Folate is a generic term used to describe a number of water-soluble, B-complex compounds, the most common of which is folic acid. This vitamin is an essential component in numerous, critical biochemical reactions involving cell growth and function, and the synthesis of amino acids, and DNA (deoxyribonucleic acid), the vital building-blocks of the genetic code.
      Among folate’s more important biochemical reactions is its involvement in the conversion of homocysteine to methionine. In a manner similar to vitamin B6 and vitamin B12 in this regard, the lowering of homocysteine levels is an important factor in the potential reduction of risk in heart disease.

      The most recent National Academy of Sciences Dietary Reference Intakes Study for folate has suggested a daily requirement similar to the current U.S. Food and Drug Administration’s (FDA) RDI of 400 mcg, with several new, important qualifications, especially for pregnant women or those planning a pregnancy. The new recommendations are summarized by age and gender group in the following table.

      Natural, dietary sources of this vitamin, most often referred to as food folate, are found in the greatest concentrations in such foodstuffs as dark green leafy vegetables (spinach, etc.), liver (esp. chicken), fortified cereals, whole grains, beans (esp. lentils), citrus and other fruits, nuts and seeds.
      Folate is such an important dietary component, particularly for women of child bearing age, that breads, cereals, pasta, and other grain-based foods have been fortified with this vitamin by law in the U.S. since 1998.

      Folate deficiency is most commonly caused by inadequate dietary intake, and has been associated with numerous maladies, the most common of which is macrocytic anemia (decreased oxygen carrying capacity of the blood due to malformation of red blood cells), the symptoms of which include general weakness, fatigue, irritability and shortness of breath, degrees of which vary with the severity of the anemia. Symptoms of such a general nature can, of course be the result of numerous other causes.
      Among other important effects associated with folate deficiency are neural tube defects (see Current Issues: NTDs below), and increased risk of cardiovascular disease from a rise in blood homocysteine levels (Current Issues: Cardiovascular disease).
      Folate deficiency has also been observed in chronic alcoholics, primarily as the result of inadequate dietary intake and perhaps, but to a lesser degree, from intestinal malabsorption of the vitamin itself. Similar reports have suggested that smokers can also suffer folate deficiency but, here again, the cause appears to be the result of inadequate intake rather than a specific inhibitory effect from smoking itself.
      Although less common, dietary deficiency has also been reported from various folate-drug interactions. If you are taking any of the following prescription or over-the-counter drugs, it would be a good idea to check with your health care provider about any possible need for folic acid supplementation: phenobarbital, methotrexate, diphenylhydantoin (phenytoin, Dilantin), pyrimethamine, trimethoprim, triamterene, trimetrexate, sulfasalazine, or very large doses (4000 mg/day+) of common anti-inflammatory agents such as acetaminophen, ibuprofen and aspirin.

      Dietary supplements containing folate are usually in the form of folic acid, a very stable, synthetic form of this vitamin which is more readily absorbed than food sources of folate. In fact, as much as twice the amount of this vitamin is absorbed from fortified foods and supplemental sources as folic acid, than for equal amounts consumed from dietary sources as food folate.
      It is for this reason that individuals whose dietary intake of food folate is inadequate, and particularly women of child bearing age who are anticipating a pregnancy, should seriously consider folic acid supplements.

      Generally speaking, individuals who consume large amounts of folate as part of a normal diet, including foods that have been fortified with folate, are reasonably safe from any ill-effects. Several studies have reported that large amounts of supplemental folate added to the diet resulted in such varied effects as neurological problems, hypersensitivity, and even some types of cancer. For the most part, however, these reports have not been corroborated and supplemental folate can not be singled out as a causative effect.
      It has been demonstrated that severe, or prolonged vitamin B12 deficiency can result in neurological defects, in some cases leading to irreversible dementia. In connection with this condition, it has also been shown that excessive supplemental folate can precipitate, obscure, or even mask vitamin B12 deficiency, making the latter difficult to diagnose, and thereby worsening its damaging effect. Anyone at risk of vitamin B12 deficiency should be cautious when considering large dosages of supplemental folate.
      In consideration of the preceding, the recent National Academy of Sciences Dietary Reference Intakes study for folate has recommended Tolerable Upper Intake Levels (UL) for this nutrient, which are listed in the Reference Values table above.

