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If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
Folate is another name for vitamin B9. We need folate to create healthy red blood cells, and it helps make and repair DNA and RNA. Along with vitamin B12, it works to convert homocysteine to methionine, an essential amino acid for building new blood cells, among many other functions. High homocysteine levels are also a known risk factor for cardiovascular disease, and it’s thought that folate helps to regulate this.
Folate is available in multiple forms. The best way to get it is naturally, through folate-rich foods. Vegetarians will be happy to know that beans, legumes, nuts, and seeds are all great sources, as are leafy greens, citrus, and avocados (USDA, n.d.). For those not getting enough folate through their diet, methylfolate or folic acid supplements may be in order.
Folate is essential for pregnant women, as low folate levels are associated with higher risks of neural tube defects (NTDs). These are issues with the brain, spine, or spinal cord that are present at birth.
Folate is so essential that the many governments, including the US, mandated folic acid fortification of cereal grain products. Fortification in the US began in 1998 and is considered one of the greatest successes in public health. Studies estimated it led to a 13 to 30% reduction in NTDs. Other countries have found similar results (Imbard, 2013).
Folate is already in many of the foods we eat, whether naturally or through grain enrichment with folic acid. A 2002 study found only 7% of participants had folate levels below the estimated daily requirement after given foods fortified with folic acid, while nearly half of them had been below that level before exposure to fortified foods (Choumenkovitch, 2002).
Because of this near-universal fortification, there isn’t much need for most people to worry about low folate levels. Except for some individuals with specific conditions, healthcare professionals don’t often recommend folic acid supplementation. Plus, if you take a multivitamin in the morning, there’s probably plenty in there already.
Taking extra folic acid or folate is often touted as beneficial for several conditions. Even though many of these claims lack scientific backup, would it hurt to take extra? It’s a vitamin, after all, and vitamins can’t be harmful, right? Well, that’s not always the case, as we’ll discuss below. High levels of folate can lead to dangerous medical conditions, just as a folate deficiency could.
Risks of high folate levels
The risks of high folate are related to another topic: the difference between folate and folic acid.
Pure folate is what’s naturally found in many foods. It isn’t very stable and doesn’t fare well with long-term storage, so we can’t make a vitamin supplement of folate. Folic acid, however, is a synthetic, stable formulation. Our bodies can’t use folic acid as it is. We have to metabolize it first to get the folate we can use.
We can only break down so much at a time, though, and we’re often left with excess unmetabolized folic acid floating around our bodies. Studies have suggested that most Americans have excess folic acid already (Smith, 2008).
What are normal folate levels?
Is excess folic acid dangerous? Possibly.
As we mentioned above, sometimes both a deficiency and an excess of folate or folic acid are linked to similar conditions—including certain types of cancers. A 2007 study found low folate levels carried an increased risk of colorectal cancer. Giving modest folic acid supplements suppressed growth of colorectal tumors, but excessive supplementation increased the risk of tumor growth again (Kim, 2007). Some research has found a possible connection to prostate cancer as well. One study found men taking folic acid supplements nearly three times likelier to develop prostate cancer than those that didn’t (Figueiredo, 2009).
It’s an area ripe for further ongoing studies. But trends are suggesting that supplement overkill may increase the risk of certain cancers. And that’s an important distinction to note: increased risk is more often associated with supplement use—meaning folic acid—than high folate levels from naturally occurring folate. In fact, the prostate cancer study cited above found that high folate intake, if strictly from natural dietary sources, was associated with lower cancer risk (Figueiredo, 2009).
A second issue with high blood folate is that it might mask cobalamin (vitamin B12) deficiencies.
Low levels of either folate or B12 can cause megaloblastic anemia (Socha, 2020). That may sound like the name of a weapon from a Transformers movie, but it’s very real and very dangerous. Anemia means low red blood cells, and megaloblastic means the cells produced are malformed and oversized. When it’s the result of a vitamin B12 deficiency, it’s often called pernicious anemia.
In addition to anemia, low vitamin B12 levels can cause serious problems in the nervous system.
What does B12 deficiency have to do with folate? It’s thought that high folate concentrations in the blood—whether from food or from supplements—might effectively fix the anemia caused by having low B12. Because anemia is often one of the first ways healthcare providers might notice a B12 deficiency, supplementing with too much folic acid and fixing the anemia would essentially “mask” the B12 deficit (Smith, 2008). This might delay diagnosis and allow other neuropathic damage to continue unnoticed until symptoms become severe.
High folate might have other harmful effects relating to low B12. A study of elderly Americans in 2007 found that high folate blood levels for patients with normal B12 indicated lower risks of anemia and cognitive impairment. But in patients with low B12, high folate was associated with a higher risk (Morris, 2007). It Isn’t entirely understood yet why this happens, and studies continue.
A third issue is specific to folic acid. Unmetabolized folic acid molecules can bind to many of the same cell receptors that folate does. Because of this, some researchers believe that excess folic acid could block usable folate from doing its job (Smith, 2008). This is an area still being researched, though.
Pernicious anemia: what is it, symptoms, diagnosis, treatment
Folate supplements may interact with some medications. These include (NIH, n.d.):
- Methotrexate. Folate may lower methotrexate’s anticancer effects. However, it may be beneficial to take folate if taking methotrexate for autoimmune disorders. Your healthcare provider will guide you if you’re taking methotrexate.
