Is Acetaminophen the cause of Autism?
- mfulk78
- Oct 8
- 6 min read
Part II - after the interview.
After completing the interview with Dr. William Parker, I thought that it would be useful to relook at this discussion with the new information in hand. The initial question has not changed for me. The first and most fundamental question to ask is this: What is the true value of acetaminophen in health compared with the potential risk if the associated findings are indeed correct?
Dr. Parker and colleagues believe that Autism can be accounted for to the tune of 94.5% by the use of acetaminophen and critical timepoints in a child's life when oxidative stress levels are high. That is a very high bar to reach and one that I struggle to wrap my brain around in truth. I believe this to be unlikely but hope that there is truth here. For me, after listening to him for over an hour, I fall into the category of there is enough smoke here in the data that acetaminophen is a potential serious risk factor for autism. Thus, I would not recommend using it during pregnancy or the first 2 years of life until better data says that it is truly safe. This risk reward benefit analysis slants towards risk significantly. Which is why I suspect that Dr. Makary and the FDA posted this information:
"“The FDA is taking action to make parents and doctors aware of a considerable body of evidence about potential risks associated with acetaminophen,” said FDA Commissioner Marty Makary, M.D., M.P.H. “Even with this body of evidence, the choice still belongs with parents. The precautionary principle may lead many to avoid using acetaminophen during pregnancy, especially since most low-grade fevers don’t require treatment. It remains reasonable, however, for pregnant women to use acetaminophen in certain scenarios.”
Evidence in recent years has suggested a correlation between acetaminophen use during pregnancy and subsequent diagnosis of conditions like autism and ADHD. Multiple large-scale cohort studies, including the Nurses’ Health Study II and the Boston Birth Cohort, find this association. Some studies have described that the risk may be most pronounced when acetaminophen is taken chronically throughout pregnancy.
It is important to note that while an association between acetaminophen and neurological conditions has been described in many studies, a causal relationship has not been established and there are contrary studies in the scientific literature. It is also noted that acetaminophen is the only over-the-counter drug approved for use to treat fevers during pregnancy, and high fevers in pregnant women can pose a risk to their children. Additionally, aspirin and ibuprofen have well-documented adverse impacts on the fetus."(FDA.gov)
So, is acetaminophen the cause of ASD?
In my current view, the connection is likely associative but now "maybe" causative. Women prone to needing antipyretics and analgesics often have underlying immunometabolic conditions that may drive up oxidative burdens leading to stressed detoxification pathways. These pathways will then struggle to cleanly metabolize acetaminophen leading to bioaccumulation of NAPQI, a toxic metabolite. The three main detox pathways for acetaminophen are glucuronidation, oxidation and sulfation. In babies, the glucuronidation pathway is not significantly active. In children with ASD, sulfation pathways are impaired leaving oxidation as the principle pathway to clear acetaminophen if given to a person at infancy. (Clarke et. al. 2022) However, other studies disagree with this contention. (Cook et. al. 2017)There is evidence that glucuronidation pathways can also be hampered in ASD children especially when looking at endocrine disrupting chemicals.
So on balance, IF (an unknown) there is a genetic predisposition for weakened metabolism of acetaminophen in the face of increased oxidative stress, then there is a very plausible argument for harm to a neonate when a mother takes or the neonate is taking acetaminophen.
Again, regardless of all of this so far, acetaminophen is not benign. It significantly stresses glutathione activity, increasing oxidative stress and prolonging the persistence of toxins, thereby fueling a vicious cycle of inflammation if inflamed. You take the medicine to reduce symptoms, but without addressing root causes, recurrent use follows. The why you need acetaminophen while pregnant becomes super important. Are you under massive metabolic and immunological stress from dietary choices, chemical exposures, mental stress, sleep deprivation, infection, lack of sun exposure, and so much more.
Thus, I reiterate that acetaminophen use may be more of a proxy for maternal health status, while its own mechanism, glutathione depletion and potential epigenetic effects, could exacerbate risk in vulnerable settings like the neonatal period or infancy with a genetical susceptible child.
As Dr. William Parker noted:
“The association of ASD with numerous factors that cause oxidative stress, including metabolic abnormalities, genetic polymorphisms, infections, antibiotic use, and other medical conditions, is consistent with the fact that acetaminophen metabolism is more hazardous in the presence of oxidative stress, a condition associated with risk factors for ASD.” (Parker et al., 2023)
His point highlights the fetal vulnerability in states of oxidative stress, increasingly common in industrialized nations. There is clearly smoke here; whether there is truly fire remains to be seen. I am on the fence.
More interesting data:
What about the cord blood data from Jama Psychiatry? "Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations." (Ji et. al. 2019)
Personally, I neither use nor recommend acetaminophen because of its effects on glutathione depletion and potential epigenetic alterations. In a country where ASD now affects roughly 1 in 30 children, we must minimize avoidable risks. Occasional use in pregnancy is likely safe, but repeated or chronic use, particularly in young children, concerns me. Fever is not the enemy; it is a natural defense against infection. Cool compresses can be effective when fevers rise above 103°F. For fevers between 100–102°F, I typically recommend no medication unless otherwise indicated. I definitely believe that repeated use is not a good idea.
One of my colleagues recently asked, What if a pregnant woman has recurrent headaches or pain? Tylenol is all that’s recommended. My response: find and address the root cause first. A single dose is unlikely to cause harm, but repeated use without understanding the underlying issue raises concern. Ultimately, acetaminophen use in pregnancy should be discussed between each patient and her obstetrician, weighing risks and benefits carefully. However, I find the FDA's precautionary statement to be in keeping with preventative medicine and human health in general.
Dr. Parker argues that acetaminophen use in pregnancy and early childhood represents a major, not minor, risk for ASD. His recent paper underscores the need for urgent, rigorous study.
"Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment. We conclude that the very early postpartum period poses the greatest risk for acetaminophen-induced ASD, and that nearly ubiquitous use of acetaminophen during early development could conceivably be responsible for the induction in the vast majority, perhaps 90% or more, of all cases of ASD. Despite over a decade of accumulating evidence that acetaminophen is harmful for neurodevelopment, numerous studies demonstrate that acetaminophen is frequently administered to children in excess of currently approved amounts and under conditions in which it provides no benefit. Further, studies have failed to demonstrate long-term benefits of acetaminophen for the pediatric population, leaving no valid rationale for continued use of the drug in that population given its risks to neurodevelopment." (Parker et. al. 2023)
Finally, Dr. Peter Attia will be posting a deep dive into this space soon. I look forward to his assessment as he is a master at scientific study analysis. I am very curious to see his review of the Ahlquist paper from 2024 that Dr. Parker thinks is profoundly flawed.
My take home after all of this analysis is simple: I find that acetaminophen does not offer a compelling case for use in light of the possible risk association for fetal neurological disruption. I am counseling mothers and fathers to avoid acetaminophen in all cases unless there is an extenuating need for use and that should be discussed with their provider. This ensures that a variable that could be part of the autism story is removed pending further data. In truth, if everyone stopped the use of acetaminophen in pregnancy and early childhood, we would have an answer to the association versus causation story in 2 to 4 years. Now, I can get behind that!
Dr. M
Above image from Jones et. al. 2024 in Life
Image below from Zhao et. al. 2023
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