During a White House press conference on autism, Food and Drug Administration Commissioner Marty Makary shared that the agency would be filing a federal register notice to label the drug leucovorin as treatment for autism.
“Hundreds of thousands of kids, in my opinion, will benefit,” he claimed during the Sept. 22, 2025 event.
Shortly after Makary’s announcement, prominent physician groups, including the American Academy of Pediatrics and the American Psychiatric Association, released statements debunking his dubious claims about the drug as treatment for autism.
“It will require many more years of research before we know if leucovorin is an appropriate treatment for individuals with autism,” the American Psychiatric Association’s same-day statement read. “Autism spectrum disorders exist on a spectrum of neurodiversity. The country must focus its resources on expanding access to care and building the evidence-base for future treatments.”
Rewire News Group asked three autism experts what parents need to know about the risks and benefits of leucovorin.
What is leucovorin?
Leucovorin is folinic acid, an active form of folate (also known as B9) that doesn’t need to be broken down by enzymes to be used in the body. It is available in pill or IV form. While most individuals can obtain the folate their bodies need through beans and leafy greens, or via vitamin supplements, some cannot properly metabolize folate and need prescription medication to maintain proper cell functioning.
Autism or Autism Spectrum Disorder (ASD) is a neurological and developmental disorder that is characterized by differences in social communication; restrictive, repetitive behaviors that may manifest in motor movements, speech, or interests and challenges with transitioning from one activity or setting to another; and over- or under- reactivity to sensory input.
These characteristics occur on a spectrum, meaning that each autistic individual has different areas in which they may need support, which may include behavioral, occupational, physical, and speech language therapies, along with accommodations to help manage sensory sensitivities and other needs in daily life.
David Mandell, a professor and the director of the Penn Center for Mental Health who conducts autism research, told RNG he was shocked by Makary’s announcement.
“The evidence for leucovorin was the same as for hyperbaric oxygen or mega doses of vitamin D,” Mandell said. “There is really no evidence at all that these are meaningful treatments.”
As a double board-certified child, adolescent, and adult psychiatrist who treats autism, Ritu Goel was especially concerned about the confusion and doubt this announcement caused for parents of autistic children, some of whom are desperate to find anything that may help their child connect and communicate with them.
“Every … parent now has, suddenly, this hope that, ‘Oh, I give this tablet to my child, and they will be better,’” Goel said.
The reality is far more complicated.
“The major reason we prescribe leucovorin to people is because they’re in cancer treatment, usually chemotherapy, and the leucovorin helps protect healthy cells,” Mandell said.
When taken with methotrexate, which prevents folate absorption, leucovorin helps prevent side effects from cancer treatment such as acute kidney injury or failure, and pulmonary toxicity, which can result when methotrexate destroys healthy cells as well as cancer cells. For cancers such as colorectal cancer, leucovorin can be added to a chemotherapy drug to enhance its ability to destroy cancer cells.
In March 2026, the FDA approved the new labeling of leucovorin (previously labeled for use in cancer treatment and for certain anemias) as treatment for a rare disease called cerebral folate deficiency, which has less than 50 cases documented in medical literature.
Patients with cerebral folate deficiency can’t metabolize folate, Mandell said.
“They have symptoms that mirror those of autism,” he said.
Some research on cerebral folate deficiency has claimed improvement in “autistic behaviors,” such as communication differences and irritability after taking folinic acid.
But people with the deficiency can “also have severe epilepsy, lots of developmental regression,” Mandell added.
Despite Makary’s September announcement, autism was not added to the FDA’s list of approved uses for leucovorin.
Leucovorin and autism: the science
Alycia Halladay, a biopsychologist who serves as the chief science officer of the Autism Science Foundation, said that the FDA’s September announcement felt concerning because the research on leucovorin as treatment for autism to date has been done outside the FDA clinical trial process. Those trials are how the agency typically determines a medication’s safety and efficacy, appropriate dosages, potential side effects, and adverse reactions linked to the medication.
“[It meant] there was going to be no regulatory oversight, there was going to be no scientific review, that someone in the high ranks of the FDA had decided that this was going to be approved, and there was not going to be a process to evaluate it,” Halladay said.
The evidence produced by this research linking leucovorin and improvements in autistic children is also weak, she added.
The present discussion about autism and leucovorin originated from a 2005 study of 28 pediatric patients with cerebral folate deficiency. Folate-blocking autoantibodies were identified in most of these patients, and further studies determined up to 75.3 percent of the autistic children studied had these antibodies.
Continued research included trials that seemed to indicate improvement in verbal communication after taking leucovorin.
Mandell, too, identified several issues with the few trials published, including that they used small sample sizes. To test “medications that we give regularly to people” in the general population, he said, best practice would be to “have hundreds of people in each group.” The differences recorded in those taking leucovorin were unlikely to be statistically significant, Mandell added. Additionally, he said, the researchers relied heavily on measures of folate antibodies that he said don’t indicate folate deficiencies.
