Excess folic acid during pregnancy harms brain development of mice
Researchers found too much folic acid was just as detrimental as too
little

Date:
October 5, 2020
Source:
University of California - Davis Health
Summary:
A study of pregnant mice found high levels of folic acid were
associated with significant changes in brain development of
offspring.



FULL STORY ==========================================================================
A UC Davis MIND Institute study of pregnant mice found that high amounts
of folic acid during pregnancy harmed the brain development of embryos.

Researchers say the findings indicate that more investigation is needed
about the best recommended dosage for pregnant women.


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"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," said
Ralph Green, UC Davis distinguished professor of pathology and medicine
and a corresponding author of the study.

The research, published Sept. 30 in Cerebral Cortex, 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.

"It's not subtle. It's substantial," said Konstantinos Zarbalis,
associate professor in the Department of Pathology and Laboratory
Medicine and also a corresponding author of the research. "It makes a
marked difference in brain structure if you take very high amounts of
folic acid." Paradoxically, changes in the brain due to too much folic
acid mimicked those associated with a deficiency of folic acid. "This,
to me, was an even more important insight," said Zarbalis, who is
also on the UC Davis MIND Institute faculty. 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.

Folic acid and pregnancy Folic acid (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. 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.

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 like epilepsy and take anticonvulsants, have
generally been advised to take much higher doses of folic acid.

"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," said Zarbalis.

Zarbalis and Green suspect that the problem lies in the way folic acid
is metabolized by the body and have plans to investigate the phenomenon further.


========================================================================== Story Source: Materials provided by
University_of_California_-_Davis_Health. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Angelo Harlan De Crescenzo, Alexios A Panoutsopoulos, Lyvin Tat,
Zachary
Schaaf, Shailaja Racherla, Lyle Henderson, Kit-Yi Leung, Nicholas
D E Greene, Ralph Green, Konstantinos S Zarbalis. Deficient
or Excess Folic Acid Supply During Pregnancy Alter Cortical
Neurodevelopment in Mouse Offspring. Cerebral Cortex, 2020; DOI:
10.1093/cercor/bhaa248 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201005170836.htm

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