one report or complementary model.
- Most studies had unclear risk of selection or performance bias.
Limitations
- Only one observational human study identified.
- No randomized clinical trial found.
- Evidence overwhelmingly preclinical.
- Most studies had unclear risk of selection or performance bias.