Tylenol, Autism, and Pregnancy—The Safe Way to Take it to Avoid the Potential Risk
Hi all. In this article I’ve detailed what I believe are the key mechanisms of Tylenol’s mild potential for harm on the neonatal brain and how to prevent those potential harms. This is the information that I believe is missing from virtually all reports on this topic and where I think the research/public health focus should be in the future. Also briefly, regarding autism more generally, I do not believe that Tylenol is the chief driver of autism in any shape or form. Hope you enjoy…
~ Dr. Malek
Recently, the FDA under the Trump administration took an initial step towards officially recognizing potential harms of Tylenol (acetaminophen, also called Paracetamol) supplementation during pregnancy.
The claim is that Tylenol has the potential to increase the risk of autism in the children of pregnant mothers who use it.
That’s significant because Tylenol is the most frequently recommended painkiller and fever-reducer in pregnancy given its widely perceived safety relative to things like NSAIDs (Advil, etc.). The potential that the Tylenol they’re taking could be affecting the brains of their children is obviously incredibly scary to mothers and can create a lot of uncertainty later on; i.e. “Did my Tylenol cause this? Did I unwittingly do this to my child?”
(Note that focus was also placed in the recent official proceedings on Leucovorin, which is really just folinic acid, but more on that another day. In the meantime, please consider sharing my article as I’m detailing some essential information that I haven’t seen readily available anywhere else).
Let me start, briefly, with the following question:
Does pregnancy use of Tylenol actually increase the risk of autism in children?
The studies looking directly at this question are observational studies. That’s important to remember. That is, they look at whether taking Tylenol during pregnancy is statistically correlated, on a broad level, with the development of autism in children.
Multiple observational studies (see this and this; the latter is a meta-analysis) have found small associations between maternal use of acetaminophen and risk of the child developing autism post pregnancy.
So this announcement from the Trump administration is not really anything new. In fact, the observational studies I mentioned prompted warning statements from other bodies years ago (see this Consensus Statement published in 2021 in Nature, for example) regarding a potential link between prenatal acetaminophen and autism (and multiple other neonatal issues, by the way).
However, this evidence is absolutely not conclusive. Note that another study, for example, went even deeper and looked at siblings of children who developed autism after prenatal acetaminophen exposure. Put simply, they found that those siblings were not less likely to develop autism! In other words, for a given mother, children born from pregnancies in which that mother took Tylenol were not more likely to develop autism than children born from pregnancies in which that mother did not take Tylenol.
That suggests no relationship.
This is quite important, because this sibling-controlled study is arguably the single most carefully designed study on the issue. But it does not rule it out.
In fact, in my opinion:
I do think Tylenol exposure has the potential to contribute to autism development, but I do not think that is sufficiently causal alone.
Why do I think that?
Firstly, there are multiple plausible convergent mechanisms by which acetaminophen may adversely impact neonatal neurological function. These mechanisms are based on many decades of basic research into the metabolism and biochemical effects of acetaminophen.
Secondly, those mechanisms do overlap with other mechanisms more closely implicated specifically in autism development.
And thirdly, we have the (albeit controversial) observational data above.
And—like it or not—having a strong plausible mechanism in combination with observational data is one of the strongest indications of causality you can get in medicine.
Remember: calling a study “observational” is not some kind of insult.
Reflective of one of those funny quirks of our 21st century, how often do we see quite reasonable objective claims about mechanisms and potential causality irreverently dismissed with that perfunctory chant, that all too familiar “Correlation does not equal causation, dude!” drilled into the head of every smug high school science student.
Of course, that is correct; correlation does not, in fact, equal causation. We know that. But taking note of correlation is extremely important. So much so that, without our ability to infer broader ideas from observations and apparent correlations, we’d know very little about the empirical world at all!
Even more so, observational studies are the very backbone of research on adverse outcomes and potential harms. We must—absolutely must—draw inferential conclusions (carefully and deliberately) from such observational studies on the adverse effects of drugs and exposures.
So these studies on acetaminophen should not be dismissed as merely “observational” but should be considered as important contributory evidence alongside sufficiently plausible mechanistic explanations.
