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Circumcision and Autism: A most important but forgotten study




In the 24 lines of evidence demonstrating that exposure of susceptible babies and children to acetaminophen causes many if not most cases of autism spectrum disorder (ASD), a few stand out to me.


Several lines of evidence come together to tell us that inflammation and something called oxidative stress create susceptibility. These lines of evidence, all together, are very important, but none of these lines of evidence really stand out to me above the others. On the other hand, a few lines of evidence stand out to me because they are very unusual, almost unexpected, and tend to rule out certain arguments that acetaminophen can’t be a trigger for autism.


The Circumcision Connection

One of the big stand-outs is the finding by Frisch and Simonsen in 2015 that circumcised boys have double the risk of infantile autism compared to boys who are not circumcised (https://pmc.ncbi.nlm.nih.gov/articles/PMC4530408/). This should be, quite frankly, shocking.


You would think that this would give most folks a pause for concern when considering circumcision for their child. But the average pediatrician has never even heard about Frisch and Simonsen’s study.  We will be publishing a blog about “Word Salads in Science” to explore why this study might have been ignored and forgotten, so stay tuned.


So, why is this study so wonderful? It describes an association, which, as all scientists know well, of course, does not prove causation. Indeed, Frisch and Simonsen didn’t have records of acetaminophen use, and hypothesized that it was the injury of circumcision rather than any drug that was connected somehow to ASD (more on that later). So, this study definitely can’t be considered proof that exposure of susceptible babies and children to acetaminophen leads to autism.


But, science is sometimes not so simple. Here I’ll consider other factors and information we have available, and what it means when we put all of the pieces together.


Putting the Pieces Together

If Frisch and Simonsen are correct, then either circumcision itself or something connected with circumcision is probably causing ASD. We conclude that because the association doesn’t have another reasonable explanation. Some associations tell us absolutely nothing, and can be explained by literally countless changes that occur through time or by countless differences between cultures. This is not one of those.


The next question is, what are the things about a circumcision that might cause ASD? Here are three possibilities that have been presented in the scientific literature.

  1. Something is different about people who decide to circumcise their children, and that’s the problem.

  2. The minor surgical procedure itself, which causes pain and bleeding, is the problem.

  3. Something given with the procedure, such as a topical anesthetic or acetaminophen, is the problem.

 

The first option is interesting. This is the option favored by some people critical of Frisch and Simonsen’s study. So, let’s consider it: The boys in the study are apparently from the same culture, with one difference identifiable between them: a minor surgical procedure.  Frisch and Simonsen separated out Jewish individuals and determined that this was not the source of the association with ASD. Something is apparently causing the prevalence of infantile ASD to double with circumcision… something connected with circumcision, or circumcision itself. Apparently not a culture that uses circumcision.


I understand that, so far, the logic is not infallible. Maybe many of the boys who are circumcised are from a culture that is yet to be identified and, maybe that unidentified culture has yet to be identified factors which cause inflammation? Maybe. We could come back to this possibility if nothing else pans out. But if everything falls into place and makes sense, we don’t need to come back to highly unlikely explanations. That’s Occam’s Razor. It’s a wonderful scientific tool. The simplest explanation that fits all of the observations is probably the correct explanation.


Given everything else we know, the choice between these next two options (“b” and “c” above) is obvious. History is repeating itself: Schultz found in 2008 that it was acetaminophen given with a vaccine, not the vaccine itself, which was responsible for regressive autism (https://pubmed.ncbi.nlm.nih.gov/18445737/). So, we’ll pick the acetaminophen, not the circumcision. But, let’s give circumcision a closer look anyway. After all, circumcision was the answer favored by Frisch and Simonsen themselves, when they wrote their study.


Could the Procedure Actually Be the Connector?

The question is, could the actual procedure of circumcision cause ASD, without acetaminophen? To answer that question, we consider how such an explanation would fit into the bigger picture. We consider how deficiency in social awareness is a hallmark of ASD, and how acetaminophen adversely affects social awareness in adults (https://pmc.ncbi.nlm.nih.gov/articles/PMC6455058/). We consider that cord blood acetaminophen is very strongly associated with ASD (https://pubmed.ncbi.nlm.nih.gov/31664451/), that newborns in general are deficient in enzymatic pathways to safely process acetaminophen, and that children with autism are exceptionally deficient in enzymatic pathways to safely process acetaminophen. We previously discussed these issues here: https://pubmed.ncbi.nlm.nih.gov/37321575/.  

We consider that ASD is rare in the presence of chronic shortages of modern medications (https://pubmed.ncbi.nlm.nih.gov/39202661/), despite the fact that ritual religious practices are much older than modern medications.


At the same time, we can’t think of a plausible mechanism by which a minor surgical procedure would cause long-term damage to social awareness. That does not seem plausible from a biological perspective. Animals get injured. Animals, with the exception of humans, don’t have a high prevalence of ASD as far as we know, despite some having complex social systems that utilize the same neurological mechanisms that our human brains use. Furthermore, many cases of ASD are very severe. It is easy to envision a chemical injury causing such a severe brain injury. But a minor surgical procedure with no complications? No. No plausible mechanism is conceivable at the present time. From that perspective, the idea is nonsensical.


It Can’t Be Circumcision Alone

Based on all of that (and much more, but this is enough for now), we don’t think that circumcision alone can cause ASD. It doesn’t add up.


In other words, the reason for acetaminophen use in the Frisch and Simonsen study is not apparently the cause of ASD.


We are going to zero straight in on acetaminophen rather than topical anesthetics because we aren’t working in the blind. We have a lot of other information pointing at acetaminophen, and none pointing at topical anesthetics. Again, we can come back to topical anesthetics if acetaminophen doesn’t work out. We will accept the unlikely if everything else proves impossible. But we would like to avoid the unlikely if possible.


Here is yet another strong argument that it is acetaminophen rather than circumcision that is critical in the induction of ASD. When considering the frequently observed association between ASD and routine use of acetaminophen during pregnancy and early childhood, the indication for (reason for) acetaminophen use is frequently considered as a “confounding factor” for the induction of ASD.* The study by Frisch and Simonsen contains a unique indication. This is not the usual fever, infection, or chronic adult pain that causes most administrations of acetaminophen during pregnancy or early childhood.

*This view is in error, and is discussed elsewhere in great detail (https://pubmed.ncbi.nlm.nih.gov/39202661/), but that it not important for this discussion.

 

Logically, it looks like this:


The study by Frisch and Simonsen gives us a way to zero in on acetaminophen as a factor in the induction of ASD, excluding indications (reasons) for acetaminophen use as the cause. Taken together with dozens of studies which show that typical acetaminophen use during pregnancy and childhood is associated with ASD, Frisch and Simonsen’s results reveal that the common denominator is acetaminophen.


The Common Denominator is Acetaminophen

Don’t get me wrong: There is NO SINGLE STUDY that tells us without reasonable doubt that exposure of susceptible babies and children to acetaminophen is a cause of many if not most cases of autism. Frisch and Simonsen weren’t able to monitor acetaminophen use during circumcision, and acetaminophen use during that procedure is often not documented. Other drugs potentially used with circumcision were not considered, as I pointed out above, and could hypothetically be the culprit. This study, by itself, does not tell us anything conclusively. Indeed, I listed seven of our 24 lines of evidence above when deciding that it was acetaminophen, not the surgical procedure itself, that is critical in the induction of ASD.


That being said, the study by Frisch and Simonsen provides an independent and excellent addition to the other 23 lines of evidence pointing at acetaminophen as critical in the induction of ASD.



To read all 24 lines of evidence, read these two studies:

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