Also indexed as: Folate, Methylfolate, Vitamin B9

What does it do? 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, such as AMP, needed for protein synthesis in all cells. Therefore, rapidly growing tissue, such as a fetus, and rapidly repaired 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.

The requirement for folic acid doubles during pregnancy, while deficiencies of folic acid during pregnancy is associated with low birth weight and an increased incidence of neural tube defects in infants. In one study, women who were at high risk of giving birth to babies with neural tube defects were able to lower their risk by 72% by taking folic acid supplements prior to and during pregnancy. 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. Such supplementation would protect against the formation of neural tube defects during the time between conception and when pregnancy is discovered. Waiting to begin supplementation until pregnancy has been diagnosed may increase the risk of birth defects.

Folic acid is needed to keep homocysteine (an amino acid by-product) levels in blood from rising. A growing body of evidence suggests that an elevated homocysteine level is a risk factor for heart disease and may also be linked to several other diseases. Folic acid and certain other B vitamins function as cofactors for enzymes that can lower homocysteine levels. Research has shown that supplementing with folic acid reduces homocysteine levels. 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.

In 1996, the FDA required 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.

A diet low in folic acid has been associated with a high incidence of pre-cancerous polyps in the colon, suggesting that folic acid may prevent the development of colon cancer. Two studies have shown that reduced folic acid levels are associated with an increase in the incidence of cancer in people with ulcerative colitis and a third study showed the degree of abnormal cell growth decreases as folic acid intake increases. Three large population studies showed that low folic acid intake is associated with an increased risk of colorectal cancer.  

In addition, decreased blood levels of folic acid are associated with an increased risk of colon cancer in women. Long-term supplementation with folic acid from a multivitamin has been found in one large population study to be associated with a reduced risk of colon cancer. However, 15 years of supplementation was necessary before a significant reduction in colon-cancer risk became apparent. In that study, folic acid from dietary sources alone was associated with a modest reduction in the risk of colon cancer.

Total folic acid intake was not associated with overall risk of breast cancer in a preliminary study. However, among women who consumed at least 1.5 alcoholic beverages per day, the risk of breast cancer was highest among those with low folic acid intake. Current use of a multivitamin supplement was associated with a 26% lower breast cancer risk among women who consumed at least 1.5 alcoholic beverages per day, compared to those who never used a multivitamin supplement.

Who is likely to be deficient? Many people do not consume the recommended amount of folic acid. Scientists have found that people with heart disease commonly have elevated blood levels of homocysteine, a laboratory test abnormality often controllable with folic acid supplements. This suggests that many people in Western societies have had a mild folic acid deficiency. In fact, it has been suggested that increasing folic acid intake could prevent an estimated 13,500 deaths from cardiovascular diseases each year.

Folic acid deficiency has also been common in alcoholics, people living at poverty level, those with malabsorption disorders or liver disease, and women taking the birth control pill. Recently, elderly people with hearing loss have been reported to be much more likely to be folic acid deficient than healthy elderly individuals. A variety of prescription drugs including cimetidine, antacids, some anticancer drugs, triamterene, sulfasalazine, and anticonvulsants interfere with folic acid.

Deficiency of folic acid can be precipitated by situations wherein the body requires greater than normal amounts of the vitamin, such as pregnancy, infancy, leukemia, exfoliative dermatitis, and diseases that cause the destruction of blood cells.

The relationship between folic acid and prevention of neural tube defects is partly thought to result from the high incidence of folate deficiency in many societies. To protect against neural tube defects, the U.S. Food and Drug Administration has mandated that some grain products provide supplemental folic acid at a level expected to increase the dietary intake by an average of 100 mcg per day per person. In 1999, scientific evidence began to prove the folic acid added to the U.S. food supply was having positive effects, including a partial lowering of homocysteine levels. As a result of folic acid added to the food supply, fewer Americans will be depleted compared with the past. However, many doctors and the Centers for Disease Control in Atlanta believe that optimal levels of folic acid intake may still exceed the amount now being added to food by several hundred micrograms per day.

How much is usually taken? Many doctors continue to 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, often extending this recommendation to others as well, in an attempt to reduce the risk of heart disease by lowering homocysteine.

Are there any side effects or interactions? 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.

Vitamin B12 deficiencies often occur without anemia (even in people who don’t take folic acid supplements). Some doctors do not know that the absence of anemia does not rule out a B12 deficiency. If this confusion delays diagnosis of a vitamin B12 deficiency, the patient could be injured, sometimes permanently. This problem is rare and should not happen with doctors knowledgeable in this area using correct testing procedures.

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 ask their prescribing doctor before using any folic acid–containing supplements. Until recently, methotrexate was believed to help people with rheumatoid arthritis also by interfering with folic acid metabolism. However, recent research has shown this is not so. In fact, people with rheumatoid arthritis taking methotrexate should supplement large amounts of folic acid. The same now appears to be true for people with severe psoriatic arthritis who are taking methotrexate. However, high levels of folic acid should not be taken without clinical supervision.

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.²⁹

Certain medications may interact with folic acid. Refer to the drug interactions summary for a list of those medications. It is recommended you discuss the use of folic acid and your current medication(s) with your doctor or pharmacist.

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