Vitamin B9 (Folic acid) Disease Prevention - Part 1

Pregnancy complications

Neural tube defects: Fetal growth and development is characterized by widespread cell division. Adequate folate is critical because of its roles in DNA and RNA synthesis. Neural tube defects (NTD) result in either anencephaly or spina bifida, which are devastating and sometimes fatal birth defects. The defects occur between the 21^st and 27^th days after conception, a time when many women do not realize they are pregnant. The risk of NTD in the United States prior to fortification of foods with folic acid was estimated to be one per 1000 pregnancies. Results of randomized trials have demonstrated 60% to 100% reductions in NTD cases when women consumed folic acid supplements in addition to a varied diet during the periconceptional period (about 1 month before and 1 month after conception). The results of these and other studies prompted the U.S. Public Health Service to recommend that all women capable of becoming pregnant consume 400 mcg of folic acid daily to prevent NTD. The recommendation was made to all women of childbearing age, because adequate folic acid must be available very early in pregnancy, and because many pregnancies in the U.S. are unplanned. Despite the effectiveness of folic acid supplementation, it appears that less than half of women who become pregnant follow the recommendation. In order to decrease births affected by NTD, the FDA implemented legislation in 1998 requiring the fortification of all enriched grain products with folic acid. The required level of folic acid fortification in the U.S. was estimated to provide 100 mcg of additional folic acid in the average person's diet, though it probably provides more than this, due to overuse of folic acid by food manufacturers.

Other pregnancy complications: Adequate folate status may also prevent the occurrence of other types of birth defects, including certain heart defects and limb malformations. However, the support for these findings is not as consistent or clear as support for NTD prevention. Low levels of dietary folate during pregnancy have also been associated with increased risk of premature delivery and infant low birth weight. More recently, elevated blood homocysteine levels, considered an indicator of functional folate deficiency, have been associated with increased incidence of miscarriage, as well as pregnancy complications like preeclampsia and placental abruption. Thus, it is reasonable to maintain folic acid supplementation throughout pregnancy, even after closure of the neural tube in order to decrease the risk of other problems in pregnancy.

Cardiovascular diseases (heart disease, stroke, and peripheral vascular diseases)

Homocysteine and cardiovascular diseases: The results of more than 80 studies indicate that even moderately elevated levels of homocysteine in the blood increase the risk of cardiovascular diseases. An analysis of the observational studies of blood homocysteine and vascular disease indicated that a prolonged decrease in plasma homocysteine level of only 1 micromole/liter resulted in about a 10% risk reduction. The mechanism by which homocysteine increases the risk of vascular disease remains the subject of a great deal of research, but may involve adverse effects on clotting, arterial vasodilation, and thickening of arterial walls. Although increased homocysteine levels in the blood have been consistently associated with increased risk of cardiovascular diseases, it is not yet clear whether lowering homocysteine levels will reduce cardiovascular disease risk. Consequently, the American Heart Association recommends screening for elevated total homocysteine levels only in "high risk" individuals, for example those with personal or family history of premature cardiovascular disease, malnutrition or malabsorption syndromes, hypothyroidism, kidney failure, lupus, or individuals taking certain medications (nicotinic acid, theophylline, bile acid-binding resins, methotrexate, and L-dopa). Most research indicates that a plasma homocysteine level of < 10 micromoles/liter is associated with a lower risk of cardiovascular disease and a reasonable treatment goal for individuals at high risk.

Folate and homocysteine: Folate-rich diets have been associated with decreased risk of cardiovascular disease. A study that followed 1,980 Finnish men for 10 years found that those who consumed the most dietary folate had only 45% the risk of an acute coronary event when compared with those who consumed the least dietary folate. Of the three vitamins that regulate homocysteine levels, folic acid has been shown to have the greatest effect in lowering basal levels of homocysteine in the blood, when there is no coexisting deficiency of vitamin B₁₂ or vitamin B₆ (see Nutrient interactions). Increasing folate intake through folate-rich foods or supplements has been found to lower homocysteine levels. A supplement regimen of 400 mcg of folic acid, 2 mg of vitamin B₆, and 6 mcg of vitamin B₁₂ has been advocated by the American Heart Association if an initial trial of a folate-rich diet (see Sources) is not successful in adequately lowering homocysteine levels. Although increased folic acid intake has been found to decrease homocysteine levels, it is not presently known whether increasing folic acid intake will result in decreased rates of cardiovascular diseases. However, several randomized placebo-controlled trials are presently being conducted to determine whether homocysteine lowering through folic acid supplementation reduces the incidence of cardiovascular diseases. Since the initiation of fortification of the U.S. food supply with folic acid, blood homocysteine levels in the population have declined.