Leucovorin, Tylenol, Vaccines, and other Hot Topics: What the Science Really Says

About this episode

In this episode, I'm breaking down three topics that spark intense debate but deserve clear, science-backed answers: leucovorin therapy for autism, acetaminophen (Tylenol) use during pregnancy, and vaccines.

After 25 years in practice and thousands of conversations with parents, I've heard the same questions:

"What caused my child's autism?"

"Was there something I did?"

I'll start with a developmental framework that actually makes sense—comparing your child's development to a growing tree, where genetics are the seed and environment is the soil.

Here's what we'll cover in this episode:

Leucovorin (Folinic Acid): Why some autistic children can't get folate into their brains, how leucovorin bypasses that blockage, and the real improvements I've seen in language and communication. I'll explain folate receptor autoantibodies, cerebral folate deficiency, and why this prescription therapy isn't just another supplement.

Tylenol in Pregnancy: What the largest study of 2.5 million children revealed, why the link to autism disappeared when researchers compared siblings, and how to think about this decision based on evidence, not fear.

Vaccines & Autism : The research spanning millions of children, when a personalized vaccine schedule makes medical sense, and how to have the right conversation with your doctor.I'll also address that recent circumcision-autism headline and what early stress biology actually means for development.Most families don't know that autism-specific medical therapies exist or that integrating them with behavioral and developmental treatments changes outcomes. I'm on a mission to change that.

This episode is for you if: You're a parent seeking clarity, a professional supporting families, or anyone who wants to understand autism beyond the headlines.

Transcript

Click a time to play the video from that point. This transcript comes from the episode’s captions and may contain small errors.

Welcome to Magnificent Minds, where we explore the science of child development with both heart and reason, bringing clarity, compassion and scientific evidence to questions that matter deeply to families. In this episode, we'll look at three topics that often spark intense conversation and confusion. First, Leucovorin therapy a prescription form of folate that may help a subset of autistic children. Second, Tylenol used during pregnancy and what large scale studies actually show about risk and vaccines. The science and the myth, and what that means for the decisions you make for your own child.

We'll also touch briefly on a recent claim linking circumcision and autism, and talk about what to do when headlines outpace the evidence. My goal today is not to convince you of a particular viewpoint. It's to help you understand what the science says, where the limits of that science are, how all of it fits into a whole child model of care. Over the past 25 years, I've sat with thousands of parents in my clinic office, and the conversation almost always comes around to questions like, what caused my child's autism? Was there something I did? So I want to start today by walking you through the answer.

And the truth is, autism isn't caused by one thing, one event or one moment in time. But there is a framework I use that I think really helps make sense of it. It's one that combines what we know about genetics, biology and environment into something simple, visual, and grounded in nature. Because we all come from nature. And I believe the best way to understand child development is to think about the growth of a tree. So a tree grows out of a seed that carries a blueprint to guide how it will grow. Your child also has that blueprint in the form of genes that shape how your child grows, how their brain wires, how their cells communicate, and the growth of the seed is influenced by its environment.

Like soil rich in nutrients, appropriate sunlight or shade water. In human terms, that soil, that air. The sunlight is everything a child experiences nutrition, sleep, stress, the prenatal environment, learning opportunities, relationships, love, stimulation, all of it matters. Sometimes the seeds themselves carry differences, small genetic variations that make the brain more sensitive to what's happening in the soil and the environment. And sometimes the soil and other aspects of the environment provide too little of what the child needs, or introduces stressors that challenge those sensitive seeds.

When those two things interact, the seed in the soil development can take a different path. It's not the wrong path. It's not broken. It's not less. It's just different. And that's what we see in autism, a neurodevelopmental difference that arises from how genes and environment come together as the brain grows. So as I see it, our role as parents, clinicians, teachers, therapists is to provide a nurturing environment with the right support for what that particular child needs to grow and thrive. And it's different for all children.

