Micronutrients: Folate

Micronutrients: Folate
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A water soluble B vitamin also known as B9 and folacin, folate is a naturally occurring nutrient in foods, while folic acid is the synthetic form found in enriched foods and dietary supplements.

Folate is best known for its role in the prevention of neural tube defects, which are birth defects of the brain and spine, specifically anencephaly and spina bifida. Folate also is an essential nutrient for enzyme reactions in protein and vitamin metabolism, as well as DNA and RNA synthesis.

Roles in health
In addition to reducing the risk of NTDs, folate is crucial in decreasing the risk of pregnancy complications including anemia, preterm birth, congenital heart defects and oral clefts.

Although folate is vital early in pregnancy during rapid cell division, growth and development, approximately 35 percent of non-pregnant women do not meet dietary intake recommendations of folate without the use of dietary supplements.

Trials show roughly 90 percent of NTDs and 40 percent of congenital heart anomalies are preventable when women of childbearing age supplement with 400 to 800 micrograms of folic acid for four weeks pre-conception and eight weeks post-conception. Timing is critical, as neural tube defects occur in the first few weeks of pregnancy.

In 1998, the U.S. Food and Drug Administration mandated folic acid fortification of enriched grain products to reduce NTDs. In 2016, the FDA approved the voluntary inclusion of corn masa flour to help Latinas who have a higher prevalence of NTDs. Folic acid fortification of grains has prevented NTDs in approximately 1,300 babies each year, and NTDs in the U.S. have declined by 35 percent since 1998.

Folate, along with vitamins B6 and B12, has been studied for its protective role in age-related cognitive decline with mixed results. Inadequate folate consumption may increase dementia.

There also may be an association between low blood folate levels and depression and response to antidepressant medication, but more research is needed to understand the relationship.

Folic acid supplementation can impact levels of homocysteine, an amino acid in the blood that, when high, is a risk factor for heart disease. However, folic acid’s role in reducing the risk of cardiovascular disease is unproven.

Current recommendations
Many organizations including the U.S. Preventive Services Task Force recommend women consume a supplement with a minimum of 400 to 800 micrograms of folic acid if they are capable of becoming pregnant. In 2017, after a thorough review of the literature, the USPSTF confirmed this recommendation. Women with a history of NTDs are advised to supplement with 4,000 micrograms of folic acid, in addition to folate from a varied diet.

Life Stage Recommended Amount Tolerable Upper Limit
Birth to 6 months* 65mcg DFE
Infants 7-12 months* 80mcg DFE
Children 1-3 years 150mcg DFE 300mcg
Children 4-8 years 200mcg DFE 400mcg
Children 9-13 years 300mcg DFE 600mcg
Teens 14-18 years 400mcg DFE 800mcg
Adults 19+ years 400mcg DFE 1,000mcg
Pregnancy 600mcg DFE 800mcg (14-18 years):
1,000mcg (19+ years)
Breast-feeding 500mcg DFE 800mcg (14-18 years);
1,000mcg (19+ years)
*Adequate Intake

 


 

Food sources mcg/serving Rating
3 ounces braised beef liver 215mcg Excellent
½ cup boiled black-eyed peas 105mcg Excellent
½ cup boiled Brussels sprouts 78mcg Excellent
½ cup sliced raw avocado 59mcg Good
1 cup raw spinach 58mcg Good
½ cup frozen chopped broccoli, cooked 52mcg Good
½ cup canned kidney beans 46mcg Good

The recommended dietary allowance is in dietary folate equivalents, or DFE, because folic acid in supplements and fortified foods is more easily absorbed (1 microgram DFE equates to 1 microgram folate and 0.5 to 0.6 microgram folic acid). Bioavailability of supplemental folic acid is 100 percent when consumed on an empty stomach and 85 percent when consumed with food, while the bioavailability of folate from food sources is estimated to be about 50 percent.

Sources of folate and folic acid
Folate occurs naturally in a variety of foods, and many foods are fortified with folic acid. Folic acid is available in multivitamins, prenatal vitamins, singularly and in B-complex dietary supplements.

