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Leucovorin for Autism? Dr. Richard Frye Explains What Parents Need to Know

  • Children with autism may have underlying medical issues—like nutrient deficiencies, gut problems, or folate transport disorders—that impact behavior and learning. Dr. Richard Frye’s research shows that addressing these issues can dramatically improve outcomes, especially in speech and language development.
  • Folinic acid (leucovorin) is an active form of vitamin B9 that bypasses common folate metabolism problems in children with autism, helping the brain function more effectively.
  • Dr. Frye’s team found that up to 75% of children with autism tested positive for antibodies that block folate from reaching the brain. When treated with prescription folinic acid, many children saw significant improvements in speech, behavior, and sleep in just a few months.
  • Parents can ask their pediatrician to start with simple labs—like iron, zinc, and vitamin D—or request the FRAT blood test, which checks for folate receptor autoantibodies. You can learn more about leucovorin and the testing at fratnow.com or autismdiscovery.org.
  • Dr. Mary Barbera’s free BECA assessment helps parents track language, self-care, and problem behaviors at home—so you can measure progress before and after any medical or therapy changes. 

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When your child is diagnosed with autism, you may hear a lot about behavior therapy, speech therapy, and IEPs. But what if there are underlying medical issues making everything harder—speech delays, poor sleep, tantrums, picky eating—and they’re being missed?

In this episode of the Turn Autism Around podcast, I sat down with Dr. Richard Frye, a Harvard-trained pediatric neurologist and autism researcher, to discuss a powerful—but often overlooked—tool in helping kids with autism: folinic acid (also called leucovorin).

We talked about:

  • Why functional medicine is different from traditional medicine

  • What leucovorin is and how it helps some children

  • What to ask your pediatrician

  • How to know if your child might benefit from leucovorin based on the research

Let’s break it all down.

Why Looking Into Medical Issues for Autism Matters

Most people think of autism as just a “behavioral” diagnosis—but that’s only part of the story. Dr. Frye reminded us that autism is a complex neurological condition, and many children also have underlying medical issues that interfere with communication, learning, and behavior.

Kids with autism may struggle with:

  • GI issues (constipation, pain, reflux)

  • Poor sleep

  • Low iron or zinc

  • Chronic inflammation

  • Folate transport issues (more on that below)

Unfortunately, these problems are often missed by traditional pediatricians—especially when a child is not able to communicate how they’re feeling.

“The success of the child is proportional to how much the parent can advocate.” — Dr. Richard Frye

That’s where functional medicine comes in. Unlike traditional medicine—which often treats symptoms in isolation—functional medicine looks at the whole child, asking why symptoms are happening. 

It emphasizes root causes, personalized lab testing, and medical-nutritional approaches that support the brain and body from the inside out. For many children with autism, this can lead to meaningful improvements in speech, sleep, behavior, and overall health. 

We will discuss how to get help from your tranditional pediatrician but you may also need to seek out functional medicine support. 

What Is Leucovorin (Folinic Acid)?

You may have heard of folic acid, the common B-vitamin added to prenatal vitamins and cereals. But leucovorin (folinic acid) is a different, more advanced form.

lecovorin autism. what is leucovorin for autism?
What is leucovorin and how can it help kids with autism?

Here’s the difference:

  • Folic acid is a synthetic form that must be converted in the body to be usable.

  • Folinic acid (leucovorin) is already active, meaning it skips the conversion step—and that matters if your child’s body has trouble with that conversion.

Folinic acid is used medically to:

  • Help children with cerebral folate deficiency (CFD)—a condition where folate doesn’t get into the brain properly

  • Support speech, behavior, and neurological development

  • Protect healthy cells during certain cancer treatments (which is why it’s sometimes confused as a “cancer drug”)

“Folate is crucial for healing and brain function, but in many kids with autism, it can’t get into the brain. Leucovorin bypasses that block.” — Dr. Frye

Why Folinic Acid Might Help Kids with Autism

Dr. Frye’s research found that up to 75% of children with autism have antibodies that block folate from getting into the brain. This is known as folate receptor alpha autoantibody syndrome (or cerebral folate deficiency). It can be detected with a simple blood test called the FRAT test.

When these kids received folinic acid, many showed:

  • Improved verbal communication

  • Less frustration and fewer behaviors

  • Better sleep and overall functioning

In one study, children who tested positive and received leucovorin had a 77% response rate in just 3 months.

“Even if a child doesn’t start speaking, improved communication—like using a device or pictures—can significantly reduce problem behaviors.” — Dr. Frye

How to Know If Your Child Might Benefit From Leucovorin

The FRAT blood test (Folate Receptor Antibody Test) is available at fratnow.com and is one way to assess if your child might have a folate transport issue. While not every child responds the same, those who test positive for these antibodies are more likely to benefit from leucovorin treatment.

