Transcription
[Music] medcra.com. Welcome to another MedCram video. Today we're going to be talking about the recent announcement from the White House that Tylenol use in pregnancy may be contributing to autism rates.
This is Dr. Roger Schweld. I'm a board-certified internal medicine physician, also board-certified in pulmonary disease, critical care medicine, and also sleep medicine. And I'm also the founder of medcram.com where we have medical education videos for healthcare providers and also for those people who are interested at medcram.com.
The first thing we're going to talk about is how acetaminophen, or as it's known Tylenol, or paracetamol as it's known in Europe, how is it actually metabolized? The other thing I should mention as well is that Tylenol is found in a lot of different medications. So, you really need to look at medications. Look on the back and see if you see acetaminophen, paracetamol, because it's usually paired with a lot of over-the-counter medications. And if you just look for Tylenol on the label, you're not going to find everywhere where acetaminophen actually is.
So, most of the metabolism occurs in the liver and that's about 90% so long as it's a reasonable dose. And obviously, this can be super saturated in an overdose. And this is known as glucuronidation and sulfation. And that gives us a non-toxic product. And actually about 2% of it is excreted in the urine. 5 to 9% of it gets metabolized to a very toxic chemical called NAPQI, and that's N-acetyl-p-benzoquinone imine. This actually is done through the cytochrome P450 system, which is in the liver as well. And this NAPQI is a major pro-oxidant and causes significant oxidative stress. And if it's not dealt with, it can actually lead to cell death.
So the body has a way of metabolizing this to a non-toxic substance. But unfortunately, it utilizes something called glutathione and uses the reducing agents from glutathione and converts it into an oxidized version. And so this glutathione, which the body uses as an antioxidant, is used up very quickly, especially when there's high doses of Tylenol, for instance, in overdose cases. In overdose cases, not all of this can go down here to the non-toxic, and so it backs up into this portion here, which causes the NAPQI to skyrocket, and then it causes a complete depletion of glutathione.
Now, this is something that I deal with not too infrequently in the intensive care unit when people come in with Tylenol overdose because what we will do to replace the cysteine and the reducing agents here so that the body can metabolize this appropriately is we'll actually give NAC, which is N-acetylcysteine.
Here's the part that I want you to think about. If you're having a situation where your stores of antioxidants or the increase in pro-oxidant situation causes the storehouse of glutathione to be reduced so that you're having too much oxidative stress, for instance, it's possible that just certain amounts of acetaminophen or even chronic use at lower levels could deplete glutathione because of this system of metabolism. And so it may be possible for someone to go around perfectly fine, limping along, I guess you could say, with some oxidative stress, and the occasional use of acetaminophen could actually cause a reduction in glutathione and cause processes that require antioxidants in the cell to not have those antioxidants.
And this is important because when we're talking about autism, it is related and there have been studies that have shown that it is related to oxidative stress and also mitochondrial dysfunction, which requires antioxidant therapy and things of that nature for it to work because that is where oxidative stress is produced. And so there is biological plausibility here of a way that this could be contributing. This is just a theory at this point here in the presentation. And the question is, is whether or not there's actual evidence that would be more strongly suggestive.
So here's a paper that was published in August of 2025 titled "Evaluation of the Evidence on Acetaminophen Use and Neurodevelopmental Disorders Using the Navigation Guide Methodology." The Navigation Guide is a systematic and transparent methodology used to evaluate the quality and strength of evidence in environmental health research, particularly for assessing the impact of environmental exposures on health outcomes. Developed to address the limitations of traditional narrative reviews, it adapts rigorous systematic review principles from clinical sciences, such as those used in the GRADE system, that is, the Grading of Recommendations, Assessment, Development, and Evaluation, to environmental epidemiology. The Navigation Guide involves defining a specific research question using a PICO, which is a Population, Exposure, Comparator, Outcome framework, conducting comprehensive literature searches, assessing studies for risk of bias, such as confounding and selection bias, exposure misclassification, etc., and synthesizing evidence to rate its overall quality and strength. It emphasizes objectivity, consistency, and triangulation across study types, such as observational and experimental, to strengthen causal inference, making it particularly useful for evaluating complex associations like prenatal acetaminophen exposure and neurodevelopmental disorders, as seen in this reviewed study.
