New UNC study shows lack of folic acid in late pregnancy hurts memory, thinking

January 15, 2004

CHAPEL HILL — Folic acid is not just critical for brain development in embryos during the earliest stages of pregnancy, but it is a key to healthy brain growth and function late in pregnancy too, scientists at the University of North Carolina at Chapel Hill have discovered.Humans and other mammals lacking sufficient folic acid shortly before they are born can suffer lifelong brain impairment, the UNC animal studies indicate. Such research can never be done directly in growing human fetuses for obvious reasons, scientists say.”In the past few years, folic acid has been the single greatest success story in nutrition and in preventing birth defects,” said Dr. Steven Zeisel, professor and chair of nutrition at the UNC schools of public health and medicine. “Spina bifida, the early birth defect in which the spinal cord doesn’t close, and anencephaly, a condition in which the brain doesn’t form normally, can be eliminated between 50 and 85 percent of the time if women get sufficient folic acid before they become pregnant.”

Women need to take the vitamin before conception because their baby’s brain starts to form during the first few weeks afterward when people don’t know if they are pregnant, Zeisel said.

“There has been a tremendous public health effort to get women to take folic acid before they become pregnant,” he said. “Our whole nation’s food supply has been fortified in the grains to try to help people get more of it.”

But until now, most scientists and doctors believed that folic acid consumption was important only during the first weeks following conception.

“This new study shows for the first time that having too little folic acid available causes impaired development of areas of the brain important for memory and for thinking,” Zeisel said. “The take-home message is that it is extremely important that women not stop taking folic acid after the first weeks but continue until they give birth. Taking a supplement is wise since half of the women in this country are deficient in folic acid in their regular diet.”

Besides supplements, the best sources of folic acid are green leafy vegetables such as spinach and greens, orange juice and cereals fortified with the vitamin, he said. Folic acid takes its name from the word “foliage.”

A report on the findings appears in the January issue of the Journal of Nutrition, the leading nutrition research journal. Besides Zeisel, authors are research assistants Corneliu N. Craciunescu and Mei-Heng Mar, graduate student Elliott C. Brown, and Dr. Craig D. Albright, research associate professor of nutrition, all at the UNC School of Public Health. Dr. Marie R. Nadeau of the U.S. Department of Agriculture Human Nutrition Center on Aging at Tufts University also participated in the work.

The experiments involved feeding pregnant mice and rats high, normal or low amounts of folic acid in otherwise healthy diets, Zeisel said. Researchers then examined fetuses’ brains and looked specifically at stem, or progenitor, cells that divide and give rise to various forebrain structures.

“In the babies of folic acid-deficient mothers, the stem cells divided less than half as much as in the babies of mothers on normal diets so there were less than half the number of stem cells available to help populate the brain,” he said. “In addition, the number of cells that were dying off was much greater — twice as high as it should have been. “So not only were fewer cells being born, but many more were dying so that there were many fewer available to form important areas of brain. That means that those parts will be abnormal permanently, and that the folic acid story does not end soon after the beginning of pregnancy.” Essentially, folic acid is somehow promoting stem cell growth and survival so that the brain can form good memory centers, Zeisel said. To the researchers’ knowledge, no one had ever looked before at folic acid’s effects on brain in late pregnancy. “In mice and rats, the brain centers we are talking about are almost identical to those in human beings, and — along with what we already know our human folic acid needs — that’s why we think these animal findings are applicable to humans,” Zeisel said. “We have every reason to believe that this is true for pregnant women. It likely is the best evidence we’re going to get because these experiments can never be done in humans.”

The National Institutes of Health and the Center for Environmental Health Susceptibility supported the new research.

This news release was researched and written by David Williamson of University News Services.

Note: Zeisel can be reached at (919) 966-7218 or steven_zeisel@unc.edu

UNC School of Public Health contact: Lisa Katz, (919) 966-7467 News Services contact: David Williamson, (919) 962-8596