A recent large-scale observational study published in JAMA Network Open examined how prescribing patterns of leucovorin, also known as folinic acid, have changed among children diagnosed with autism spectrum disorder (ASD). The findings highlight a rapid increase in prescriptions in 2025 and early 2026, following major media coverage and public statements by US political figures suggesting possible benefits of the drug for autism-related speech challenges.
Leucovorin is a biologically active form of folic acid. It is sometimes used in medical settings to address folate metabolism issues. In small clinical studies, it has shown potential for improving verbal communication in some folate-deficient children with autism. However, there is still no strong large-scale clinical evidence confirming its effectiveness or safety for widespread ASD treatment.
This article rewrites and explains the findings of the study in clear terms, including background context, methodology, results, and implications.
Interest in leucovorin as a possible therapy for autism increased significantly after public statements in 2025 from US government leaders suggesting that potential causes of autism and possible treatments would soon be identified. Later that year, leucovorin was publicly mentioned as a possible option for addressing speech-related challenges in children with ASD.
Following these statements, media coverage expanded the public discussion. Reports and televised segments highlighted anecdotal cases where children appeared to show improvements in speech after taking leucovorin off-label. Advocacy organizations also amplified attention to the drug.
Despite this growing attention, researchers emphasize that there is limited scientific evidence supporting leucovorin as a standard treatment for autism. Most existing studies are small, and randomized controlled trials at a large scale are still lacking.
The study analyzed electronic health records from the Epic Cosmos database, which includes data from more than 300 million patients across thousands of hospitals and clinics in the United States.
Researchers focused on:
ASD diagnoses were identified using standardized SNOMED-CT coding systems. Prescription rates were measured as the number of leucovorin prescriptions per 100,000 outpatient encounters among children with autism.
The study followed standard reporting guidelines for observational research and was reviewed as exempt by an institutional review board.
The analysis included over 838,000 children with autism and nearly 12 million outpatient encounters.
One of the most notable findings was the dramatic increase in leucovorin prescribing over time.
This represents more than a 24-fold increase compared with the earlier baseline period.
After November 2025, prescribing levels stabilized but remained significantly higher than earlier years.
Among children receiving leucovorin:
This distribution aligns with typical autism diagnosis patterns, which are more frequently identified in early school-age years.
The study suggests that external influences may have played a major role in the increase in prescriptions.
Two key factors were identified:
In early 2025, a televised news segment highlighted a child with autism who reportedly experienced improvements in speech after starting off-label leucovorin. The segment gained widespread attention and was later shared by autism advocacy organizations.
Later in 2025, US government officials publicly referenced leucovorin as a potential option for autism-related speech difficulties. Following these statements, prescription rates increased even more rapidly.
The timing suggests that both media exposure and policy-level attention may have influenced prescribing behavior, even in the absence of strong clinical trial evidence.
In March 2026, the US Food and Drug Administration approved leucovorin for a specific medical condition involving cerebral folate transport deficiency linked to genetic variants in the FOLR1 gene.
However, this approval did not extend to autism spectrum disorder. As a result, use of leucovorin for ASD remains off-label.
This distinction is important because it highlights the gap between regulatory approval for specific rare conditions and broader use in neurodevelopmental disorders.
The authors of the study suggest that the rise in leucovorin prescriptions among children with autism may represent a real-world response to media and policy signals rather than evidence-based guideline changes.
They also note that:
Despite these limitations, the data provide insight into how medical practice can shift quickly in response to external information sources.
The study has several important limitations:
These limitations mean that the findings should be interpreted as trends in medical practice rather than evidence of treatment effectiveness.
This research is important because it shows how quickly clinical prescribing behavior can change in response to external influences such as media reports and public statements.
It also highlights a broader issue in healthcare: treatments can become widely used before strong scientific validation is available. This can create challenges for clinicians, families, and policymakers trying to evaluate safety and effectiveness.
The authors suggest that ongoing monitoring is needed to understand how leucovorin is being used in pediatric autism care and whether its use aligns with emerging scientific evidence.
The study published in JAMA Network Open reports a substantial rise in leucovorin prescriptions among children with autism between 2025 and early 2026. This increase appears closely associated with media coverage and public policy discussions, despite limited clinical evidence supporting its use for ASD.
While early research and anecdotal reports have suggested potential benefits in some cases, there is currently no large-scale clinical trial evidence confirming leucovorin as an effective autism treatment. Regulatory approval remains limited to specific rare genetic conditions.
Further research is needed to determine whether leucovorin has a meaningful role in autism care and to ensure that prescribing practices are guided by robust scientific evidence.
Rothman JM, Kwan B, Longhurst CA, et al. Rates of Leucovorin Prescriptions for Children With Autism. JAMA Network Open. 2026;9(5):e2613286. doi:10.1001/jamanetworkopen.2026.13286
This article is a rewritten educational summary of a peer-reviewed research letter. It is intended for informational only and does not constitute medical advice, diagnosis, or treatment recommendations. Readers should consult qualified healthcare professionals before making any medical decisions related to autism spectrum disorder or medication use.
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