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Folic Acid

Also indexed as: Folate, Methylfolate, Vitamin B9

Illustration

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.

Where is it found?

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

Folic acid has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings Health Concerns
3Stars

Birth defects prevention

Depression

Gingivitis (periodontal disease) (rinse only)

High homocysteine (in combination with vitamin B6 and vitamin B12)

Pap smear (abnormal) (in women taking oral contraceptives)

Pregnancy and postpartum support

Schizophrenia (for deficiency)

2Stars

Anemia (for thalassemia if deficient)

Atherosclerosis

Breast cancer (reduces risk in women who consume alcohol)

Canker sores (for deficiency only)

Celiac disease (for deficiency only)

Colon cancer (prevention)

Heart attack

Preeclampsia

Sickle cell anemia (for lowering homocysteine levels)

Skin ulcers

Ulcerative colitis

1Star

Alzheimer’s disease

Bipolar Disorder/Manic Depression

Crohn’s disease

Dermatitis herpetiformis (for deficiency)

Diarrhea

Down’s syndrome

Epilepsy

Gingivitis (periodontal disease) (pill)

Gout

HIV support

Lung cancer (reduces risk)

Osteoporosis

Peripheral vascular disease

Psoriasis

Restless legs syndrome

Seborrheic dermatitis

Stroke (for high homocysteine only)

Vitiligo

3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

Many people consume less than 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 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.1

Folic acid deficiency has also been common in alcoholics, people living at poverty level, those with malabsorption disorders or liver disease (e.g., cirrhosis), 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 people.2 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.3

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. As a result of folic acid added to the food supply, fewer Americans will be depleted compared with the past. In 1999, scientific evidence began to demonstrate that the folic acid added to the U.S. food supply was having positive effects, including a partial lowering of homocysteine levels.4 In the same year, however, a report from the North Carolina Birth Defects Monitoring Program suggested the current level of folic acid fortification has not reduced the incidence of neural-tube defects.5 Many doctors and the Centers for Disease Control in Atlanta6 believe that optimal levels of folic acid intake may still be higher than the amount now being added to food by several hundred micrograms per day. A low blood level of folate has also been associated with an increased risk of miscarriage.7

People with kidney failure have an increased risk of folic acid deficiency.8 Recipients of kidney transplants often have elevated homocysteine levels, which may respond to supplementation with folic acid.9 The usual recommended amount of 400 mcg per day may not be enough for these people, however. Larger amounts (up to 2.4 mg per day) may produce a better outcome, according to one double-blind trial.10

Folate deficiency is more prevalent among elderly African American women than among elderly white women.11

Which form is best?

Folic acid 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. Women with a recent history of giving birth to babies with neural tube defects participated in a study to determine which form of folic acid is best absorbed—dietary folic acid or folic acid from supplements.12 They received either orange juice containing 400 mcg of folic acid per day or a supplement containing the same amount. Overall, the supplement folic acid was better absorbed than the folic acid from orange juice.

How much is usually taken?

Many 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 in an attempt to reduce the risk of heart disease by lowering homocysteine levels. Since the FDA mandated addition of folic acid to grain products, many people who eat grains have followed the new recommendation of supplementing only 100 mcg of folic acid per day. However, studies have found that this amount of folic acid is inadequate to maintain normal folate levels in a significant percentage of the groups assessed.13 It now appears that, for pregnant women, supplementing with at least 300 mcg (and optimally 400 mcg) of folic acid per day is sufficient to prevent a folate deficiency, even if dietary intake is low.

Are there any side effects or interactions?

Folic acid is not generally associated with side effects.14 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.15 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 do not 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 inhibit folic acid absorption.16 People taking proteolytic enzymes are advised to supplement with folic acid.

Are there any drug interactions?
Certain medicines may interact with folic acid. Refer to drug interactions for a list of those medicines.

References:

1. Russel RM. A minimum of 13,500 deaths annually from coronary artery disease could be prevented by increasing folate intake to reduce homocysteine levels. JAMA 1996;275:1828–9.

2. Houston DK, Johnson MA, Nozza RJ, et al. Age-related hearing loss, vitamin B-12, and folate in elderly women. Am J Clin Nutr 1999;69:564–71.

3. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency. A Guide for the primary care physician. Arch Intern Med 1999;159:1289–98 [review].

4. Jacques PF, Selhub J, Bostom AG, et al. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999;340:1449–54.

5. Meyer RE, Oakley GP Jr. Folic acid fortification. Lancet 1999;354:2168 [letter].

6. Oakley GP Jr. Eat right and take a multivitamin. N Engl J Med 1998;338:1060–1 [editorial].

7. Nelen WL, Blom HJ, Steegers EA, et al. Homocysteine and folate levels as risk factors for recurrent early pregnancy loss. Obstet Gynecol 2000;95:519–24.

8. Makoff R. Vitamin replacement therapy in renal failure patients. Miner Electrolyte Metab 1999;25:349–51 [review].

9. Bostom AG, Gohh RY, Beaulieu AJ, et al. Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial. Ann Intern Med 1997;127:1089–92.

10. Beaulieu AJ, Gohh RY, Han H, et al. Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients. Arterioscler Thromb Vasc Biol 1999;19:2918–21.

11. Stabler SP, Allen RH, Fried LP, et al. Racial differences in prevalence of cobalamin and folate deficiencies in disabled elderly women. Am J Clin Nutr 1999;70:911–9.

12. Neuhouser ML, Beresford SA, Hickok DE, Monsen ER. Absorption of dietary and supplemental folate in women with prior pregnancies with neural tube defects and controls. J Am Coll Nutr 1998;17:625–30.

13. Bailey L. New standard for dietary folate intake in pregnant women. Am J Clin Nutr 2000;71(Suppl):1304S–7S [review].

14. Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr 1989;50:353–8.

15. Wald NJ, Bower C. Folic acid, pernicious anaemia, and prevention of neural tube defects. Lancet 1994;343:307.

16. Russell RM, Dutta SK, Oaks EV, et al. Impairment of folic acid absorption by oral pancreatic extracts. Dig Dis Sci 1980;25:369–73.

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