Autism & Cerebral Folate Deficiency.

Growing Evidence.

U.S. Centers for Disease Control and Prevention (CDC) data (CDC ASD Report) shows the prevalence of ASD has been increasing in the US in recent decades, with a reported prevalence of 27.6/1000 as of 2020.

Growing evidence suggests that nutritional and environmental factors play a role in ASD. Several studies have investigated the potential link between folate status and ASD risk. Folate (vitamin B9) is essential for DNA synthesis, methylation, and other important cellular processes in its reduced form.

Research shows that a cerebral folate deficiency can be tied to an increased risk of ASD.

Specifically: Schmidt et al. (2011) found that mothers of ASD children were more likely to have lower levels of plasma folate during pregnancy than mothers of neurotypical children. Frye et al. (2013) and Adams et al. (2011) found that ASD children have lower levels of folate in their blood than their neurotypical counterparts.

Clinical trials (Frye et al. 2016, Ramaekers et al. 2016, Renard et al. 2019) reveal that 70% of autistic children produce an antibody to the folate receptor alpha (FRA). This is the high-affinity folate transporter, responsible for pumping folate across the blood-brain barrier (BBB) to higher concentrations in the brain than the plasma.

Treatment.

These same trials found that supplementing with leucovorin (folinic acid) at 0.5-1 mg/kg body weight) alleviated some ASD symptoms, particularly in relation to communication, for two-thirds of the children presenting with the antibody, within the 3-month trial. The improvement was more pronounced for younger children, with the greatest impact for those under 6, and a reduced effect over 15. The antibody is made in response to a dietary element, identified by Ramaekers et al (2009) as deriving from bovine milk products.

The antibody does not affect the low-affinity transporter, which moves folate across the BBB equivalent to plasma concentrations. Thus, supplementation with high doses of leucovorin alleviates this folate anemia, allowing reduced folate to cross the BBB and restore cerebral folate levels.

Overall, evidence indicates that folate status plays a critical role in the development and progression of ASD, and that folate supplementation in children who have the folate receptor autoantibody has therapeutic promise. Given the absence of side effects and toxicity concerns with leucovorin, some pediatricians and psychiatrists have prescribed a course of leucovorin for children who are positive for the folate receptor antibody. Additionally, it is expected that the improved communication may help families begin to modify their diet to reduce the antigenic load and provide a more long-term benefit.

Physicians, we’re here to help.

Salud Santa Barbara will work with your office and with the FRA testing company to cover the co-pay costs of the blood test of any of your Santa Barbara Medi-Cal patients under 18 years of age.

Obtaining a Blood Test for the Folate Receptor Antibody ➚