Folic Acid

Folic acid is a B vitamin needed for cell replication and growth. Folic acid helps form building blocks of DNA, the body’s genetic information, and building blocks of RNA needed for protein synthesis in all cells. Therefore, rapidly growing tissues, such as those of a fetus, and rapidly regenerating cells, like red blood cells and immune cells, have a high need for folic acid. Folic acid deficiency results in a form of anemia that responds quickly to folic acid supplementation.

In 1996, the FDA began to require that all enriched flour, rice, pasta, cornmeal and other grain products contain 140 mcg of folic acid per 100 grams. Among people who do not take vitamin supplements, this amount of food fortification has been associated with increased folic acid levels in the blood and decreased blood levels of homocysteine.

Key uses for Folic Acid 

• Birth defects prevention

• Depression: A deficiency of folic acid can disturb mood; a large percentage of depressed people have low folic acid levels.

• Gingivitis (periodontal disease) (rinse only): A 0.1% solution of folic acid used as a mouth rinse (5 ml taken twice a day for 30 to 60 days) has reduced gum inflammation and bleeding in people with gingivitis in double-blind studies.

• High homocysteine (in combination with vitamin B6 and vitamin B12): Folic acid is needed to keep blood levels of homocysteine (an amino acid by-product) from rising. A growing body of evidence suggests that an elevated homocysteine level is a risk factor for many diseases, especially heart disease. Of the B vitamins with a role in homocysteine metabolism, folic acid appears to be the most important in lowering homocysteine levels for the average person.

• Pap smear (abnormal): Large amounts of folic acid–10 mg per day–have been shown to improve the abnormal Pap smears of women who are taking birth control pills. Folic acid does not improve the Pap smears of women who are not taking oral contraceptives.

• Pregnancy and postpartum support: The requirement for folic acid doubles during pregnancy, while deficiencies of folic acid during pregnancy are associated with low birth weight and an increased incidence of neural tube defects (e.g., spina bifida) in infants. Most doctors, many other healthcare professionals, and the March of Dimes recommend that all women of childbearing age supplement with 400 mcg per day of folic acid. If a woman waits until after pregnancy has been discovered to begin taking folic acid supplements, it will probably be too late to prevent a neural tube defect.

• Schizophrenia: People with schizophrenia may have a greater tendency to be deficient in folic acid than the general population and may show improvement when given supplements.

Other potential uses for Folic Acid

• Anemia (for deficiency): Folic acid deficiency results in a form of anemia that responds quickly to folic acid supplementation. 

• Atherosclerosis and heart attack: While several trials have consistently shown that folic acid lowers homocysteine levels, the amounts used vary from study to study. Many doctors recommend 500–800 mcg of folic acid per day.

• Breast cancer (reduces risk in women who consume alcohol)

• Canker sores (for deficiency only) 

• Celiac disease: The malabsorption that occurs in celiac disease can lead to multiple nutritional deficiencies, including folic acid deficiency.

• Colon cancer (prevention): Folic acid appears to protect against alcohol-induced DNA damage. Increasingly, researchers believe that folic acid may be able to protect against some of the colon cancer-causing effects of alcohol.

• Preeclampsia: In one preliminary study, women with high homocysteine and a previous pregnancy complicated by preeclampsia who supplemented with 5 mg of folic acid and 250 mg of vitamin B6 per day successfully lowered homocysteine levels.

• Sickle cell anemia: Deficiencies of folic acid occur more frequently in people with sickle cell anemia than in others and are a cause of high homocysteine levels. A double-blind study of children with sickle cell anemia found that children given 5 mg per day of folic acid had less painful swelling of the hands and feet compared with those receiving placebo, but blood abnormalities and impaired growth rate associated with sickle cell anemia were not improved. These amounts of folic acid are much higher than is typically used and should only be taken under the supervision of a doctor. In the treatment of sickle cell anemia, folic acid is typically supplemented in amounts of 1,000 mcg daily.

• Ulcerative colitis (UC): Studies have found that people with UC who have been taking folic acid supplements or who have high blood levels of folic acid have a reduced risk of colon cancer compared with other individuals with UC. Individuals with UC who are taking the drug sulfasalazine, which inhibits the absorption of folic acid, are at particularly high risk of developing folic acid deficiency.

Where is it found?

• Beans, leafy green vegetables, citrus fruits, beets, wheat germ, and meat are good sources of folic acid.

How much is usually taken?

• Most doctors recommend that all women who are or who could become pregnant take 400 mcg per day in order to reduce the risk of birth defects. Some doctors also extend this recommendation to other people, as well, in an attempt to reduce the risk of heart disease by lowering homocysteine levels.

• For people who frequently eat grain products, the amount needed to be taken in supplement form may be lowered by approximately 100 mcg per day, because of the FDA’s mandated addition of folic acid to many grain products.

Which form of Folic Acid is best?

• Folate naturally found in food is much less available to the body compared with synthetic folic acid found both in supplements and added to grain products in the United States.

Are there any side effects or precautions?

• Folic acid is not generally associated with side effects. However, folic acid supplementation can interfere with the laboratory diagnosis of vitamin B12 deficiency, possibly allowing the deficiency to progress undetected to the point of irreversible nerve damage. Although vitamin B12 deficiency is uncommon, no one should supplement with 1,000 mcg or more of folic acid without consulting a doctor.

• Folic acid is needed by the body to utilize vitamin B12.

• Proteolytic enzymes and antacids inhibit folic acid absorption. People taking either of these are advised to supplement with folic acid.

• Folic acid–containing supplements may interfere with methotrexate therapy in people with cancer. People using methotrexate for cancer treatment should consult their prescribing doctor before using any folic acid–containing supplements.

• People with rheumatoid or psoriatic arthritis who are taking methotrexate should supplement with relatively large amounts of folic acid in order to reduce the toxicity of the drug. However, a physician should be consulted to determine the proper way to combine folic acid with methotrexate.

• A preliminary study showed that people taking diuretics for at least six months had significantly lower blood levels of folic acid as well as significantly higher levels of homocysteine, compared with people not taking diuretics.

Potential adverse drug interactions

• Chemotherapy (Methotrexate only)

• Medroxyprogesterone (Cycrin®, Depo-Provera®, Provera®): Folic acid may interfere with the drug’s effects.

• Methotrexate (Abitrexate): Folic acid may interfere with the drug’s anticancer effects. However, folic acid is often recommended when methotrexate is being used for rheumatoid arthritis. Consult a physician.

• Piroxicam (Feldene®): Folic acid may interfere with the drug’s effects.

• Sulindac (Clinoril®): Folic acid may interfere with the drug’s effects.