So, let's see here what this study showed. There's been some studies that have shown no connection between autism and Tylenol use, for instance, the Swedish twin study. But there are a number of studies that actually do show a connection. And this is one that has been published recently that looked at a number of studies, specifically 46 studies. They did a systematic review using the Navigation Guide methodology. They analyzed 46 studies on the association between prenatal acetaminophen exposure and neurodevelopmental disorders. Those are NDDDs like autism spectrum disorder and attention deficit hyperactivity disorder, known as ADHD, in offspring, finding that the majority, 27 studies, reported positive associations. That means that as the risk went up in the Tylenol group, the endpoint of autism also went up.
They found that acetaminophen, the most common pain and fever reliever used by over 50% of pregnant women worldwide, crosses the placenta and may disrupt fetal brain development through mechanisms such as oxidative stress, interesting, endocrine disruption, and epigenetic changes, as supported by experimental evidence. While observational limitations prevent definitive causation claims, confounding factors like maternal illness were addressed. The review recommends cautious use of acetaminophen during pregnancy, the lowest dose for the shortest duration under medical guidance to balance the risks against untreated conditions. Further research is urged to confirm causality, explore mechanisms, and develop safer alternatives.
So this is interesting because it seems as though this study is showing a link, but they cannot say that it is causal, and they do believe that the biological connection here could be through oxidative stress.
Now, as many of you who are regular listeners to MedCram, we have discussed quite extensively the connection in COVID-19, oxidative stress, and sunlight. And I don't have to remind many of you that we actually do have data that is now coming out that shows that melatonin, which is probably the most powerful antioxidant, it's actually even more powerful than glutathione, is being made in the mitochondria and can affect major changes in terms of oxidative stress. And it also is interesting that sunlight, specifically infrared light, has been shown to increase that type of antioxidant effect. This is from Russell Ryder, 2019. It has now been shown that the mitochondria produce melatonin in many cells in quantities which are orders of magnitude higher than that produced in the pineal gland. The subcellular melatonin does not necessarily fluctuate with our circadian clock or release into the circulation system, but instead has been proposed to be consumed locally in response to the free radical density within each cell, in particular, in response to near-infrared exposure.
So folks, let me clarify exactly what's going on here. What we're saying here is that there is evidence that seems to link autism, which is a mitochondrial dysfunction disorder among other things, with acetaminophen use. And we've just showed through the well-known metabolism of acetaminophen that it can exacerbate oxidative stress, especially if there is a reduction in available antioxidants. We've now also shown that sunlight, particularly contains within it infrared light, which can increase the antioxidant effects. So if you were to remove sunlight, you would see that very clearly the body's ability to produce antioxidants would be limited.
Now, Scott Zimmerman and Russell Ryder have also shown in this very article that the optics of the human body, including a woman who is pregnant, that as the uterus grows and the wall of the uterus thins, this opens up a window of transmission specifically of infrared light, which has been shown specifically to increase melatonin production in the mitochondria. In fact, this paper that was just published in Nature Scientific Reports this year in July, just a month before, titled "Longer Wavelengths in Sunlight Pass Through the Human Body Which Have a Systemic Impact Which Improves Vision," published by Glenn Jeff Lab at University College London, shows in this study that sunlight can pass right through the human body and it causes changes in the mitochondria that can actually have an effect remotely. And of course, that would not exclude the neuron brain cells in a fetus. In fact, we actually have good data and photographs here. This is Robert Fosbury, who was a co-author on that study, showing in fact that near-infrared light does pass through the tissue. We have very good evidence now that has been published and that we have reviewed here on our MedCram channel that near-infrared light specifically from the sun can penetrate through the skin out the other side, affect changes at the mitochondrial level that reduce oxidative stress, increase ATP, increase carbon dioxide production because metabolism is improved, and reduce glucose in the systemic circulation because of that increased use of fuels.
Also from that article, we have seen very clearly that the very type of light that actually induces this has been decreasing in a systemic way for the last 200 years. Is it possible that the human body, in areas where there is advanced technology, where we can go inside and we can have fluorescent light bulbs and LED bulbs and low-E glass, as we get less and less of this beneficial infrared light, could it be putting our bodies into a state of reduced antioxidants and increased oxidative stress so that when we are exposed to medicines like acetaminophen, which can exacerbate mildly that balance, could that be causing and increasing the risk of autism?
