Folates are found in foods ranging from their namesake green leafy vegetables to black-eyed peas to beef liver. They’re a family of B vitamins crucial for DNA synthesis and cell division.
“Folate is involved in the production of white and red blood cells,” says Andy Bellatti, MS, RD, a dietitian based in Las Vegas, Nevada. “Low intakes can cause a particular type of anemia (folate-deficiency anemia), which is different from iron-deficiency anemia. Folate also helps prevent spinal cord-related birth defects, which is why it is such an important nutrient for pregnant women.”
Folic acid is a synthetic form of folate, according to the American Pregnancy Association, which is used in supplements and food fortification. Our bodies absorb it more readily than folate, and folic acid is also more shelf-stable.
Preventing neural tube defects
Malformations of the brain and spine such as spina bifida and anencephaly, known as neural tube defects, are more likely to occur in babies whose mothers had folate deficiency in very early pregnancy, according to the Centers for Disease Control and Prevention.
Because the window of vulnerability occurs before many women even know they’re pregnant—and because many pregnancies are unplanned—the U.S. Preventive Services Task Force has recommended since 2009 that every woman of childbearing age take 400-800 micrograms (0.4-0.8 milligrams) of folic acid daily to prevent neural tube defects.
The U.S., Canada, and several other countries now fortify grain-based foods like bread, pasta, and rice with folic acid to provide further protection, according to the National Institutes of Health. Click here for 7 foods high in folic acid and folate.
Who else needs folic acid supplements?
“Most of us consume enough folic acid through a balanced diet, especially since 1998 when foods started being fortified with folic acid,” says Melissa Majumdar, MS, RD, CSOWM, LDN, a dietitian and the metabolic and bariatric coordinator at Emory University Hospital Midtown in Atlanta, Georgia.
Good food sources of folate include asparagus, Brussels sprouts, spinach, and mustard greens; beef and beef liver; fruit and fruit juices, especially oranges; peas, beans, and nuts, according to Majumdar.
Nutrient malabsorption, alcohol use disorder or a limited diet can increase the risk of folate deficiency, she notes. “People taking medication for epilepsy or ulcerative colitis or who have had bariatric surgery should talk to their doctor or registered dietitian nutritionist about having their folic acid levels taken,” she says.
Drugs linked to folate deficiency
Several epilepsy medications can contribute to folate deficiency, and some have been linked to birth defects, says the Epilepsy Foundation. For this reason, folic acid supplements are especially crucial for women with epilepsy. Higher doses of folic acid may be recommended for women who must continue taking anticonvulsant drugs during pregnancy.
Drugs known as folate antagonists work by preventing folate from being converted to its active form, and, unsurprisingly, they’re also associated with folate deficiency. These include the anticancer medications aminopterin and methotrexate; sulfasalazine, used to treat ulcerative colitis; the malaria drug pyrimethamine; triamterene, a diuretic for treating heart failure; and others.
How much is too much?
The risk of getting too much is higher with folic acid versus folate. Like other B vitamins, Majumdar notes, folic acid is soluble in water, and any excess is usually excreted in the urine.
“For adults, 1000 mcg is the established tolerable upper limit,” Majumdar said. “Most multivitamins contain 400 mcg.
“Large amounts of folic acid supplementation without consulting a registered dietitian or doctor could mask a B12 deficiency,” she added. Also known as pernicious anemia, B12 deficiency is easily treatable with injections of the vitamin, but if left untreated can cause permanent nerve damage.
Folate deficiency and anemia
Folate deficiency can lead to macrocytic anemia, in which red blood cells become abnormally enlarged but are low in hemoglobin. Symptoms of folate-deficiency anemia include fatigue, poor appetite, pale skin, and irritability.
U.K. hematologist Lucy Wills discovered that yeast or yeast extract—the British delicacy known as Marmite—could correct macrocytic anemia in pregnant Bombay textile workers, reporting her findings in 1931.
A decade later, chemists at the University of Texas in Austin reported isolating the anti-anemia factor from four tons of spinach. They suggested the name “folic acid,” from the Latin word folium, for leaf.
Mutant gene blunts folate’s effects
About 25 percent of Hispanics, 10 percent of whites and Asians and 1 percent of African Americans have mutations in a gene, MTHFR, that impairs their ability to convert folic acid and folate into their active form, 5-methyltetrahydrofolate (5-MTHF), according to the U.S. National Library of Medicine Genetics Home Reference. The mutations can lead to folate deficiency, and may also increase a woman’s risk of having a child with a neural tube defect.
Taking an 5-MTHF supplement instead of folic acid could be beneficial for some people with MTHFR mutations, Majumdar said. But there is little scientific evidence to back manufacturers’ claims that 5-MTHF is more effective than folic acid for everyone.
What’s a dietary folate equivalent?
“Consumers may notice that nutrition facts labels are switching from the use of micrograms (mcg) to mcg DFEs (dietary folate equivalent),” Majumdar noted. This is meant to reflect the greater bioavailability of folic acid versus folate, she explained. For example, 1 mcg of folate from food is equivalent to 0.6 mcg of folic acid from supplements or fortified foods taken with food, or 0.5 mcg of folic acid supplements taken on an empty stomach.
“Manufacturers are not required to include folate on nutrition facts labels, but if they do, it is listed in DFEs,” she added.
Even though several illnesses have been associated with folate deficiency, including cancer and heart disease, most studies to date haven’t borne out anticancer or heart-healthy benefits for folic acid supplements. But there is consistent evidence that folic acid supplements can lower stroke risk in people with high blood pressure.
One randomized controlled trial—a type of study that’s considered the gold standard for scientific evidence—found that adults with hypertension who’d never had a heart attack or stroke had a 21 percent lower risk of stroke if they took 800 mcg of folic acid daily. The findings were published in the Journal of the American Medical Association.
The authors of the study suggested that “targeted folic acid therapy” for people with higher-risk MTHFR genotypes and low folate levels could help reduce strokes.