Pediatric group does not recommend leucovorin for autism
What did the American Academy of Pediatrics have to say?
Writing in the news section of the Web site for the American Academy of Pediatrics on 31 October 2025, Melissa Jenco published a press release entitled “AAP: Evidence too limited to recommend leucovorin broadly for autistic children.” Here is her lede:
The AAP does not recommend routine use of leucovorin (folinic acid) for autistic children due to limited evidence on its safety and effectiveness, according to new interim guidance.
Ms. Jenco referred to two publications from the AAP, one that provided “interim guidance” and another that is an “FAQ.” She noted that early studies focused on children and adults with documented “cerebral folate deficiency” and “suggested potential benefits to communication and behavior for some autistic children” with that condition.1
I read the additional documents to which Ms. Jenco referred. Both are aimed at physicians as readers. At the time that I read them, the documents had been updated 31 October 2025.
“Interim Guidance from the American Academy of Pediatrics: Use of Leucovorin in Autistic Pediatric Patients” essentially explained the same ideas that Ms. Jenco summarized in the press release.
“Frequently Asked Questions (FAQs) for Pediatricians and other Prescribing Pediatric Clinicians: Leucovorin Use in Autism and Cerebral Folate Deficiency” provided more detailed and nuanced information. For examples, here are three questions and my summary of the answers:
Q: Can I test for FRAAs in my autistic patients?
A: Not really. Tests haven’t been validated and are conducted by different labs that likely use different methods and criteria for diagnosis.Q: What do the studies say about leucovorin in autism?
A: The evidence for leucovorin and use for autism is currently limited. Small studies show benefits to communication and behavior for some autistic children, specifically those with CFD or evidence of folate metabolic differences. LargerQ: Are there side effects to leucovorin?
A: Yes (including irritability, GI upset, dematiptts, anaphylaxis!, and more) and prescribing physicians should monitor for these side effects.
The FAQ covers a total of 10 questions, 7 more than I’ve listed here. Readers should read them; the writing seemed clear and accessible (gobbledygook free!) in my estimation.
Conclusion
As I wrote previously (23 September 2025), leucovorin has not been shown to be beneficial. There are a couple of promising preliminary studies with highly selected subgroups of children (and adults). In the “bottom line” of the FAQ document, the AAP wrote, “Current evidence is insufficient to support prescribing leucovorin for autism in the absence of CFD” (emphasis in the original.
Footnote
The description of the studies and findings should be familiar to regular readers of Special Education Today, because our post of 23 September 2025, “Leucovorin as therapy for autism: What is it, what does it do, and does it work?,” reached the same conclusion.