It’s my fall semester, and I normally have my Wednesday mornings free; I chose to spend it with my mentor Dr. Oskin. One of his first patients of the day was a teenage male who carried a diagnosis of autism spectrum disorder. The mom was very pleased with her son’s progress, because he is starting to talk more! Even her son’s pediatrician noticed a huge improvement in his language. Up until recently, her son had been non-verbal for the most part, which all changed once they began treatment with a vitamin called folinic acid.
There’s a good chance many of you have heard of folinic acid, because you’re all such incredible parents/caretakers who will never stop learning how to help your child with autism, and I greatly admire that. Even if you have heard of folinic acid, maybe you didn’t exactly understand what it was or how it related to your child with autism. My goals are to help you understand exactly what it and why it might help your child. Let me start with what it is. Folinic acid is a B-vitamin (vitamin B9) that looks really similar to folic acid. Folic acid is a synthetic vitamin added to processed foods to give it some nutritional value. Folate is the general category of these compounds and can be supplied in either synthetic form, or natural form from whole foods like leafy green vegetables, fruit, legumes, nuts and seeds. Folic acid is considered inactive, and must be “turned on” by a few different enzymes so it can be useful to our bodies. Our bodies convert folic acid to active forms of folate, such as folinic acid and 5-methylenetetrahydrofolate (methylfolate), through enzymes such as dihydrofolate reductase (DHFR) and MTHFR (Methylenetetrahydrofolate reductase), respectively. .
Here, let me simplify this for you:
Folic Acid → Folinic Acid → Methylfolate
You may be wondering, so what does all of this have to do with my child with autism? There is a recently discovered condition called cerebral folate deficiency, which basically means the brain isn’t getting enough folate. If you refer back to the above flow chart, we can see less folate means less folinic acid and less methylfolate. Our bodies require methylfolate and folinic acid to make neurotransmitters (norepinephrine, dopamine and serotonin), glutathione, DNA, and myelin for our neurons, all incredibly important for proper brain health and brain development. Infants with cerebral folate deficiency seem to be neurotypical up until about 4-6 months. Around 4-6 months, they can begin to regress developmentally and develop neurological symptoms, which can present like speech delay , high muscle tone, and seizures1. Sound familiar? It’s a very similar picture to a child diagnosed with autism spectrum disorder. Children with cerebral folate deficiency have antibodies produced by immune cells (called autoantibodies) that are attacking folate receptors at the entrance of the brain, which prevent the brain from getting the folate it needs. The standard treatment for this is folinic acid (also know as Leucovorin Calcium in its prescription form), because folinic acid can get into the brain without the folate receptor2.
As it turns out, children with autism can also have autoantibodies to the folate receptor alpha, cleverly called folate receptor alpha autoantibodies (FRAA). Not all autistic children have them, but one study showed out of 93 children with autism, 75.3% had FRAA3. In a study of 70 children with autism and FRAA, 44 children were given folinic acid, and the other 9 were the control group. In about 4 months, those given folinic acid experienced significant improvement in verbal communication, receptive and expressive language, attention, and stereotypical behavior, with minimal side effects3. In another study of 48 children with autism and FRAA, 23 children were given folinic acid and 25 children received a placebo. Those who received folinic acid experienced improved verbal communication compared to those who received placebo2.
While I was researching this whole topic, I came across something interesting that I’d like to share. Cow’s milk contains folate receptors, which look incredibly similar to the folate receptors human’s have. If we are exposed to bovine folate receptors, our bodies may see them as foreign invaders and start to make antibodies to them. Because bovine and human folate receptors look so similar, antibodies to bovine folate receptors may also react with our own folate receptors. One study took 12 children with FRAA on folinic acid, and eliminated milk from their diets. After milk was eliminated, the number of folate receptor autoantibodies was significantly decreased, which correlated to improvements in seizures, abnormal movements (ataxia), communication and stereotypes. Milk was then reintroduced in 9 of those patients, and this caused their folate antibodies to significantly increase4. One possible reason infants may develop FRAA is if they start dairy formula, or if mom has been consuming milk and has formed antibodies herself, which are being passed through the breast milk.
I believe it is important to get your child tested for the FRAA if they have a diagnosis of autism. Even though these studies are small, the results are significant. Sure, we could wait for larger studies before having every kid with autism get tested, but why wait? Imagine giving your child the gift of language so they can tell you how much they love you for all the work you’ve put in to helping them.
Action Steps:
- If your child has autism, talk to your doctor about getting the Folate Receptor Antibody Test through Iliad Neuroscience. This is a blood test.
- Use this peer-reviewed study to show to your doctor:
Works Cited:
- Gordon N. Cerebral folate deficiency. Developmental medicine and child neurology. 2009;51(3):180-182. doi: 10.1111/j.1469-8749.2008.03185.x.
- R E Frye, J Slattery, L Delhey, B Furgerson, T Strickland, M Tippett, A Sailey, R Wynne, S Rose, S Melnyk, S Jill James, J M Sequeira, E V Quadros. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Molecular Psychiatry, 2016; DOI: 10.1038/mp.2016.168
- Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cerebral folate receptor autoantibodies in autism spectrum disorder. Molecular Psychiatry. 2013;18(3):369-381. doi:10.1038/mp.2011.175.
- Ramaekers VT, Sequeira JM, Blau N, Quadros EV. A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Developmental medicine and child neurology. 2008;50(5):346-352. doi:10.1111/j.1469-8749.2008.02053.x
About the Author
Scott Spiridigliozzi is a 4th year naturopathic medical student at Southwest College of Naturopathic Medicine in Tempe, Arizona. He is excited to graduate in June 2018. It is his passion to serve the pediatric population, specifically those with autism, ADHD, Lyme disease, and other chronic conditions. He strives to help children feel their absolute best mentally, emotionally, and physically so they can enjoy being a kid, engage in social activities with their peers, feel great about who they are, and have no limitations on who they can become and what they can accomplish. In his free time, he enjoys cooking, playing guitar, hanging out with his cat, and hiking! He plans on opening up a family medicine practice in the northeast, somewhere close to his home in New York.
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