What is Leucovorin and Why is it Being Used for Autism?

What is Leucovorin and Why is it Being Used for Autism?

Recently, you may have heard about a medicine being used to treat autism called leucovorin.  Leucovorin is not a new medicine, and doctors have used it for decades.  At the beginning of the year (2026) though, leucovorin got a lot of attention because some doctors were using it as an off-label treatment for autism.  In March, it was approved by the FDA to treat a disease called “Cerebral Folate Deficiency.”

So, what is leucovorin?  Why is it being used for autism?  And can it even help treat autism?

What is Leucovorin?

Leucovorin is a man-made form of folate, also called vitamin B9.  Your body used vitamin B9 to make DNA and help cells divide.  Most people get enough vitamin B9 from their diet, but some people have medical problems that require supplementation.

One of these problems is cancer – some cancer treatments make it hard for your body to use vitamin B9.  Typically, leucovorin is used as a stand-on for vitamin B9 in patients receiving chemotherapy.

Leucovorin is also used to treat a condition called cerebral folate deficiency (CFD). People with CFD have very low levels of folate in their brains.  This can cause developmental regression, seizures, and problems with walking and balance.  In many cases, CFD is caused by an autoimmune condition that blocks folate from reaching the brain.  Leucovorin can cross the blood-brain barrier and provide the brain with a form of folate it can use.

Why is it Being Used For Autism?

Interestingly, many of the symptoms of CFD are similar to autism.  Research has shown that 58%-76% of people with autism have the same antibodies that people with autoimmune CFD have.  Some studies have shown that using leucovorin for autistic people with these antibodies can help with their symptoms.  Using leucovorin to treat autism is still being researched to determine if it is a beneficial treatment.

In September 2025, the FDA announced the idea to approve leucovorin for nonspecific CFD.  This approval was controversial because it did not follow the normal approval process.  Some medical associations like the American College of Medical Toxicology believe there was not enough evidence that leucovorin is beneficial for all types of CFD or autism.  They believe there needs to be more data before recommending it and increasing the cost of healthcare.  In March 2026, the FDA approved leucovorin for a specific type of CFD only.

Currently, research supporting leucovorin as a treatment for autism is still evolving.  Some research shows that it can improve language skills, attention, and adaptive functioning in autistic children who share antibodies with CFD.  However, it is unclear whether or not leucovorin could help all autistic people.  Most of the studies that found a benefit of leucovorin for autistic people were relatively small and have been conducted within the same group of researchers (the results need to be replicated by independent research groups).

Should You Take Leucovorin?

There is a lot of information about how to treat autism, and it can be hard to know what works and what doesn’t.  It is important to remember that autism is a spectrum, and everyone is different – in this case, not all autistic people have antibodies that overlap with CFD.  Some research has shown that leucovorin can improve symptoms in autistic people who also have CFD-antibodies and it has been used off label to treat some patients, but it didn’t help everyone with autism.  Because it is not an FDA approved autism treatment, it may not be covered by insurance and it can be expensive.  It is important to talk to your doctor to know if it is right for you or your child.

Article by Jacob Struble and The Autism Toolkit

Sources

Frye, R. E., Rossignol, D. A., Scahill, L., McDougle, C. J., Huberman, H., & Quadros, E. v. (2020). Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder. In Seminars in Pediatric Neurology (Vol. 35). W.B. Saunders. https://doi.org/10.1016/j.spen.2020.100835

ACMT position statement: Use of leucovorin for autism spectrum disorder – the Bergen Record. American College of Medical Toxicology. (2026, July 7). https://www.northjersey.com/press-release/story/210048/acmt-position-statement-use-of-leucovorin-for-autism-spectrum-disorder/

Frye, R. E., Slattery, J., Delhey, L., Furgerson, B., Strickland, T., Tippett, M., Sailey, A., Wynne, R., Rose, S., Melnyk, S., James, S. J., Sequeira, J. M., & Quadros, E. V. (2018). Folinic acid improves verbal communication in children with autism and language impairment: A randomized double-blind placebo-controlled trial. Molecular Psychiatry, 23(2), 247–256. https://doi.org/10.1038/mp.2016.168

Rossignol, D. A., & Frye, R. E. (2021). Cerebral folate deficiency, folate receptor alpha autoantibodies and leucovorin (folinic acid) treatment in autism spectrum disorders: A systematic review and meta-analysis. Journal of Personalized Medicine, 11(11), 1141. https://doi.org/10.3390/jpm11111141

National Libraries of Medicine

Leucovorin- StatPearls – NCBI Bookshelf. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK553114/