Study By University Of California-Davis Warns Mothers To Be That Too Much Folic Acid During Pregnancy Could Harm Brain Development Of Embryos
: A new study by researchers from University Of California-Davis along with experts from Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children- California and University College London have found that high levels of folic acid during pregnancy could harm brain development of embryos.
Folate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency. Consequently, adequate folate consumption, in the form of folic acid (FA) fortification and supplement use, is widely recommended and has led to a substantial increase in the amount of FA intake during pregnancy in some populations.
In this research, the study team shows that that either maternal folate deficiency or Folic Acid excess in mice results in disruptions in folate metabolism of the offspring, suggesting diversion of the folate cycle from methylation to DNA synthesis. Paradoxically, either intervention causes comparable neurodevelopmental changes by delaying prenatal cerebral cortical neurogenesis in favor of late-born neurons. These cytoarchitectural and biochemical alterations are accompanied by behavioral abnormalities in FA test groups compared with controls. The study findings point to overlooked potential neurodevelopmental risks associated with excessively high levels of prenatal FA intake.
The study findings are published in the peer reviewed journal: Cerebral Cortex https://academic.oup.com/cercor/advance-article-abstract/doi/10.1093/cercor/bhaa248/5913010?redirectedFrom=fulltext
The researchers studied animal models involving pregnant mice and found that high amounts of folic acid during pregnancy harmed the brain development of embryos.
The study team says the findings indicate that more investigation is needed about the best recommended dosage for pregnant women.
Dr Ralph Green, University of California-Davis distinguished professor of pathology and medicine and a corresponding author of the study told Thailand medical News, "We believe there's a Goldilocks effect with folic acid. Too little is not good, too much is not good; you have to get it just right."
The study involved pregnant mice who were given either a normal amount of folic acid, 10 times the recommended amount, or none. The offspring of the mice that received the largest amount showed significant brain changes.
Dr Konstantinos Zarbalis, Associate Professor, Department of Pathology and Laboratory Medicine and corresponding author of the research warned, “It is not subtle. It's substantial. It makes a marked difference in brain structure if you take very high amounts of folic acid."
Surprisingly changes in the brain due to too much folic acid mimicked those associated with a deficiency of folic acid.
Dr Zarbalis, who is also on the University of California-Davis MIND Institute faculty said, "This, to me, was an even more important insight.”
He noted that in humans, research shows that impaired folate uptake into the brain can cause cerebral folate deficiency, a syndrome that is often associated with the development of autism.
Typically Folic acid ie the synthetic form of vitamin B9, or folate supplementation is widely recommended for women of child-bearing age. It has been shown to substantially reduce the risk of neural tube defects, such as spina bifida, in children.
To date, research, including studies at the MIND Institute, has also shown that prenatal vitamins that include folic acid have a protective effect against the development of autism and other disorders.
Dr Green was on the panel with the National Academy of Sciences and the Institute of Medicine (now called the National Academy of Medicine) that determined the recommended daily intake of folic acid (400 mcg) and the maximum daily safe upper limit (1000 mcg). He was also on the Food and Drug Administration (FDA) panel that recommended adding folic acid to foods, which led to the fortification of all cereals and grains with folic acid mandated by the Federal Government in 1998.
Dr Green commented, "Addition of folic acid to the diet was a good thing, and I have supported fortification, but there is a 'best amount' of folic acid, and some people may be getting more than is optimal."
Normally women who have given birth to a child with neural tube defects or who have certain conditions like epilepsy and take anticonvulsants have generally been advised to take much higher doses of folic acid.
Dr Zarbalis added, "In animal models, we have indications that very high amounts of folic acid can be harmful to brain development of the fetus, and the clinical community should take this indication seriously, to support research in this area to reevaluate the amount of folic acid that is optimal for pregnant women.
Both Dr Zarbalis and Dr Green suspect that the problem lies in the way folic acid is metabolized by the body and have plans to investigate the phenomenon further.
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