Folate and folic acid are forms of a water-soluble B vitamin. Folate occurs naturally in food, especially leafy green foods. Thus folate gets its name from the Latin word "folium" for leaf. Folic acid is the synthetic form of this vitamin that is found in supplements and fortified foods.

A key observation of researcher Lucy Wills nearly 70 years ago led to the identification of folate as the nutrient needed to prevent the anemia of pregnancy. Dr. Wills demonstrated that the anemia could be corrected by a yeast extract. Folate was identified as the corrective substance in yeast extract in the late 1930s and was extracted from spinach leaves in 1941.

Folate is necessary for the production and maintenance of new cells. This is especially important during periods of rapid cell division and growth--conditions that are especially prevalent when any form of healing or growth is occurring. Thus bodily demands for folate increase during injury, disease, infancy, and pregnancy.

Folate is needed to make DNA and RNA, the building blocks of cells. It also helps prevent changes to DNA that may lead to cancer. Both adults and children need folate to make normal red blood cells and prevent anemia.

What foods provide folate?

Leafy greens such as spinach and turnip greens, dry beans and peas, fortified cereals and grain products, and some fruits and vegetables are rich food sources of folate. Some breakfast cereals (ready-to-eat and others) are fortified with 25 percent or 100 percent of the Daily Value (DV) for folic acid. The table of selected food sources of folate and folic acid suggests dietary sources of this vitamin. In 1996, the Food and Drug Administration (FDA) published regulations requiring the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products. This ruling took effect January 1, 1998, and was specifically targeted to reduce the risk of neural tube birth defects in newborns. Since the folic acid fortification program took effect, fortified foods have become a major source of folic acid in the American diet. Synthetic folic acid that is added to fortified foods and dietary supplements has a simpler chemical structure than the natural form of folate, and is absorbed more easily by the body. After digestion and absorption however, the two forms are identical and function in exactly the same man.

What is the Recommended Dietary Allowance for folate for adults?

The Recommended Dietary Allowance (RDA) is the government’s recommended average daily dietary intake level that is considered sufficient to meet the nutrient requirements of nearly all (97 to 98 percent) healthy individuals in each life-stage and gender group. Unfortunately, for most individuals who prefer optimum health and disease prevention, the RDAs are abysmally low.

The National Health and Nutrition Examination Survey (NHANES III 1988-91) and the Continuing Survey of Food Intakes by Individuals (1994-96 CSFII) indicated that most adults did not consume adequate folate. However, the folic acid fortification program has increased folic acid content of commonly eaten foods such as cereals and grains. Unfortunately, the foods containing folic acid supplementation are junk, processed, and fast foods. The only diet that could come close to providing adequate folic acid would be one comprised predominantly of fresh vegetables, fruit, nuts, seeds, beans and grains.

When can folate deficiency occur?

A deficiency of folate can occur when your need for folate is increased (stress, disease, poor diet, illness, optimum health), when dietary intake of folate is inadequate (i.e., the typical American diet), and when your body excretes (or loses) more folate than usual. Medications that interfere with your body's ability to use folate may also increase the need for this vitamin. Some situations that increase the need for folate include:

• pregnancy and lactation (breastfeeding)
• alcohol abuse
• malabsorption
• kidney dialysis
• liver disease
• certain anemias.

Medications can interfere with folate utilization, including:

• anti-convulsant medications (such as dilantin, phenytoin, and primidone)
• Metformin (sometimes prescribed to control blood sugar in type 2 diabetes)
• Sulfasalazine (used to control inflammation associated with Crohn's disease and ulcerative colitis)
• Triamterene (a diuretic)
• Methotrexate.

  Signs of folate deficiency: Signs of folic acid deficiency are often subtle. Diarrhea, loss of appetite, and weight loss can occur. Additional signs are weakness, sore tongue, headaches, heart palpitations, irritability, and behavioral disorders (1, 20). Women with folate deficiency who become pregnant are more likely to give birth to low birth weight and premature infants, and infants with neural tube defects. In adults, anemia is a sign of advanced folate deficiency. In infants and children, folate deficiency can slow growth rate. Some of these symptoms can also result from a variety of medical conditions other than folate deficiency. It is important to have a physician evaluate these symptoms so that appropriate medical care can be given.

  Who may need extra folic acid to prevent a deficiency? Women of childbearing age, people who abuse alcohol, anyone taking anti-convulsants or other medications that interfere with the action of folate, individuals diagnosed with anemia from folate deficiency, and individuals with malabsorption, liver disease, or who are receiving kidney dialysis treatment may benefit from a folic acid supplement.

