Natural sources of vitamin B9

Folate on the Brain: A Natural Approach to Treating Autism Spectrum Disorders

Autism is more a constellation of symptoms than a disease with a single cause. In fact, there is often more than one causative factor involved in autism and similar diagnoses. One basic tenet of naturopathic medicine is to treat the cause. In autism spectrum disorders (ASD), many cases have a genetic component that is “hard-wired”, so to speak, and therefore not theoretically treatable. However, some genetic changes have associated treatments. And if these and other contributing causes are also successfully identified and treated, this can result in significant improvements.

One area of focus is identifying and treating issues with how the body utilizes folate, an essential nutrient also known as vitamin B9. Folate is required in multiple metabolic processes required for healthy brain function. Some of these processes ultimately make DNA and RNA as well as keep harmful chemicals that may cause neuro-inflammation at bay.

Rich sources of folate include dark leafy greens, asparagus, beats, chickpeas and liver. Folate is generally absorbed in the small intestine. After absorption, it requires a specific protein transporter called folate receptor alpha (FRα) to make its way to the brain.

MTHFR and beyond:

The methyltetrahydrofolate (MTHFR) gene has been a hot topic in research for many chronic health conditions - from ASD to autoimmune conditions and cardiovascular disease. This gene produces the MTHFR enzyme, which helps convert circulating folate, which is in the form of tetrahydrofolate (THF), to its usable form, 5-methyl-tetrahydofolate. Mutations in the MTHFR gene have been found to be somewhat more prevalent in ASD(1). These mutations are fairly common, and supplementation of methyl folate can be helpful in mitigating its effects. That being said, MTHFR is only one small piece to a larger picture—think of an engine that has several gears required for it to work properly. If one gear breaks, others get overloaded and dysfunction ensues. There are other mutations, or polymorphisms, that can affect the pathways that MTHFR is connected to; these have also been shown often to be present in ASD(1). Generally speaking, these polymorphisms lead to trouble in detoxification pathways, DNA and RNA repair, changes in neurotransmitter levels, and increased oxidative stress, all of which can affect the brain. In ASD, these polymorphisms have associations with decreased cellular uptake of folate as well as depleted sources of SAMe, cysteine and glutathione. It is important to note that there is variability across the spectrum, depending on the particular genetic profile of the person(2). This is why testing for these polymorphisms should be an essential diagnostic tool. With testing, nutrient supplementation can be optimized to meet the specific needs of the individual.

-The folate cycle & related pathways-

-The folate cycle & related pathways-

Arguably more important than MTHFR or related polymorphisms, recent research shows that many people with ASD may have trouble getting folate to the brain. This may be attributed to the presence of antibodies to FRα, a specific transporter that is required to allow circulating folate into the fluid surrounding the brain.  A study of 93 children with ASD showed that 75.3% of them had antibodies that either bound to or blocked FRα, thereby inhibiting the uptake of folate into the brain.  In study participants that had antibodies to FRα, high doses of leucovorin, which contains a metabolically active form of folate called folinic acid, significantly improved language and communication as well as attention and stereotypical behavior.  This means that in individuals who test positive for FRα antibodies, high doses of folinic acid may yield a dramatic improvement.  

Beyond supplementation, a low-allergenic diet can lower the body’s immune response in general. Specific food allergies or sensitivities can be tested for via skin prick or serum testing. Adhering to such a diet can result in fewer FRα antibodies and improved folate uptake.  

Please consult with your or your child’s physician to discuss an optimized diagnostic and treatment regimen, for what could quite possibly result in dramatic improvements!


  1. James, S. J., Melnyk, S., Jernigan, S., Cleves, M. A., Halsted, C. H., Wong, D. H., Gaylor, W. (2006). Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics, 141B(8), 947–956.
  2. James, S. J., Cutler, P., Melnyk, S., Jernigan, S., Janak, L., Gaylor, D. W., & Neubrander, J. A. (2004). Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. The American Journal of Clinical Nutrition, 80(6), 1611–1617.