Researchers studied what happens when pregnant mice get five times the normal amount of folic acid, a B vitamin that’s usually good for pregnancy. They found that extra folic acid changed how genes work in the baby’s brain and affected chemical markers that control which genes turn on and off. These changes involved genes important for brain connections and learning. While folic acid is important to prevent birth defects, this study suggests that getting too much might cause problems with how the brain develops. The findings are from lab studies in mice, so scientists need to do more research to understand if this applies to humans.

The Quick Take

  • What they studied: Whether giving pregnant mice five times the normal amount of folic acid (a B vitamin) would change how their babies’ brains developed at the genetic level
  • Who participated: Laboratory mice during pregnancy and their newborn pups. The study examined brain tissue from the babies at birth to look for genetic changes
  • Key finding: Excess folic acid changed how 646 genes worked in the baby mouse brains and altered chemical markers on 910 different DNA regions. These changes affected genes involved in brain connections, learning, and protecting brain cells from damage
  • What it means for you: This research suggests that while folic acid is important during pregnancy to prevent birth defects, getting too much might not be better. If you’re pregnant or planning to be, talk to your doctor about the right amount of folic acid rather than assuming more is always better. This is early research in mice, so more studies are needed before changing medical recommendations

The Research Details

Scientists gave pregnant mice either normal amounts of folic acid or five times the normal amount. They then examined the brains of newborn mice to see what changed. They used two main tools: one that reads which genes are turned on or off (RNA-seq), and another that looks at chemical tags on DNA that control gene activity (methylation sequencing). These tags are like sticky notes on genes that tell them whether to be active or quiet.

The researchers focused on the cerebral cortex, which is the outer layer of the brain responsible for thinking, learning, and memory. By comparing the brains of babies exposed to normal versus excess folic acid, they could identify specific changes caused by too much of the vitamin.

This type of study is important because it helps scientists understand what happens at the molecular level—the smallest building blocks of life—when something changes during pregnancy. By studying mice first, researchers can safely explore potential risks before considering human studies.

Understanding how excess folic acid affects developing brains is crucial because many countries add folic acid to foods and doctors recommend supplements during pregnancy. If too much folic acid causes problems, pregnant people need to know the right amount to take. This research helps explain the biological mechanisms—the actual chemical processes—that might cause problems, rather than just observing that problems exist.

This study was published in a peer-reviewed nutrition journal, meaning other scientists reviewed it before publication. The researchers used advanced molecular techniques (RNA-seq and whole genome bisulfite sequencing) that are considered reliable methods for studying genes. However, the study was conducted in mice, not humans, so results may not directly apply to people. The abstract doesn’t specify how many mice were studied, which would help assess the study’s strength. The findings suggest a mechanism for potential harm but don’t prove that humans would experience the same effects at typical supplementation levels.

What the Results Show

When pregnant mice received five times the normal amount of folic acid, their babies’ brains showed significant changes in gene activity. Specifically, 646 genes had different activity levels compared to babies from mothers with normal folic acid intake. Many of these genes are involved in protein translation—the process where cells read genetic instructions and build proteins needed for brain function.

The study also found changes in chemical markers (called methylation) on 910 different regions of DNA. These markers act like switches that turn genes on and off. The affected regions included genes involved in glutamatergic synapses (connections between brain cells that are crucial for learning and memory), neurodevelopment (how the brain grows and develops), and glutathione pathways (systems that protect brain cells from damage).

These findings suggest that excess folic acid doesn’t just pass through the body harmlessly—it actually changes how the developing brain works at a fundamental genetic level. The changes affected multiple interconnected systems in the brain, not just isolated genes.

The researchers noted that their findings align with previous work showing that excess folic acid can disrupt how brain cells connect to each other. The changes in gene expression and methylation patterns suggest that excess folic acid may interfere with normal brain development by affecting multiple pathways simultaneously. The involvement of glutathione pathways is particularly notable because these systems protect brain cells from oxidative stress (a type of cellular damage), suggesting that excess folic acid might compromise the brain’s natural defense mechanisms.

This research builds on earlier studies showing that folic acid is essential during pregnancy to prevent neural tube defects (birth defects of the brain and spine). However, it adds to growing evidence that more folic acid isn’t always better. Previous research has suggested that excess folate might have unintended effects, and this study provides molecular evidence of how those effects might occur. The findings support the idea that there’s an optimal range for folic acid intake during pregnancy—enough to prevent defects, but not so much that it causes other problems.

This study was conducted in mice, not humans, so we can’t be certain the same effects occur in pregnant people. The mice received five times the normal amount of folic acid, which is a very high dose—it’s unclear if typical human supplementation levels would cause similar changes. The study examined brains at birth but didn’t follow the mice as they grew to see if the genetic changes caused actual behavioral or developmental problems. The abstract doesn’t specify the number of mice studied, making it difficult to assess how reliable the findings are. Additionally, the study doesn’t explain why these genetic changes happen or whether they would actually harm brain development in humans.

The Bottom Line

Based on this research, pregnant people should follow their doctor’s recommendations for folic acid supplementation rather than taking extra doses. Standard prenatal vitamin recommendations (typically 400-800 micrograms daily) are designed to prevent birth defects while avoiding excess. If you’re pregnant or planning pregnancy, discuss folic acid intake with your healthcare provider rather than self-supplementing with additional amounts. This research suggests that the current medical recommendations may be appropriate, but more human studies are needed before any changes to guidelines. Confidence level: Moderate—this is early research in animals that suggests a potential concern, not definitive proof of harm in humans.

Pregnant people and those planning pregnancy should be aware of this research, especially if they’re considering taking more folic acid than recommended. Healthcare providers should know about these findings when counseling patients about supplementation. People with a family history of neurodevelopmental disorders might want to discuss folic acid intake with their doctor. This research is less relevant for non-pregnant adults, as it specifically addresses prenatal exposure during a critical window of brain development.

If excess folic acid does affect human brain development, the changes would likely occur during pregnancy when the brain is rapidly developing. Effects might not be obvious at birth but could potentially appear as the child grows and develops. More research is needed to understand if and when problems might become apparent. This is why long-term follow-up studies in humans would be important.

Want to Apply This Research?

  • Track daily folic acid intake from all sources (prenatal vitamins, fortified foods, and supplements) to ensure it stays within recommended ranges (400-800 mcg daily for pregnant people). Log the specific amount from each source to identify if you’re accidentally exceeding recommendations.
  • Use the app to set a daily folic acid target based on your doctor’s recommendation and log all sources of intake. Create a reminder to take only your prescribed prenatal vitamin rather than adding extra supplements. If you’re considering additional supplementation, use the app to prompt a conversation with your healthcare provider before adding anything.
  • Maintain a monthly review of average folic acid intake to ensure consistency with medical recommendations. If planning pregnancy, start tracking intake before conception to establish baseline habits. Share monthly summaries with your healthcare provider during prenatal visits to confirm you’re in the optimal range.

This research describes laboratory findings in mice and does not establish that excess folic acid causes harm in human pregnancies. Current medical guidelines recommend 400-800 micrograms of folic acid daily during pregnancy to prevent birth defects, and these recommendations remain appropriate based on extensive human research. Do not change your folic acid intake based on this study alone. If you are pregnant, planning pregnancy, or have concerns about folic acid supplementation, consult with your healthcare provider or obstetrician. This article is for educational purposes and should not be considered medical advice. The findings presented are preliminary and require further research in human populations before clinical recommendations would change.