Mandell, Halladay, and Goel all referenced the same highly scrutinized, now retracted, 2024 study often used to support a link between leucovorin and autism treatment. With 77 children studied, it was one of a handful of randomized clinical trials that have been completed to date. Just over a year later—and four months after Makary’s announcement—it was retracted due to data and statistical errors.
For the experts RNG spoke to, the study’s retraction solidified the concern that the data resulting from research on the drug’s use for autistic children is not solid.
“You have this drug that maybe made tiny improvements in a couple of studies but had not really been consistent,” Halladay said. “Some studies looked at language, another study looked at challenging behavior. So there wasn’t consistency there—it wasn’t reproduced, and there was no safety data.”
How does leucovorin work?
While using leucovorin for autistic patients has only recently received widespread attention in the nation’s capital, it has been prescribed off-label for more than a decade.
Goel shared three cases in which she prescribed leucovorin to autistic children determined to have folate receptor autoantibodies, which some scientists believe prevent folate from crossing the blood-brain barrier.
Two of the three children showed improvements in language after several months. In one case, she said, an autistic 6-year-old “responded with some language, a couple of words, phrases, and easier transitions.”
“Some … might now start using a few more words … Maybe [be] more interested in making their needs known,” Goel added. “So, some language, that’s where we see the difference. But it is not a drastic change.”
Goel also said that the children were also undergoing other therapies that might have contributed to their improvement, like intensive early intervention and speech therapy.
Does leucovorin have side effects?
Using the medication is not without risk, experts said.
Leucovorin can cause side effects, including irritability and GI issues including diarrhea. Goel said this can be especially challenging for autistic children, who are very sensitive to side effects and often are already dealing with gut issues and restrictive diets.
Doctors still know little about whether the drug is safe for children, Mandell added.
“We have no data on what the medium or long-term safety profile of leucovorin in children is,” Mandell said. “[And] now we’re talking about giving this drug to children indefinitely, starting at a very young age.”
Mandell, along with Halladay and Goel, also referenced the dangers of parents purchasing folinic acid supplements, which are not FDA-regulated and may contain potentially harmful ingredients.
Goel said parents should always consult with their child’s doctor before using supplements because of possible interactions and side effects.
“I can’t say enough that our children who are on [the] spectrum, their brains are very sensitive to the side effects,” Goel said.
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Why is the MAHA movement interested in leucovorin?
Mandell and Halladay said that the September announcement may have been Health and Human Services Sec. Robert F. Kennedy Jr. delivering on his April 2025 promise that by September of the same year, HHS would “know what has caused the autism epidemic, and [will] be able to eliminate those exposures.”
Many in the autism community were offended by Trump administration officials’ consistent framing of autism as a disease that needs a cure, rather than a neurotype and developmental disorder.
“We are horrified by comments that call for ‘ending’ autism, a crude, yet plain, endorsement of eugenics demonstrating a callous lack of understanding of what autism is,” the nonprofit group Autism Self Advocacy Network said in a statement following the FDA announcement. “Autism is a natural part of human diversity. Autistic people usually enjoy a good quality of life when we have the supports we need.”
But Kennedy’s background as a lawyer means that he approaches problems by looking for evidence that will prove his hypothesis and discarding any data that disproves it, rather than employing the scientific method, Mandell said.
While autism has been a particular target of this administration, including repeated claims connecting vaccines and acetaminophen to autism, both of which have decades of scientific research proving the contrary, Halladay said the current administration has seemed intent on undermining the scientific method and “dismantling trust in science.”
This has included budget cuts and criticisms leveled at federal health institutions such as the CDC, and placing blame on vaccines, environmental toxins, and processed foods for chronic conditions while making policy changes that widen health disparities.
Impact of the FDA’s leucovorin announcement
Beyond contributing to what many scientists view as the Trump administration’s undermining of trust in their work, the leucovorin announcement appears to already be impacting autistic children and their families—and the clinicians who care for them.
In March 2026, the Lancet released a study reporting a 71 percent increase in outpatient prescriptions for leucovorin for patients aged 5 to 17 between Sept. 22 and Dec. 7, 2025.
Halladay said she has spoken to clinicians who have been flooded with requests for leucovorin.
“For every conversation that they have with [a] family about this, it’s 10 to 15 minutes away from another patient,” she said.
Goel worries that parents may now forego other evidence-based treatments, either because they believe that leucovorin will help their child or because they’re spending their limited financial resources on the medication.
“It is a complementary treatment,” Goel said. “It is not a replacement for speech therapy, behavioral therapy, education intervention. … They do need those early interventions, and they make a difference.”
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