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Folic Acid and Autism: A Systematic Review of the Current State of Knowledge
Bianka Hoxha1, Malvina Hoxha2, Elisa Domi2
1Department of Chemical-Pharmaceutical and Biomolecular Technologies, Faculty of Pharmacy, Catholic University "Our Lady of Good Counsel", Rruga Dritan Hoxha, 1000 Tirana, Albania.
Insights
Folic acid may influence autism risk and symptoms. Research suggests prenatal supplementation might offer protection, while supplementation in diagnosed children shows some symptom improvement. Further trials are needed.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Folic acid is crucial for fetal development, cell division, and tissue growth.
- Emerging research suggests folic acid's role in childhood behavior and as a potential modifiable risk factor for autism spectrum disorders (ASD).
Purpose of the Study:
- To systematically review the potential role of folic acid in autism spectrum disorders.
- To investigate the underlying mechanisms linking folic acid to ASD.
Main Methods:
- Systematic review of existing studies on folic acid and autism spectrum disorders.
- Analysis of data concerning prenatal supplementation, supplementation in diagnosed children, genetic factors (MTHFR), and immunological markers (FRAA).
Main Results:
- Prenatal folic acid supplementation (600 µg) shows a potential beneficial effect on ASD risk, though results are conflicting.
- Supplementation with folic acid and/or folinic acid in children with ASD has improved neurologic and behavioral symptoms and one-carbon metabolites.
- Increased frequency of auto-antibodies against folate receptor alpha (FRAA) and the influence of MTHFR polymorphisms on ASD risk are reported.
Conclusions:
- Folic acid plays a complex role in autism spectrum disorders, with potential benefits from prenatal supplementation and improvements in diagnosed children.
- Mechanisms may involve folate metabolism, folate receptor alpha antibodies, and MTHFR gene variations.
- Further large-scale, long-term clinical trials are essential to confirm folic acid's protective role in ASD.
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.
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