FOLIC ACID (folacin, folate)

Folic Acid is a water-soluble vitamin and a member of the B COMPLEX family. Folic acid is essential for cell division (especially in RED BLOOD CELLS and the immune system), for growth and for reproduction. The Reference Daily Intake (RDI) for folic acid is 400 mcg for adults while the RDA (RECOMMENDED DIETARY ALLOWANCE) is 200 mcg for men and 180 mcg for women (who are not pregnant or lactating). Approximately half of women of childbearing age consume less than the RDA for this vitamin.

Folic acid deficiency is one of the most common vitamin deficiencies worldwide, and Americans are likely to eat too little folate containing foods. Specific groups more likely to be folate deficient include: alcoholics; women taking oral contraceptives or who are pregnant; people who rely on convenience foods; and elderly people. A variety of drugs interfere with folic acid uptake and utilization: oral contraceptives, GLUCOCORTICOIDS, barbiturates, ANTACIDS, ASPIRIN, Dilantin for epilepsy, and some anticancer drugs.

Deficiency symptoms include fatigue, sore tongue, mental disturbances, megaloblastic anemia, digestive disturbances and growth problems. Mild folate deficiency that does not cause anemia has been linked to NEURAL TUBE DEFECTS (SPINA BIFIDA), TOXEMIA of pregnancy, some types of CANCER (lung, esophagus, breast, colon) and cervical dysplasia, a precancerous state. Researchers have found that the risk of heart attack and heart disease is greater with low folic acid consumption. The link seems to be HOMOCYSTEINE, a byproduct of the amino acid METHIONINE. High homocysteine levels in blood increases the risk of atherosclerosis, leading to heart attacks and strokes. Homocysteine accumulates with suboptimal folic acid intake and homocysteine possibly injures blood vessels. Most people’s level of homocysteine drops with supplemental folic acid, at least 400 mcg daily. There is yet no clinical study demonstrating that lowering homocysteine levels protects against heart disease.

In the body folate forms an important enzyme helper (COENZYME) called tetrahydrofolate. This coenzyme transfers single-carbon fragments from amino acid breakdown to create building blocks (PURINES and THYMINE) of DNA and RNA. Inadequate supply of these building blocks reduces the rate of DNA synthesis, hence of cell replication. Tetrahydrofolate also plays an important role in recycling METHIONINE, an essential AMINO ACID, from homocysteine. Methionine is required to synthesize CHOLINE (employed in neurotransmitter synthesis to help carry signals between nerve cells) and EPINEPHRINE (a hormone synthesized by adrenal glands to help adapt the body to stress).

Sources of folic acid include dark green leafy vegetables, BEANS (legumes), BROCCOLI, SPINACH, citrus fruits, breakfast cereals, nuts, LIVER, SALMON and whole GRAINS. Cooking and food processing destroy this fragile vitamin. It has not yet been added back to processed foods.

Doses of folic acid in the range of 5 to 10 mg per day may reduce the risk of some kinds of cancer. A randomized, double-blind prevention trial performed in the United Kingdom (Medical Research Council Vitamin Study, 1991) concluded that folic acid supplementation starting before pregnancy can be recommended for women at high risk of having a pregnancy with neural tube defects. The U.S. government recommended that women of childbearing age take 400 mcg of folate daily. The U.S. FDA proposed in 1993 that bread and grain products such as cornmeal, flour, rolls, rice and noodles be fortified with 0.14 mg folic acid per 100 g (3-5 oz) serving, or 40 to 70 mcg per slice of fortified bread. This level is below the amount needed by women.

Folate supplements are not considered to be toxic at the usual therapeutic doses. Huge doses (10 to 20 g per day) may induce convulsions in epileptics. Folate supplementation may mask a VITAMIN B12 deficiency, common in older Americans, and this can lead to nerve damage. Consequently, folate and vitamin B12 are administered together when used therapeutically.

Morrison, H.J., Schaubel, D., Desmeules, M., and Wigler, D.T., “”Serum Folate and Risk of Fatal Coronary Heart Disease,” Journal of the American Medical Association, 275 Uune 26,1996), pp. 1893-96.

Effects of Folic Acid Deficiency on Tumor Cell Biology
Richard F. Branda

Vitamins and Minerals in the Prevention and Treatment of Cancer.
Maryce M. Jacobs, PhD. Ed.

Because folate deficiency affects several important characteristics of tumor cells, inadequate levels of this vitamin may contribute to the progression of malignancies. Studies in mice indicate that folate deficient B16 melanoma cells produce more metastases than folate replete control cells. While the exact mechanism responsible for this enhanced metastatic capacity has not been elucidated, the effect appears to be mediated, at least in part, by the increased genetic instability and membrane adherence of folate deficient cells, rather than by the associated changes in cell size and cell cycle traverse. These experiments indicate that folate deficiency may be an important dietary factor influencing the spread of cancer. Since metastasis formation is a primary determinant of cancer morbidity and mortality, the consequences of folate deficiency require more careful consideration in patients with malignancies.

FOLIC ACID – Reference List