Folate: Benefits, Dosage, and Safety

What folate is

Folate is a water-soluble B vitamin naturally present in some foods, added to others, and available as a dietary supplement. "Folate" is the generic term covering naturally occurring food folates (in the tetrahydrofolate, or THF, polyglutamate form), folic acid (the fully oxidized monoglutamate form used in fortified foods and most supplements), and 5-MTHF (methylfolate). It was formerly known as folacin and is sometimes called vitamin B9. Total body content is estimated at 15 to 30 mg, about half stored in the liver.

What it does

• Acts as a coenzyme or cosubstrate in single-carbon transfers for the synthesis of nucleic acids (DNA and RNA)
• Supports the metabolism of amino acids, including the conversion of homocysteine to methionine in the synthesis of S-adenosyl-methionine, an important methyl donor
• Enables the methylation of deoxyuridylate to thymidylate in DNA formation, which is required for proper cell division
• Adequate maternal folate before and during early pregnancy supports normal neural tube development

How much folate per day

These are population reference values from the NIH and the Dietary Reference Intakes. They are targets for healthy people, not personal prescriptions. The last column is the Tolerable Upper Intake Level, the most you should get from all sources combined.

Deficiency and who is at risk

Megaloblastic anemia (large, abnormally nucleated red blood cells) is the primary clinical sign, with symptoms of weakness, fatigue, difficulty concentrating, irritability, headache, heart palpitations, and shortness of breath. Deficiency can also cause soreness and shallow ulcerations on the tongue and oral mucosa, changes in skin, hair, or fingernail pigmentation, gastrointestinal symptoms, and elevated blood homocysteine. Isolated folate deficiency is uncommon in the United States; it usually coexists with other nutrient deficiencies linked to poor diet, alcohol use disorder, and malabsorptive disorders. Insufficient maternal folate raises the risk of neural tube defects and is associated with low infant birth weight, preterm delivery, and fetal growth retardation.

Who may need more

• Women and teen girls who could become pregnant (400 mcg folic acid daily from supplements, fortified foods, or both, in addition to dietary folate, to reduce neural tube defect risk)
• Pregnant women and teens (RDA rises to 600 mcg DFE per day)
• Breastfeeding women and teens (RDA 500 mcg DFE per day)
• People with alcohol use disorder
• People with malabsorptive disorders (celiac disease, inflammatory bowel disease, tropical sprue)
• People with an MTHFR C677T gene variant, who may use 5-MTHF more easily (though those who could become pregnant should still take folic acid, not 5-MTHF)

Food sources

Beef liver (braised, 3 oz: 215 mcg DFE), boiled spinach (1/2 cup: 131 mcg), black-eyed peas (1/2 cup: 105 mcg), fortified breakfast cereals (25% DV: 100 mcg), enriched white rice (1/2 cup: 90 mcg), asparagus (4 spears: 89 mcg), brussels sprouts (1/2 cup: 78 mcg), enriched spaghetti (1/2 cup: 74 mcg), romaine lettuce, avocado, broccoli, mustard greens, kidney beans, and orange juice. Folic acid is added to enriched bread, flour, cornmeal, pasta, and rice, to fortified breakfast cereals, and to fortified corn masa flour.

Forms and absorption

Folic acid is the most common supplement and fortification form (fully oxidized monoglutamate). 5-MTHF (also called L-methylfolate, L-5-MTHF, or methylfolate) is also available and may be better used by people with an MTHFR C677T variant. Bioavailability: about 85% of supplemental folic acid is bioavailable when taken with food, and nearly 100% when taken on an empty stomach, versus about 50% for folate naturally present in food. Because of this, intakes are expressed as dietary folate equivalents (DFE): 1 mcg DFE = 1 mcg food folate = 0.6 mcg folic acid from fortified food or supplements taken with food = 0.5 mcg folic acid taken on an empty stomach. The bioavailability of 5-MTHF is the same as or greater than folic acid, but formal mcg-to-mcg DFE conversion factors for 5-MTHF have not been established (FDA allows a conversion factor up to 1.7). Common adult supplement doses are 680 to 1,360 mcg DFE (400 to 800 mcg folic acid); children's multivitamins commonly provide 340 to 680 mcg DFE (200 to 400 mcg folic acid).

Safety, excess and interactions

Too much

Folate naturally present in food and beverages is not harmful. Risks are associated with high intakes of synthetic folic acid from supplements and fortified foods. High folic acid intake can mask (hide) a vitamin B12 deficiency by correcting the megaloblastic anemia while allowing the neurological damage from B12 deficiency to progress, potentially causing permanent damage to the brain, spinal cord, and nerves; large doses might also worsen symptoms of B12 deficiency. High doses of folic acid (above the adult upper limit of 1,000 mcg) may increase the risk of colorectal cancer and possibly other cancers in some people, and might accelerate progression of established cancers, so caution is advised especially for people with a history of colorectal adenomas. Excess folic acid can also exceed the body's capacity to metabolize it, leaving unmetabolized folic acid in the blood, whose biological significance is not fully clear.

Interactions to know

• Methotrexate (Rheumatrex, Trexall): folate supplements can interfere with methotrexate when it is used to treat cancer (methotrexate inhibits dihydrofolate reductase); patients should consult their provider before supplementing.
• Antiepileptic / antiseizure medications, such as phenytoin (Dilantin), carbamazepine (Carbatrol, Tegretol, Equetro, Epitol), and valproate (Depacon): these can reduce blood levels of folate, and folate supplements can in turn reduce blood levels of these medications.
• Sulfasalazine (Azulfidine), used for ulcerative colitis: inhibits intestinal folate absorption and can cause folate deficiency.

How status is measured

Folate status is measured with serum folate (a value above 3 ng/mL indicates adequacy, but it is sensitive to recent intake) and erythrocyte (red blood cell) folate, which reflects longer-term status (above 140 ng/mL indicates adequacy). Plasma homocysteine is used as a functional indicator (it rises when folate is inadequate) but is not highly specific because it is also affected by kidney function and vitamin B12 and other micronutrient deficiencies; common elevated-homocysteine cutoffs are 12 to 16 micromol/L.

Regulated by the FDA as a dietary supplement ingredient under DSHEA, not as a drug; supplements are not FDA-approved to diagnose, treat, cure, or prevent disease. The FDA sets the Daily Value (DV) for folate at 400 mcg DFE for adults and children age 4 and older and requires folate to be listed in mcg DFE (with added folic acid also listed in mcg). Since January 1998 the FDA has required fortification of enriched grain products with 140 mcg folic acid per 100 g, and since 2016 has permitted voluntary addition of up to 154 mcg folic acid per 100 g to corn masa flour.

What the evidence supports

We grade the strength of evidence behind each common reason people take folate, mirroring how the NIH describes it.