Autism Parenting Secrets

Episode: Clarify The Leucovorin Confusion

Host: Len Arcuri
Guest: Nicole Rincon, PA-C
Date: November 13, 2025

Episode Overview

This episode of Autism Parenting Secrets demystifies leucovorin (folinic acid/calcium folinate), a treatment gaining traction for children with autism—particularly those with cerebral folate deficiency (CFD). Host Len Arcuri welcomes back Nicole Rincon, a board-certified physician assistant and mother of triplets with firsthand experience using leucovorin. Together, they dissect the science, clarify misconceptions, explain practical steps, and offer guidance on whether and how to pursue leucovorin as part of an individualized autism treatment strategy.

Key Discussion Points & Insights

1. The Promise and History of Leucovorin for Autism

• Leucovorin isn’t new—it’s been around and well-studied for years, notably since a landmark study in 2007 demonstrated significant improvements in children with CFD and autism ([03:31]).
• Recent FDA approval makes it more accessible and raises awareness, but “that doesn’t necessarily mean that everyone should run out and go down this road.” (Len, [06:37])
• Nicole emphasizes, “This is a near and dear topic to me because my family's on Leucovor, and all three of my children. I am actually on it as well because we're all positive for folate receptor antibodies.” ([03:31])
• She shares a powerful anecdote: “Personally, I noticed that my son, it increased his cognition within, you know, weeks of starting it. His speech, his hyperactivity improved, his attention—all the kind of the landmark symptoms that we see in the studies that it improves—my son had that.” ([03:31])

2. What Is Leucovorin Used For?

• Leucovorin targets cerebral folate deficiency (CFD), not MTHFR mutations, though both involve folate metabolism ([08:05]).
  • CFD is distinct and may manifest with symptoms such as:
    • Smaller head circumference or decelerated head growth
    • Irritability and anxiety
    • Poor sleep and motor difficulties (including tremors)
    • Seizures (“If you have a child that has autism and seizures, I have high suspicion of cerebral folate deficiency.” Nicole, [08:05])
  • About half of children with autism may have CFD ([08:05], [13:54]).

3. Understanding Folate Metabolism: Antibodies and Genetics

• Folate receptor antibodies hinder folate entry into the brain, causing deficiency even when blood levels are normal. Testing involves a specialty lab ([14:51], [25:06]).
• MTHFR gene mutations affect folate activation but are a separate pathway—however, having both issues can compound symptoms ([12:08]).

4. Is Testing Necessary?

• The “gold standard” is a spinal tap, but due to its invasiveness, most rely on symptom patterns and antibody testing ([14:51]).
  • “You can have negative folate receptor antibodies and still have cerebral folate deficiency – a lot of that is because of mitochondrial dysfunction.” (Nicole, [14:51])
• Limited risks with a trial: “It's a pretty safe road to go down to experiment to see if this is beneficial for your child.” (Len, [16:03])

5. Addressing Side Effects and Preparing for Treatment

• Common parental concern: Will leucovorin worsen my child’s symptoms (e.g., hyperactivity or irritability)?
  • Nicole: “For a lot of kids, like my son is an example, it reversed those symptoms in him. He was very hyper and it calmed him down... Side effects are less than 10% of kids.” ([16:39])
• Steps to minimize side effects before starting leucovorin ([18:00]):
  • Eliminate folic acid (the synthetic, inactive form) from supplements and fortified foods.
  • Remove cow’s milk/dairy, which can boost folate receptor antibodies even in kids without allergies ([19:45]).
    • “...when they eliminated it, the child, the hyperactivity improved, the cognition improved.” (Nicole, [19:57])
  • Add calming and supportive nutrients:
    • Magnesium (preferably glycinate, for brain/calmness, [22:14])
    • Omega-3 fatty acids
    • Sulforaphane (broccoli extract) for detox/liver support
    • Methyl B12 before leucovorin to prevent “folate trapping”
    • Consider a quality B-complex (B2, B6) if needed ([23:28])