We've known now since 2003 that the amount of time that is out of the home has been steadily decreasing. And during the COVID pandemic, there was a very large drop, understandably, in time outside the home. But then we learned behaviors, for instance, by having food delivered to our homes or using Amazon to have things delivered. And we have not recovered from that. We have not gone back up to even where we would have been before if that trend had continued.
But there is also other data. This is a paper that was published in 2019 titled "Birth Seasonality and Risk of Autism Spectrum Disorder," which clearly shows that there was an increased risk of autism in those offspring that were born in the fall, i.e., they had conceived in the wintertime, and lowest for those spring births, which were conceived in the summertime. Indicating that once again, sunlight early in pregnancy may be a factor, and it may be a factor because it is improving the oxidative balance not only in the mother but also in the fetus, which is exposed to that infrared radiation.
Here's another study looking at autism prevalence in the United States with respect to solar UVB doses, and it showed an inverse relationship between the amount of solar UVB radiation and the incidence of autism. Here's another paper published in 2017 titled "A Review of Prevalence Studies of Autism Spectrum Disorder by Latitude and Solar Irradiance Impact." And in this report, they reviewed 25 studies that were published between 2011 and 2016 using comparable diagnostic criteria. And the results suggested a tendency for the prevalence rates of autism spectrum disorder to be lowest in countries near the equator and for this rate to increase as latitude increases as you go toward the poles. These findings provide some support not just for the vitamin D hypothesis, but notice what they say here, but also for a new proposition that along with UVB radiation, the entire solar radiation spectrum, which reaches the Earth, may play a role in autism spectrum disorder. While these results are both novel and encouraging in terms of the potential efficacy of exposure to natural sunlight, further research is warranted before results can be considered definitive and before the implications of the findings can be implemented clinically.
There is also a report of research that one in 16 Somali children that moved from Somalia to the state of Minnesota are now being diagnosed with autism.
So let me tell you that I believe that there is ample evidence to look at further research, and I would use this platform to specifically ask the President of the United States and those in charge of healthcare to make sure that this line of reasoning is being looked at. The amount of sunlight that we are being exposed to on a regular basis is whittling away. The amount of infrared light that we are exposed to is also very small. I would also particularly add that there is a new rule in the Department of Energy that is a carryover from many years past that in 2028 the types of LED bulbs that will be sold in the stores is going to have to change because of a new ruling raising the lumens per watt ratio from 45 lumens per watt to more than 125 lumens per watt, thus making it almost impossible to have any infrared light whatsoever. It's difficult enough with 45 lumens per watt to have bulbs that can be designed and engineered to add back infrared light. But the LED bulbs that we purchase in the stores have no infrared light in them currently. This is an area that we've discussed before, and I would again ask the administration and specifically the Department of Energy to look at this rule because if it is true that sunlight is impacting autism, this new rule is not going to make anything better.
Regarding the use of Tylenol for fever, I did agree with the presentation where they said that there is evidence that the use of Tylenol in infections in some studies has been associated with a prolonged course of that infection. And we actually discussed this previously in a MedCram lecture that talked about whether we should automatically treat fevers with Tylenol. As we've said before, certainly there are some fevers that need to be treated because they are so high. They can cause very high rates of tachycardia and also of seizures. But if we're dealing with a routine fever of 101, 102, I believe that the risks and the benefits lay on the side of allowing that fever to do what it needs to do because there are so many downstream effects of that elevated temperature, not the least of which is the elevation of interferon, one of the major effector molecules in the innate immune system.
So, I hope this has been an interesting discussion. I wanted to first of all explain exactly what's going on with the metabolism of Tylenol, explain the connection with oxidative stress, and say why this oxidative stress is an important idea and topic to discuss, especially when it comes to autism, but also when it comes to describing our regular health, because mitochondrial dysfunction is tied to many chronic diseases that we're seeing a lot of here in the United States. I hope this was helpful. If you liked it, subscribe and leave us a comment. And also join us at medcra.com. Thanks for joining us. [Music]