Folic Acid Safety, Interactions, and Health Outcomes

Key points

  • All people capable of becoming pregnant should get 400 micrograms of folic acid daily to help prevent neural tube defects.
  • Numerous studies have found folic acid to be safe and effective at recommended amounts.
  • Although unmetabolized folic acid may be in the bloodstream, no confirmed health risks have been found.
  • Getting the recommended amount of folic acid does not delay detection of vitamin B12 deficiency.
Focused view of a small, white vitamin tablet and glass of water in a person's hand

Overview

CDC recommends all people capable of becoming pregnant get 400 micrograms (mcg) of folic acid daily. Getting 400 mcg of folic acid each day helps prevent some serious birth defects called neural tube defects (NTDs).

Folic acid is safe and effective at recommended amounts

Groups of experts worldwide regularly review all available research on folic acid. Each group has consistently concluded that folic acid is safe and effective at the recommended amounts. Taking 400 mcg of folic acid per day has not been shown to cause harm.

The well-established effectiveness of folic acid in preventing NTDs has been shown through randomized controlled trials and food fortification programs.12345 The US Preventive Health Task Force consistently supported recommendations for 400–800 mcg of folic acid as a Grade A recommendation. This means it is a strong recommendation based on consistent findings. Additional information continues to be assessed as it becomes available.

No health risks identified from unmetabolized folic acid

Folic acid not used by the body is called "unmetabolized folic acid." Folic acid is absorbed by the intestines into the bloodstream and then converted to other forms of folate by the liver. The liver is capable of processing only a certain amount of folic acid at one time. Unused folic acid in the blood goes to the kidneys and leaves the body in urine.

Since the beginning of mandatory folic acid fortification, most people have had some unmetabolized folic acid circulating in their blood.6 Although some people have been concerned about unmetabolized folic acid in the blood, no confirmed health risks have been found.789

Folic acid doesn't delay identification of vitamin B12 deficiency

Early studies suggested that folic acid supplementation could mask the anemia of vitamin B12 deficiency and delay diagnosis. However, current laboratory tests can measure a person's vitamin B12 status. This means that vitamin B12 deficiency can be readily detected and diagnosed.

A recent study looked at anemia among people with vitamin B12 deficiency before and after folic acid fortification. This study found that folic acid fortification did not make it more likely for people to have undetected vitamin B12 deficiency.10

When taking supplements, more is not better. If you can become pregnant, you need 400 mcg of folic acid daily. You can get this from vitamins or fortified foods. This is in addition to eating foods rich in folate. However, your doctor may ask you to take more for certain reasons.

Folic acid's role in supporting health

Folic acid and hypertension

Hypertension, or abnormally high blood pressure, increases the risk for having a stroke. A large study in China found that adults with hypertension who took 800 mcg of folic acid daily lowered the occurrence of stroke by 21%.1112

Folic acid and cardiovascular disease

A study looked at the results of 30 randomized control trials involving more than 80,000 people. This study suggested a 10% lower risk of stroke among those taking folic acid. The study also found a 4% lower risk of overall cardiovascular (heart and blood vessel) disease among those taking folic acid supplements.13

Folic acid and arsenic exposure

In many countries in the world, arsenic in the water results in chronic (constant) arsenic exposure. A randomized control trial in Bangladesh found that taking 400 mcg of folic acid daily for 12 weeks reduced total blood arsenic levels by 13.6%. The authors stated that taking folic acid to lower blood arsenic levels may help reduce the risk of illnesses that can result from arsenic poisoning.14

Folic acid and anemia

Low blood folate concentrations can lead to anemia in both men and women. There are different types of anemia, and they have a variety of causes. The type of anemia that can be caused by very low blood folate concentrations is called megaloblastic anemia.15 Folic acid helps prevents this type of anemia.

What research shows about folic acid and cancer

Anyone being treated for cancer should consult their doctors before taking any supplements. Supplements (including those with folic acid) can interfere with cancer medications. It is important to discuss all supplements with your healthcare provider.

Research on folic acid and cancer risk

A recent analysis of data from 13 randomized control trials including about 50,000 individuals found no increase or decrease in cancer cases among those taking folic acid. This includes cancers of the large intestine, prostate, lung, breast, and other sites.16

Folic acid and colorectal cancer

A 2007 study investigated the effect of 1,000 mcg of folic acid daily on preventing colorectal adenomas (growths). The study found that people who had recently had colorectal adenomas and were taking folic acid supplements had an increased risk of developing additional adenomas after 6 years of follow-up.17 However, many large studies and a meta-analysis (the results of many studies combined together into a single analysis) has not found a relationship between folic acid supplementation and developing additional colorectal adenomas.18192021

The Centers for Disease Control and Prevention continually monitors the latest research on the effects of folic acid on colorectal cancer.

