Tylenol, Folate Deficiency, Autism, and The Changing Chemical/ Environmental Burden on Humans

This is going to be a very very long post and a bit off topic from my normal discorse, but it is probably the most important post I have ever written. Lets take a moment to talk about the recent report released by RFK that folate deficiency and tylenol use in pregnancy is correlated with autism in children because Im seeing a lot of opinions and little to no data. Let me walk you through why this signal in the data is a valid conjecture.

First, we need to talk about the toxin burden post WWII and the shift to processed foods- I promise it will be relevant.

The time period from 1950-1970 (Post World War II) is known as the "Great Acceleration" and marks a dramatic inflection point for human toxin burden. The war effort produced a massive innovation in synthetic chemistry and after the war these technologies were commercialized on an unprecendented scale. Since the 1950s the chemical production has increased over 50-fold. The U.S. alone has seen an increase from 20 million metric tons of synthetic compounds to over 500 million metric tons today. Plastic production was around ~2 million metric tons in 1950 but, as of 2020, it was ar 400 million metric tons- not to even touch the topic of microplastics and their ubiqitious presence in every aspect of human life. Pesticide production increased signficantly post 1950 and began with toxic chemicals such as DDT. Many of the worst have been banned but the ones we didnt ban likely cause equal cumulative harm- just over a longer scale of time.

Silent Spring by Rachel Carson was published in 1962 and with that came a large public movement speaking out about what we were doing to our planet and ourselves. This led to the creation of the EPA in 1970 and the Clean Air and Water Acts. Its important to note that while the worst "legacy" chemicals (PCB's, leaded gasoline, some pesticides) were banned or phased out it did not reduce the overall chemical burden but changed the composition (types of chemicals) of the chemical burden.

We are currently in the era of the "Unseen" chemicals. Now the burden has shifted from large-scale industrial pollutants to consumer product chemicals. This includes chemicals such as:

-Flame retardants (PBDEs) added to furniture, electronics, and building materials. PBDEs are not chemically bound to the products they are added to and leach out into the dust and air.

-Phthalates and Bisphenols (BPA) are used in plastics, food can linings, cash register receipts, and personal care products. These compounds are known endocrine disruptors.

-Per- and Polyfluoroalkyl Substances (PFAS), also known as "Forever Chemicals", are used in non-stick cookware, waterproof clothing, and firefighting foam. They are called forever chemicals because they persist in the environment indefinitely and bioacculumate (build up) in humans.

-Medications and Personal Care Products- Pharmaceuticals and antimicrobials (antibiotics, triclosan in hand soap) pass through wasterwater treatment plants and into the waterways where they impact the native wildlife (which eventually turn into the food we eat), are incorperated into rainwater that waters our plants, and eventually make it back into our water supply.

Now quanitifying the burden of these chemicals on the human body is a bit difficult, but we do have some data.

A study in 2005 by the Environmental Working Group tested the umbilical cord of 10 newborn babies in the U.S.- they found an average of 200 industrial chemicals and pollutants in each child, including pesticides, PCBs, and PFAS. Our babies have a toxin burden before they even make it out of the 'safety' of their mothers womb.

These chemicals were virutally non-existant before 1950- now PFAS are found in the blood of ~97% of Americans, BPA is found in the urine of over 90% of Americans, and the vast majority of people have detectable levels of phthalates.

While levels of some legacy chemicals (like lead and DDT) have decreased in humans thanks to regulation, they have been replaced by a suite of newer chemicals (PFAS, brominated flame retardants, modern pesticides) that are now universally detected in human biomonitoring studies. The overall toxicant burden has not decreased- it has shifted and likely increased in complexity.

So why does this matter?

These compounds cause significant cellular and DNA damage the longer they stick around and your folate and methylation pathways have to compenstate to repair this damage. Your liver functions to remove these chemicals from your blood and body in a process involving different enzymes grouped into Phase I and Phase II detox. Because of this chronic- I dont think Im being dramatic when I say poisioning- our Phase I (mediated by cytochrome P450 enzymes) and Phase II (glutathione, glucuronidation, sulfation, etc.) systems are now constantly engaged. They dont get a break. This constant activity consumes essential co-factors (vitamins, minerals) and conjugating agents like glutathione (Phase II detox). This creates a scenario where an additional insult-like a few doses of medication (Tylenol), a nutrient deficiency (like folate), a virus, or a period of stress- can more easily overwhelm a system that is already running near capacity for many individuals. Especially in pregnancy when a growing fetus is much more susceptible to toxin damage.