  Folic acid is very important for all women who may become pregnant. Adequate folate intake during the periconceptual period, the time just before and just after a woman becomes pregnant, protects against a number of congenital malformations including neural tube defects (21). Neural tube defects result in malformations of the spine (spina bifida), skull, and brain (anencephaly). The risk of neural tube defects is significantly reduced when supplemental folic acid is consumed in addition to a healthful diet prior to and during the first month following conception. Women who could become pregnant are advised to eat foods fortified with folic acid or take supplements in addition to eating folate-rich foods to reduce the risk of some serious birth defects. Taking 400 micrograms of synthetic folic acid daily from fortified foods and/or supplements has been suggested. The Recommended Dietary Allowance (RDA) for folate equivalents for pregnant women is 600 micrograms.

  Folate deficiency has been observed in alcoholics. A 1997 review of the nutritional status of chronic alcoholics found low folate status in more than 50 percent of those surveyed. Alcohol interferes with the absorption of folate and increases excretion of folate by the kidney. In addition, many alcohol abusers have poor quality diets that do not provide the recommended intake of folate. Increasing folate intake through diet, or folic acid intake through fortified foods or supplements, may be beneficial to the health of alcoholics.

  Anti-convulsant medications such as dilantin increase the need for folate. Anyone taking anti-convulsants and other medications that interfere with the body's ability to use folate should consult with a medical doctor about the need to take a folic acid supplement.

  Anemia is a condition that occurs when red blood cells cannot carry enough oxygen. It can result from a wide variety of medical problems, including folate deficiency. Folate deficiency can result in the formation of large red blood cells that do not contain adequate hemoglobin, the substance in red blood cells that carries oxygen to your body's cells. Your physician can determine whether an anemia is associated with folate deficiency and whether supplemental folic acid is indicated.

  Several medical conditions increase the risk of folic acid deficiency. Liver disease and kidney dialysis increase excretion (loss) of folic acid. Malabsorption can prevent your body from using folate in food. Medical doctors treating individuals with these disorders will evaluate the need for a folic acid supplement.

  Cautions: Beware of the interaction between vitamin B12 and folic acid. Folic acid supplements can correct the anemia associated with vitamin B12 deficiency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B12 deficiency. Permanent nerve damage can occur if vitamin B12 deficiency is not treated. Whenever intake of supplemental folic acid exceeds 1,000 micrograms (mcg) per day, supplemental B12 (1000-10,000 mcg. per day) should be taken as well, to prevent folic acid from masking symptoms of vitamin B12 deficiency.

  It is very important for older adults to be aware of the relationship between folic acid and vitamin B12 because they are at greater risk of having a vitamin B12 deficiency. If you are 50 years of age or older, make sure you are also taking B-12 if you take a supplement that contains folic acid.

  Current issues about folate:

  Folic acid and heart disease

  A deficiency of folate, vitamin B12, or vitamin B6 may increase your level of homocysteine, an amino acid normally found in your blood. An elevated homocysteine level is an independent risk factor for heart disease and stroke. The evidence suggests that high levels of homocysteine may damage coronary arteries or make it easier for blood clotting cells called platelets to clump together and form a clot.

  Folic acid and cancer

  Low blood levels of folate are associated with a greater risk of cancer. Folate is involved in the synthesis, repair, and functioning of DNA, our genetic map, and a deficiency of folate may result in damage to DNA that may lead to cancer. Several studies have associated diets low in folate with increased risk of breast, pancreatic, and colon cancer. Findings from a study of over 121,000 nurses suggested that long-term folic acid supplementation (for 15 years) was associated with a decreased risk of colon cancer in women aged 55 to 69 years of age. Researchers are continuing to investigate which cancers are prevented by enhanced folate intake. Until research is complete, since it is harmless, folic acid supplements should be recommended to reduce the risk of cancer.

  Folic acid and methotrexate for cancer Folate is important for cells and tissues that rapidly divide. Cancer cells divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer. Methotrexate is a drug often used to treat cancer because it limits the activity of enzymes that need folate. Unfortunatley, methotrexate can be toxic, producing side effects such as inflammation in the digestive tract that make it difficult to eat normally. Leucovorin is a form of folate that can help "rescue" or reverse the toxic effects of methotrexate.

  Folic acid and methotrexate for non-cancerous diseases

  Low dose methotrexate is used to treat a wide variety of non-cancerous diseases such as rheumatoid arthritis, lupus, psoriasis, asthma, sarcoidoisis, primary biliary cirrhosis, and inflammatory bowel disease. Low doses of methotrexate can deplete folate stores and cause side effects that are similar to folate deficiency. Both high folate diets and supplemental folic acid may help reduce the toxic side effects of low dose methotrexate without decreasing its effectiveness. Anyone taking low dose methotrexate for the health problems listed above should consult with a physician about the need for a folic acid supplement.

  This information was based on a fact sheet developed by the Clinical Nutrition Service, Warren Grant Magnuson Clinical Center, National Institutes of Health (NIH), Bethesda, MD, in conjunction with the Office of Dietary Supplements (ODS) in the Office of the Director of NIH. The mission of ODS is to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, disseminating research results, and educating the public to foster an enhanced quality of life and health for the U.S. population.