ABSTRACT L‐carnitine (LC) and acetyl‐L‐carnitine (ALC) aid in the transfer of fatty acids inside the mitochondria and may alleviate toxic syndromes marked by oxidative stress, poor β‐oxidation, hyperammonemia, and mitochondrial dysfunction. The adjunctive role of LC/ALC in acute drug and chemical poisonings was assessed in this systematic study. Clinical studies, mechanistic models, and animal experiments involving LC/ALC in valproic acid, aluminum phosphide, organophosphates, paracetamol (acetaminophen), methanol and other toxic alcohols, and anthracycline cardiotoxicity were found by searching PubMed, Scopus, and Web of Science between February and July 2025. PRISMA guidelines and predetermined criteria were used in the selection of the study. Two reviewers did a basic domain‐based bias appraisal, screened records, and extracted data using a standardized form. The results were narratively synthesized and organized by toxin and research type due to significant variation in design, demographics, dose, and outcomes. Nineteen research studies satisfied the requirements for inclusion. Adjunctive LC decreased lipid peroxidation, enhanced cholinesterase activity, and decreased atropine/oxime needs in organophosphate poisoning, according to two clinical studies, although there was no discernible mortality effect. A mortality signal was observed when LC was combined with N‐acetylcysteine, whereas paraffin oil performed marginally better in some outcomes. Three small randomized trials in aluminum phosphide poisoning suggested improvements in oxidative stress markers, cardiac function, ventilation needs, and intensive care course. Although case series and modeling suggest LC for hyperammonemia and hepatoprotection, especially in conjunction with extracorporeal clearance, a retrospective cohort in valproate toxicity revealed no kinetic or survival advantage. Preclinical evidence points to better results in methanol models, anthracycline cardioprotection, and paracetamol hepatoprotection (in combination with N‐acetylcysteine). In general, LC/ALC was well tolerated. Rather than taking the place of proven antidotes and supportive treatment, LC/ALC seems to enhance mitochondrial activity and redox balance. In actual use, LC may be taken into consideration in cases of severe valproate toxicity with hyperammonemia or hepatotoxicity, as well as an adjuvant in certain organophosphate and aluminum phosphide poisonings within thorough resuscitation protocols. However, its application in cases of paracetamol, methanol, and anthracycline toxicity should remain primarily investigational. To identify the patient categories most likely to benefit, standardized dose and sufficiently powered pragmatic trials are required, especially in cases of organophosphate and paracetamol poisoning. LC/ALC targets common oxidative and mitochondrial pathways in a number of significant poisonings. Evidence currently available points to promising preclinical protection against paracetamol hepatotoxicity, methanol intoxication, and anthracycline cardiotoxicity, as well as clinically significant adjunctive effects in aluminum phosphide and organophosphate poisoning. Although survival benefits are still unknown, these medicines are generally safe, accessible, and biologically plausible; pragmatic trials are needed to clarify patient selection, dosage, and indications.
Rezaee et al. (Sun,) studied this question.