Last week, the Trump administration dropped a bombshell by announcing that the FDA had given the green light to leucovorin, a generic drug, as a treatment for autism.
This decision sent shockwaves across the medical community because it completely sidestepped the agency’s typically thorough and lengthy approval process.
Leucovorin – also known as folinic acid, a derivative of vitamin B9 – is known for its use in certain cancer treatments. It counteracts the harmful side effects of methotrexate, a common chemotherapy drug. Experts argue that bypassing established, science-backed protocols could set a troubling precedent, potentially compromising patient safety and undermining trust in the FDA.
In a statement, FDA commissioner Martin Makary announced that the drug will now be approved for patients with cerebral folate deficiency (CFD), a condition that is sometimes linked to autism spectrum disorders.
The National Organization for Rare Disorders states that infants with cerebral folate deficiency usually show symptoms between 4 to 6 months old, starting with irritability and trouble sleeping. As they grow in the first few years, they may also experience slow head growth, delays in physical and mental development, low muscle tone, poor coordination and seizures.
While a handful of studies have hinted at some positive effects of leucovorin in children with autism, many in the autism research community and advocacy groups are waving red flags, suggesting that the excitement surrounding these findings may be a bit over the top. They argue that jumping to conclusions based on limited evidence could mislead families seeking effective treatments.
The consensus seems to be that while the preliminary results are intriguing, they don’t yet offer a solid foundation for widespread adoption. More rigorous, comprehensive research is needed to fully understand the implications and potential benefits of leucovorin therapy.
“Current studies on high-dose leucovorin are very preliminary,” Danielle Hall, director of health equity at the Autism Society of America, told The Guardian. She warns that premature claims about its efficacy could lead to “false hope” and “misinterpretation that leucovorin represents a ‘cure’.”
Here’s what you should know about leucovorin, according to the experts.
What is leucovorin?
Leucovorin is “very similar to folic acid,” explains Dr. David Mandell, a psychiatry professor at the University of Pennsylvania Perelman School of Medicine, in a recent interview. The key difference is that leucovorin has been “altered in a way that makes it easier to get through the blood-brain barrier for people who can’t metabolize folic acid,” he adds.
Folic acid, a man-made version of folate, and also known as vitamin B9, is important for making red blood cells and is vital for healthy cell growth and function, according to the Mayo Clinic. You can find folate naturally in foods like leafy greens, beans, nuts and fruits such as oranges and bananas. It is particularly important for people who are newly pregnant or planning to become pregnant.
Dr. Edward Quadros, a professor at SUNY Downstate who studies how the body absorbs folate, explained that “Not having enough folate during fetal development causes abnormalities of the brain,” he explained to The Guardian.
Specifically, it can cause severe birth defects in the brain and spine, known as neural tube defects (NTD). To help prevent this, the CDC advises anyone who might become pregnant to take 400 mcg of folic acid each day.
Per Drugs.com, the side effects of leucovorin are usually not serious and mostly include stomach discomfort. It has been used off-label to help treat people with cerebral folate deficiency for about 20 years.
The connection between not having enough folate and autism isn’t entirely clear.
In a notice published in the Federal Register last week, the FDA said that it is approving leucovorin tablets based on studies conducted from 2009 to 2024, which showed that the tablets “improve certain symptoms.”
This seems to be a major change from the usual way the agency has approved medications. The FDA’s own website states that getting a drug approved is a complicated and lengthy process. It requires many years of clinical trials, thorough research reviews, and inspections of the factories where the drugs are made.
Some specialists found it puzzling that the FDA had connected CFD and autism.
“What percentage of autistic people have folate deficiencies is still under investigation,” explained Dr Matthew Lerner, associate professor and director of the Life Course Outcomes research program at the AJ Drexel Autism Institute at Drexel University. However, he stressed that it’s “certainly not a majority”.
Dr. Elliott Gavin Keenan, a researcher at the AJ Drexel Autism Institute, says that many people see autism as just one condition. However, he points out that autism can actually arise from different causes, such as genetics and high levels of stress experienced by mothers during pregnancy.
“It’s really a spectrum of different disorders, and they all probably have different treatments.”
Has leucovorin been used to treat autism in the past?
Until now, leucovorin was never officially approved for autism treatment, but for over a decade, many have been curious about its potential benefits, leading to its off-label use in this context. Doctors say that some families have turned to leucovorin as a way to manage certain symptoms associated with autism, despite the lack of diligent and precise scientific endorsement. It’s a bit of a gray area, as parents and caregivers often seek alternatives when traditional therapies don’t yield the desired results.
While anecdotal evidence exists and some swear by its effects, the medical community remains cautious, advocating for further research to clarify its role and efficacy in autism treatment.
“To take the promise of something like leucovorin seriously, you need rigorous, double-blind, placebo-controlled, transparent trials,” Lerner advises.
