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Folate & Folic Acid
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[Folate and folic acid: What is it? | What foods provide folic acid]
[Recommended Daily Allowance | When can Folate & Folic Acid Deficiency Occur?]
[Signs of Folate & Folic Acid Deficiency | Who May Need Folic Acid Supplements]
[Caution About Folic Acid Supplements | Issues and Controversies]
[Table of Food Sources | References]

Folate and folic acid: What is it?
Folate and folic acid are necessary for the production and maintenance of new cells2. This is especially important during periods of rapid cell division and growth such as infancy and pregnancy. Folate and folic acid are needed to make DNA and RNA, the building blocks of cells. Folate and folic acid also help prevent changes to DNA that may lead to cancer3. Both adults and children need folate and folic acid to make normal red blood cells and prevent anemia4.

Folate and folic acid are forms of a water-soluble B vitamin. Folate occurs naturally in food. Folic acid is the synthetic form of this vitamin that is found in supplements and fortified foods1. Folate gets its name from the Latin word "folium" for leaf. 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.

L-Methylfolate - the bioactive form of folic acid

L-methylfolate is the active form of folate in the blood and the only type that can cross the blood-brain barrier. Unfortunately, some people fail to convert folic acid to l-methylfolate, and thus do not receive the full nutritional benefits of folic acid.  When the body does not convert enough folic acid to L-methyl folate, excess levels of homocysteine may accumulate.

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What foods provide folate or folic acid?
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 vitamin5. 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 products6-8. This ruling took effect January 1, 1998, and was specifically targeted to reduce the risk of neural tube birth defects in newborns9. 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 manner.

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What is the Recommended Dietary Allowance for folate and folic acid for adults?
The Recommended Dietary Allowance (RDA) is the average daily dietary intake level that is sufficient to meet the nutrient requirements of nearly all (97 to 98 percent) healthy individuals in each life-stage and gender group 10. The 1998 RDAs for folate and folic acid are expressed in a term called the Dietary Folate and Folic Acid Equivalent. The Dietary Folate and (Folic Acid) Equivalent (DFE) was developed to help account for the differences in absorption of naturally occurring dietary folate and the more bioavailable synthetic folic acid11. The 1998 RDAs for folate expressed in micrograms (mcg) of DFE for adults are10:

Life-Stage

 Men

 Women

Pregnancy Lactation

Ages 19+

400 mcg

400 mcg    

All Ages

 

 

600 mcg 500 mcg
*1 mcg vitamin D + 40 International Units (UI)

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 folate10, 12, 13. However, the folic acid fortification program has increased folic acid content of commonly eaten foods such as cereals and grains, and as a result diets of most adults now provide recommended amounts of folate equivalents14.

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When can folate or folic acid deficiency occur?
A deficiency of folate or folic acid can occur when your need for folate is increased, when dietary intake of folate or folic acid is inadequate, and when your body excretes (or loses) more folate and folic acid than usual. Medications that interfere with your body's ability to use folate or folic acid may also increase the need for this vitamin1, 6, 15 -19. Some situations that increase the need for folate and folic acid include:

  • Pregnancy and lactation (breastfeeding)
  • Alcohol abuse
  • Malabsorption
  • Kidney dialysis
  • Liver disease
  • Certain anemias

Medications can interfere with folate and folic acid 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

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Signs of folate and folic acid deficiency
Signs of folate or 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 disorders1, 20. Women with folate or folic acid 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 and folic acid deficiency. In infants and children, folate and folic acid deficiency can slow growth rate. Some of these symptoms can also result from a variety of medical conditions other than folate or folic acid deficiency. It is important to have a physician evaluate these symptoms so that appropriate medical care can be given.

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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 or folic acid, individuals diagnosed with anemia from folate or folic acid 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 and folic acid 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 defects21. Neural tube defects result in malformations of the spine (spina bifida), skull, and brain (anencephaly)10. 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 conception5, 22, 23. 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 suggested10. The Recommended Dietary Allowance (RDA) for folate equivalents (folic acid) for pregnant women is 600 micrograms folic acid10.

Folate and folic acid deficiency has been observed in alcoholics. A 1997 review of the nutritional status of chronic alcoholics found low folate and folic acid status in more than 50 percent of those surveyed24. Alcohol interferes with the absorption of folate and folic acid and increases excretion of folate and folic acid by the kidney. In addition, many alcohol abusers have poor quality diets that do not provide the recommended intake of folate or folic acid17. 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 and folic acid25,26. Anyone taking anti-convulsants and other medications that interfere with the body's ability to use folate and folic acid should consult with a medical doctor about the need to take a folic acid supplement27-29.

Anemia is a condition that occurs when red blood cells cannot carry enough oxygen. Anemia can result from a wide variety of medical problems, including folate or folic acid deficiency. Folate and folic acid 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 cells4. 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 folate and 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 supplement1.

