Folate, also known as vitamin B9, is essential for neurological development, neurotransmitter production, and proper mitochondrial function..

US President Donald Trump's recent speech on autism treatment has generated a great deal of controversy and, above all, many questions. EneviaWe believe that clear and well-explained scientific information is the best tool for families to make informed decisions about their children's health.

In his speech, Trump mentioned that a supplement called folinic acid (leucovorin) could cure certain subtypes of autismThese words have sparked hope in some, but also concern and confusion.

Our objective in this article is not to confirm or reject these statements, but explain what we know so far from science: what is the cerebral folate deficiency (CFD), how it relates to autism, what studies exist on folinic acid, and what steps families can take if they suspect this problem may be affecting their children.

What is brain folate deficiency?

Folate, also known as vitamin B9, is essential for neurological development, neurotransmitter production, and the proper functioning of mitochondria, the "energy factories" of our cells.

In some children, even though blood folate levels are normal, folate cannot properly enter the brain, which is known as Brain Folate Deficiency (CFD).

This can occur mainly for two reasons:

1. Autoantibodies against folate receptor alpha (FRα):
   These antibodies “block” the transport of folate to the brain.
2. Genetic mutations in the gene FOLR1:
   Alterations in this gene prevent the receptor from functioning correctly.

Various studies have found that Between 47% and 70% of children with autism have positive FRα autoantibodies. This means that Nearly one in two children with ASD could be affected for this condition.

A key study published in 2013 by Dr. Richard Frye and colleagues found that these autoantibodies are highly prevalent in children with Autism Spectrum Disorder (ASD), suggesting that in some cases, DFC could be an underlying cause of certain symptoms, especially those related to language and communication.

The relationship between DFC and autism

Researchers such as Dr. Richard Frye and Dr. Daniel Rossignol have spent years studying the connection between folate metabolism and autism.

In a double-blind clinical trial with placebo group, Frye and his team treated children with autism who had language difficulties using folinic acid (leucovorin), an active form of folate that can cross the blood-brain barrier by other pathways.

The results were very encouraging:

• Improvements significant in verbal communication, especially in children with positive FRα autoantibodies.
• Advances in other areas such as attention, hyperactivity, repetitive behaviors and irritability.
• The benefits were observed from the 12 weeks of treatment, with no serious adverse effects reported.

A meta-analysis conducted by Dr. Rossignol confirmed that folinic acid not only improves language, but can also impact social communication and other core symptoms of autism, always in a well-defined subgroup of children.

This reinforces the idea that autism is not a single condition, but rather a set of distinct biological causes that require personalized approaches.

Diagnosis: How to know if your child could benefit

Not all children with ASD need to be evaluated for FCD. However, doctors often consider this test when, in addition to an autism diagnosis, the child exhibits any of the following symptoms:

• Significant language delay.
• History of developmental regression (loss of acquired skills).
• Seizures or epilepsy.
• Coordination and balance problems (ataxia).
• Family history of autoimmune diseases.

Most commonly used tests:

1. Blood test for folate and vitamin B12 (usually normal in DFC).
2. FRα autoantibody test (FRAT TEST) Click here to get it) , which is done on serum and helps predict response to treatment.
3. Lumbar puncture to measure folate levels in cerebrospinal fluid (confirmatory in complex cases).
4. Genetic study, when a mutation is suspected in FOLR1.

Important fact: If the child has positive FRα antibodies, There is a high probability that it will respond favorably to treatment with folinate.

Treatment with folinic acid (Leucovorin)

Folinic acid is a form of folate that can bypass the blockage caused by autoantibodies, reaching the brain and restoring its function.

Recommended dose in clinical studies:

• Start with 5-10 mg per day, gradually increasing to 2 mg/kg/day.
• Maximum 50 mg per day, divided into two takes.
• This was the dose used in Frye's study.

Expected effects:

• Improvement in expressive and receptive language.
• Greater social interaction and non-verbal communication.
• In some cases, progress in learning and reduction of problematic behaviors.

Changes usually appear after several weeks, although some children show improvement sooner.

Side effects and precautions

In general, leucovorin is well toleratedThe most common adverse effects are mild and temporary:

• Insomnia or excitement.
• Increased irritability or tantrums.
• Headaches.

These effects are usually improved by adjusting the dose or avoiding nighttime administration.

The role of cow's milk

A curious but clinically relevant aspect is that The folate protein present in cow's milk resembles the human FRα receptor, which can “activate” the production of autoantibodies.

For this reason, Many specialists recommend removing cow's milk during treatment, which has been shown reduce antibody levels and improve clinical response.

What science says so far

• Folinic acid can make a big difference in a specific subgroup of children, especially in language and communication.
• The evidence is promising, but  Larger, multicenter clinical trials are lacking to establish official guidelines.

At Enevia we believe that Every child with autism is unique and deserves a personalized evaluation.

If your child has autism and any of the signs mentioned, talk to your pediatrician or Make an appointment with Enevia's medical professionals on the possibility of evaluating FRα autoantibodies. (Take the FRAT test)

A proper diagnosis can open the door to safe and potentially life-changing treatment. Research on CFD shows us that autism has multiple biological causes, and understanding these differences brings us closer to more precise and effective care.

And remember, at Enevia we are your health ally.

Bibliography

Frye, RE, Sequeira, JM, Quadros, EV, James, SJ, & Rossignol, DA (2013). Folate receptor alpha autoantibodies are prevalent in children with autism spectrum disorder. Autism Research, 6(4), 239-245.

Frye, RE, Slattery, J., Delhey, L., Furgerson, B., Strickland, L., Tippett, M., … & Rossignol, DA (2018). Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Molecular Psychiatry, 23(9), 1955-1965.

Frye, R.E., & Rossignol, D.A. (2016). Metabolic and mitochondrial abnormalities in autism and their relationship to the gut microbiome. Translational Psychiatry, 6(5), e799.

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