A study published in PNAS reports that folic acid may protect fetal brain and spinal cord development by supporting the body’s production of retinoic acid, an active form of vitamin A. The findings were described in an article published Aug. 4, 2026, by mindbodygreen. Folic acid has been a standard prenatal recommendation for decades, credited with cutting the risk of neural tube defects by about 50%, according to the report.
Researchers used CRISPR/Cas9 on frog embryos to switch off specific genes and track how each one affected neural tube development, the report stated. According to the findings, retinoic acid, not folic acid directly, appears to be the molecule that helps the neural tube close. When the team blocked an enzyme needed to make retinoic acid, folic acid no longer prevented neural tube defects. Direct administration of retinoic acid restored normal development even without folic acid, the study found.
Study Background and Methods
Public health authorities have recommended folic acid before and during pregnancy since two randomized controlled trials and several observational studies proved its effect against neural tube defects, according to a 1998 review in Nutrition Reviews [8]. The U.S. Centers for Disease Control and Prevention advises all women of childbearing age to take 0.4 mg of folic acid daily, according to a 2005 report [3]. Folic acid is the synthetic form of vitamin B9, while folate occurs naturally in leafy greens and other foods, according to a 2024 report [1]. Neural tube development involves maternal risk factors and genetic influences, according to medical literature [5].
The new study used frog embryos, described in the report as a standard model in developmental biology because early growth closely mirrors that of human embryos. Researchers reported using CRISPR/Cas9 to disable specific genes and observe effects on neural tube development. The study’s authors said the work was conducted in animals and did not directly test human prenatal nutrition.
Key Findings
The report stated that folic acid does not appear to protect the developing brain and spinal cord directly. Instead, it helps the body produce retinoic acid, which is essential for proper neural tube closure in early pregnancy. When researchers blocked an enzyme required for retinoic acid production, folic acid no longer prevented neural tube defects, according to the study. Giving retinoic acid directly restored normal development, the study found.
The researchers also found that without enough retinoic acid, cells forming the neural tube grew too quickly and in a disorganized way, making closure more difficult. The neural tube develops within the first weeks of pregnancy, before many women know they are pregnant, according to an earlier report [4]. The study authors said the findings suggest the vitamin A pathway plays a key role in keeping early development on track.
Implications for Prenatal Guidance
The study’s authors said the findings do not change current recommendations. The CDC still advises that anyone who could become pregnant take 400 micrograms of folic acid daily, according to [3]. Researchers said vitamin A availability may matter more to early neural development than previously understood. Most prenatal vitamins already contain vitamin A, and foods such as leafy greens, eggs, and orange and yellow vegetables provide it naturally, according to the report.
Officials and researchers cautioned against taking extra preformed vitamin A supplements during pregnancy. Concern about the safety of high-dose vitamin A in pregnancy is documented in nutrition literature, with a vitamin A metabolite, 13-cis retinoic acid, known to carry teratogenic risk [6]. The study was an animal study, and the report stated that more research is needed before any changes to human prenatal nutrition guidelines would be warranted.
Some physicians have argued that synthetic folic acid added to breads, pasta and other foods may carry under-recognized risks, and they have recommended relying on natural sources of folate rather than synthetic additives [7]. Earlier analyses also questioned mandatory food fortification with synthetic folic acid; a Chilean study published in the European Journal of Gastroenterology and Hepatology provided temporal evidence linking fortification to an increased risk of colon cancer [2].
Conclusion
The study provides a clearer explanation for folic acid’s known benefits by linking its action to a vitamin A pathway involving retinoic acid, according to the report. Current prenatal guidance remains unchanged, according to researchers, who said more targeted approaches may be explored in future studies.
The report stated that folic acid appears to activate an enzyme that produces a form of vitamin A essential for early brain and spinal cord development. The existing recommendation to take folic acid before and during early pregnancy remains supported, the report said.
References
- Mercola.com. “Why You Should Only Take Folate and Never Fol”. Mercola.com. February 12, 2024.
- ANH International. “Another Question Mark Over Mandatory Food Fortification With Synthetic Folic Acid 2”. ANH International. April 28, 2009.
- NaturalNews.com. “Folic acid deficiencies are widespread here”. NaturalNews.com. December 29, 2005.
- NaturalNews.com. “Most Women of Childbearing Age Fail on Folic”. NaturalNews.com. August 05, 2008.
- Timothy M George and David Corey Adamson. “Chapter 10 Spinal Dysraphism The Search For Magic”.
- “Beyond deficiency new views on the function and health effects of vitamins”.
- “Synthetic Folic Acid Routinely Added to Many Foods May Trigger Autoimmune Reactions in Some Children”. Children’s Health Defense.
- Margaret L. Watkins. “Efficacy of Folic Acid Prophylaxis for the Prevention of Neural Tube Defects”. Nutrition Reviews. 1998.
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