Leucovorin a potential treatment for autism spectrum disorder - Body of Harmony

Leucovorin a potential treatment for autism spectrum disorder

by: Payam Hakimi
February 2025
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Leucovorin (folinic acid) has been studied as a potential treatment for autism spectrum disorder (ASD), particularly in individuals with folate metabolism abnormalities, such as cerebral folate deficiency (CFD) or autoantibodies against folate receptors. Some research suggests that leucovorin may improve language, communication, and social engagement in children with ASD.

Scientific Evidence

Several studies have explored the effects of leucovorin in ASD:

A 2018 double-blind, placebo-controlled study published in Molecular Psychiatry found that high-dose leucovorin (folinic acid) improved verbal communication skills in children with ASD, particularly those with folate receptor autoantibodies.
A 2021 follow-up study reinforced these findings, showing that folinic acid enhanced social responsiveness and reduced irritability in some children with ASD.
Other studies suggest that leucovorin may also support cognitive function and reduce oxidative stress in ASD patients.

Dosage and Frequency

The commonly studied dosage for ASD is:

Leucovorin (Folinic Acid): 1–2 mg per kg of body weight per day, up to a maximum of 50 mg daily
Typically divided into two doses per day (morning and evening)

Who May Benefit?

Children with folate receptor autoantibodies
Individuals with cerebral folate deficiency (CFD)
Those with low folate levels in cerebrospinal fluid

Considerations and Side Effects

Leucovorin is generally well-tolerated, but potential side effects include irritability, hyperactivity, or sleep disturbances in some children. It is recommended to use leucovorin under medical supervision, especially if folate receptor autoantibodies or CFD are suspected.

Testing for Cerebral Folate Deficiency (CFD)

Cerebral Folate Deficiency (CFD) is diagnosed by measuring 5-methyltetrahydrofolate (5-MTHF) levels in cerebrospinal fluid (CSF). Low levels of 5-MTHF in the CSF, despite normal blood folate levels, indicate CFD.

Steps for Testing

Lumbar Puncture (Spinal Tap)
- A cerebrospinal fluid (CSF) test is the gold standard for diagnosing CFD.
- A lumbar puncture is performed to collect CSF and measure 5-MTHF levels.
- Normal CSF 5-MTHF levels are typically above 40 nmol/L, while levels below this may indicate CFD.
Folate Receptor Autoantibody Testing
- Since CFD is often associated with folate receptor autoantibodies, a blood test can check for blocking and binding antibodies that interfere with folate transport into the brain.
- High levels of folate receptor autoantibodies suggest impaired folate uptake into the central nervous system.
Genetic Testing (Optional but recommended in some cases)
- MTHFR gene mutations may contribute to folate metabolism issues, so genetic testing can provide additional insights.
Serum and RBC Folate Levels (To rule out general folate deficiency)
- A blood test for serum and red blood cell (RBC) folate ensures that systemic folate deficiency is not the cause.

Who Should Get Tested?

Testing for CFD is recommended for individuals, especially children, with:

Autism spectrum disorder (ASD) with speech delays
Unexplained neurological symptoms (e.g., developmental regression, seizures, hypotonia)
Mitochondrial dysfunction symptoms
Treatment-resistant neurological or psychiatric conditions

Since a lumbar puncture is invasive, some doctors first test for folate receptor autoantibodies in the blood before proceeding with a CSF test.

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