Tylenol and Autism, Cause and Effect

Shag Rock (Rapanui) at Sumner Christchurch February 2008 Bob Eregli, from Christchurch Library 

A floodtide of extraordinarily heated opinion pieces has recently swept in and swirled around treasured landmarks in the healthcare landscape – much the way Spring Tides once swept around Shag Rock at the entrance to Christchurch Harbor in New Zealand on which Shags (cormorants) perched looking for fish to catch at high tide.

The swirling opinions centered initially on whether SSRIs cause Autism. See

• Unsafe Safety Systems – and the linked media comments
• FDA Panel
• Adam Urato
• Something About Mary

But they have risen further and are now swirling about a Does Tylenol Cause Autism rocky outcrop.  See

• Health News Review – the comments following this
• Partnerships in HealthCare
• Epidemiology of Autism
• Pregnancy Acetaminophen or Paracetamol

It may be impossible to frame a response in a way that will work for everyone.  A lot depends on what gets asked.

Does Tylenol Cause Autism

This question leads to one set of responses.  If by Cause Autism is meant that Tylenol causes all cases of Autism then the answer is clearly no Tylenol is not responsible for Autism across the board.

What we now call Autism is a recent creation as shown by an astonishing escalation in the apparent number of cases since 1980. This new autism has very little to do with the Autism that was first described in the 1930s, which, even though there were islands of high functioning or unusual skills, now looks very much like it involves an element of brain damage.

Milder cases of neurodevelopmental delay have since been thrown into the Autism mix. Also thrown in is a pathologization of normal variation, such that many who may be somewhat introverted and anxious are being diagnosed as Autistic.

The term Autism Spectrum Disorder (ASD), now widely used, pretty well concedes the point that it covers a set of what might be totally different conditions with very different causes.

There are incentives for parents of children and adults on their own behalf to seek out an ASD diagnosis as it offers access to benefits and other supports and can create valuable space for someone.

An explosion in disability claims and payments for mental health conditions from younger folk, however, seems to be bringing welfare systems in many countries close to both economic and political collapse. The political collapse pitches some who figure the situation is completely out of control and so many people cannot be truly disabled in an older sense of that word, against others who feel compelled to resist any attempt to roll-back what are viewed as hard-won human rights.

Can Tylenol Cause Autism?

This is a similar sounding question.  It translates into does Tylenol have the capacity to in some cases cause something that might get diagnosed as Autism or ASD.

Before tackling this, we need to note that Tylenol is also implicated in causing Attention Deficit Hyperactivity Disorder (ADHD), which can be viewed as close to the opposite to Autism Spectrum Disorder (ASD).

If some cases of ASD are viewed as states that until recently would have been seen as introversion (a normal and for many admirable variation), some of us until recently called extraverts (not as generally likeable as introverts at least in Britain) are now more likely to be diagnosed as ADHD.

The idea that Tylenol might cause two polar opposite conditions seems wrong. Here cause and effect meets a confusing clinical mess. It is not uncommon now for younger people in particular to be diagnosed as having both ADHD and ASD.

This happens partly because neither of these conditions have clear diagnostic tests or solid markers.  Anyone can claim them and some are liable to cancel, ghost or deplatform anyone who might cast doubt on whether it’s valid to diagnose so many people in particular with Adult ADHD.

Tylenol & Neurodevelopmental Delay

Unlike tuberculosis, ulcers or diabetes, which they can have, animals do not get diagnosed with ADHD or ASD.  Animals do however show neurodevelopmental delay and we do too and whatever about Tylenol and Autism, we need to pinpoint the causes of this.

If Tylenol Can Cause Autism, it seems almost certain that this autism will feature neurodevelopmental delay.

At present medical clinics do not tease out whether some of the folk getting ASD or ADHD diagnoses also have evidence of neurodevelopmental delay.

The problem with the epidemiology studies flying back and forth is that people bringing problems that might be caused by Tylenol to clinics end up mixed into a soup of ADHD and ASD diagnoses that are not caused by Tylenol.

On one side we have Ahlqvist claiming to have run the biggest study ever in Sweden, but whose methodology looks pretty dodgy. On the other side claims by Baccarelli from Harvard and studies by Liew from Yale, also have problems and are not on their own conclusive.

