That same day, RFK Jr. said that the Food and Drug Administration would soon approve a new treatment for autism, a form of folate (vitamin B9) known as leucovorin. However, like the acetaminophen link, the evidence supporting the use of leucovorin for autism rests on shaky grounds, to say the least. And many experts are concerned about what might happen to people with autism and their families if the drug becomes widely used.
“The idea of doing this for everyone — we’re going to see side effects, we’re going to see negative consequences,” Audrey Brumback, a pediatric neurologist who specializes in autism and other neurodevelopmental conditions at UT Health Austin, told Gizmodo.
a shocking affair
Leucovorin (folinic acid) is a form of the vitamin folate, also known as vitamin B9. Folate has many functions, from helping the body make red blood cells to aiding the healthy development of the fetus. This is why doctors now recommend pregnant women take folic acid (a synthetic form of folate) supplements, because low folate levels increase the risk of babies being born with neural tube birth defects. Leucovorin has historically been used to counteract the toxic side effects of some chemotherapy drugs. But it is also effective in treating a rare condition called cerebral folate deficiency or CFD.
CFD is characterized by low levels of folate in the brain but normal levels in the blood (this difference also makes it difficult to detect). Low brain levels can then cause neurological symptoms such as seizures and intellectual disability, as well as trouble with speech and coordination; These symptoms usually begin to appear around the age of two.
This condition is usually caused by faulty antibodies that attack a protein called folate receptor alpha (important for the transport of folate across the blood-brain barrier), but it can also be linked to a rare inherited genetic mutation in the FOLR1 gene, which encodes folate receptor alpha. However, leucovorin may be transported via a different delivery method than folate receptor alpha, meaning it may increase folate levels in the brain of people with CFD. The sooner children with CFD are treated with leucovorin, the more likely they are to avoid the developmental delays it causes, although the therapy may still help older patients.
Some symptoms of CFD are similar to those found in severe cases of autism, and some research has shown that people with autism are more likely to have CFD or antibodies to folate receptor alpha. Based on this early research, some scientists are really optimistic about the potential for leucovorin to help children with both autism and CFD.
During the September announcement, RFK Jr. claimed that leucovorin was an exciting therapy that could benefit “a large number of children” with autism. The current FDA Commissioner, Marty Macri, further stated that leucovorin could potentially help “hundreds of thousands of children”, which would represent a large portion of American children diagnosed with autism (a 2016 study estimated that at least 1.5 million children in the US were diagnosed with autism, although this is a figure that has certainly increased). And in its own announcement, HHS said that leucovorin would become the first “FDA-recognized therapeutic” for children with cerebral folate deficiency and autistic traits.
Yet the actual language of the FDA decision only extends the labeling of leucovorin to the treatment of CFD, with barely any mention of autism. And many scientists and doctors in the field are not so optimistic about the drug’s future as a treatment for autism.
“The idea of using a drug off-label is not new, and is not a problem in itself. It’s just that on what basis are we making this recommendation?” Brumback said. “It’s not a strong evidence base. We’re basically still in the anecdotal stage.”
The research supporting leucovorin for treating autism is remarkably thin, and it has recently become even thinner. Last week, the European Journal of Pediatrics retracted a trial of leucovorin supplements in children with autism after outside scientists discovered statistical inconsistencies that cast doubt on the study’s results and conclusions (the authors said they intended to revise and resubmit their study). The trial was one of only five such trials ever conducted, and the largest ever conducted with 77 children.
Apart from these studies, there is no sufficient data supporting the basic premise of the treatment. Scientists are not sure whether children with autism are actually more likely to have CFD, or whether CFD or its cause (antibodies to folate receptor alpha or FOLR1 mutation) may be a driver of autism. We are also not sure whether CFD can be reliably detected through screening antibody levels, which is the method used in some studies.
Autism is a complex condition that can be caused by many different things that happen early in development, although genetic factors play a major role. It is therefore possible that some children’s autism may be closely related to CFD or its causes. But according to behavioral child neurologist Shafali Jeste, that subset, even if it existed, is unlikely to reach hundreds of thousands.
“Autism is extremely heterogeneous, and it is a behavioral diagnosis that is based on thousands of different causes and profiles and brain pathways. So it is very unlikely that we will have a pill that universally addresses one core symptom,” said Jeste, chair of pediatrics at the University of California, Los Angeles. “And so I think when drugs like leucovorin are promoted as a cure or treatment for the core symptoms of autism that works in all children, it’s problematic.”
