Folic Acid
Description
Many substances give rise to folic acid (vitamin B-9). However, the use of the term is limited to pteroylmonoglutamate. Pteroylmonoglutamate is the form from which the active coenzymes are derived. The larger group of substances that give rise to folacin in the body are known as folates.
Folacin plays an essential role in metabolism, in particular in rapidly proliferating cells, such as red blood cells, white blood cells, or cells of the intestinal mucous membrane. Several of folacin's biochemical functions involve blood formation.
Folacin is an important constituent of the enzyme tetrahydrofolic acid which plays a role in the synthesis of various chemical components of DNA and RNA nucleoproteins.
Method of Action
Tetrahydrofolic acid is a folacin enzyme that acts as a carrier for single carbon groups (i.e., methyl groups) from one substance to another. It is of primary importance in the synthesis of purine and pyrimidine bases which are constituents of DNA and RNA.
Tetrahydrofolic acid also plays a role in formation of methionine from its precursor homocystine; in the formation of choline from its precursor ethanolamine; synthesis of histidine and its conversion to glutamic acid.
Folacin is important for the conversion of phenylalanine to tyrosine; the formation of part of the hemoglobin structure; the metabolism of long chain fatty acids in the brain; and the formation of both red blood cells and white blood cells in the bone marrow.
Folacin is absorbed through the upper part of the intestinal tract; this absorption occurs via active transport and diffusion. Vitamin C and various antibiotics facilitate its absorption.
Properties & Uses
Folacin is used in treating nutritional megaloblastic anemia caused by folate deficiency. Folacin is also effective in treating the megaloblastic anemia of pregnancy and infancy. Other anemias, which fail to respond to vitamin B-12, can be treated with folacin.
Additionally, it is useful for relieving symptoms of tropical sprue, such as anemia and gastrointestinal disturbance.
The folacin antagonist aminopterin has been useful in inhibiting the excessive white blood cell production characteristic of the potentially lethal disorder leukemia. Aminopterin tends to interfere with the formation of the active coenzyme necessary for the production of white blood cells.
Folacin supplementation is advised in the treatment of alcoholic patients, due to increased requirements and folacin depletion typical in these individuals. In a study conducted by the Medical Research Council Vitamin Study Research Group it was indicated women, who previously had babies with some type of neural tube defect, who took four milligrams of folic acid daily from the time they began trying to become pregnant through the 12th week of pregnancy reduced the risk of recurrence by 72%.
Consequence of Deficiency
Folacin deficiency is the most common hypovitaminosis of humans, primarily affecting the indigent population of the world. Deficiency symptoms include poor growth, megaloblastic anemia, and other blood disorders, as well as gastrointestinal tract disturbances.
The main consequence of a deficiency of folate is a change in nuclear morphology. These nuclear alterations are termed "megaloblastic" in reference to nucleated red blood cells in the bone marrow. Morphological changes are also noticed in the stomach, small intestine, uterine cervix, and vagina.
Several substances interfere with the normal absorption of folate. Ethanol appears to affect folate metabolism as well as its absorption. Antitumor agents interfere with folate utilization and it has been suggested that anticonvulsants interfere with the absorption of free folacin. Inadequate utilization of folates can be attributed to drugs that interfere with folate metabolism. Some evidence suggests that oral contraceptives alter folate metabolism, as megaloblastic changes occur to the cervicovaginal epithelium. The megaloblastic anemia of scurvy has been associated with defective utilization of folates.
Folacin deficiency primarily occurs in tissues with a high rate of cell proliferation. A high incidence of deficiency of folacin in pregnant women has led the Food and Nutrition Board to recommend that women ingest an additional 400 micrograms per day during pregnancy, on a prescription basis. This supplement should only be given if the woman does not have anemia. Folacin, by correcting the magaloblastic anemia, prevents the diagnosis of pernicious anemia, which itself usually prevents conception. Fetal damage has been associated with a folacin deficiency.
An individual with folacin deficiency is more susceptible to environmental carcinogens. A deficiency of folate promotes the breakage of chromosomes at fragile sites. If the cell cannot synthesize the constituents of DNA, deficiency might prohibit normal differentiation and replication. Furthermore, inadequate folate levels may reduce the production of white blood cells and hinder the body's ability to produce antibodies.
Toxicity Factors
There are no known symptoms of folacin toxicity.
Recommended Dietary Allowance
| age | RDA (mcg) | RNI (mcg) |
| infants/children | ||
| 0-6 months | 25 | 50 |
| 6-12 months | 35 | 50 |
| 1-3 years | 50 | 70 |
| 4-6 years | 75 | 100 |
| 7-10 years | 100 | 150 |
| males | ||
| 11-14 years | 150 | 200 |
| 15+ years | 200 | 200 |
| females | ||
| 11-14 years | 150 | 200 |
| 15+ years | 180 | 200 |
| pregnancy | 400 | 300 |
| lactation | ||
| (1st 6 months) | 280 | 260 |
| (2nd 6 months) | 260 | 260 |
The average American diet contains about 0.6 milligrams of total folacin activity. The adult Recommended Dietary Allowance (RDA) standard of 400 micrograms daily covers variances in need and in the amount of available folacin in foods. There is an increased requirement for folacin during pregnancy and lactation. Physiologic stress, such as occurs in periods of disease and growth, increases the requirement.
For over thirty years, Recommended Daily Amounts has existed in the United Kingdom. It has been used to measure the adequacy of an individual's diet. However, in 1991 the Committee on Medical Aspects of Food Policy (COMA) gave forth a whole new set of figures upon the request of the Department of Health's Chief Medical Officer. Reference Nutrient Intake (RNI) is one of these sets collectively known as "Dietary Reference Values." RNI is an amount of a nutrient that is enough for almost every individuals, even someone who has high needs for the nutrient. This level of intake is, therefore, considerably higher than what most people would need. If individuals are consuming the RNI of a nutrient they are most unlikely to be deficient in that nutrient.
Requirements can vary with individual metabolic rate; hemolytic anemia and hyperthyroidism need higher quantities. Consumption of alcohol also increases the need for folacin.
Naturopathic doctor, J.D. Wallach, N.D. D.V.M. who established values for nutrients first in zoology, regards 1,000 mcg as a more realistic figure.
Food Sources
| Asparagus | Beef (lean) |
| Brewer's yeast | Broccoli |
| Collard greens | Cowpea |
| Beans | Egg |
| Fish | Green leafy vegetables |
| Lentil | Organ meat |
| Wheat |
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