Anyway, epidemiology studies are not often thought as decisive when it comes to deciding cause and effect.  The tobacco companies were, for several decades, able to push back against epidemiology studies that looked compelling by arguing they showed correlations and not causation. There are few things a corporation likes better than Epi studies – they are always able to mount their own Epi which can be guaranteed to cast doubt on claims of a link.  As tobacco companies put it – Doubt is our Product.

One of the authors on the Ahlqvist study, Brian Lee, has a remarkable track record of involvement in multiple studies of possible medications taken in utero triggering problems, all of which conclude there is no link or a far less serious risk than we once thought.   See Brian Lee Orcid.

The case for Tylenol and a capacity to cause Autism does not lie with Epi studies.

Tylenol causes neurodevelopmental delay in the offspring of pretty well all the pregnant animal species tested.  It would be unusual if we were spared.

Tylenol has effects on the epigenomic expression of autism susceptibility genes.  There are a range of physical factors that have been implicated in triggering autism from nicotine to thimerosal (mercury in vaccines).  None have as wide ranging an effect on autism susceptibility genes as Valproic Acid (valproate, Depakote, Epilim) which is widely accepted, even by Viktor Ahlqvist and colleagues, as causing an autism spectrum disorder – called valproate spectrum disorder.

None that is except Tylenol – see slide.

Valproate is an anticonvulsant, and almost all anticonvulsants seem to come with some risk of leading to autism spectrum conditions. It is not widely known but Tylenol has anticonvulsant properties.

Tylenol also has a toxic metabolite – NAPQI – which has been, and perhaps still is the commonest trigger of liver failure needing liver transplants. NAPQI is not produced normally when we take Tylenol.  It takes other stressors to trigger NAPQI production, such as alcohol use. While pregnancy is a normal state, it is also physiologically challenging and we do not know enough to be confident nothing can go wrong.  Failing to take the problem seriously may prevent us finding some simple remedies to ensure NAPQI is not produced.

Quite apart from the toxic effects for which we depend on expert input, ideally from both sides of the debate, there is another important element that can be understood without a background in biology.

Sensory input from the early nervous system is the main driver of brain development.  Sensory input provides the girders or stanchions on which the developing brain is hung.  Drugs acting on the serotonin system mute sensory input, often dramatically so.  While this can be useful later in life when we are stressed, it is something to take into account as Tylenol, along with SSRIs, works on the serotonin system and those who find it helpful report a sensory muting effect.

Given that some forms of what later gets called autism spectrum disorder in animals and us are linked to a delay or abnormality in brain development, this clear pathway to problems suggests that it may not be irrational to be cautious until we know more.

Who Calls the Shots?

Whose place is it to make the decision to be cautious or not?

Among the most important factors to take into account is that Tylenol offers no beneficial effect to roughly 50% of us.  Many of us take ibuprofen like compounds which work obviously and quickly for us in contrast to Tylenol which seems to do nothing for us.  At present, every pregnant woman is advised to take Tylenol – even though she may know it does nothing for her.

Is it responsible to withhold information about possible risks from the 50% of women unlikely to get a benefit?  The calculus a woman has to make is quite different if she knows she responds well to Tylenol.

Airing these matters is not about guilt-tripping women.  Women who are or who are thinking about getting pregnant do more research than any other group and are likely better than almost any other group at weighing the benefits and risks.

Can withholding information that gets in the way of them doing this be justified?  Is there really someone who knows better than they do?.

The concerns about Tylenol extend to children up to the age of 2.  Our Epigenome remains unstable/open until 2 years of age, after which it become less pervious to outside influences.

Finally, the onus to warn lies with companies not FDA or academics.  The onus to warn does not arise when there is a clear cause and effect.  It arises when there are grounds to think there might be a problem.

Rachel Weinstein, an epidemiologist working for Johnson and Johnson, seemed acutely aware of this when in early 2018 she wrote a rather frank email to a colleague – see Rachel to Jesse.

Photo of Rapanui Rock, Christchurch Library,  Wikipedia, 21 May 2014

Shag Rock might have been there for Cormorants for several centuries more but Christchurch was hit by an earthquake in 2011 and the Rock was reduced to less than half its previous size.