Department of Nutrition Student Projects

Submission Date

4-22-2026

Document Type

Capstone

Degree Name

Master of Nutrition Science (MS)

First Mentor

Angela Taylor, DCN, CNS, LDN, IFMCP

Second Mentor

Stephanie Petrosky, D.C.N., M.H.A., RDN, FAND, FNAP

Keywords

autism spectrum disorder (ASD), folic acid, unmetabolized folic acid (UMFA), folate, folinic acid, 5-methyltetrahydrofolate (5-MTHF), bioavailability, bioactivity, folate receptor autoantibodies (FRAAs), reduced folate carriers (RFCs), folate receptor alpha (FRɑ), proton-coupled folate transporter (PCFT), dihydrofolate reductase (DHFR), cerebral folate deficiency (CFD)

Abstract

The prevalence of Autism spectrum disorder (ASD) has risen significantly over the past five decades, now affecting approximately 1 in 31 children. This literature review examined whether folinic acid, compared with other forms of vitamin B9 (synthetic folic acid, dietary folate, and 5-methyltetrahydrofolate), modulates ASD symptoms including verbal communication, motor skills and social interaction, particularly in children positive for folate receptor alpha autoantibodies (FRAAs). A thorough search of PubMed, Google Scholar, Nature, and ScienceDirect, primarily from 2015–2026, identified five randomized controlled trials (RCTs) and one meta-analysis evaluating folinic acid at standardized doses of 2 mg/kg/day with a maximum dose of 50 mg/day over 10–12 weeks. Folinic acid produced statistically significant improvements (p < 0.05) across verbal communication, social interaction, and motor skills, with medium-to-large effect sizes. Clinical significance was confirmed by response rates of 67% and number-needed-to-treat values as low as 1.8 in FRAAs-positive children. Only one RCT stratified by FRAAs status, with increased benefit in this subgroup. No serious adverse events occurred. Consumption of a dairy-free diet has shown to be beneficial for children with ASD, primarily those positive for FRAAs. Mammalian dairy products produced by cows, sheep, goats, and camels, among others, contain a high structural similarity in the FOLR1 gene that contributes to the increase in FRAAs through molecular mimicry. Therefore, elimination of these products from the diet of children with ASD may show symptom improvement. These findings support the hypothesis that high-dose folinic acid is both statistically and clinically superior to other vitamin B9 forms for symptom modulation in pediatric ASD when FRAAs are present. Routine FRAAs screening, folinic acid supplementation slowly increased to 2 mg/kg/day, and a dairy-free diet offer a safe, evidence-based, personalized approach to improve symptoms of ASD in children. Larger, long-term studies to identify dietary causes of increased FRAAs are needed.

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