Signs of deficiency
Folate deficiency is rare in the United States, but can be caused by inadequate dietary intake, alcoholism, smoking and conditions that alter nutrient absorption. People with the MTHFR genetic polymorphism are unable to convert folate to the active form.

Signs of deficiency include sores in the mouth and changes in skin color, hair and fingernails. Inadequate intake of folate or vitamin B12 can result in megaloblastic anemia with symptoms including fatigue, weakness and shortness of breath.

Toxicity
Toxicity could result by exceeding the UL with folic acid supplements. High doses of folic acid supplements could lead to un-metabolized folic acid and may mask pernicious anemia, in which the body cannot properly absorb vitamin B12.

Potential drug interactions
Folic acid supplements may interfere with methotrexate, reduce blood levels of anti-epileptic and anti-seizure medications, and lower serum folate levels. Sulfasalazine, used for ulcerative colitis, and cholesterol-lowering agents may impair folate absorption and cause deficiency.

Bottom line
Diet alone may not provide adequate folate for women of reproductive age. Those women should eat a folate-rich diet and take folic acid supplements at least one month before conception and continuing throughout pregnancy.

References

Agnew-Blais, J. et al. Folate, Vitamin B6 and Vitamin B12 Intake and Mild Cognitive Impairment and Probable Dementia in the Women’s Health Initiative Memory Study. J Acad Nutr Diet. 2015 Feb; 115(2): 231–241.
Bailey R, Pac S, Fulgoni V. Estimation of Total Usual Dietary Intakes of Pregnant Women in the United States. Published June 21, 2019. Accessed August 27, 2019.
Czeizel AE, Dudas I, Vereczkey A, Banhidy F. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects. Nutrients. 2013;5(11):4760-4775.
Final Recommendation Statement: Folic Acid for the Prevention of Neural Tube Defects: Preventative Medication. U.S. Preventive Services Task Force website. Published January 10, 2017. Accessed August 27, 2019.
Finer LB, Zolna MR. Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception. 2011;84(5):478-485.
Folate – Fact Sheet for Health Professionals. National Institutes of Health Office of Dietary Supplements website. Updated July 19, 2019. Accessed August 27, 2019.
Greenberg JA, Bell SJ, Guan Y, Yu YH. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol. 2011;4(2):52–59.
Halsted CH, et al. Metabolic interactions of alcohol and folate. J Nutr. 2002;132(8 Suppl):2367S-2372S.
Institute of Medicine, Food and Nutrition Board, authors. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.
Micronutrient Information Center: Folate Summary. Oregon State University Linus Pauling Institute website. Updated 2014. Accessed August 27, 2019.
Mitchell, Laura E. The US Preventive Services Task Force Statement on Folic Acid Supplementation in the Era of Mandatory Folic Acid Fortification editorial. JAMA. 2017;317(2):183-189.
Pfeiffer CM, et al. Dietary supplement use and smoking are important correlates of biomarkers of water-soluble vitamin status after adjusting for sociodemographic and lifestyle variables in a representative sample of US adults. J Nutr. 2013;143(6):957S-965S.
Pitkin RM. Folate and neural tube defects. Am J Clin Nutr. 2007;85:285S–288S.
Roberts, E., Carter, B., & Young, A. H. . Caveat emptor: Folate in unipolar depressive illness, a systematic review and meta-analysis. J Psychopharmacol. 2018;32(4), 377–384.
Rossi RE, Whyand T, Murray CD, et al. The role of dietary supplements in inflammatory bowel disease: a systematic review. Eur J Gastroenterol Hepatol. 2016;28:1357-64.
Shiliang Liu, K.S. et al Joseph, Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes Clinical Perspective. Circulation, 2016; 134 (9): 647.
Tinker SC, et al. Folic acid intake among U.S. women aged 15-44 years, National Health and Nutrition Examination Survey, 2003-2006. Am J Prev Med. 2010;38(5):534-542.
Williams J, et al; Centers for Disease Control and Prevention. Updated estimates of neural tube defects prevented by mandatory folic acid fortification—United States, 1995-2011. Morb Mortal Wkly Rep. 2015;64(1):1-5.

Kathleen Zelman
Kathleen Zelman, MPH, RDN, is the nutrition director of WebMD.