And in my opinion, considering the observational data and potential explanations in tandem, we’re at a stage where we can say that Tylenol can feasibly contribute to the development of autism when (and only when) there are other factors at play.
But it is incredibly important that this focus on Tylenol does not distract us from those other factors—those other factors that are, for all intents and purposes, apparently the real drivers of autism development.
But that’s a topic for another day.
The Importance of Understanding the Mechanisms of Tylenol’s Potential Harms
But if Tylenol really is a risk factor for autism development—if it really can contribute (however slightly) to adverse effects on the neonatal brain—then what I believe researchers and public health officials should be focusing more attention upon are the mechanisms that mediate those effects.
Because by focusing on mechanisms, we’ll be able to (1) figure out the true, fundamental pathophysiology of autism via inference and (2) learn to prevent those negative effects in pregnant mothers who choose to take Tylenol.
Regarding (2), I personally believe we’re pretty much there already.
Exactly HOW Tylenol Might Harm Babies’ Brains
In spite of the swarm of media coverage on the recent FDA decision, I haven’t seen any real discussion of exactly how acetaminophen might harm the fetal brain.
Not surprising really, because the Achilles’ Tendon—or one of the many Achilles’ Tendons (if you can have more than one)—of Modern Medicine is its indelible fractionalization of the human body:
It doesn’t see the human body as a coherent system with truly understandable mechanisms and patterns of behavior. Rather, it sees it as a black box that responds to inputs—whether those inputs be toxins or treatment—via some mathematically determinable statistical distribution; and the distribution makes the beast.
Modern Medicine (for lack of a better term—no offense intended) hates mechanisms. It hates function. It hates “why.”
But I’d argue that that is exactly what we need to focus more upon.
So WHY might Tylenol hurt babies’ brains?
When you take Tylenol, it’s turned into something called NAPQI in the liver. This is a toxic, oxidative molecule that the body ultimately has to get rid of. To do so, your liver uses up glutathione—the body’s “master antioxidant” (a rightfully earned title)—using up NADPH in turn, which in turn uses up folate through one-carbon metabolism (i.e. methylation).
The oxidative stress generated by NAPQI and glutathione/NADPH depletion also harms your stores of something called tetrahydrobiopterin. Any phenylketonurics reading will recognize that molecule; it’s that all-important BH4 involved in producing neurotransmitters like dopamine (albeit indirectly).
Most fundamentally, in my opinion, the negative effects of Tylenol are mediated by oxidative stress, i.e. electron strippage.
(Please bear that in mind as that’s probably the single most important piece of information regarding Tylenol and babies’ brains, though I haven’t really seen this discussed anywhere in the mainstream.)
Again, and in other words, Tylenol is potentially harmful because it by nature stresses the body’s redox balance.
This teaches us something about autism: namely, that part of many cases of autism is uncontrolled brain-impacting oxidative stress (a long, LONG discussion for another day).
And it also teaches us how to mitigate the dangers of using Tylenol in pregnancy!
How to Mitigate the Oxidative Damage of Tylenol in Pregnancy
Firstly, and most obviously, it becomes important for pregnant and prenatal women to investigate their redox status. In other words, they should try to get a gauge of how robust their antioxidant systems are.
That’s easier said than done of course. But there are some labs that can help, things like:
Glutathione levels, especially reduced vs oxidized
Glutathione peroxidase levels
Selenium levels
OxLDL
Antioxidant nutrient markers (vitamin C, CoQ10, etc.)
Transsulfuration markers (particularly important)
etc.
If a woman intending pregnancy identifies an issue with oxidative stress management via labs like the above, it absolutely behooves her to take general measures towards dampening that oxidative stress as well as specific measures towards addressing the very root of her oxidative stress issues.
It could be an estrogen metabolism issue, a liver detoxification issue, an aldehyde metabolism issue, B6 toxicity, heavy metals, etc. that are causing her to be uniquely susceptible to oxidative stress, and she’ll have to narrow in on that specific driver of her vulnerability and fix it.
Generally however, it will help in the meantime to focus on:
A non-oxidative diet pattern
Avoiding heavy metals
Being careful with uncontrolled bleach/chlorine usage
Ensuring ample intake of nutritional antioxidants like vitamin C, A, CoQ10, E (but in the correct forms, because the wrong forms can legitimately do more harm)
etc.
