Saturday, January 21, 2012

Tylenol and Autism?

I know.  The link seems silly.  Tylenol is for babies, right?  Far safer than aspirin for fever, after all.  Pediatricians recommend acetaminophen (tylenol) all the time.

Let me not mislead you, for everything I am about to write about is tenuous.  And yet all doctors will have a wrinkle-nosed reaction to tylenol, simply because if you overdose on the stuff, even in small amounts, you run the risk of dying a horrible death.  Tylenol breaks down to NAPQI which breaks down the master antioxidant of the body, glutathione, in large amounts, and kills the liver and kidneys and brain.  Who cares if it is the liver, which repairs itself at a rapid rate -- what about the lungs?  Or the brain?  "Real" antioxidants are more than a vitamin pill.  We need to make our own.

In autism, there is an increased level of inflammation (1):

There are an increasing number of reports that anomalies in the immune system may play a role in autism. This has been found at the molecular, pathological, and epidemiological level. Altered lev- els of immunoglobulins, cytokines and inflammatory markers have been identified in the serum, cerebral spinal fluid, and autopsy brain tissues of autistic patients. Gastrointestinal inflammation in autism as well as pathological evidence of neuroinflammation involving activation of brain microglia has been shown. An increase in head circumference in autistic children, a consistent finding in autism, may involve neuroinflammation.
More interesting information (and a related blog post from some time ago):

Numerous studies have attempted to measure the prevalence of autism and asthma in the population. Both asthma and autism have had a similar apparent rise in the number of cases since approximately 1980, over the past 30 years, and in both disorders these have been repeatedly referred to as ‘‘epidemics”. In autism, this apparent rise in cases is highly controversial  and may be whole or in part due to increased disease awareness and/or expansion and reclassification of diagnostic criteria.
 The following discussion is not intended to judge the validity of disease prevalence studies in asthma or autism; it is simply to point out interesting minor anomalies in those curves. In disease prevalence curves of both autism and asthma in the US, the sharp rise in cases began in approximately 1980. In the period from 1980 to 1990 there were two slight downturns in the slope of the curves, after 1982 and after 1986. Both curves continue markedly upward after 1988 into the 1990s. In addition, there are similar slight downturns in slopes of the curves at the same times from independent and geographically disparate studies in both asthma and autism including; asthma hospitalizations, autism cases in Minnesota, autism in north east London, and autism in an urban area in Sweden.
Four significant events related to acetaminophen use occurred between 1980 and 1990. The first was the CDC caution in 1980 concerning the relationship of aspirin to the risk of Reyes Syndrome which was followed by a public and professional warning by the United States Surgeon General regarding a possible Reyes Syndrome–aspirin association. These cautions against the use of aspirin as a fever reducer in children were largely responsible for the replacement of aspirin by acetaminophen as a pediatric antipyreticIn 1982 and again in 1986 there were product tampering cases where acetaminophen tablets were laced with cyanide resulting in eight deaths. Acetaminophen sales collapsed after each tampering event, but recovered in less than a year in each case. These dates roughly correspond to the slight downturns in asthma and autism cases.
Personally, I do not give my children acetaminophen and I do not take it myself.  It should be known that I think fevers come into play for a reason, to kill germs, and I do not administer medicines to my children explicitly for fever control unless the fever is dangerously high, or the children are in pain due to headache or ear infections or whatever.

The data I present here is definitely preliminary.  The alternatives for fever reduction, aspirin and NSAIDS, all have downsides as well (NSAIDS can cause kidney and gut damage and aspirin can be deadly in children as well).  I would just caution parents not to be too free with Tylenol.  I know that many parents pre-treat their children prior to immunizations, for example, and I think that is a bad idea.  Exercise prudence.  That's my message, in a nutshell.

Good luck.

For more explanation about autism and antioxidants, please see my next post.


  1. Thanks for the post. I know at least two people who will be very interested to read this entry and perhaps even make comment.

    Paracetamol (as we call it here in Blighty) has been linked to a few issues related to autism.

    (a) The work of Rosemary Waring (now retired from Birmingham University) springs to mind and her very, very interesting work on sulphate (sorry UK spelling) levels in relation to autism.

    The theory goes that paracetamol is normally metabolised via two main routes: sulphation or glucuronidisation. Rosemary suggested that because plasma levels of sulphate were low but quite high levels of sulphate were being 'dumped' in the urine in some cases of autism (with some pretty impressive p-values), that various enzymes linked to sulphation seem to be awry. The stats she produced on what happens to the metabolism of paracetamol in quite a few people with autism bear this data out. Sulphate, aside from being required to 'detox' certain phenols, also has some important functions with regards to a nice, healthy, un-leaky gut (sulphated mucoproteins smooth and continuous). OK so the link is more about what paracetamol does to sulphate...

    (b) Fever is an interesting thing with regards to autism spectrum conditions. Aside from fever being cited as one possible factor in the onset of symptoms in a few cases of autism (, there is also a body of evidence to suggest that fever can actually alleviate some of the symptoms associated with autism (in the short-term). This paper kinda sums it up:
    The logic therefore being that paracetamol and its anti-pyretic qualities might not necessarily be the best thing in cases of autism..