Citing a lack of strong evidence, organizations such as the American Academy of Pediatrics have recommended against routine use of leucovorin for autism. But both Jeste and Brumback have found families who have asked about the treatment or who are currently using it for their children. Jeste does not prescribe leucovorin herself, while Brumback has stopped issuing new prescriptions since Trump’s announcement. But they are willing to talk to families about the treatment and support those who decide to use it.
“I would never judge because I think parents are trying to do the right thing with their kids. So it’s very reasonable to wonder and ask about leucovorin,” Jeste said. “I’m very prepared to answer questions and honestly, we don’t have that evidence right now.”
While leucovorin is generally well tolerated when used for chemotherapy, it is also not risk-free. The AAP says it may cause symptoms such as vomiting, diarrhea, and alopecia. And there is at least a possibility that it may cause more serious complications with long-term use for autism.
“This is a very specific population of people who are undergoing chemotherapy for cancer. And so taking the vitamins in high doses has side effects that we probably wouldn’t notice in that population,” Brumback said, noting that some other forms of vitamin B can cause nerve damage when taken in large doses. “For me, that’s enough to say Primum non nocere [Latin for “First, do no harm”]. This is especially true for children who are most severe, who cannot communicate when they are in pain or discomfort; Having something that could potentially cause neuropathy is a nonstarter for me.”
Both Brumback and Jeste are also specialists who see patients with more severe autism. And they worry that families prescribed leucovorin by general practitioners may be less likely to get appropriate follow-up and care. Some people may also turn to leucovorin supplements which is much less regulated and may be less safe to consume than the doctor-prescribed version.
The future of autism treatment
One possible reason why leucovorin is in the spotlight from the Trump administration is the lack of other readily adopted treatments for autism, especially in the most severe cases. Since taking over HHS, RFK Jr. has promised to provide new insights into autism, while claiming that researchers have not done enough to find concrete answers.
Yet only recently has there been real progress in developing effective behavioral interventions for autism that can improve people’s quality of life, Jeste says. Within the next 10 years, he also hopes that we will begin to develop treatments for severe cases of autism linked to specific genetic mutations.
“One benefit of this whole leucovorin conversation is that it has forced us as a medical and scientific community to be more rigorous about how we talk about science, how we talk about what we know, and why we might be skeptical about certain studies,” she said.
In the most likely scenario, leucovorin would follow the example of secretin, a hormone that showed early promise in the 1990s but fell to the ground when several clinical trials failed to validate that promise. If true, this drug could become a curious footnote in the history of autism research.
That said, RFK Jr. and his allies are already setting the stage for the government to officially endorse their worst favorite theories about autism. They have refused to accept the mainstream consensus that rising rates of reported autism are largely due to expanded diagnostic criteria and greater awareness, for example. Last year, he ordered HHS to launch a new study examining the alleged link between vaccines and autism — a link that has been refuted by a plethora of research conducted over the past several decades.
So even if the propaganda behind leucovorin has not been validated and is not widely used, Kennedy may still succeed in further promoting his anti-science agenda.
“I think it’s put parents in a very difficult situation because they don’t know who to trust and who to listen to. Our government is saying that as a medical community we’re not necessarily doing the right thing with our patients. I mean, that’s a really hard message to hear,” Jeste said. “So I’m very sympathetic to the uncertainty and confusion this has caused.”
Although RFK may claim to have the best interests of people with autism in mind, he seems to have outdated ideas about their lives. In April 2025, he said that autism “destroys families” and that children with autism “will never pay taxes, they’ll never have a job, they’ll never play baseball, they’ll never write poetry, they’ll never go on a date.”
Of course, many people with autism have done and continue to do all of these things. And even for the most severe cases of autism, there is often a lack of support, resources, and social understanding that causes people and their families to suffer much more than the condition itself. People with autism deserve recognition, respect, and quality care, including interventions and treatments supported by evidence. That’s something Brumback hopes won’t be forgotten in all this mess.
He said, “Having autism should not be pitied; it should not be seen as something the family should be embarrassed about – it is part of life.” “I want it to be a message of positivity; helping people where they are and having an appreciation for human life.”
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