Published: November 21, 2025
Norton Children’s Neuroscience Institute, affiliated with the UofL School of Medicine, has issued the following statement for community providers regarding the use of leucovorin in autism.
There has been increasing public interest in leucovorin (also called folinic acid or known by the brand name Wellcovorin) as a possible treatment for autism. This information was devised to help provide the background science regarding this interest.
Leucovorin is an active form of folate (vitamin B9), which is important for DNA and RNA production, brain and nerve development, and neurotransmitter synthesis. In most people, folate enters cells through specific receptors — FOLR1 being the main transporter — and is essential to get folate across the blood-brain barrier. If those receptors are blocked, as in the case of certain medications such as methotrexate, or by antibodies that interfere with folate transport, leucovorin can enter through an alternate pathway and serve as a substitute source of folate.
Some small studies have proposed that a subset of children with autism may have low folate levels in the brain, a condition called cerebral folate deficiency (CFD). This has been in part proposed to be due to folate receptor alpha autoantibodies (FRAAs), which can reduce folate transport into the brain. However, FRAAs are sometimes present in typically developing children as well, and their clinical significance remains uncertain. Testing for these antibodies is available only in specialized laboratories and usually is not covered by insurance. Confirming CFD through cerebrospinal fluid testing requires a lumbar puncture, which is invasive and rarely performed outside research settings.
Leucovorin is currently approved by the Food and Drug Administration (FDA) for use in certain chemotherapy regimens, both to mitigate toxicity and to enhance drug effectiveness. It is not currently approved for treating autism or CFD, though the FDA is reviewing CFD as a potential indication.
Research examining leucovorin in autism has been limited by small sample sizes and inconsistency in how outcomes were measured. Studies have used varying endpoints, such as improvements in communication, adaptive behavior, ataxia or specific autism rating scales, making it difficult to compare results or draw firm conclusions. Some studies report benefits in language or social domains, particularly in children with FRAAs in high amounts, while others found no measurable change, depending on the scales used.
In summary, leucovorin is not a cure for autism, and current evidence is limited to guide routine use. It may be helpful in specific cases involving folate-transport issues, but further research using standardized measures and larger cohorts are needed. Decisions about treatment should be individualized and made in collaboration with the treating physician.
Furthermore, individuals with an autism diagnosis deserve respect, dignity, and evidence-based care that supports their strengths and goals. If you have further questions about leucovorin or related treatments, please feel free to reach out.