Some trees need more shade. Some need richer soil. Some grow slower. Others surprise you with blossoms that you didn't expect. And that's why when we talk about things like what we're talking about today, medical treatments, like Leucovorin environmental exposures during fetal life, like Tylenol or vaccines that an infant or child receives. These are all pieces of the environment that can influence growth and development. Another reason these topics are so important and why I'm grateful they're getting more attention, is because most parents today still aren't fully aware how important and urgent it is for their child to access autism specific medical therapies.

And you know, they aren't aware that it's even better if these medical therapies are integrated with ABA and with developmental therapies like occupational therapy and speech language therapy. Today, most children are still getting piecemeal, fragmented services, often with excessive 40 hour per week ABA programs that can cause more harm than good. So I wish every parent knew from the moment of diagnosis that their child can have something so much better. A complete and integrated medical, ABA and developmental therapies program.

So I'm on a mission with my entire team of 2000 clinicians at Cortica to try to change that. So with that foundation, let's get into the specifics of some of these hot topics. And we will start with Leucovorin. Leucovorin is something that sits right at the crossroads of genetics and metabolism. It's a nutrient that fuels DNA, neurotransmitters, and brain growth. And it's an autism medical therapy that's been getting a lot of attention lately. Leucovorin is a form of folate, and folate is a B vitamin, specifically vitamin B9.

Now leucovorin is also called folinic acid. These are two different names used to refer to the same thing. And what is it exactly? Well, it is a form of folate that's already in its active state. So the body can easily use it. So you can think of Leucovorin as a version of folate that's turned on and ready for the body to use. Now folic acid, on the other hand, which you're probably more familiar with, is a synthetic version of folate. And it's the version that's turned off.

It's the form that you often find in. So over the counter supplements, it's the form used to fortify certain food products like enriched flour, bread or cereal. And it needs the body to go through additional steps to turn it on before it can be used. The brain needs a lot of folate to be able to grow and to function. For some people, particularly those with genetic differences. So genetic variants, or who have, metabolic inefficiencies, that conversion process to turn on folic acid can be sluggish, leaving less active folate available to the brain.

So the brain and body need folate to do some very important things like, making DNA, which is the building block of genes, the body's instruction manual. It provides the information our cells need to grow and to function. It's also very important for supporting a process called methylation, which determines which genes are turned on or turned off. Methylation is like, I like to think of it as putting chemical sticky notes in our genetic instruction manual to tell the cell which parts to read and which parts to skip.

Folate is important for making neurotransmitters. Folate is needed to make dopamine, serotonin, and norepinephrine, and folate is also really important for forming healthy red blood cells, which carry oxygen throughout the body, and low folate can lead to anemia. So here's a simple way I like to think about it. If you have a choice between the off version folic acid and the on version leucovorin you would choose the on version. Now let me say a little more about how folate gets into the brain, where it's so crucial for the brain to be able to learn to function and to grow.

So folate crosses into the brain through specialized transport systems, mainly one called the folate receptor alpha. So you may have heard about the blood brain barrier. This is a protective barrier that keeps the brain safe from many harmful substances that might be in the in the blood. Folate crosses that barrier mainly through a special receptor. Some children with autism have antibodies that block this receptor. So folate can't get into the brain as efficiently. These are called Folate receptor autoantibodies.

Now we don't know for sure why these antibodies form, and why they seem to be more common in autism. But one theory is that it has to do with differences in how the immune system is functioning. The immune system may be more prone to form defenses, which is what antibodies are. They are meant to defend the body against things like viruses and other infections. And sometimes those defenses get other effects, like in this case, blocking an important receptor for folate transportation into the brain. Now, reduce levels of folate in the brain have been found in some children.

This is called cerebral folate deficiency. So where does Leucovorin come into play in all of this? Well, it happens that leucovorin is a form of biologically active folate. Folate that's turned on and it can get into the brain better than folic acid, even when those folate receptors are blocked. There are some other forms of fully that, like leucovorin are turned on. These include L methyl folate and another one called five methyl tetra hydra folate. So if you see these names on supplement labels, you know that these act in similar ways to leucovorin.