    More recently (thanks to @LVNJen) at least one person has linked paracetamol to the rise in autism cases:

  2. The asthma/tylenol link is interesting but what about the birth spacing link between autism. Some believe longer birth intervals allow mother to replenish her nutrition stores. Could perhaps a combination inflammatory drugs/foods and diet
    (or bodily stores) low in fat solubles cause these issues too?

    (don't have access to this but it looked intruiguing)

  3. I don't even know where this idea came from that any slight elevation in temp requires urgent medication.

    It seems quite intuitive to me that infectious processes, and our response to which altering the thermoregulatory centers in our brain to shift our basal temp upward is clearly adaptive. While an out of control fever is clearly a medical risk, disrupts metabolic processes, leads to seizures in children with immature nervous systems... I think you should be more concerned with your OVERWHELMING SEPSIS and imminent hemodynamic collapse.

    I tend to think popping pills at a temp of 101 is probably an artifact from old timey medication advertisements. Sort of how you can find all sorts of advices in ancient advertising that is just insane, like feeding babies tablespoons of bottled sugar to make them "fat an healthy".

    When I was a very small child I would always wonder why tooth paste advertisements always showed such a grotesque serving of toothpaste on the toothbrush - more than anyone would ever use. As I got a bit older it occurred to me they do this in the hopes that people will over apply toothpaste, and buy it more often. I know this because for many years as a child I would apply lots and lots of toothpaste to the toothbrush specifically because of all the advertisements I saw as a small child.

    I wonder if part of the reason tylenol is associated with autism is a specific result of masking infectious processes that then go on to truly damage the nervous system of children prone to it. Immunological dysfunction is quite related to autism, as you state. As a nurse I can say the only thing tylenol does is delay treatment for infections. You wait just a little bit longer, because the first symptom is masked. Perhaps the correlation between tylenol and autism is that more parents wait to take their children to the ER until morning time because the fever went down slightly, meanwhile the immune system is causing irreversible damage to the child's nervous system.

  4. I get extremely wary when someone suggest to have found a possible connection with Autism. First we had Wakefield, that hack, who hallucinated about colitis after vaccination. Then came Mikovits, who found "OMG, XMRV in Autism too!!1!" – probably because she put the XMRV VP62 plasmid in the samples in the first place.

    And come one, two and a half data points that show a slight up-tick? SRSLY?

    And regarding the possible common biomedical pathways that others have found: It is my experience that these associations go away when tested in larger sample sizes. They should test them, but it is news if they find something then. Right now it is the prudent thing to check if this is not a result of small sample sizes and little data.

    (Not that I would want to pooh-pooh Tylenol use – I find your "policy" regarding kids and fever very very sensible)

  5. (And not to forget the fridge-mom connection that Bettelheim – that pseudo-scientific fraud – claimed to have found)

  6. Thanks for the papers, Paul - the ones I reviewed went into some detail about the sulfation issue. And, like you, I would certainly caution anyone against suggesting that there is ONE single cause of the autism spectrum disorders -- nor are they one disorder, obviously, but most likely the final common pathway of a number of different pathologies.

    In that light we have to consider genetic (and epigenetic) vulnerability + insults to the brain affecting energy metabolism, inflammation, and oxidation. Acetaminophen is one of those chemicals that has a plausible mechanism of disrupting some of these pathways, and of course we have to make the obvious caveat that kids who take more tylenol are more likely dealing with inflammation/infection than kids who don't. (Though for asthma, as I mention in the next sentence, we can compare ibuprofen-taking families to tylenol-taking families). For most people it doesn't make a difference. For some, it might. And autism is an extremely tenuous link - there is much stronger data (though very little in the way of randomized trials, though there are *some*) to suspect acetaminophen plays a role in asthma.

    But yes, Tony, it seems every fraud in the land has taken on autism.

  7. Being Venus - I wrote about autism and interpregnancy interval here:

  8. Thanks Dr D.

    Absolutely spot on about the lack of any single factor universally being involved in all autism onset. As for being one single condition, whilst DSM-V is in many ways trying to 'cajole' the diagnosis into one condition (albeit a spectral one), many people don't see it this way.

    Glad you mentioned that lovely word 'epigenetics' because the genetics of autism are about as messy as you can get as detailed by this interesting database recently published:

    I think there is a slow sea-change with regards to epigenetics and autism (and other conditions). Not to be too much of a 'look at me', I have a post coming up soon on this topic and concepts such as 'Lamarckism' making a come-back with the 'Barker hypothesis' as a template. Methlyation, methylation and the histone code.

    All in all, it's complicated.

  9. What about Ibuprofen? Can it cause the same kind of thing to happen?

  10. Unknown: no data with respect to autism I am aware of. For asthma, there was a trial where kids with ibuprofen seemed to develop asthma at a lower rate than kids who took tylenol. Which I find scary.

  11. Yeah, this one I guess:

    Asthma Morbidity After the Short-Term Use of Ibuprofen in Children

    In general ibuprofen is safest and most effective for kids, unless I miss something. This is also the conclusion of the PITCH trial:

    Hay, A D, N M Redmond, C Costelloe, A A Montgomery, M Fletcher, S Hollinghurst, and T J Peters. “Paracetamol and Ibuprofen for the Treatment of Fever in Children: The PITCH Randomised Controlled Trial.” Health Technology Assessment (Winchester, England) 13, no. 27 (May 2009): iii–iv, ix–x, 1–163.