Vitamin B9 (Folic Acid)
Overview
Folic acid functions with vitamin B12 in many genetic, metabolic, and nervous system processes. Folic acid helps protect against heart disease, birth defects, osteoporosis, and certain cancers. It is vital to DNA and RNA synthesis, and therefore is critical to cell division, maintenance of the genetic code, regulation of cell division, and transfer of inherited characteristics. As many as 15% of people may have a genetic mutation causing higher homocysteine levels. This results in an increased risk for heart disease, and, in women, increased risk of having children with neural tube defects. Folic acid is essential to protein metabolism, notably for its role in reducing homocysteine levels by converting it to methionine.
The Framingham Heart Study (1998) found that folic acid supplementation reduced homocysteine levels by about 25%. In 1998, researchers at the Harvard School of Public Health published data from the Nurses Health Study showing that intake of folic acid and vitamin B6 well above the current RDA reduced the risk of congestive heart disease (CHD) by about 30%. The study tracked 80,082 women over a 14-year period.
Deficiency of folic acid has been linked to several birth defects, including the neural tube defect spina bifida. Up to half of neural tube defects are believed to be preventable if women of childbearing age supplement their diet with folic acid. Adequate intake of folic acid should begin several weeks before and continue through at least the first four weeks of pregnancy. Women who have previously had a child with neural tube defect can reduce the risk of recurrence by about 70% through supplementation with up to 4 mg folic acid per day. Studies suggest that the levels of folic acid necessary to prevent neural tube defects are more easily derived from fortified foods and supplements than from natural food sources alone.
Increased homocysteine concentrations in the blood may also play a role in osteoporosis by interfering with collagen cross-linking, leading to a defective bone matrix. Folic acid helps produce neurotransmitters such as serotonin and dopamine. These regulate brain functions including mood, sleep, and appetite. Correcting folic acid deficiency has reversed mental or psychological symptoms in some, particularly in the elderly. Folic acid exerts a mild antidepressant effect. Supplementation optimizes the effect of the drug Prozac.
At particular risk for folate deficiency are the elderly, alcoholics, psychiatric patients, people taking certain medications, and women taking contraceptive pills. Folic acid is required for the formation of healthy red and white blood cells. Folic acid deficiency causes macrocytic anemia in which the red blood cells are fewer in number, larger in size, and contain less oxygen-carrying hemoglobin than normal cells. Folic acid deficiency may play a role in cancer development, particularly cancers of the cervix, lung, and colon, possibly through its action in DNA synthesis. In a study published in 1996, researchers examined the relationship between folate status and colorectal cancer in male smokers involved in the alpha-tocopherol beta-carotene (ATBC) study. Those with diets higher in folic acid had significantly reduced risk of colon cancer. Low blood levels of folic acid may increase the risk of cervical dysplasia. Low folic acid intake may also contribute to rheumatoid arthritis, constipation, cataracts, headaches, and infertility.
Dietary Sources
Food processing (e.g., boiling, heating) can destroy folic acid. Food stored at room temperature for long periods can also lose its folic acid content.
As of January 1998, commercial grain products have been fortified with 140 mcg of folic acid per 100 g of grain product. This will result in an average increase in folic acid intake of 100 mcg per day.
Constituents/Composition
Folic acid occurs in food in its unactivated form (folate).
B9 supplements are available as both folic acid and folinic acid (5-methyl-tetra-hydrofolate). While folic acid is the more stable compound, folinic acid is the most efficient at raising body stores.
Commercial Preparations
Folic acid is widely available in multivitamin and B-complex preparations. Standard over-the-counter preparations include 400 mcg and 800 mcg tablets. Prescription folic acid is available in 1 mg tablets in packages of 30, 100, 1,000, and UD 100, as injections of 5 mg/ml in 10 vials. Folinic acid is available as 5 mg, 15 mg and 25 mg tablets in 30s, 100s, and UD 50s. Injections (3 mg/ml) are available.
Therapeutic Uses
Dosage Ranges and Duration of Administration
The RDA for folic acid follows.
Side Effects/Toxicology
Folic acid toxicity is rare. High doses (>15 mg) can cause gastrointestinal disturbances, sleep problems, and allergic skin reactions.
Warnings/Contraindications/Precautions
Folic acid supplementation can mask vitamin B12 deficiency. Vitamin B12 deficiency can lead to irreversible neurological damage. Therefore, folic acid supplementation should always include vitamin B12.
High dosage folic acid supplementation should be used with extreme caution in those with epilepsy. It may increase seizure activity.
Interactions
Methotrexate
In a randomized, double-blind, placebo-controlled study, folic acid supplementation (27.5 mg/week for 53 weeks) in 79 patients with rheumatoid arthritis countered the adverse effects of methotrexate without compromising therapeutic efficacy (Morgan et al. 1994).
Tetracycline
In one study, the bioavailability of tetracycline hydrochloride was reduced significantly by concomitant administration of vitamin B complex to healthy subjects (Omray 1981). Patients should be cautioned to take vitamin B complex supplements at different times from tetracycline.
References
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