It gets worse. It this were a slow increase in chemical burden then our genetics would have responded in kind- those that had mutations in the pathways that control the detox for these chemicals would have been slowly and gently reduced in the population. Evolution and genetic variability is fantastic at keeping our population adaptable- and adapt it will.

For 99% of human history (Paleolithic Era) our detoxification systems evolved to handle a certain spectrum and volume of toxins- things like plant phytotoxins, bacterial endotoxins, smoke from fires, and byproducts of metabolism. The "load" was significant but natural and relatively predictable. Now? We are exposed to an unprecedented avalanche of novel synthetic compounds (xenobiotics) that our bodies have never encountered before- plastics, pesticides, industrial chemicals, pharmaceutical drugs, and air pollutants. Our genome hasn't had enough time (just a few generations vs. thousands) to adapt and optimize for this new reality. This mismatch means the detox system (Phase I/II) and the supporting pathways (folate, methylation, transsulfuration) are now very frequently operating outside their evolutionary design specifications. Not only that- but many of these systems were set up to lean the opposite direction because that is what was best for us according to the environment at the time.

To give you some examples:

The folate and methylation pathway are fundamental cellular processes that create active folate to provide DNA components for growing cells and methyl groups that perform critical jobs such as DNA repair, turning genes on/off (epigenetics), synthesizing neurotransmitters, and building immune cells. There are common mutations (SNPs) in the folate pathway that make it less efficient- you might have heard of them (MTHFR). In the past this could have been only a minor inefficiency that wasnt a big deal, or maybe even an advantage in a world where fresh food and folate rich diets were the norm. If this pathway works too fast you can develop cancer or break down too many neurotransmitters so having a slower pathway may have been an evolutionary advantage. Now? Under the high toxic load of the 21st centry you have a constant demand for DNA repair and cellular repair. Now a slowed methylation cycle can become a major bottleneck to clearing the toxic environmmental chemicals- and the damage to your body doesnt stop until you can clear them.

The data gets worse when you look at Phase I and Phase II detox. Phase I detox is mediated by cytochrome P450 enzymes and converts toxic compounds into toxic compounds that are even more water-soluble- which frequently makes them more reactive and damaging. Phase I detox is fast and often does this reaction very quickly. Phase II, unfortunately, is slow. Its job is to take these more toxic compounds and neutralize them while also readying them for excretion. This is where glutathione comes in- its one of the main processes in Phase II. Because Phase I is a fast process and Phase II is inherently slow, there is often a buiild up of more toxic intermediates. Historically, this was fine. Even if Phase II was slow you had a much slower overall toxin load so it could be slow and it was never an issue.

Modern day humans have a plethora of mutations in these pathways- not because they dont matter now but because it didnt matter in our grandparents generation. There was no evolutionary pressure to make these mutations detrimental to human health- but now there is. It's not even that these pathways are uniquely mutation-prone. It's that the common, pre-existing genetic variations within them are now being exposed as critical weaknesses due to the unprecedented environmental pressure we face.

Even worse, there is an upper limit to how fast these pathways can go. What happens when it is running at full speed and cant handle both the toxin load and the normal functions of your body? Well, your body has to choose on which ball to drop and things start becoming dysfunctional.

Our bodies are trying to fight a 21st-century war with Stone-Age genetics. Some people have "genetically robust" DNA that handles it well (like having a high-end processing plant). Others have combinations of SNPs that create significant bottlenecks, making them highly susceptible to the modern toxic burden, leading to conditions like autism, ADHD, histamine intolerance/ MCAS, Multiple Chemical Sensitivity (MCS), certain autoimmune disorders, and chronic inflammatory illnesses.

People ask me why Im so passionate about helping people understand their genetics and their genomic set-point. Its because of this. Its because by understanding an individual's genetic makeup in these pathways, we can use targeted nutrition and lifestyle strategies (i.e. providing specific bioactive forms of folate, supporting glutathione production with NAC and alpha-lipoic acid, reducing toxic exposure) to help compensate for these genetic bottlenecks and better navigate our modern world. We just have to know where the bottlenecks are and we can work with our genetics. I refuse to accept evolution has to take our kids and our health. I cant look these mommas in the eyes and tell them their kids are the vicitms of an environment that has changed too rapidly for our own good. I have to help. And after thinking about this for literally a decade, this is the best way I can do that.