Leucovorin (Folinic Acid) Frequently Asked Questions
What is Leucovorin (Folinic Acid)?
Leucovorin, also known as folinic acid, is an activated form of folate (a B vitamin) that supports brain development, neurotransmitter production, methylation, and cellular repair. Because it does not require conversion by some enzymes that folic acid does, it may bypass certain metabolic bottlenecks.
Why is Leucovorin used for Autism Spectrum Disorder (ASD)?
Some children with ASD show problems with folate transport into the brain — for example from Folate Receptor Alpha Autoantibodies (FRAA) or other folate-metabolism issues. Leucovorin can help bypass those issues, boosting folate availability in the brain and supporting improved neural function.
What symptoms may improve with Leucovorin therapy?
While responses vary, clinical experience and research suggest potential benefits in:
Expressive and receptive language (speech)
Attention, focus, engagement
Social interaction, eye contact
Cognitive learning and processing
Decreased irritability/hyperactivity
Improved mood regulation and sleep
These changes unfold gradually, typically over weeks to months.
What does recent research say?
Key studies include:
A pilot randomized, double-blind, placebo-controlled trial in children with ASD and language impairment (dose ~2 mg/kg/day, max 50 mg/day for 12 weeks) showed significantly greater improvements in verbal communication in the folinic acid group, particularly among children positive for folate-receptor-α autoantibodies (FRAAs). PubMed+1
A 2020 review (ScienceDirect) looked at folinic acid in ASD children with folate-pathway abnormalities and reported that treatment may yield benefit, particularly when folate metabolism is impaired, but also emphasized the need for larger, rigorous trials. ScienceDirect+1
More recently, a 2025 trial found that in Chinese children with ASD, high-dose folinic acid (2 mg/kg/day up to 50 mg) for 12 weeks was well tolerated and improvements were associated with folate‐metabolism gene polymorphisms. MDPI
Is Leucovorin safe?
Yes. Folinic acid has a notable safety record in pediatrics when used appropriately under medical supervision. Although it should not be taken if there is a pre-existing folate allergy. The trials above, including the 2020 review and the 2025 trial, reported no significant safety concerns in their cohorts. ScienceDirect+1 Possible mild side effects include:
Irritability or hyperactivity (transient)
Sleep onset difficulty (adjust timing)
Mild gastrointestinal upset- constipation/diarrhea
Your provider may adjust the dose or timing if needed.
Do we need lab testing before starting Leucovorin?
Testing is not mandatory, but it may help with personalization and monitoring. Useful tests include:
Folate Receptor-α Autoantibodies (FRAA) FRAT testing
Serum or RBC Folate, Vitamin B12, Homocysteine
Methylation/folate‐pathway gene polymorphisms (e.g., MTHFR) — especially relevant given the recent trial finding genotype influenced response. MDPI
Testing can help determine if your child belongs to the subgroup likely to respond but is not required before starting Leucovorin with Functional Autism.
Is Leucovorin FDA-approved for autism?
Leucovorin is FDA-approved for other indications (e.g., methotrexate rescue therapy, some anemias). Its use in ASD remains off-label, however as of September 22, 2025 the FDA has initiated the approval process of a label update for leucovorin for cerebral folate deficiency, which has been associated with autism.
How do I start treatment through Functional Autism?
Patients who live in Arizona, Colorado, Florida, Idaho, New Mexico, Oregon, Utah or Washington may begin with a telehealth intake appointment for Leucovorin with Family Nurse Practitioner Dr. April Lam, DNP FNP-C. During this visit we’ll review your child’s medical history, developmental profile, past interventions, and current challenges. If Leucovorin is deemed appropriate, we’ll issue a prescription, provide follow-up monitoring plan. You can schedule an appointment here:
