Scientists may have found an important clue to how folic acid helps prevent serious birth defects of the brain and spinal cord.
In experiments using frog embryos and cells, researchers found that folic acid’s protective effect depended on an enzyme called ALDH1L1. That enzyme helps the developing embryo make a vitamin A-related substance that is important for normal growth.
The findings, published in the Proceedings of the National Academy of Sciences, do not change current folic acid recommendations. They also do not mean people who are pregnant or planning pregnancy should take extra vitamin A.
Folic acid, the form of vitamin B9 used in supplements and fortified foods, has long been known to lower the risk of neural tube defects. These birth defects happen very early in pregnancy when the structure that becomes the brain and spinal cord does not close properly.
What scientists have understood less clearly is exactly how folic acid helps.
To explore that question, researchers studied frog embryos with problems in early nervous system development. Folic acid helped many of the embryos develop more normally.
But when researchers blocked ALDH1L1, folic acid no longer had the same protective effect.
That suggested the enzyme was an important part of how folic acid was working.
Researchers also found that when the vitamin A-related process was disrupted, cells involved in forming the nervous system grew too quickly. Folic acid helped bring that growth closer to normal, but only when ALDH1L1 was working.
The results suggest folic acid may help early development partly by supporting signals that tell cells when and how to grow.
The researchers also tested small amounts of retinol, a form of vitamin A, in the frog embryos. In some experiments, it appeared to strengthen the effect of a low dose of folic acid.
That finding should not be taken as a reason to use extra vitamin A during pregnancy. Too much vitamin A can cause serious birth defects, and this study did not test vitamin A supplements in pregnant people.
The research also cannot show that this same process explains neural tube defects in humans. Although researchers found signs that similar biology exists in mammalian cells, human studies would be needed to confirm its role during pregnancy.
The findings may eventually help scientists understand why folic acid prevents many neural tube defects but not all of them.
For now, the study adds a possible explanation for why a long-standing nutrition recommendation works. Folic acid may help protect early brain and spinal cord development not only by supplying an essential vitamin, but also by supporting the signals that guide cells during the earliest stages of development.
The research received support from the United States-Israel Binational Science Foundation, the Israel Science Foundation, Manitoba Liquor and Lotteries, the Eliyahu Pen Memorial Fund, the Wolfson Family Chair in Genetics and Portuguese research programs supported by Fundação para a Ciência e a Tecnologia.