Folic acid supplementation not only protects developing babies from certain birth defects, but also promotes healthy brain development throughout the adolescent years, according to researchers. A study of pregnant mice discovered that high levels of folic acid were associated with significant changes in offspring brain development.
A UC Davis MIND Institute study of pregnant mice discovered that high levels of folic acid during pregnancy harmed embryo brain development. According to the researchers, the findings indicate that more research into the best recommended dosage for pregnant women is required.
“We believe folic acid has a Goldilocks effect. Too little is bad, too much is bad; you have to get it just right “Ralph Green, UC Davis distinguished professor of pathology and medicine and corresponding author of the study, agreed.
The study, published in Cerebral Cortex, involved pregnant mice who were given either a normal amount of folic acid, 10 times the recommended amount, or none at all. The offspring of the mice who received the most showed significant brain changes.
We have indications in animal models that very high amounts of folic acid can be harmful to fetal brain development, 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.
Konstantinos Zarbalis
“It’s not subtle at all. It’s significant” Konstantinos Zarbalis, associate professor in the Department of Pathology and Laboratory Medicine and corresponding author of the study, explained his findings. “High doses of folic acid make a significant difference in brain structure.”
Surprisingly, changes in the brain caused by too much folic acid resembled those caused by folic acid deficiency. “This was an even more important insight for me,” said Zarbalis, who is also on the faculty of the UC Davis MIND Institute. He mentioned that in humans, impaired folate uptake into the brain can result in cerebral folate deficiency, a syndrome that is frequently associated with the development of autism.
The researchers discovered that if a new mother has a very high level of folate right after giving birth – more than four times what is considered adequate – her child’s risk of developing an autism spectrum disorder more than doubles. Extremely high vitamin B12 levels in new mothers can also be harmful, tripling the risk that her child will develop autism spectrum disorder. If both levels are extremely high, a child’s chances of developing the disorder increase 17.6 times. Folate, a B vitamin, is naturally found in fruits and vegetables, whereas folic acid, a synthetic version, is used to fortify cereals and breads in the United States, as well as in vitamin supplements.
Folic acid and pregnancy
Supplementation with folic acid (the synthetic form of vitamin B9, or folate) is widely recommended for women of childbearing age. It has been shown to significantly reduce the risk of neural tube defects in children, such as spina bifida. Prenatal vitamins containing folic acid have also been shown in research, including studies at the MIND Institute, to protect against the development of autism and other disorders.
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.
“Addition of folic acid to the diet was a good thing, and I’ve supported fortification, but there is a ‘best amount’ of folic acid, and some people may be getting more than is optimal,” said Green.
Women who have given birth to a child with neural tube defects or who have certain conditions such as epilepsy and use anticonvulsants are generally advised to take much higher doses of folic acid.
“We have indications in animal models that very high amounts of folic acid can be harmful to fetal brain development, 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,” Zarbalis said. Zarbalis and Green believe the issue is related to how folic acid is metabolized by the body and intend to investigate the phenomenon further.
