Folic acid, also called folate, is involved in DNA and protein synthesis. It has a role in the synthesis of the amino acid methionine which is involved in lipid metabolism. Folic acid has a primary role in systems involved with the transfer of single carbon units to other substances. Such reactions include: purine synthesis, pyrimidine nucleotide synthesis, and the conversion of three amino acids. These conversions include the interconversion of the nonessential amino acids serine and glycine, the catabolism of histidine to glutamic acid, and the conversion of homocysteine to methionine.
Folic acid is absorbed primarily in the proximal third portion of the small intestine. Folate in food is in the form of polyglutamate. Excess glutamates must be split off to make folate absorbable. Approximately one-half of the stored folate is in the liver. Folate is excreted in the urine and bile.
Folic acid deficiency has six major causes:
1) <I>inadequate diet</I> of fresh fruits and vegetables, the consumption of over-processed foods in which the heat has destroyed folate, or alcoholism that is often associated with a poor diet; 2) <I>inadequate absorption</I> due to malabsorption diseases such as gluten-induced enteropathy, tropical sprue, or drugs such as anticonvulsants, barbiturates, ethanol, cholestyramine, or azulfidine; 3) <I>inadequate use</I> by metabolic block due to folic acid antagonistic drugs, enzyme deficiencies, vitamin B12 deficiency, alcohol, ascorbic acid deficiency, and dietary amino acid excess of glycine and methionine; 4) <I>increased requirement</I> due to extra tissue demand by the fetus or malignant tissue, infancy, increased metabolism, and increased *hematopoiesis**; 5) <I>increased excretion</I> due to vitamin B12 deficiency, liver disease, and kidney dialysis; and 6) <I>increased destruction</I> due to excess of antioxidant supplements.
The recommendations for folate have doubled from the 1989 RDA to the 1998 DRI due to the importance of folate in preventing neural tube defects. The current daily recommendations are as follows, 65-80 mcg for infants, 150-200 mcg for children, 300-400 mcg for adolescents, 400 mcg for adults, 600 mcg for pregnant women, and 500 mcg for lactating women. The requirements for folate increase with factors that result in an increased metabolic rate, such as infection and hyperthyroidism, and with conditions in which there is a rapid cell turnover, such as the rapid tissue growth of the fetus or malignant tissue. Requirements are also increased with high alcohol intake.
Primary folate sources include yeast, liver, fresh green vegetables, and fresh fruits such as oranges. Folate is a heat-labile substance that is easily destroyed by cooking, especially in water. Up to 50-90% of folate may be destroyed by cooking.
Folate supplementation is primarily used to prevent neural tube defects. The recommendation for fertile women is 400 mcg and increases to 600 mcg during pregnancy. The Food and Drug Administration has mandated the fortification of grain products with folate. Up to 15 mg of folate per day will not cause toxicity. Very high doses may have a convulsant effect, and a dose of 350 mg per day has been reported to cause zinc deficiency.