Leucovorin Versus Methylfolate: What’s the Difference and Why Does It Matter?

Have you ever heard of leucovorin or methylfolate and wondered what the difference? And why do some kids with autism respond really well to one but not the other? Today we’re going to break this down in a simple science-based way.

What is Folate?

Folate is a vitamin. It helps our central nervous system, our gut, our energy, and especially how our brain cells talk to each other. You can think of folate as brain fuel that helps the brain grow, repair, and make neurotransmitters like serotonin and dopamine.

But here’s the twist. There isn’t just one kind of folate. There are different forms, and our bodies don’t use them the same way.

The Two Main Active Forms of Folate

There are two main active forms that we’ll focus on in this video. Methylfolate, also called 5-MTHF or L-methylfolate, and leucovorin, which is a prescription, are also called folinic acid. Both are real, usable forms of folate in the body.

And both are way better than folic acid for most people. But they do not enter the brain in the same way, and that’s where things get very interesting.

How Does Folate Get Into the Brain?

Imagine the brain has a front door. To get inside, folate needs a special key. This key is called the folate receptor alpha.

Methylfolate uses the front door. So for most people, methylfolate works great. 5-MTHF works great.

When the Front Door Gets Blocked

Now, when the front door gets blocked, for some people, the body makes something called folate receptor autoantibodies. That’s how the front door would get blocked. These autoantibodies are tiny immune proteins that basically block the folate front door.

And they can block it in two ways. So there’s something called a blocking antibody. They sit in the lock so that methylfolate can’t get in.

And there are also binding antibodies. So they basically hide the lock, so fewer doors are available. Even if someone takes plenty of methylfolate, it can’t get into the brain.

Now this can lead to cerebral folate deficiency, where the blood folate level looks normal. So if you do a blood test, it looks normal. But the brain is actually running on empty.

Why Testing Matters

This is why testing for these autoantibodies, called the frat test, is so important.

So, Where Does Leucovorin Come In?

Methylfolate uses the front door, and leucovorin uses a side door.

Leucovorin gets into cells using a different transporter, something called the reduced folate carrier. This side door usually still works even when the front door is blocked.

So in kids or adults with folate receptor autoantibodies, leukovorin, folinic acid, may work better than methylfolate because it can bypass the block for that person and still get folate into the brain.

Once inside the cell, leucovorin is converted into the active form the brain needs.

Does That Mean Methylfolate Is Bad?

Does that mean methylfolate is bad? No, not at all.

For people without these antibodies, methylfolate works really well and is often the preferred form. However, in someone with folate receptor autoantibodies, methylfolate may struggle to get where it’s needed.

So the key question becomes, is the front door blocked or not for your child with autism?

Why Personalized Treatment Matters

This is why personalized treatment matters. This is why we never just try a supplement and hope.

Quick Summary

What Does Methylfolate Do?

It’s the ready-to-use form of folate that usually goes into the brain through the front door.

What Stops It From Working?

Folate receptor autoantibodies block this front door.

How Does Leucovorin Help?

It uses a side door, a different transporter, so it still can get folate into the brain.

Which One is Better?

It depends on whether the front door is blocked, which we test for by a FRAT test. So there’s no guessing.

Final Take-Home Message

It’s not about which folate is better. It’s about which folate works for your child’s biology.

Thank you for being here. Remember, knowledge is power. Stay informed. Be empowered. See you soon.

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