But Dr. Frye is clear—this isn’t a magic pill. Children with underlying medical problems (like poor sleep, gut issues, or iron deficiency) may not respond as well unless those are addressed too.

How to Talk to Your Pediatrician About Medical Testing

As a nurse and behavior analyst, I’ve always emphasized that behavior is communication. And if a child is in pain or has untreated medical issues, no amount of behavior therapy alone will help.

You can ask your doctor:

  • “Can we check for common issues like iron, zinc, vitamin D, and lead levels?”

  • “Is it possible to run the FRAT blood test for folate transport problems?”

  • “Can we explore GI issues or sleep concerns further?”

  • “Do you have any referrals for a functional medicine or MAPS-trained doctor?”

If your pediatrician isn’t familiar with folinic acid or functional medicine, don’t be afraid to seek a second opinion. You can also find providers through:

Next Steps for Leucovorin for Autism Treatment

Here are some simple steps if you’re curious about leucovorin and autism treatment:

  1. Talk to your doctor about getting the FRAT blood test.

  2. Consider working with a MAPS-trained physician (Medical Academy of Pediatric Special Needs) if your pediatrician is unfamiliar with biomedical or functional medicine treatments.

  3. Visit Dr. Frye’s site: autismdiscovery.org for more education.

  4. Look into support from TACA or your local autism advocacy group to help cover any costs to getting leucovorin treatment.

  5. Download my free digital assessment (BECA) to track your child’s language, self-care, and behavior progress: marybarbera.com/assessment

Final Thoughts on Leucovorin and Autism

Functional medicine doesn’t replace therapy—but it can unlock progress when medical barriers are addressed. Leucovorin isn’t the right answer for every child, but for many, it’s a game-changer.

If your child is stuck—especially with language, behavior, or sleep—this could be a missing piece.

Keep turning over stones. Keep asking questions. And remember, you don’t need to wait for everything to be perfect to take the next step forward.

Dr. Richard E Frye on the Turn Autism Around Podcast

Dr Frye is a Harvard trained Child Neurologist with an MD/PhD from Georgetown University. He is a national leader in autism. He has developed the Metabolic Learning Resource which has recently released The Folate Fix. He is President and Chief Scientific Officer of the Autism Discovery and Treatment Foundation.

Leucovorin Autism Top 5 FAQ

Leucovorin, also known as folinic acid, is a prescription form of vitamin B9 that’s already in its active, usable form.

Unlike synthetic folic acid, leucovorin bypasses common metabolic blocks—such as MTHFR mutations or folate receptor autoantibodies—that prevent folate from reaching the brain.

This makes it especially helpful for children with autism who may have difficulty converting folic acid into its active form.

The FRAT (Folate Receptor Antibody Test) is an out-of-pocket blood test that checks for autoantibodies blocking folate from entering the brain.

 Dr. Frye’s research shows that up to 75% of children with autism may test positive. If your child is not making expected progress in therapy—or has speech delays, sleep issues, or behavior problems—it may be worth discussing the FRAT test with your pediatrician.

Children who tested positive for folate receptor antibodies and were treated with leucovorin showed significant gains, especially in:

  • Expressive and receptive language

  • Behavior regulation

  • Sleep quality
    In one clinical study, 77% of children showed measurable improvement in language skills after just 3 months of treatment.

Leucovorin is a well-tolerated prescription vitamin with a strong safety profile. In most cases, side effects are minimal, though sensitive children may experience mild gastrointestinal upset. Dr. Frye emphasizes the importance of working with a knowledgeable provider, especially since dosing can vary depending on the child’s weight, age, and medical profile.

Many traditional pediatricians are unfamiliar with this treatment. You can start by:

  • Asking for basic labs (iron, zinc, vitamin D)

  • Bringing information from Dr. Frye’s research or fratnow.com

  • Seeking a second opinion from a MAPS-trained physician (medmaps.org)

Parents are encouraged to advocate respectfully and continue searching for answers if they feel their child’s medical needs are being overlooked.

Resources

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Disclaimer:
This content is for informational purposes only and is not intended to diagnose, treat, cure, or prevent any medical condition. Always consult with your child’s pediatrician, a licensed healthcare provider, or a qualified functional medicine practitioner before making changes to diet, supplements, or medical care. 

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Want to Learn how to Increase Talking & Decrease Tantrums in Children with Autism or Toddlers Showing Signs?

Want to start making a difference for your child or clients?

I’m Ready to Learn!