October 16, 2025

Acetaminophen's role in mitochondria dysfunction, Autism & ADHD


Dept of Biology, Liberty University, VA
Source: International J of Mol Science, Sep 2025

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Authors reviewed a large number of studies investigating acetaminophen's role for increasing autism and ADHD. While one Swedish study did not find an increase in autism, the majority of studies provided evidence suggesting that acetaminophen could negatively alter normal brain development in the unborn child during pregnancy. The Swedish study, which found no link, was criticized for not considering the dose taken by the mother, and for some reason did not include a mother's over-the-counter use of Tylenol. Concern was also expressed regarding the metabolite NAPQ1, which forms as acetaminophen is metabolized by the body. The metabolite is known to be highly toxic, and if the mother has low levels of glutathione (which removes free radicals generated by environmental toxins), the damage to the developing baby increases significantly. Other studies were reviewed, finding that acetaminophen inhibits endocannabinoid hormones, which are involved in brain development. This is a newly published study (Sep 2025) and provides an easy-to-read summary of current and past acetaminophen research.
ABSTRACT
One in 36 children were identified with autism in 2020, a 22% increase from 2018 and a 98% increase from 2010. Simultaneously, attention-deficit/hyperactivity disorder (ADHD) diagnoses increased 36% from 2003 to 2016–2019. Despite this surge, their etiologies remain largely unknown. However, numerous studies document higher incidences of mitochondrial abnormalities in affected individuals. Additionally, acetaminophen has been implicated in these disorders in longitudinal studies and murine models. This paper is a compilation of literature aiming to explore a theoretical framework for acetaminophen-induced mitochondrial damage in utero. It focuses on a toxic metabolite of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQ1), and its role in neuroinflammation. Based on our findings, we recommend further research studying fetal mitochondria after maternal acetaminophen usage.

Introduction
In December 2023, Judge Denise Cote barred five expert witnesses from testifying that Johnson & Johnson’s Tylenol contributed to the development of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in thousands of children, closing a multi-district litigation [1,2]. Yet, mounting epidemiological evidence suggests an association between high pre-natal and early-life acetaminophen exposure and an increased risk of ASD and ADHD diagnoses [3]. Further, in 2021, a group of 91 doctors and researchers issued a consensus statement that called for precautionary action against the use of the drug during pregnancy [4].

While the etiologies of ASD, often referred to simply as autism, and ADHD remain largely mysterious, the number of cases continues to rise. The Centers for Disease Control and Prevention (CDC) reported that one in 36 children were identified with ASD in 2020, a 22% increase from 2018 and a 98% increase from 2010 [5]. This makes ASD the fastest-growing developmental disorder, affecting more children than acquired immunodeficiency syndrome (AIDS), diabetes, and childhood cancer combined [6,7]. Estimates of the lifetime social cost for an individual with ASD is $3.6 million, and lifetime social costs to date exceed $7 trillion in the United States, expected to reach $11.5–15 trillion by 2029 [8]. Akin to autism rates, ADHD diagnoses have also climbed in the past two decades. In 2016–2019, the CDC revealed that 9.8% of children in the United States were diagnosed with the disorder, a 36% increase from 2003 [9]. Annual societal costs for children and adolescents, due to their ADHD diagnosis, have reached $33.2 billion in the United States, spanning educational and healthcare costs [10]. In 2023, the National Institute of Health contributed $306 million and $72 million to research autism and ADHD, respectively [11].