What distinguishes leucovorin is that it's a prescription medication, while the others you're likely to be able to find over the counter as supplements. Now, whenever something is a prescription medication, it's under higher quality control. And leucovorin is also available at the higher clinically effective doses needed, whereas the other forms usually aren't. So research studies, clinical trials in autism have shown that Leucovorin can improve language, communication and social interaction in autistic children, especially those who have the folate receptor antibodies.

The dose used in these studies was typically around 1 to 2mg/kg of body weight per day, up to a maximum of 50mg per day. And typically the dose is divided twice daily and given somewhere between 12 to 24 weeks. In these research studies, and also in my clinical practice and the practice of our physician group at Cortica. The most common side effects include some mild agitation, irritability, or sometimes sleep disturbance.

These kind of fall under an umbrella that we sometimes refer to as behavioral activation. So they're kind of activating to, the nervous system to the brain. And these are usually temporary and fortunately resolved with dose adjustment or just after being on the medication for a period of time as the body adapts and adjusts. And long term use has proven to be very safe when managed by a medical provider familiar with autism and metabolic treatments. So for those of you who may have your child in, you know, an ABA only program which unfortunately still today is the majority of children with autism, you likely have not been able to get an appropriate answer about Leucovorin and certainly not a prescription.

But in my clinics at Cortica, we know how important it is to deliver medical therapies paired with ABA and we've prescribed Leucovorin for hundreds of patients over the past decade as part of our whole child treatment program. Now, not every child benefits, but when they do, the improvements can be profound. So, you know, a child who was not able to speak may begin to speak. A child who struggled to engage might start making eye contact and expressing curiosity. We've seen children's language improve in their vocabulary, their use of phrases and sentences, their understanding of what others are saying, and even their back and forth conversations.

The doctors and nurse practitioners at Cortica who I work with prescribe Leucovorin because we have deep experience and expertise within our medical team with autism, with folate metabolism, with immune differences and autism, including folate receptor autoantibodies and cerebral folate deficiency. It's really important to work with an autism trained medical provider who is skilled in all these areas. You'll find that most doctors are not familiar with Leucovorin, and its use in autism. If they don't specialize in medical therapies for autism.

My team also does testing for some types of cerebral folate deficiency and for folate receptor autoantibodies. Again, these tests are very specialized and most doctors aren't familiar with them and don't order them. So it's really important to find a medical provider who is. Let's talk now about what the research shows on the connection between dairy products and folate receptor autoantibodies. So it turns out that cow's milk contains a protein that looks almost identical to the human folate receptor.

Because of that similarity, some children's immune systems can get confused when they drink milk. Their bodies may start producing antibodies that not only react to the milk protein, but also to their own folate receptor. This is what scientists call molecular mimicry. The immune system is mistaking one protein for another because it looks so similar. In some small research studies. When children who had these antibodies stopped drinking cows milk, their antibody levels went down over a few months.

When milk was reintroduced, the antibodies went back up. Some of these children also showed developmental or behavioral improvements when dairy was removed, and folinic acid was added. So when Leucovorin was added. And this is probably because Leucovorin can can really bypass that blocked receptor. So it also has other ways of getting into the brain. It's important, of course, to recognize that these studies have been small and were not designed to prove cause and effect.

They just show associations links or connections and possible trends. Also, most of the evidence comes from children with confirmed folate receptor antibodies and not from all children with autism. So while this line of research is promising, it's still considered preliminary or early. We can't say that dairy causes autism or that removing dairy will help every child. Now, to go back for a second to thinking about the growth of a seed and environmental factors that influence its growth, the genetic blueprint in the seed informs, for example, whether a child will have the biological tendency toward any of the folate disturbances we've been talking about, like cerebral folate deficiency, folate receptor autoantibodies or, difficulty converting folate from its inactive form to its active form.

So turning it from the off state to the on state, because of something like a variant in the MTHFR gene, the MTHFR gene makes an enzyme that is very important for converting folate into the active form that our cells use. Now, some people have a variation or a variant in the MTHFR gene that makes this enzyme work a little less efficiently. And that means their bodies don't convert folate as easily. So you can think of it as sort of not working at full speed. And it can be even that much more important then to supplement with an active form of folate like Leucovorin.

