Is leucovorin an option or is it too good to be true?
On February 18, 2025 – CBS News Featured a story about Leucovorin and Autism.
- You may be thinking - “Is leucovorin an option or is it too good to be true?”.
- Information about leucovorin and autism can be tricky to sort through for both caregivers and healthcare professionals, because – research is still developing.
The talking points below are a simplified summary of leucovorin and Autism research and practical considerations.
Talking Points
Ultimately – the choice to use or not use leucovorin should be made between the caregiver and healthcare professional who care for a child with autism.
What is leucovorin?
Leucovorin – also called folinic acid – is a type of folate vitamin. Folate does many things in the body – including help the brain grow and develop. Don’t confuse folinic acid with folic acid – another type of folate. The body processes these differently.
Can leucovorin cure Autism?
No. Leucovorin is not a cure for autism.
Can leucovorin children with Autism?
Many studies – including recent randomized control trials – have studied leucovorin in children with autism. Studies conducted in the United States, Singapore, India, and France show similar and promising results.
Improvements in speech and communication have been shown in children with autism taking leucovorin for 6 months.
- In studies - children taking leucovorin had more improvements compared to children taking placebo.
- However - not all children with autism have shown improvements from taking leucovorin.
Children who have folate receptor autoantibodies (FRAA) are more likely to have improvements in speech compared to children without autoantibodies. This means that Folate Receptor Autoantibody Test (FRAT® Test) may help identify the chance of a child having benefits from leucovorin. It has been reported that about 7 out of 10 children with Autism have folate receptor autoantibodies.
Reminder - research is ongoing – which means future studies may show the same or different results.
Can leucovorin children with Autism?
Specific to children with Autism – leucovorin is well tolerated. This means the chance of side effects is low. Side effects reported in studies were similar in children taking leucovorin and children taking a placebo.
There is a lot of confusion about the safety of leucovorin. This is because widely accepted use and original studies of leucovorin are in children receiving medications for pediatric cancer.
- For example - you may read that leucovorin has many side effects. However – these side effects are reported when leucovorin is used in combination with 5-flourouracil or methotrexate in children with cancer. Studies specific to leucovorin use in children with Autism have yet to identify notable side effects that are different from placebo.
- Another example - you may read that leucovorin can cause seizures. Seizures have not been reported in studies specific to children with Autism.
What age must a child be to use leucovorin?
Children aged 2 years old to 13 years old were included in the studies showing the results described above.
How long should someone take leucovorin?
Leucovorin was studied for 6 months. Which means it is unclear how long a child needs to stay on leucovorin past the 6 months.
As research continues – hopefully more information about this will become known.
Is leucovorin available?
Leucovorin and autoantibody testing may or may not be accessible for every child.
When considering leucovorin as an option - it is important for both caregivers and health professionals to also consider factors such as cost, insurance coverage, and availability in your area.
In the United States – a prescription is needed to get leucovorin at the doses used in research studies that showed improvements in speech and communication skills.
- Leucovorin for use in autism is considered off-label.
- Folinic acid is available to buy without a prescription – but it comes in lower doses and may be combined with other ingredients and vitamins. Reminder – don’t confuse folinic acid and folic acid.
What are highlights from current research?
Below are highlights from 4 recent studies, as of the date these talking points were created. Because research in this area is evolving, you might find newer research if you're reading this after the date these talking points were published.
- Wong et al. (2025): This within subjects open-label study in Singapore (10 children, ages 4-8 years) showed improvements in autism symptoms, expressive language, and social skills after 24 weeks of treatment with 2 mg/kg/day (maximum of 50mg/day) of leucovorin. No serious adverse events were reported.
- Panda et al. (2024): This randomized, double-blind, placebo-controlled trial in India (77 children, ages 2-10 years) demonstrated significant improvements in autism symptoms, behavior, and sensory processing in the leucovorin group compared to placebo after 24 weeks of treatment. Improvements were more pronounced in those with high-titer FRAAs.
- Renard et al. (2020): This placebo-controlled trial in France (19 children, ages 3-10 years) showed significant improvements in ADOS scores (social interaction and communication) after 12 weeks of treatment with leucovorin.
- Frye et al. (2018): This randomized, double-blind, placebo-controlled trial in the USA (48 children, ages 3-13 years) found significant improvement in verbal communication in the leucovorin group, particularly in FRAA-positive participants.
Key Takeaways
- At the time this article was published – leucovorin shows promising results for improving speech and communication in children with autism.
- Research is still developing – which means it’s important for you to always check if new information is similar or different to what is already known.
This simplified summary is just a starting point - for healthcare professionals and caregivers - to have deeper discussions and explore more about the topic of leucovorin and autism.
Learn More – References and Resources
We share all resources we use – paid or free – so you know where our info comes from. But the costs to access the resources listed are up to them, not us.
Scientific Articles - Leucovorin and Autism
- Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis (PubMed). Rossignol DA, Frye RE. J Pers Med. 2021;11(11):1141. - Available as free full text
- Folinic acid as a treatment for autism in children: A within-subjects open-label study on safety and efficacy (PubMed). Wong CM, Tan CS, Koh HC, et al. Int J Dev Neurosci. 2025;85(1):e10402.
- Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial (PubMed). Panda PK, Sharawat IK, Saha S, et al. Eur J Pediatr. 2024;183:4827-4835.
- Folinic acid improves the score of Autism in the EFFET placebo-controlled randomized trial (PubMed). Renard E, Leheup B, Guéant-Rodriguez RM, et al. Biochimie. 2020;173:57-61.
- Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial (PubMed). Frye RE, Slattery J, Delhey L, et al. Mol Psychiatry. 2018;23(2):247-256. - Available as free full text.
Information about Folate Receptor Autoantiboides (FRAA)
Acknowledgement
This topic was enhanced by the contributions and insights provided by pharmacy students. All the information was reviewed by a licensed professional before sharing it with you.
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