Folic Acid and Autism: A Systematic Review of the Current State of Knowledge

source extracted confidence: high 2026-04-09
#autism-spectrum-disorder #autoantibodies #dietary-supplements #folate-receptor-1 #folic-acid

Folic Acid and Autism: A Systematic Review of the Current State of Knowledge

Hoxha et al., 2021 | Cells | Systematic Review

Citation

Hoxha Bianka, Hoxha Malvina, ... Zappacosta Bruno. Folic Acid and Autism: A Systematic Review of the Current State of Knowledge. Cells. 2021-Aug-03;10(8). doi:10.3390/cells10081976

Abstract

Folic acid has been identified to be integral in rapid tissue growth and cell division during fetal development. Different studies indicate folic acid's importance in improving childhood behavioral outcomes and underline its role as a modifiable risk factor for autism spectrum disorders. The aim of this systematic review is to both elucidate the potential role of folic acid in autism spectrum disorders and to investigate the mechanisms involved. Studies have pointed out a potential beneficial effect of prenatal folic acid maternal supplementation (600 µg) on the risk of autism spectrum disorder onset, but opposite results have been reported as well. Folic acid and/or folinic acid supplementation in autism spectrum disorder diagnosed children has led to improvements, both in some neurologic and behavioral symptoms and in the concentration of one-carbon metabolites. Several authors report an increased frequency of serum auto-antibodies against folate receptor alpha (FRAA) in autism spectrum disorder children. Furthermore, methylene tetrahydrofolate reductase (MTHFR) polymorphisms showed a significant influence on ASD risk. More clinical trials, with a clear study design, with larger sample sizes and longer observation periods are necessary to be carried out to better evaluate the potential protective role of folic acid in autism spectrum disorder risk.

Key Findings

More clinical trials, with a clear study design, with larger sample sizes and longer observation periods are necessary to be carried out to better evaluate the potential protective role of folic acid in autism spectrum disorder risk.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Autism Spectrum Disorder
  • Autoantibodies
  • Dietary Supplements
  • Folate Receptor 1
  • Folic Acid
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Polymorphism, Single Nucleotide
  • Risk Factors

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: folate

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09