And this is a gene that we can test for. Now if one or more of these are present, then adding Leucovorin and doing so early in life, could be very important. It's like enriching the soil the seed grows in with a very specific nutrient selected based on precise, biological information. What's also important to know is that sometimes children who don't have these various biological markers still benefit from Leucovorin. Why? Well, we don't know for sure, but it's probably because there are other types of folate metabolism disturbances that we don't fully understand and don't have tests for yet.

So sometimes it's worth trying a treatment like Leucovorin and monitoring closely for changes, even if the biological tests we've been talking about are normal, or if they can't be done for any reason. Leucovorin is not a cure, but it is a meaningful tool for some children, particularly those with the differences in folate metabolism that we've been talking about. You can see why it is so important to work with a doctor or other medical provider who is very knowledgeable and experienced with the use of Leucovorin and with autism.

It is one piece, one very important piece to use alongside many other important medical, developmental and behavior therapies. I want to share with you some really wonderful news that a parent told me recently when their child started taking Leucovorin. Their son was able to tell them, after taking Leucovorin for a few weeks, that he felt he had more freedom, that he was able to be more calm and focused. Those were his exact words. And when he was asked about side effects, he said he had no problems.

The parents themselves told me that they could observe in him a more calm and focused, overall demeanor. And, they said they were able to actually take him to a big, baseball Major League Baseball park. On a recent family trip. And they were able to even take a tour with a tour guide. And during the tour, their son was able to stay calm and focus throughout. And this for him was very unusual because because his attention span was generally closer to maybe an hour. And this particular day, the tour lasted more than two hours.

They had actually planned, all sorts of different contingencies. You know, plans to leave if he became dysregulated. And they just said they were so struck that he remained calm and focused throughout the long tour. He never once expressed a desire to get out or repeated his words, which he often did. And the next morning, they were even able to ask him some questions about information that he had learned on the tour. And he got every question right. So this was just one of the pieces of feedback I've received recently from a parent on the positive effects of Leucovorin.

Next, let's turn to Tylenol or acetaminophen during pregnancy, a topic that's received a lot of attention in the media recently. Acetaminophen is the generic name, and Tylenol is a brand name that it's the one that most people recognize. I'll be using the term acetaminophen here because that's the medication we're talking about. With all of the recent discussion around acetaminophen and pregnancy, I think it's important to take a step back and look at the bigger picture. We know that certain substances that enter into a mother's body during pregnancy might affect the fetuses developing brain.

Some drugs have very well-established risks for brain and birth defects. For example, recreational substances like alcohol and cocaine, as well as prescription medicines that you might have heard of, like, one called isotretinoin, which you might know is the brand name Accutane. Or it comes in other names too. Or the seizure medicine called valproate. Opioid medications and nicotine are other substances that research studies have also found to have the potential to harm the developing brain. Then there are medications where there is even less research evidence.

So the possible link is truly unknown. And uncertain at this time. And that's where acetaminophen falls. So the first thing to know is that this debate is based on observational studies. These are studies where researchers collect information like surveys, medical records, or track behaviors and then analyze it to look for patterns. These kinds of studies can show links, what we sometimes call correlations or associations, but they cannot prove cause and effect. Sometimes those links matter and sometimes they're actually misleading.

So in this case, some large observational studies have found that when pregnant women used more acetaminophen, their children were later more likely to be diagnosed with autism or ADHD. But in plain language, again, just because, there is an association doesn't mean that acetaminophen caused autism. In the largest study so far, a 2024 Swedish study of 2.5 million children, researchers compared siblings. Okay, so where, one was exposed to acetaminophen, during pregnancy and and the other wasn't, and then the link disappeared.

Okay, so that tells us it was likely genetic factors rather than exposure to acetaminophen that was the true link, to autism. So Tylenol has not been proven to cause autism. But interestingly the conditions it is often used to treat like high fever infection or chronic or severe pain. These could be linked to autism. We don't yet know enough based on the current research. One thing to keep in mind, and relates to an area of my expertise and research, is the function of mitochondria.