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Caution about folic acid supplements
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. Intake of supplemental folic acid should not exceed 1,000 micrograms (mcg) per day to prevent folic acid from masking symptoms of vitamin B12 deficiency10.

It is very important for older adults to be aware of the relationship between folate / 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, ask your physician to check your B12 status before you take a supplement that contains folic acid.

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What are some current issues and controversies about folate and folic acid?
[Heart disease | Folate, folic acid and cancer | Folate, folic acid and methotrexate for cancer | Non-cancerous diseases]

Folate, Folic acid and heart disease
A deficiency of folate, folic acid, vitamin B12, or vitamin B6 may increase your level of homocysteine, an amino acid normally found in your blood. There is evidence that an elevated homocysteine level is an independent risk factor for heart disease and stroke30-41. 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 clot36. However, there is currently no evidence available to suggest that lowering homocysteine with vitamins will reduce your risk of heart disease. Clinical intervention trials are needed to determine whether supplementation with folic acid, vitamin B12 or vitamin B6 can lower your risk of developing coronary heart disease.

Folate, Folic acid and cancer
Some evidence associates low blood levels of folate and folic acid with a greater risk of cancer42. Folate and folic acid are involved in the synthesis, repair, and functioning of DNA, our genetic map, and a deficiency of folate or folic acid may result in damage to DNA that may lead to cancer43. Several studies have associated diets low in folate and folic acid with increased risk of breast, pancreatic, and colon cancer44, 45. 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 age44. However, associations between diet and disease do not indicate a direct cause. Researchers are continuing to investigate whether enhanced folate intake from foods or folic acid supplements may reduce the risk of cancer. Until results from such clinical trials are available, folic acid supplements should not be recommended to reduce the risk of cancer.

Folate, Folic acid and methotrexate for cancer
Folate and folic acid are important for cells and tissues that rapidly divide2. Cancer cells divide rapidly, and drugs that interfere with folate or folic acid 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 or folic acid. Unfortunatley, methotrexate can be toxic46-48, 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 methotrexate49. It is not known whether folic acid supplements can help control the side effects of methotrexate without decreasing its effectiveness in chemotherapy50-51. It is important for anyone receiving methotrexate to follow a medical doctor's advice on the use of folic acid supplements.

Folate, 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 disease52. Low doses of methotrexate can deplete folate and folic acid 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 effectiveness53, 54. Anyone taking low dose methotrexate for the health problems listed above should consult with a physician about the need for a folic acid supplement.

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Table of Food Sources for Folate and Folic Acid

Food

International
Units

%DV*

Ready to eat cereal, fortified w/ 100% of the DV, 3/4 c.

400

100

Beef liver, cooked, braised, 3 oz.

185

45

Cowpeas (blackeyes), immature, cooked, boiled, 1/2 c.

105

25

Breakfast cereals, fortified w/ 25% of the DV, 3/4 c.

100

25

Spinach, frozen, cooked, boiled, 1/2 c.

100

25

Great northern beans, boiled, 1/2 c.

90

20

Asparagus, boiled, 4 spears

85

20

Wheat germ, toasted, 1/4 c.

80

20

Orange juice, chilled, includes concentrate, 3/4 c.

70

20

Turnip greens, frozen, cooked, boiled, 1/2 c.

65

15

Vegetarian baked beans, canned, 1/2 c.

60

15

Spinach, raw, 1 c.

60

15

Green peas, boiled, 1/2 c.

50

15

Broccoli, chopped, frozen, cooked, 1/2 c.

50

15

Egg noodles, cooked, enriched, 1/2 c.

50

15
Rice, white, long-grain, parboiled, cooked, enriched, 1/2 c. 45 10
Avocado, raw, all varieties, sliced, 1/2 c. sliced 45 10
Peanuts, all types, dry roasted, 1 oz. 40 10
Lettuce, Romaine, shredded, 1/2 c. 40 10
Tomato juice, canned, 6 oz. 35 10
Orange, all commercial varieties, fresh, 1 small 30 8
Bread, white, enriched, 1 slice 25 6
Egg, whole, raw, fresh, 1 large 25 6
Cantaloupe, raw, 1/4 medium 25 6
Papaya, raw, 1/2 c. cubes 25 6
Banana, raw, 1 medium 20 6
Broccoli, raw, 1 spear (about 5 inches long) 20 6
Lettuce, iceberg, shredded, 1/2 c. 15 4
Bread, whole wheat, 1 slice 15 4
* DV = Daily Value. DVs are reference numbers based on the Recommended Dietary Allowance (RDA). They were developed to help consumers determine if a food contains a lot or a little of a specific nutrient. The DV for folic acid is 400 micrograms (mcg). The percent DV (%DV) listed on the nutrition facts panel of food labels tells adults what percentage of the DV is provided by one serving. Percent DVs are based on a 2,000 calorie diet. Your Daily Values may be higher or lower depending on your calorie needs. Foods that provide lower percentages of the DV also contribute to a healthful diet.

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