In addition to the above, however, it’s important that she focuses in on the specific pathways by which Tylenol mediates its own oxidative damage and ensures that those are fully covered.
Barring further testing and detailed investigation, she should ensure that she has zero problem with the production of and utilization of glutathione.
Again, glutathione is absolutely central to the body’s natural protective mechanisms against the oxidative stress of Tylenol and thus—in my opinion—becomes central to strategies to preventing Tylenol-related autism in pregnancy.
The Primacy of Glutathione for Protection Against Potential Tylenol-Exacerbated Autism
The production and utilization of glutathione is a very complex process involving dozens of mechanistic steps. A problem at any one of those steps—or a general drain on glutathione reserves—becomes a major risk factor for sustaining potential damage from Tylenol and (arguably much more importantly) other oxidative stressors in pregnancy.
Those steps involve cysteine, glutamate, glycine, NAD+, FAD, selenium, and more.
For the sake of brevity, I’d say the most easily actionable and likely impacted steps in these pathways involve cysteine, NAD, selenium, and FAD.
What’s quite amazing—and of vitally underrecognized importance—is that levels of all five of these (as well as glutathione) tend to decline as pregnancy progresses!
Due to hemodilution, fetal utilization, etc., the body simply has less of these things available to it as pregnancy goes on to perform those crucially important protective tasks that glutathione does!
In other words: glutathione availability and usability goes down as pregnancy progresses, so vulnerability to oxidative stressors (like Tylenol) goes up.
And that’s where Tylenol again comes in: Tylenol is such an oxidative stressor. Pregnant women are particularly vulnerable to the (mild) oxidative stress of Tylenol and therefore should make extra effort to ensure that they have the glutathione capacity to counteract its potential oxidative harm and potential (albeit slight) contributions to autism risk.
Should pregnant women therefore take glutathione? Liposomal glutathione, for example?
Generally no, in my opinion. Bioavailability tends to be low, and it doesn’t sufficiently compensate for utilization variables nor ensure consistent availability.
Instead, they need to focus on those factors involved in making and using glutathione.
It’s important that they assess their FAD status, their NAD+ status, their selenium, and their cysteine availability (through transsulfuration) if they intend to use Tylenol/acetaminophen with any consistency.
Again, barring the ability to test those things, it’s generally possible to very carefully supplement, though I won’t be making any recommendations here because that’s a nuanced determination and not something I can safely recommend in blanket fashion.
Selenium particularly should not be supplemented unless you have a specific reason and ideally can test your serum and/or whole blood levels, because too much selenium can be toxic.
I hope to touch more upon the rest of this in perhaps some future articles, but most importantly, keep in mind that:
The chief damage of Tylenol is oxidative in nature. That’s my strong belief, and that’s where I think the potential autism risk (if any) comes from.
It’s important that pregnant (and, better yet, prenatal) women assess their redox status (i.e. their vulnerability to oxidative stress) through targeted testing and address any idiosyncratic vulnerability.
And, more broadly, and pregnant women using Tylenol with any real consistency really should focus on carefully optimizing glutathione availability, recycling, and utilization.
I hope this gives you something to think about. Ultimately, I must say that I don’t agree with the unnuanced/dismissive approach taken on this topic by much of the mainstream. On that note, I didn’t touch upon it directly here, but could leucovorin help? Yes, likely. Though I don’t think it’s a cure for every or even most cases of autism. There are likely deeper environmental variables (immune destabilizers etc.) that impact autism risk by mechanisms not directly addressable by folinic acid.
In the meantime, please do consider sharing this article as I do believe it explains mechanisms and interventions not lucidly assessed anywhere else.
Thanks,
~ Dr. Malek
Disclaimer:
This content is for educational and informational purposes only. It is not intended to provide medical advice, diagnose, treat, cure, or prevent any disease, and it should not be relied upon as a substitute for professional medical judgment. Always consult with a qualified healthcare provider before starting, stopping, or changing any medication, supplement, or treatment, especially during pregnancy or while managing a medical condition.
