Researchers from the Hebrew College of Jerusalem and the Universidade NOVA de Lisboa have recognized a molecular pathway which will clarify how folic acid (vitamin B9) helps stop neural tube defects, linking the vitamin to a key developmental sign comprised of vitamin A.
Folic acid supplementation throughout being pregnant is the generally accepted therapy to stop neural tube defects.
“Earlier than an embryo has a recognizable mind or spinal wire, a sheet of cells known as the neural plate begins to fold upward,” mentioned Hebrew College of Jerusalem Ph.D. pupil Tamir Edri and colleagues.
“Its edges should meet and shut, virtually like a zipper, to make the neural tube. If that course of goes improper, neural tube defects may result.”
“Scientists have lengthy recognized that folic acid can assist stop many of those defects. However the vitamin appears to be doing greater than merely supplying vitamins.”
Within the new research, the authors discovered that folic acid helps swap on ALDH1L1, a gene that makes the ALDH1L1 enzyme.
“The ALDH1L1 enzyme can then assist flip a vitamin A-related molecule known as retinaldehyde into retinoic acid,” they mentioned.
“Retinoic acid acts like a set of directions, telling creating cells when to develop, what to change into, the place to go, and when to cease dividing.”
To check whether or not ALDH1L1 was really essential, the researchers used frog embryos, a standard mannequin for learning early growth.
They created embryos with neural tube closure issues after which handled them with folic acid, which helped lots of the embryos develop extra usually.
Then the scientists disrupted the ALDH1L1 gene. This time, folic acid misplaced its protecting impact.
The end result was a significant clue: with out ALDH1L1, folic acid might not rescue the creating neural tube.
The authors pushed the thought additional, demonstrating that the human ALDH1L1 can produce retinoic acid.
In addition they discovered proof that the identical organic pathway is energetic in mammalian cells, strengthening the chance that the mechanism may very well be related to people.
Edri and co-authors additionally noticed what occurred when this signaling system broke down.
“When retinoic acid ranges have been too low, the cells that might change into a part of the nervous system multiplied too rapidly. The neural plate turned abnormally expanded. Folic acid helped deliver that cell development again towards regular — however solely when ALDH1L1 was working,” they mentioned.
The findings additionally raised one other chance. As a result of ALDH1L1 makes use of a vitamin A-derived molecule to make retinoic acid, the researchers examined whether or not vitamin A and folic acid would possibly work collectively.
Of their embryo experiments, small quantities of retinol, a type of vitamin A, improved the impact of low-dose folic acid.
This doesn’t imply pregnant girls ought to begin taking further vitamin A.
The scientists warn that an excessive amount of vitamin A can itself trigger severe delivery defects, and wholesome growth is dependent upon maintaining retinoic acid ranges inside a slender vary.
“As an alternative, the invention provides us a brand new method to consider a decades-old query,” they mentioned.
“Folic acid might not defend the creating nervous system by performing alone.”
“It could work partly by serving to the embryo produce the correct amount of one other essential developmental sign at precisely the best time.”
“The discovering might additionally assist clarify why folic acid works effectively in lots of pregnancies however doesn’t stop each neural tube defect.”
“Issues within the ALDH1L1-retinoic acid pathway may very well be one attainable motive, though far more analysis is required to find out whether or not the identical mechanism operates in human being pregnant.”
The group’s paper was revealed on July 30, 2026 within the Proceedings of the Nationwide Academy of Sciences.
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Tamir Edri et al. 2026. Folic acid prevention of neural tube defects requires retinoic acid produced by ALDH1L1. PNAS 123 (31): e2616501123; doi: 10.1073/pnas.2616501123
