Can Leucovorin Help Some Children with Autism? Here’s What the Research Shows

Tatsiana Yarash

Parents of children with autism often read about new treatments online. One treatment  receiving increasing attention is leucovorin. Early research suggests it may improve  language and communication in some children with autism, but does the evidence  support its use? Autism spectrum disorder (ASD) affects how a person communicates,  interacts with others, and experiences the world around them. While speech therapy,  occupational therapy and behavioural interventions remain the foundation of autism  care, researchers continue to investigate whether treatments such as leucovorin may  benefit specific groups of children (1). Here's what current research shows. 

What Is Leucovorin and Is It Safe? 

Leucovorin, also known as folinic acid is a form of folate, also known as vitamin B9.  Unlike ordinary folic acid supplements, it is already in an active form that the body can  use more easily. Doctors have used leucovorin safely for many years to reduce side  effects of certain treatments and manage some types of anaemia. More recently,  researchers have explored whether it could help children with autism who have  abnormalities in folate metabolism (2). 

Clinical studies suggest leucovorin is generally well tolerated. However, reported side  effects included irritability, sleep disturbances, stomach upset, nausea, diarrhoea and 

rash. As with other folate supplements, leucovorin may also mask vitamin B12  deficiency. 

Leucovorin is not suitable for everyone. It should not be used in children with a rare  genetic condition called MTHFS deficiency. In this disorder, the body cannot process  folinic acid properly. Taking leucovorin can cause folinic acid to build up in the body,  which may worsen symptoms instead of improving them. Because of this, treatment  with leucovorin should only be started under the guidance of a healthcare professional  after an appropriate medical evaluation. 

Why Are Researchers Interested in Folate and Autism? 

Folate is important for brain development, learning, language, and the production of  important brain chemicals. Researchers have discovered that some children with  autism have a condition called cerebral folate deficiency (2, 3). In these children, folate  has difficulty reaching the brain even when blood folate levels are normal. Some also  have folate receptor alpha autoantibodies, which can interfere with folate transport into  the brain (2). Because leucovorin can bypass these transport problems, researchers  believe it may help improve brain function in affected children. Over the past decade,  several studies have suggested that leucovorin may improve language,  communication, attention and some behavioural symptoms in certain children with  autism. The greatest benefits have been observed in children with cerebral folate  deficiency or folate receptor alpha autoantibodies; however, larger, well-designed  studies are still needed (2). 

Ongoing clinical trials are investigating whether earlier treatment can improve  language development in young children with autism. The study may also help identify  biological markers that predict who is most likely to respond (4). 

Is Leucovorin Approved For Autism? 

Leucovorin has not been approved as a general treatment for autism. In 2026, the  U.S. Food and Drug Administration (FDA) approved leucovorin for the treatment of  cerebral folate transport deficiency, a rare genetic disorder that affects the transport  of folate into the brain and can cause developmental delays, seizures, and autism-like  features (5). Although some children with autism may have problems with folate  transport, this approval does not apply to autism spectrum disorder in general.  Furthermore, current research suggests that leucovorin may benefit children with evidence of problems transporting folate into the brain, but larger, well-designed  clinical trials are needed before it can be recommended routinely (2,4). 

In Conclusion What Families Should Know? 

The current evidence is encouraging, but leucovorin is not a cure for autism. At  present, major professional organisations do not recommend leucovorin as a routine  treatment for autism because the evidence is still limited (3). It appears most likely to 

help a specific group of children who have underlying problems with folate transport  or metabolism. Many autistic children may not experience significant benefits. 

Children should not start leucovorin without medical supervision, as testing for cerebral  folate deficiency or folate receptor alpha autoantibodies may help determine whether  treatment is appropriate. 

For now, leucovorin should be viewed as a promising area of research rather than a  proven treatment for all individuals with autism. Families interested in this therapy  should discuss it with their healthcare provider and seek guidance based on their  child’s individual needs. 

References 

1. CDC. Autism Spectrum Disorder (ASD) [Internet]. 2024 July 18. Treatment and  Intervention for Autism Spectrum Disorder [cited 2026 June 25]. Available from:  https://www.cdc.gov/autism/treatment/index.html 

2. Rossignol DA, Frye RE. Cerebral Folate Deficiency, Folate Receptor Alpha  Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum  Disorders: A Systematic Review and Meta-Analysis. J Pers Med. 2021;11(11):1141.  DOI: 10.3390/jpm11111141 

3. Howard C, Mekhail J, Ravikoff LM, Milanaik R. Clinical concerns and considerations  for leucovorin use in autism spectrum disorder. Curr Opin Pediatr. 2026;38(2):207– 11. DOI: 10.1097/MOP.0000000000001547 

4. Frye R. Early Treatment of Language Impairment in Young Children With Autism  Spectrum Disorder With Leucovorin Calcium [Internet]. clinicaltrials.gov; 2026 Apr  22 [cited 2026 June 25]. Rapport no NCT04060017. Available from:  https://clinicaltrials.gov/study/NCT04060017 

5. Commissioner O of the. FDA [Internet]. 2026 Mar 10. FDA Approves First Treatment  for Patients with Cerebral Folate Transport Deficiency [cited 2026 June 29].  Available from: https://www.fda.gov/news-events/press-announcements/fda approves-first-treatment-patients-cerebral-folate-transport-deficiency

Assessed and Endorsed by the MedReport Medical Review Board