New evidence brief finds leucovorin is not supported as a routine autism treatment

Following its release of Autism: An Evidence Brief, the Australian Academy of Health and Medical Sciences has published a new evidence brief examining leucovorin (folinic acid) and autism. The brief finds that current evidence does not support the routine clinical use of leucovorin to treat autism.

Leucovorin is the prescription drug form of folinic acid, a biologically active form of folate (vitamin B9). In March 2026, the US Food and Drug Administration (FDA) approved leucovorin for people with cerebral folate deficiency caused by a confirmed variant in the FOLR1 gene – after initiating the approval process in September 2025. This extremely rare condition is estimated to affect fewer than one in one million people. The approval does not extend to autism more broadly.

In Australia, the Therapeutic Goods Administration has not approved leucovorin to treat cerebral folate deficiency or autism.

Research into leucovorin as an autism treatment remains limited. Published trials have collectively involved fewer than 300 children. A 2024 randomised controlled trial involving about 80 children was later retracted because of errors in the reported results, concerns about the statistical analysis and an inability to reproduce the findings from the supplied data.

Other studies have important limitations, including small sample sizes, inadequate blinding, uncorrected statistical comparisons and insufficient safety data. These studies cannot reliably establish whether leucovorin is effective or identify who might benefit, the appropriate dose, or the frequency and severity of adverse effects.

The Academy’s brief notes that evidence-based social and educational supports can improve learning, participation and wellbeing for autistic children. Support should be individualised and may include inclusive classrooms, accommodating workplaces and communities that respect autistic people’s strengths and needs.

The Academy supports research into autism and the best ways to support autistic people and their families. Any change to clinical practice should be based on substantial evidence from rigours research, including large, well-designed trials that establish effectiveness, appropriate use and safety.

Read the full brief here: Leucovorin & Autism – An Evidence Brief

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