And research does show acetaminophen may impair mitochondrial function, and that there may be a subset of pregnancies that are more vulnerable to environmental factors, including medications that put stress on mitochondria. There's a lot more we need to research to fully understand what these effects might be, but it is in my view, a really, really important research area. So based on all of this, what should you do? Well, there are certainly times when acetaminophen is the safest option for managing pain or fever during pregnancy.

If it's used, it should always be used at the lowest effective dose and for the shortest duration possible, which is true any time you take a medicine. Let's turn now to look at vaccines and autism. Now, vaccines and autism have been debated for decades, and there are a few key things to know. So first, it's really important to know that there have been many large, high quality studies involving millions of children across many countries in North America, Asia and Europe. And these studies have not shown a link between vaccines and autism.

At the same time, it's important to know when a personalized approach to childhood immunization schedule, rather than following the routine schedule, might be a good idea. So if a child is seriously ill with a moderate or severe acute illness, for example, a high fever, an active infection further stressing the body is not a good idea. There are also some specific immune system differences or immune system problems. For example, children who are taking medications that are, suppressing the immune system, or children who have, some type of deficiency in their immune system.

Where, personalization and alteration of the immunization schedule is important. Sometimes, an allergic reaction or a prior complication from a vaccine. These would be reasons to modify, alter the vaccine schedule. There are also some medical situations that would warrant a, a change in the vaccine schedule. So, for example, premature or preterm infants, those who have been in the new Natal ICU, children who may have maybe had a recent blood transfusion or even treatment with immune globulin for a medical condition.

So there are a number of medical situations where changing the vaccine schedule is important. Every decision made in medicine, including the use of vaccines for a particular child, should be based on weighing the potential benefits of an intervention with the potential risks. And that's why I think it's so important that discussions around vaccines are happening between you and a doctor who you trust and who knows every aspect of your child's medical history, including the medical history of family members, and who listens to any hesitation or concern that you have and takes them seriously.

So I personally rarely speak about vaccines and autism in public, but I talk about it with my patients all the time, and we figure it out together to ensure the decisions we make. Maximize benefits to your child, like protecting against serious, preventable infections and minimize all risks, especially any risks to brain development. Before we wrap up, I want to take a moment to address a very recent headline linking newborn circumcision, Tylenol use and autism. This is a good example of an eye catching claim that is not backed by sound scientific evidence.

So for parents who may have made these decisions, it's important to remember this is not something to feel blame or guilt about, but what is worth exploring further through high quality research is how early stressful experiences of any kind might influence brain and body development. When I say stress, I'm referring broadly to biological stress. The cascade of chemical and physiological changes that happen in response to difficult experiences. These responses include rises in stress hormones like cortisol and norepinephrine, chemicals that act like the body's built in alarm system.

They help us react quickly to challenges to keep us alert, ready to move. At the same time, the sympathetic nervous system, which is often called the fight or flight system, kicks into gear in stressful situations. It's like pressing the gas pedal in a car. You know, the heart beats faster, blood pressure goes up. Blood is sent to the muscles so the body can respond to danger. These kinds of physiological responses to stress happen in a fetus. A newborn, an infant, a young child, adolescent, adult.

And when the system stays revved up for too long in that state of stress, it can take a toll. The body starts borrowing energy from other systems, slowing things like digestion, growth, and immune repair. Even at the cellular level, stress changes how our mitochondria, the tiny power plants in our cells, how they work. They start producing extra energy for the short term. But like an engine running too hot, they also give off more, exhaust or toxins, and can cause more of what's called oxidative stress.

And that's when, unstable oxygen molecules called called free radicals begin to build up and can damage cells over time. If this pattern of stress happens repeatedly in early life, whether from medical procedures, illness, emotional strain, it can subtly shape how a child's brain and body grow and adapt. Every child's system responds differently. And that's where the real opportunity for research lies. To understand how stress biology interacts with genetics and brain development, and how that knowledge might guide more effective therapies for autism.

Thank you so much for listening. If you'd like to learn more, you can check out my book, Magnificent Minds or visit Cortica’s website online, where you can find information about where our clinics are located and all the services we provide. And of course, keep following this podcast for more conversations about autism, neuroscience, and building a bright future for your child.