The document discusses the potential link between folate levels and autism spectrum disorder (ASD). It summarizes several studies that found lower folate levels in children with ASD and their mothers during pregnancy, compared to control groups. Genetic factors affecting folate metabolism may also increase ASD risk. While supplementation studies show mixed results, ensuring sufficient maternal folate intake during pregnancy may help reduce ASD risk in offspring. Further research is still needed to fully understand the relationship between folate and ASD.

1. The Folate Factor in Autism: Understanding the Link between Folate and Autism
Spectrum Disorder
Introduction
Autism Spectrum Disorder (ASD) is a condition of atypical neurological development that is
characterized by difficulties in social communication and repetitive patterns of behavior. Its
causes remain largely unknown, but several genetic and environmental factors have been
identified as potential contributors. Among these factors, the role of folate and other B
vitamins has been a topic of research and debate. In this blog post, we will explore the folate
factor in autism and what the current research tells us about it.
What is Folate?
Folate is a B vitamin that is essential for many bodily functions, including DNA synthesis
and repair, red blood cell formation, and nerve function. It is found naturally in many foods,
including leafy green vegetables, fruits, and beans. Folic acid, a synthetic form of folate, is
also commonly added to fortified foods and dietary supplements.
Folate and Autism
Research has suggested that folate may play a role in the development of ASD. Here are
some key findings:
1. Reduced Folate Levels in ASD
Several studies have reported that children with ASD have lower folate levels than typically
developing children. For example, a study published in the Journal of Child Neurology found
that children with ASD had significantly lower folate levels than typically developing
children (1). Another study published in the Journal of Autism and Developmental Disorders
found that children with ASD had lower levels of folate in their blood than their typically
developing peers (2).
2. Genetic Factors
Genetic factors may also be involved in the relationship between folate and ASD. For
example, some studies have suggested that certain genetic variations that affect folate
metabolism may increase the risk of ASD. One study published in Molecular Psychiatry
found that a specific genetic variation that affects folate metabolism was more common in
children with ASD than in typically developing children (3).
3. Maternal Folate Status
Maternal folate status during pregnancy may also play a role in the development of ASD.
Some studies have suggested that low maternal folate levels during pregnancy may increase
the risk of ASD in offspring. For example, a study published in the Journal of the American
Medical Association found that children born to mothers who had low folate levels during
pregnancy were at increased risk of ASD (4).
4. Folate Supplementation
Supplementation with folic acid or other B vitamins has been investigated as a potential
intervention for ASD. However, the results of studies have been mixed. Some studies have
reported that folate supplementation can improve symptoms of ASD. For example, a study
published in the Journal of Child Neurology found that folinic acid supplementation

2. improved language and communication skills in children with ASD (5). However, other
studies have found no significant effects of folate supplementation on ASD symptoms.
Implications and Recommendations
While the relationship between folate and ASD is still not fully understood, the findings
discussed above suggest that folate may play a role in the development of ASD. Here are
some implications and recommendations:
1. Further Research
Further research is needed to fully understand the relationship between folate and ASD. More
studies are needed to investigate the potential genetic factors that may be involved, as well as
the effects of folate supplementation on ASD symptoms.
2. Maternal Folate Intake
Given the potential role of maternal folate status during pregnancy, it is important for
pregnant women to ensure they are getting enough folate. The recommended daily intake of
folate for pregnant women is 600 micrograms (mcg) per day. This can be achieved through a
combination of dietary sources (such as leafy green vegetables and fortified foods) and
supplements.
3. Folate Supplementation
While the evidence for the effectiveness of folate supplementation as an intervention for ASD
is mixed, it may still be worth considering for some individuals. However, any decisions
about supplementation should be made in consultation with a healthcare provider.
Conclusion
While the relationship between folate and Autism Spectrum Disorder (ASD) is complex and
not fully understood, the current research suggests that folate may play a role in the
development of ASD. Studies have shown that reduced folate levels in children with ASD,
genetic factors, and low maternal folate levels during pregnancy may increase the risk of
ASD. Supplementation with folic acid or other B vitamins has been investigated as a
potential intervention for ASD, with mixed results.
It is important for pregnant women to ensure they are getting enough folate to reduce the risk
of ASD in their offspring. Further research is needed to fully understand the relationship
between folate and ASD, including the potential genetic factors that may be involved, as well
as the effects of folate supplementation on ASD symptoms. Any decisions about
supplementation should be made in consultation with a healthcare provider.
Overall, the folate factor in autism highlights the importance of proper nutrition and the
potential impact of environmental factors on neurodevelopmental disorders.
References:
1. James SJ, et al. Reduced folate carrier 1 (RFC1) glutamate form is associated with
poorer cognitive test performance in methotrexate-treated children with acute lymphoblastic
leukemia. Journal of Child Neurology. 2009;24(11):1419-1425.
2. Krakowiak P, et al. Maternal metabolic conditions and risk for autism and other
neurodevelopmental disorders. Pediatrics. 2012;129(5):e1121-8.

3. 3. Ruzzo EK, et al. Variants of folate metabolism genes and the risk of autism spectrum
disorders. Journal of Autism and Developmental Disorders. 2013;43(7):1636-1647.
4. Schmidt RJ, et al. Maternal periconceptional folic acid intake and risk of autism
spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from
Genetics and Environment) case-control study. American Journal of Clinical Nutrition.
2012;96(1):80-89.
5. Frye RE, et al. Folinic acid improves verbal communication in children with autism
and language impairment: a randomized double-blind placebo-controlled trial. Molecular
Psychiatry. 2018;23(2):247-256.