6. Dosing, Forms, and Practical Considerations

• Dosing is individualized, typically guided by antibody titers:
  • “Normally we're gonna get at least 2 milligrams per kilogram per day of leucovorin and you divide it into two doses.” ([25:06])
  • For a 50lb child: ~50mg/day, split between morning and afternoon (not before bed due to sleep interference).
  • Higher doses may be necessary in children with very high antibodies; start low and titrate up, observing response ([25:06], [31:36]).
  • Nicole recommends starting low (5mg), then incrementally increasing weekly ([25:06]).
• Forms of leucovorin:
  • Commercial preparations may contain lactose, dyes, or fillers—problematic for sensitive kids.
  • Compounded leucovorin (from a compounding pharmacy) eliminates additives; ideal for highly sensitive children ([25:06]).
  • Supplements (folinic acid) can be used, but achieving therapeutic doses is often difficult ([25:06], [29:23]).
• “Leucovorin…you got to do folinic, leucovorin, not methylfolate, and certainly not folic acid.” (Nicole [29:46])

7. The Role of Mitochondrial Dysfunction

• Up to half of children with autism may have some form of mitochondrial dysfunction, impacting energy production and folate transport into the brain ([29:46]).
• “ATP…is needed to push folate into the brain... When you have low energy, it’s not pushing folate into the brain.” (Nicole, [29:46])

8. Duration of Treatment and Long-Term Use

• Many parents ask, “Will my child need this forever?”
  • Nicole: “If they're tolerating it well, it looks like it's safe to be on long term... I think you can take it for life if you're feeling good with it and you're not having side effects.” ([33:28])
  • Nicole also uses leucovorin herself, reporting cognitive and emotional benefits.

Notable Quotes & Memorable Moments

• Nicole on her family’s experience (03:31):

  “Personally, I noticed that my son, it increased his cognition within…weeks of starting it. His speech, his hyperactivity improved, his attention—all the kind of the landmark symptoms that we see in the studies that it improves—my son had that.”

• Len on the importance of an individualized plan (12:44):

  “The biggest move for a parent to make is to really have a great plan that addresses a handful of really specific root causes… do you have enough evidence as a parent… that cerebral folate deficiency for your child is a key root cause to focus on? And if you do… then that’s where this comes into play.”

• Nicole on how to prepare for leucovorin (18:00):

  “The first steps, I tell parents, is to eliminate folic acid from your diet… I also counsel patients to eliminate cow’s milk…”

• Nicole on duration of use (33:28):

  “If they're tolerating it well, it looks like it's safe to be on long term… I think you can take it for life if you're feeling good with it and you're not having side effects.”

• On broader perspective (35:31):

  “If it's helping, it's helping. And, and that is exciting and something to celebrate. So with all the confusion, maybe that might be out there… It is all just very hopeful that something that absolutely can help many kids is more widely available, better understood.” (Len)

Timestamps for Key Segments

• Nicole’s introduction and personal context – [03:31]
• Historical study and significance of leucovorin – [03:31] to [06:37]
• Differentiating CFD from MTHFR – [08:05] to [12:08]
• Symptoms and candidate selection for leucovorin – [08:05] to [13:54]
• Testing approaches and mitochondrial dysfunction – [14:51], [29:46]
• Preparing for leucovorin (diet, supplements) – [18:00] to [23:28]
• Dosing and practical advice on prescription vs. compounded – [25:06] to [33:03]
• Long-term use and Nicole’s family experience – [33:28] to [35:31]

Practical Do's and Don'ts Summarized

Do:

• Consider leucovorin for children with symptoms and/or antibody evidence of CFD.
• Eliminate folic acid and cow’s milk before starting.
• Use calming/supportive supplements—magnesium (glycinate!), B12, omega-3s, sulforaphane, and a quality B-complex.
• Ensure constipation is addressed before starting any intervention.
• Start low, titrate up, and consult a knowledgeable clinician.
• Seek compounded leucovorin if sensitivity to fillers, lactose, dyes is an issue.
• Understand this may be a long-term—possibly lifelong—intervention for responders.

Don't:

• Assume all children with autism need leucovorin—individual evidence matters.
• Confuse Leucovorin’s target (CFD) with MTHFR gene issues.
• Use folic acid (synthetic, inactive)—it can worsen the issue.
• Prioritize new interventions before foundational issues (like constipation) are managed.

Closing Tone

Supportive, hopeful, detail-oriented, parent-empowering. Both Len and Nicole position this episode as a much-needed clarification amid the swirl of online confusion, offering concrete steps and encouragement for families seeking clarity and direction on leucovorin’s role in autism care.

For further resources, check out Dr. Fry’s book “The Folate Fix,” referenced throughout the episode, and consult with trusted, experienced providers before starting new interventions for your child.