Understanding Leucovorin: A Controversial Proposal for Autism Treatment

The US government recently made headlines with its controversial guidance regarding the prevention and treatment of autism in children. Among the recommendations, it suggests using the drug leucovorin to potentially improve speech difficulties associated with autism — a prospect that has sparked both interest and skepticism within the medical community.

Leucovorin is a form of folic acid, a vital B vitamin naturally present in foods like legumes, citrus fruits, and fortified grains. The medication is mainly used in cancer therapies, particularly alongside the chemotherapy agent fluorouracil, to enhance its effectiveness by boosting the production of DNA in cancer cells. Additionally, leucovorin helps mitigate the toxic side effects of methotrexate, another chemotherapy drug, by providing healthy cells with the folate they need for DNA synthesis.

Folate plays an essential role in DNA construction and cellular growth, making it critically important during pregnancy to prevent birth defects such as spina bifida. This connection has led to the hypothesis that low levels of folate in the brain, known as cerebral folate deficiency, could contribute to autism spectrum disorders. Children with cerebral folate deficiency initially show no symptoms but later exhibit speech difficulties, seizures, and intellectual challenges, many of which overlap with autism features.

Some recent studies have explored the potential of leucovorin in alleviating autism symptoms. A 2021 review of 21 studies indicated that children who received leucovorin generally showed improvements, but emphasized the need for larger, more rigorous research. A 2024 small-scale trial involving about 80 children found that those given folinic acid, a derivative of leucovorin, displayed more significant improvements in autism symptoms compared to placebo. Similarly, a 2025 study in China observed that children receiving folinic acid had enhancements in social reciprocity skills.

However, despite these promising findings, the evidence so far is not robust enough to justify a widespread change in clinical practice. More extensive clinical trials are required to confirm the safety and effectiveness of leucovorin for autism treatment.

It is important to note that leucovorin, like all medications, carries potential side effects, including allergic reactions, seizures, and gastrointestinal symptoms such as nausea and vomiting. Therefore, its use should be carefully monitored by healthcare professionals.

In conclusion, while the US Food and Drug Administration now permits doctors to prescribe leucovorin for autism symptoms, international guidelines, such as those in Australia, have yet to endorse its routine use. The current stance emphasizes the importance of relying on evidence-based practices and continued research to better understand leucovorin’s potential role in autism therapy.