What Is Leucovorin? Inside The Drug The FDA Says May Treat Autism

While Secretary of Health and Human Services Robert F. Kennedy Jr. has made headlines with controversial claims linking acetaminophen (Tylenol) use during pregnancy to autism, the Food and Drug Administration (FDA) is examining how currently approved medications may help treat some types of autism. Leucovorin (Wellcovorin), a drug originally approved to counter the toxic effects of cancer treatments, has been reclassified by the FDA for use in treating symptoms of cerebral folate deficiency (CFD).

Leucovorin is a form of folic acid that can be used alongside drugs that often reduce folic acid levels in the body. CFD is a rare condition that prevents folate from being absorbed into the brain, which can lead to developmental delays. According to the FDA, these delays can resemble features of autism, including difficulties with social interaction, repetitive behaviors, and problems with coordination. The FDA based its decision to repurpose leucovorin on its own systematic review of the available research.

(Read how autism might be detected before childbirth.)

Although this reclassification may benefit people with CFD, autism researcher Helen Tager-Flusberg, Ph.D., says leucovorin cannot treat most children with autism. "In this case, it's very dubious how many children are going to benefit from this treatment," Tager-Flusberg told MedPage Today. "It is completely irresponsible to be touting this as a treatment for autism."

Your body needs folate (vitamin B9) to make red blood cells and support your brain. While most adults can get the recommended 400 micrograms of folate from beans, nuts, and leafy greens, pregnant women are advised to aim for at least twice that to reduce the risk of birth defects. That's why prenatal supplements usually supply plenty of folic acid, the synthetic form of folate.

Because leucovorin is a reduced form of folate, research has explored its use in children with autism spectrum disorder (ASD). For example, a 2024 clinical trial in the European Journal of Pediatrics reported that children who took folinic acid (leucovorin) for 24 weeks showed improvements in autism symptoms and behavior compared with a placebo.

Some children with ASD have autoantibodies that block folate from entering the brain, leading to CFD. Other children may have soluble folate-binding proteins in their blood that also interfere with folate transport to the brain, producing the same outcome. A 2022 article in the Journal of Personalized Medicine examined how leucovorin might help children with these proteins. In that small study of 12 young children, leucovorin improved behavioral issues as well as social and communication difficulties.

Of course, these are very small studies. A 2021 systematic review in the Journal of Personalized Medicine pooled the results of 20 studies to see the overall effect of leucovorin on ASD. Among people with CFD, leucovorin was associated with improvements in autism symptoms. However, the review emphasized that more large, well-controlled trials are still needed.