- Antiepileptic medications, such as phenytoin, carbamazepine, and valproate. Folate and these medications have shown a double-negative effect, each lowering the others’ serum levels.
How much folate does one need?
The US National Institutes of Health (NIH) recommends most adults need 400 micrograms of DFE daily. What is DFE? It stands for dietary folate equivalent. Nutritionists use that term because of the different ways our bodies process natural folate versus folic acid. Simply put, ounce for ounce, we get more folate from folic acid than we can from natural folate in foods. How much we process also varies if we get the folic acid attached to food like enriched grain versus straight in a pill (NIH, n.d.).
For example, a serving of lentils with 200 micrograms of folate would provide the same folate as a slice of bread with 120 mcg of folic acid, which would be the same as a 100 mcg folic acid pill. Confusing! But if you’re counting folate numbers, there isn’t too much need to worry. Supplements and enriched products will list both the folic acid weight and DFE, and the target for most adults is that 400 micrograms of DFE a day.
Who needs extra folic acid?
Aside from those with a poor diet, some people have low folate for other reasons. Many conditions can increase folate usage or prevent its absorption. These include, but are not limited to (Maron, 2009):
- Celiac disease
- Crohn’s disease
- Inflammatory bowel syndrome (IBS)
- Diabetic enteropathy
- Liver disease
- Sickle cell anemia
Folate deficiency may also be a side effect of some medical procedures. Stomach surgeries such as gastric bypass, bowel surgery, and dialysis can affect folate levels (Maron, 2009). Some medications may also lower folate, including sulfasalazine, often prescribed for ulcerative colitis.
Sickle cell anemia: what is it, symptoms, treatment
Unless you have one of the above conditions and your healthcare provider has suggested them, folate supplements may not do much for you. They could even have detrimental effects.
The good news is, natural food folate hasn’t been linked with all of the problems of too much folic acid. As with most vitamins, natural sources are usually the best way to get folate. If you’re on the avocado toast bandwagon, congrats—you’re probably getting most of your daily folate fix the healthiest way already.
- Choumenkovitch, S. F., Selhub, J., Wilson, P. W. F., Rader, J. I., Rosenberg, I. H., & Jacques, P. F. (2002). Folic acid intake from fortification in United States exceeds predictions. The Journal of Nutrition, 132(9), 2792–doi: 10.1093/jn/132.9.2792 Retrieved from https://pubmed.ncbi.nlm.nih.gov/12221247/
- Figueiredo, J. C., Grau, M. V., Haile, R. W., Sandler, R. S., Summers, R. W., Bresalier, R. S., et al. (2009). Folic acid and risk of prostate cancer: Results from a randomized clinical trial. Journal of the National Cancer Institute, 101(6), 432–435. doi: 10.1093/jnci/djp019 Retrieved from https://pubmed.ncbi.nlm.nih.gov/19276452/
- Imbard, A., Benoist, J.-F., & Blom, H. J. (2013). Neural tube defects, folic acid and methylation. International Journal of Environmental Research and Public Health, 10(9), 4352–4389. doi: 10.3390/ijerph10094352 Retrieved from https://pubmed.ncbi.nlm.nih.gov/24048206/
- Kim, Y.I. (2007). Folate and colorectal cancer: An evidence-based critical review. Molecular Nutrition & Food Research, 51(3), 267–292. doi: 10.1002/mnfr.200600191 Retrieved from https://pubmed.ncbi.nlm.nih.gov/17295418/
- Maron, B. A., & Loscalzo, J. (2009). The treatment of hyperhomocysteinemia. Annual Review of Medicine, 60, 39–54. doi: 10.1146/annurev.med.60.041807.123308 Retrieved from https://pubmed.ncbi.nlm.nih.gov/18729731/
- Morris, M. S., Jacques, P. F., Rosenberg, I. H., & Selhub, J. (2007). Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. The American Journal of Clinical Nutrition, 85(1), 193–200. doi: 10.1093/ajcn/85.1.193 Retrieved from https://pubmed.ncbi.nlm.nih.gov/17209196/
- National Institutes of Health Office of Dietary Supplements (n.d.). Folate. Retrieved February 6, 2021, from https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
- Smith, A. D., Kim, Y.-I., & Refsum, H. (2008). Is folic acid good for everyone? The American Journal of Clinical Nutrition, 87(3), 517–533. doi: 10.1093/ajcn/87.3.517 Retrieved from https://pubmed.ncbi.nlm.nih.gov/18326588/
- Socha, D. S., DeSouza, S. I., Flagg, A., Sekeres, M., & Rogers, H. J. (2020). Severe megaloblastic anemia: Vitamin deficiency and other causes. Cleveland Clinic Journal of Medicine, 87(3), 153–164. doi: 10.3949/ccjm.87a.19072 Retrieved from https://pubmed.ncbi.nlm.nih.gov/32127439/
- U.S. Department of Agriculture (n.d.). FoodData Central. Generated interactively: Retrieved February 6, 2021, from https://fdc.nal.usda.gov/fdc-app.html#/?component=1187
Dr. Steve Silvestro is a board-certified pediatrician and Senior Manager, Medical Content & Education at Ro.