Print
Content Source:
Folic Acid
  1. De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B, Evans JA, Van den Hof MC, Zimmer P, Crowley M, et al. Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med 2007;357(2):135-42. doi: 10.1056/NEJMoa067103.
  2. De Wals P, Tairou F, Van Allen MI, Lowry RB, Evans JA, Van den Hof MC, Crowley M, Uh SH, Zimmer P, Sibbald B, et al. Spina bifida before and after folic acid fortification in Canada. Birth Defects Res A Clin Mol Teratol 2008;82(9):622-6. doi: 10.1002/bdra.20485.
  3. Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327(26):1832-5.
  4. Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong LY, Gindler J, et al. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999;341(20):1485-90.
  5. Prevention of Neural Tube Defects: Results of the Medical Research Council Vitamin Study. Lancet, 1991:131-7.
  6. Pfeiffer CM, Sternberg MR, Fazili Z, Yetley EA, Lacher DA, Bailey RL, Johnson CL. Unmetabolized Folic Acid Is Detected in Nearly All Serum Samples from US Children, Adolescents, and Adults. J Nutr 2015;145(3):520-31. doi: 10.3945/jn.114.201210.
  7. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am J Clin Nutr 2010;91(6):1733-44. doi: 10.3945/ajcn.2009.28671.
  8. Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B, Selhub J, McTiernan A, Yasui Y, Oral E, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006;136(1):189-94.
  9. Sweeney MR, Staines A, Daly L, Traynor A, Daly S, Bailey SW, Alverson PB, Ayling JE, Scott JM. Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification? BMC Public Health 2009;9:295. doi: 1471-2458-9-295 [pii]10.1186/1471-2458-9-295.
  10. Qi YP, Do AN, Hamner HC, Pfeiffer CM, Berry RJ. The prevalence of low serum vitamin B-12 status in the absence of anemia or macrocytosis did not increase among older U.S. adults after mandatory folic acid fortification. J Nutr 2014;144(2):170-6. doi: 10.3945/jn.113.183095.
  11. Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Chen D, He M, et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA 2015;313(13):1325-35. doi: 10.1001/jama.2015.2274.
  12. Stampfer M, Willett W. Folate supplements for stroke prevention: targeted trial trumps the rest. JAMA 2015;313(13):1321-2. doi: 10.1001/jama.2015.1961
  13. Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc 2016;5(8). doi: 10.1161/JAHA.116.003768.
  14. Gamble MV, Liu X, Slavkovich V, Pilsner JR, Ilievski V, Factor-Litvak P, Levy D, Alam S, Islam M, Parvez F, et al. Folic acid supplementation lowers blood arsenic. Am J Clin Nutr 2007;86(4):1202-9.
  15. Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF, 3rd, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PM, et al. Biomarkers of Nutrition for Development-Folate Review. J Nutr 2015;145(7):1636S-80S. doi: 10.3945/jn.114.206599.
  16. Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J, Manson JE, Hankey GJ, Spence JD, et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet 2013;381(9871):1029-36. doi: 10.1016/S0140-6736(12)62001-7.
  17. Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007;297(21):2351-9.
  18. Wien TN, Pike E, Wisloff T, Staff A, Smeland S, Klemp M. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ open 2012;2(1):e000653. doi: 10.1136/bmjopen-2011-000653.
  19. Carroll C, Cooper K, Papaioannou D, Hind D, Tappenden P, Pilgrim H, Booth A. Meta-analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancer. Aliment Pharmacol Ther 2010;31(7):708-18. doi: 10.1111/j.1365-2036.2010.04238.x.
  20. Baggott JE, Oster RA, Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials. Cancer Epidemiol 2012;36(1):78-81. doi: 10.1016/j.canep.2011.05.003.
  21. Qin X, Cui Y, Shen L, Sun N, Zhang Y, Li J, Xu X, Wang B, Xu X, Huo Y, et al. Folic acid supplementation and cancer risk: A meta-analysis of randomized controlled trials. Int J Cancer 2013. doi: 10.1002/ijc.28038.