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High maternal folic acid could be as harmful as it is beneficial for fetal brain development

Posted February 24, 2014
This news or article is intended for readers with certain scientific or professional knowledge in the field.

Dietary folic acid has long been associated with decreased risk of neurodevelopmental disorders, such as autism and birth defects, and therefore supplements are a standard recommendation during pregnancy. However, high amounts of synthetic folic acid in our diets raise concerns about possible negative health effects, especially in the context of brain development and neuropsychiatric conditions, which have increased in incidence in recent years.

Diet rich in folate, as well as synthetic folic acid supplements and fortified foods have become a standard recommendation during pregnancy. Credit: Barron / Creative Commons

Diet rich in folate, as well as synthetic folic acid supplements and fortified foods have become a standard recommendation during pregnancy. Credit: Barron / Creative Commons

Scientists suggest maternal folic acid is responsible for global epigenetic changes in offspring’s genome, which manifest in altered gene expression in otherwise highly regulated developmental process. As a general idea, such changes could be as disadvantageous to the developing fetus as they are beneficial.

A new study published in Epigenetics & Chromatin this month demonstrates maternal folic acid significantly alters DNA methylation patterns in developing brains in mice, while a number of affected genes are related to autism and other neurological disorders.

DNA methylation is an epigenetic modification, which can serve as an “extra code” on top of the genetic code, playing a major role in gene expression regulation.  Large body of evidence suggests DNA methylation can be influenced by environmental factors, including those experienced by the mother during pregnancy, as well as such dramatic events as preterm birth.

Fetal epigenome is particularly sensitive to external influences, and any triggers in maternal lifestyle or nutritional choices could bring about major remodeling of developmental gene expression.

The study demonstrates substantial changes in methylation patterns of offspring’s cerebral hemispheres in mice, whose diets were enhanced with high amounts of folic acid – equivalent to the amount of recommended dietary supplements for pregnant women.

It should be noted that the researchers report methylation bias in relation to the sex of the fetus, suggesting folic acid could have differential effects on boys vs. girls, regardless to whether these effects are beneficial or not.

Amongst epigenetically altered regions, a number of genes were identified to be involved in neural development, and several autism-related genes were found to be downregulated in response to high folic acid supplementation. Reduced activity of these genes has been associated with increased risk of autism spectrum disorders and other neurological diseases, inviting further investigation of potential negative effects of excess folic acid in maternal diet.

Epigenetic involvement in autism has been suggested before, however none in relation to dietary supplements during pregnancy. In fact, folic acid has been reported to reduce the risk of autism in some studies, however, conclusive evidence in the matter is still lacking.


Disclaimer: This article is not intended to serve as a medical advice. Please follow your doctor’s instructions. Contact a medical professional if you need help.

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