On March 10, 2026, the U.S. Food and Drug Administration (FDA) made a significant decision regarding the drug leucovorin, a synthetic form of vitamin B9. The agency approved leucovorin for the treatment of a rare genetic disorder known as cerebral folate deficiency, but notably declined to approve it as a treatment for autism spectrum disorder (ASD), despite recent endorsements from prominent political figures suggesting otherwise.
Leucovorin is traditionally used in oncology to help manage side effects of chemotherapy, but in recent months it has been thrust into the spotlight for a very different reason. Last year, high-profile figures including former President Donald Trump, Health and Human Services Secretary Robert F. Kennedy Jr., and then-FDA Chief Marty Makary publicly promoted leucovorin as a promising therapy for autism. This endorsement stirred considerable excitement and hope among many families seeking effective treatments for autism, a complex neurodevelopmental condition characterized by challenges in social communication and repetitive behaviors.
However, the FDA’s scientific review panel ultimately concluded that there is insufficient evidence to support leucovorin’s use for autism treatment. The agency’s decision emphasizes that while leucovorin can be effective in addressing cerebral folate deficiency—a condition caused by mutations in the FOLR1 gene that lead to folate deficiencies in the brain—it does not have the same therapeutic potential for autism. Cerebral folate deficiency is an extremely rare condition, affecting fewer than one in a million people, though its exact prevalence is not well established. It manifests with neurological symptoms that can superficially resemble aspects of autism, such as communication difficulties, but it is a distinct disorder with a specific genetic cause.
Leading experts in autism research have welcomed the FDA’s clarification. David Mandell, a professor of psychiatry at the University of Pennsylvania who specializes in autism, underscored that “autism is not caused by a folate deficiency,” and that the scientific data suggesting such a link are outdated and weak. Helen Tager-Flusberg, a psychologist and autism researcher at Boston University, also stressed the importance of distinguishing between cerebral folate deficiency and autism. She pointed out that while leucovorin is justified for treating the former, the FOLR1 gene implicated in cerebral folate deficiency has never been associated with autism, which is a broad diagnosis believed to arise from a complex interplay of genetic and environmental factors.
Despite the FDA’s clear stance, the prior endorsements by political leaders have already had tangible effects. Since the public promotion of leucovorin as a potential autism treatment, prescriptions for the drug used off-label—that is, prescribed for conditions other than those officially approved—have surged dramatically. Mandell noted a 71% increase in leucovorin prescriptions for children, reflecting the heightened demand driven by the hope and expectations generated by these high-profile endorsements.
This surge in off-label use raises concerns among medical professionals and researchers. Off-label prescribing is legal and sometimes medically appropriate, but it requires careful consideration of the evidence supporting the drug’s safety and efficacy for the unapproved use. In the case of leucovorin for autism, the scientific evidence remains insufficient, and families are at risk of spending significant amounts of money on a treatment that lacks proven benefit. Mandell lamented that “many families [have] paid out of pocket for this drug when they could have been using that money for better purposes,” highlighting the potential harm caused when political and untested theories outpace rigorous scientific evaluation.
The FDA’s decision serves as a reminder of the critical importance of evidence-based medicine, particularly in fields like autism research where families are often desperate for effective interventions. It also underscores the challenges that arise when political figures and public officials make premature claims about medical treatments without adequate scientific backing. The resulting confusion can lead to misplaced hope, financial strain, and potential neglect of more effective therapies or support services.
Looking forward, it remains to be seen how the FDA’s official position will influence the ongoing off-label use of leucovorin for autism. While the agency has clarified that the drug is not approved for this purpose, changing prescribing behaviors and public perception may take time. Researchers and clinicians emphasize the need for continued education and communication to ensure families receive accurate information about autism treatments.
In summary, the FDA’s recent approval of leucovorin strictly for cerebral folate deficiency—and its refusal to endorse the drug for autism—marks an important moment in the intersection of science, medicine, and public policy. It highlights the necessity of grounding treatment decisions in robust scientific