Scientists have discovered that while adding folic acid to foods helps prevent birth defects, getting too much of it—especially from supplements—might actually harm your nervous system and brain development. The problem gets worse if you don’t have enough vitamin B12. Think of folic acid and B12 like dance partners: they need to work together in the right amounts. When one is too high and the other is too low, your body’s ability to build and repair DNA gets disrupted. This review of 60 years of research suggests we should rethink how much folic acid we add to foods and consider including more vitamin B12 in fortification programs.

The Quick Take

  • What they studied: Whether too much folic acid from fortified foods and supplements could harm the brain and nervous system, especially when vitamin B12 levels are low
  • Who participated: This wasn’t a single study with participants—instead, scientists reviewed and summarized findings from hundreds of studies conducted over the past 60 years
  • Key finding: Evidence suggests that excess folic acid, particularly from supplements, may harm brain cell development and nerve function, especially when vitamin B12 is deficient. The damage appears related to how much folic acid you consume and for how long
  • What it means for you: You probably don’t need to worry about folic acid in regular foods, but if you’re taking high-dose folic acid supplements without checking your B12 levels, it might be worth discussing with your doctor. This is especially important for pregnant people, since the balance affects developing babies

The Research Details

This is a comprehensive review article, meaning scientists gathered and analyzed all the research they could find about folic acid, B12, and nervous system health from the past 60 years. They looked at historical records, clinical observations from doctors, population-level studies, and laboratory experiments. By combining all this evidence, they identified patterns and trends that a single study couldn’t show.

The researchers examined studies from both before and after countries started adding folic acid to grain products (which began in the 1990s). This allowed them to compare what happened to people’s health before and after fortification started. They also looked at how folic acid and B12 work together in your body at the molecular level—the tiny chemical processes that keep your cells functioning properly.

A review like this is important because it can spot patterns that individual studies might miss. By looking at decades of research together, scientists can see if certain effects consistently appear across many different studies and populations. This approach is especially valuable for understanding potential harms that might take years to develop or only show up in certain groups of people.

This review was published in a respected peer-reviewed journal, meaning other experts checked the work. However, because it’s a review rather than a new experiment, its strength depends on the quality of the studies it analyzed. The authors appear to have done thorough research, but readers should know that reviews can sometimes emphasize findings that support the author’s viewpoint. The recommendations suggest moving away from current fortification practices, which is a significant claim that would need careful consideration by public health experts.

What the Results Show

The research shows that excess folic acid appears to interfere with normal brain cell development in ways similar to having too little folic acid or too little B12. This is surprising because it suggests there’s a ‘sweet spot’—too little is bad, but too much is also bad.

When folic acid levels are high and B12 levels are low at the same time, the damage to brain development appears to be greatest. This is concerning because folic acid fortification can actually lower B12 levels in some people, creating this dangerous combination.

The evidence suggests that the harm from excess folic acid depends on two things: how much you’re exposed to and for how long. Someone taking high-dose supplements for years might face greater risk than someone eating fortified bread occasionally.

The researchers found that excess folate disrupts the ‘one-carbon cycle’—a crucial chemical pathway in your body that controls how DNA is built and repaired, and how genes are turned on and off. When this pathway gets disrupted, it can affect not just the person taking the supplements, but potentially their children and grandchildren through changes in how genes are expressed.

The review also found that vitamin B12 deficiency is an independent risk factor for neural tube defects (birth defects of the brain and spine), and in some countries where B12 deficiency is more common than folate deficiency, this may be a bigger problem than previously recognized. Additionally, the research suggests that the current approach of adding only folic acid to foods, without balancing it with B12, may be creating new health problems while trying to solve old ones.

Folic acid fortification was introduced in the 1990s specifically to prevent neural tube defects in babies, and it has been very successful at that goal. However, this review suggests that while we’ve solved one problem, we may have created another by not paying enough attention to the balance with B12. Previous research focused mainly on whether we had enough folate; this review shifts attention to whether we might have too much.

This is a review of existing research rather than a new study, so it can only be as good as the studies it reviews. Some of the older studies may not have measured things as precisely as modern research does. The review doesn’t provide new experimental data, so some of its conclusions are based on interpreting patterns across many different types of studies. Additionally, while the evidence is concerning, the review doesn’t quantify exactly how many people might be harmed or how severe the harms might be in real-world situations. Public health organizations would need to weigh this evidence against the proven benefits of fortification before making changes.

The Bottom Line

Based on this evidence: (1) General population: Continue eating fortified foods as they are—the amounts in regular food are likely safe. (2) Supplement users: If you’re taking folic acid supplements, especially high doses, discuss this with your doctor and ask about your B12 levels. (3) Pregnant people: Work with your healthcare provider to ensure you’re getting adequate folate and B12 in the right balance, rather than assuming more folic acid is always better. (4) Public health: Consider reformulating fortification programs to include vitamin B12 alongside folic acid, or use natural folate forms instead of synthetic folic acid. Confidence level: Moderate—the evidence is substantial but comes from reviewing existing research rather than new studies.

This matters most for: pregnant people and those planning pregnancy, people taking high-dose folic acid supplements, people with B12 deficiency or at risk for it (vegans, older adults, people with certain digestive conditions), and public health officials designing fortification policies. This is less immediately relevant for people eating a balanced diet with adequate B12 from food sources.

The effects described in this research develop over time—they’re not immediate. Brain development effects would be most critical during pregnancy and early childhood. The changes to gene expression and epigenetic effects could take months to years to develop and might affect future generations. If you’re concerned, changes to supplementation could be discussed with your doctor now, but you wouldn’t expect immediate effects from stopping supplements.

Want to Apply This Research?

  • Track your folic acid and B12 intake sources: note any supplements you take (brand, dose, frequency), fortified foods you eat regularly, and any B12-containing foods. Compare this to your lab results if you’ve had B12 testing done. This creates a personal picture of your folate-B12 balance.
  • If you’re taking folic acid supplements, use the app to: (1) log your current supplement use, (2) set a reminder to discuss B12 status with your doctor, (3) track any symptoms that might relate to B12 deficiency (fatigue, numbness, memory issues), and (4) if your doctor recommends changes, use the app to track your new routine and any changes you notice.
  • Create a quarterly check-in: every three months, review your supplement intake and any symptoms you’ve noticed. If you’ve made changes based on your doctor’s advice, track whether you feel different. Keep records of any lab work showing B12 and folate levels so you can see trends over time. This long-term tracking helps you and your doctor understand what balance works best for your body.

This review presents evidence suggesting potential concerns about excess folic acid intake, but it does not mean you should stop taking folic acid supplements or avoid fortified foods without medical guidance. Folic acid fortification has successfully prevented serious birth defects and remains an important public health measure. If you are pregnant, planning pregnancy, taking folic acid supplements, or have concerns about your folate or B12 levels, consult with your healthcare provider before making any changes. This summary is for educational purposes and should not replace professional medical advice. Individual circumstances vary, and your doctor can assess your specific situation and needs.