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Abstract
Acetaminophen (APAP) overdose is one of the most common causes of acute liver injury. The current standard-of-care treatment for APAP hepatotoxicity, N-acetyl-l-cysteine, is highly effective when administered early after overdose, but loses efficacy in later-presenting patients. As a result, there is interest in the identification of new treatments for APAP overdose patients. Natural products are a promising source of new treatments because many are purported to have hepatoprotective effects. In fact, a great deal of research has been done to identify natural products that can protect against APAP-induced liver injury. However, serious concerns have been raised about the rigor and human relevance of these studies. Here, we systematically reviewed the APAP-natural product literature from 2013 to 2023 to determine the veracity of these concerns and the scope of the potential problem. The results substantiate the concerns that have been previously raised and point to concrete steps that can be taken to improve APAP-natural product research.
Acknowledgments
The authors thank Dr. Hartmut Jaeschke for critical review of this manuscript.
Disclosure statement
In the last five years, MRM has consulted for Acetaminophen Toxicity Diagnostics, LLC, GlaxoSmithKline, Alkermes, and Butler Snow LLP. He has also received research funding from Haleon, the AASLD Foundation, and Bergstrom Nutrition. IKK has received research funding from Bergstrom Nutrition. These organizations had no role in this study, including in the conception, design, execution, writing, editing, or publication of the study. The remaining authors declare no conflicts.
Additional information
Funding
Notes on contributors
Alexander J. Layman
Alexander J. Layman, BS, is a Research Technician in the Dept. of Environmental Health Sciences in the Fay W. Boozman College of Public Health at the University of Arkansas for Medical Sciences (UAMS). He earned his BS in Biology from Henderson State University in Arkadelphia, Arkansas, USA. His current research is focused on the effects of natural products in experimental acetaminophen toxicity.
Scott M. Alsbrook
Scott M. Alsbrook, MS, is Instructor in the Dept. of Environmental Health Sciences in the Fay W. Boozman College of Public Health at UAMS. He earned his BS in Environmental Science and MS in Applied Data Analytics from the University of Central Arkansas. His current research focus is geographic information systems applications in environmental health.
Igor K. Koturbash
Igor K. Koturbash, MD, PhD, is Professor and Chair in the Dept. of Environmental Health Sciences in the Fay W. Boozman College of Public Health at UAMS and Co-Director of the Center for Dietary Supplements Research. He earned his MD from the Ivano-Frankivsk State Medical University in Ukraine and his PhD in Biomolecular Sciences from the University of Lethbridge in Canada. His research interests include 1) the safety and biological effects of dietary supplements and 2) radiation toxicity.
Mitchell R. McGill
Mitchell R. McGill, PhD, is Associate Professor in the Dept. of Environmental Health Sciences in the Fay W. Boozman College of Public Health at UAMS, with additional appointments in the College of Medicine. He is also a member of the Center for Dietary Supplements Research. He earned his BA in Biology from the University of Missouri – Kansas City and his PhD in Toxicology from the University of Kansas School of Medicine. His research interests include 1) mechanistic and clinical aspects of acetaminophen hepatotoxicity, 2) development of biomarkers of liver injury for clinical and regulatory applications, and 3) fundamental mechanisms of liver repair.