The Trump administration is touting an old generic drug as a new treatment for autism despite limited evidence, sparking unease among doctors and scientists who say the medication needs to be studied further.
In a press conference and media appearances, President Trump and top health officials have praised the benefits of leucovorin, a synthetic form of vitamin B9 that requires a prescription.
The drug has been approved by the Food and Drug Administration to ease the side effects of certain kinds of chemotherapy drugs like methotrexate, though it has been used off-label to treat people diagnosed with cerebral folate deficiency (CFD).
CFD is an extremely rare neurological condition characterized by low levels of vitamin B9 in the brain. Not everyone with CFD has autism, and not everyone with autism has CFD.
Leucovorin can help folate reach the brain, so the theory is leucovorin can improve speech and cognitive abilities in people with autism, so long as they also have folate deficiency.
During a press briefing in the White House on Monday when Trump directly linked Tylenol and acetaminophen to autism, FDA Commissioner Marty Makary stood alongside Trump and announced the agency’s approval of leucovorin.
He said it was likely to help “hundreds of thousands” of children with autism
“Mr. President, you told us to do what’s medically right — to go bold and not worry about the corporations and the lobbyists,” Makary said. “So that’s what we’re here doing today.”
In an interview with TMZ, Centers for Medicare and Medicaid Services Administrator Mehmet Oz suggested leucovorin could be used for “reversing autism.”
Oz said he’s spoken with doctors who are conducting clinical trials on children with autism, and he doesn’t want to wait for the full results.
“What do you tell a mom of a three-year-old whose kid has autism? Do you tell them to wait five years and see?” Oz said.
But scientists and experts said the administration is promoting an unproven drug with a limited safety record.
There’s a sliver of potential, but more research is needed, and they said they are concerned the White House is potentially giving false hope to millions of families.
Even if the drug is made widely available, there’s a scarcity of autism specialists who would be able to prescribe it. Not all children with autism may qualify for a prescription and the potential for meaningful results is uncertain.
“The general consensus is it’s way too early to recommend this as a treatment,” said Alycia Halladay, the chief science officer of the Autism Science Foundation.
Halladay said the clinical trials on leucovorin have been extremely limited, involving only a few dozen participants each. They haven’t looked at the same outcomes, and the results haven’t always been replicated. The drug is safe for use in children with cancer, but the safety for children with autism hasn’t been studied.
“So if the administration would like to go ahead and make more money available to do a large-scale trial, that would be welcome,” Halladay said, adding that based on the current evidence, leucovorin shouldn’t meet FDA’s criteria for approval.
The FDA flipped the typical drug approval process on its head when, on its own accord, it approved a new use for Wellcovorin, GlaxoSmithKline’s branded version of leucovorin. GSK hadn’t marketed the drug since 1999.
But contrary to what Makary and Oz have said, FDA only approved leucovorin for adults and pediatric patients with cerebral folate deficiency, not autism.
The agency said it based the new indication on a review of studies from 2009 to 2024 that found orally administered leucovorin calcium tablets “improve certain symptoms.”
“It was very disingenuous for the press conference to say, okay, we’re going to make this available to people with autism. They didn’t, and there’s no evidence that it even works in everyone with autism,” Halladay said.
Large place-controlled studies would be needed to pinpoint who would benefit from the medicine and at what specific dose, said Audrey Brumback, a physician-scientist specializing in child neurology at the University of Texas, Austin.
But treatment for CFD involves periodic spinal taps to measure folate levels and make sure the dose being given is working.
“We’re certainly not going to be doing that for every child who has autism to make sure that they’re getting the right dose,” Brumback said.
She also noted that people with autism have multiple symptoms beyond brain dysfunction, and B vitamins have multiple effects, so it could be hard to pinpoint if symptoms are being alleviated or if the underlying condition of autism is being changed.
“So if it were to help sort of an associated issue that the person was having, it might appear that the core autism is better, but really, it’s just the person is at their best, or they’re not at their worst anymore,” Brumback said. “They’re really talking about leucovorin as disease modifying therapy rather than symptomatic therapy. And maybe they’re talking about both. But I think that that’s an important distinction.”
In an interview with Brian Kilmeade on Fox News radio, Oz indicated that type of data will come, eventually.
“We’re going to give it. Marty’s changing the label” to allow the drug to be covered by Medicaid and the Children’s health Insurance Program, Oz said. “A doctor’s going to prescribe this and we’re going to collect data on how effective this is.”
