Autism SPECTRUM DISORDER and cerebral folate deficiancy

 Clinical studies on leucovorin (folinic acid) suggest it may improve language and communication in a subset of children with autism, particularly those with Cerebral Folate Deficiency (CFD). The U.S. Food and Drug Administration (FDA) is updating leucovorin's labeling to include CFD, a condition sometimes associated with autism.  

 CFD has also been reported in a broader patient population with neuropsychiatric symptoms, including autistic features, and detectable serum autoantibodies to the folate receptor alpha; however, there are limitations on the available data for the use of leucovorin in this population and additional studies are needed to assess safety and efficacy. 

Dr Veluchamy  has extensive experience with cerebral folate deficiency.  Previously, between 2010 -2018 Dr. Veluchamy studied this condition in several children  with the epilepsy  and used to perform lumbar punctures to collect cerebrospinal fluid and tested at Medical Neurogenetics lab in Atlanta.

In some individuals with autism, folate (vitamin B9) has difficulty crossing the blood-brain barrier. This can lead to CFD, where folate levels are low in the brain despite appearing normal in the blood. 

• Folate receptor autoantibodies: A common cause of CFD in autism is the presence of autoantibodies against the folate receptor alpha (FRAA), which can block folate from entering the brain. Studies have found a high prevalence of FRAAs in children with autism.
• Bypassing the blockage: Leucovorin, also known as folinic acid, is a reduced form of folate that can bypass this blockage and be transported into the brain by a different, less efficient carrier. This process increases folate levels in the brain, helping with functions such as neurotransmitter production. 

FRAT®(Folate Receptor Autoantibody Test) is a diagnostic blood test that screens for autoantibodies to the Folate Receptor Alpha (FRa), known as Folate Receptor Autoantibodies.

The presence of Folate Receptor Autoantibodies suggests that folate (vitamin B9), which is an essential vitamin for proper growth and neurological function, is not being properly transported to the brain and into cerebrospinal fluid (CSF), among other tissues where Folate Receptor Alpha may be found.

 Several small-scale and preliminary studies have explored the effects of leucovorin for children with autism:

• Frye et al. (2016): A double-blind, placebo-controlled trial of 48 children with autism showed that high-dose leucovorin improved verbal communication compared to a placebo. The benefit was most significant in children who tested positive for FRAAs.
• EFFET trial (2020): A small placebo-controlled study in France involving 19 children found significant improvement in Autism Diagnostic Observation Schedule (ADOS) scores for the leucovorin group, particularly in communication and social interaction.
• Panda et al. (2024): A randomized controlled trial in India concluded that oral folinic acid was effective and safe in reducing autism symptoms, with more pronounced benefits in those with high levels of FRAAs.
• Ongoing trials: Larger, ongoing placebo-controlled trials are further investigating the efficacy of leucovorin for improving social communication in young children with ASD. 

Leucovorin is generally well-tolerated, but some side effects have been reported, particularly when starting treatment. These include: 

• Irritability and agitation
• Hyperactivity
• Insomnia
• Headaches
• Gastrointestinal discomfort 

According to some researchers, these side effects often resolve with continued use, and the dose may be started low and slowly increased to minimize them 

Not a cure: Healthcare officials and researchers emphasize that leucovorin is not a "cure" for autism but may help manage specific symptoms in certain individuals.

For a subset of people: The treatment is primarily targeted at the subset of people with autism who also have CFD, though some studies suggest benefits even without a confirmed CFD diagnosis.

Leucovorin is a prescription medication and should only be used under the supervision of a physician.

Regulation and safety: Leucovorin is a drug that is FDA-regulated for specific medical uses, which includes ensuring quality and safety under medical supervision. Over-the-counter supplements like folic acid are not subject to the same level of strict regulation.  

Dosage: Prescription doses of leucovorin are much higher and are prescribed for a specific medical purpose. For example, a prescription dose could be around 50 mg, while an OTC supplement might contain only 800 micrograms (or 0.80 mg) per pill.  

Medical need: You should only take leucovorin if prescribed by a doctor, as it is a powerful medication used for specific, serious conditions. OTC folic acid is intended for general nutritional supplementation.