Treating a folate deficiency may lead to improvement in verbal communication and other behaviors in children with autism spectrum disorder (ASD).
A double-blind placebo-controlled trial of Folinic acid demonstrated significant improvement in verbal communication and other behaviors in children with autism spectrum disorder (ASD) that were found to have a folate receptor antibody that impaired folate transport into the cerebral space.
What is Folate?
Folate is water soluble vitamin (B9) that is essential for DNA synthesis and repair, myelination (i.e. insulation around neurons), and production of neurotransmitters such as serotonin. Folate is transported across the blood brain barrier as 5-methyltetrahydrofolate (5MTHF). 5MTHF is the active form of folate.
Cerebral Folate Deficiency and Autism
Cerebral folate deficiency is a neurological disorder discovered over 10 years ago. Patients who have issues with folate availability in cerebral folate concentrations exhibit developmental delay and regression at approximately 2 years of age. Affected children start to lose mental and motor skills due to a lack of 5MTHF in the brain. Children with ASD were found to have similar symptoms and research discovered that autistic patients were found to have high rates of an antibody that interferes with folate receptor alpha. These antibodies produced symptoms similar to CFD due to the reduced the transport of 5MTHF across the blood brain barrier and a subsequent deficiency.
Could Folinic Acid Help Mitigate Symptoms of Autism?
A double-blind placebo-controlled trial of folinic acid to treat patients with folate alpha receptor antibodies demonstrated significant improvements in communication as well as overall behavior compared to a placebo. Some patients experienced significant improvements as soon as two weeks into the study. Here is a link to one family’s experience.
How Can I Tell if My Child May Have a Folate Deficiency?
Plasma folate levels do not correlate with cerebral folate levels since the problem is with transport across the blood brain barrier. This often means that blood levels of folate are normal while cerebrospinal levels of 5MTHF are low. Fortunately, there is a commercially available test to see if patients have the antibodies called the Folate Receptor Alpha Antibody Test (FRAT®). This test is used as an indirect marker for folate levels in the brain. If a patient has the antibodies then it can be reasonably assumed there would be a folate deficiency.
Using Folinic Acid to Treat Autism
Leucovorin (Folinic acid) has been used in medical practice for decades to counter-act the side effects of common chemotherapy medications. Folinic acid has an excellent safety profile and is a vitamin that is well tolerated by patients. This medication is notably different from other “treatments” for autism spectrum disorder which lacked strong medical research to demonstrate statistically significant benefit compared to placebo. There is currently a 5 site trial to determine if Leucovorin can be approved for treatment of CFD in autistic patients with folate receptor alpha antibodies.
Leucovorin may finally provide a treatment that improves language development and restrictive behaviors for a select population of patients with ASD.