      Neural tube defects (NTDs). Numerous studies have repeatedly shown that inadequate intake of folate has a significant potential for resulting in neural tube defects in first trimester fetuses. The period from one month prior to conception to one month after conception appears to be the most critical time during which women should ensure adequate intake of this vitamin. While inconsistencies in the reports remain, as to the extent that intake of food folate vs. supplemental folate will help to reduce the risk of NTDs in this regard, there is sufficient evidence to recommend supplemental folic acid to a proper dietary intake of food folate (Reference Daily Intake). The evidence is strong enough, in fact, that the U.S. Food and Drug Administration (FDA) has mandated that food manufacturers in the U.S. fortify certain grain based products with folic acid (Food Sources).
      NTDs are defects in the development of the central nervous system of post-conception embryos which are manifested in a number of related birth defects, some of which can be fatal. There are some forms of NTDs that are congenital, and typically not preventable by adequate intake of dietary and supplemental folate.

      Cardiovascular disease. The relationship between certain forms of cardiovascular disease and high levels of homocysteine has been demonstrated in numerous studies dating back to the 1970s. The risk of coronary heart disease, for example, has repeatedly been shown to be greater in the presence of high homocysteine levels, even in the absence of tobacco smoking.
      Although there are congenital causes of homocystinuria (high levels of homocysteine) that are not related to diet, it has been well documented that folate deficiency can, and does lead to markedly elevated levels of homocysteine which, in turn, increases the risk potential of coronary heart disease.
      Although not all studies exactly agree, there appears to be a level of folate intake above which homocysteine concentration is no longer depleted. In other words, as to folate intake, more may not be better in the reduction and management of high homocysteine levels, and that a moderate level of folate supplementation may be more effective in this regard. As is always the case in studies of this nature, there exists the possibility that the effects seen may not be due to folate intake alone, but also the result of lifestyle differences, as well as dietary and supplemental sources of other compounds in the subjects tested. Although not absolute by any means, there are increasing indications that supplemental folate may contribute significantly to the risk reduction of at least some forms of vascular disease. An additional factor that appears relatively certain, is that vitamin B6 and vitamin B12 also contribute to the reduction of homocysteine levels and likely play a significant role in the reduction of risk of heart disease as well.
      In consideration of the relatively minor degree to which health risks can be associated with the use of supplemental folic acid, the recent National Academy of Sciences Dietary Reference Intakes study has suggested a Tolerable Upper Intake Level of folate of 1000 mcg for adults (see Reference Daily Intake table).

      Cancer. There have been numerous studies that have evaluated the potential effects of folate supplementation on the reduction of some forms of cancer. The results of this work are by no means as clear as the relationship that has been established between folate and NTDs or cardiovascular disease, but suggest that this avenue of pursuit certainly has some merit.
      One of the reports indicated that the effect of supplemental folate was better associated with the reduction of a cancerous disease process in individuals already predisposed to the disease, rather than as a preventative measure alone and, that folate deficiency did not, in itself, pose the potential as a carcinogenic effect. Other reports have demonstrated that a potential reduction of certain forms of cancer growth (bronchial and cervical, to be specific) was possible, but either the results could not be corroborated in subsequent studies or the amount of supplemental folate required to effect the results was excessive and might pose other, unrelated hazards. Still other reports relating to the reduction of colon and rectal cancer also showed promising results but, as before, the true significance of this work is somewhat premature to assess with the confidence necessary to establish a causal relationship with folate supplementation.

      Psychiatric and mental disorders. The possible relationship between folate intake and mental disorders is not new, and reports continue to suggest that folate deficiency can be linked to mood disorders and other changes in mental function. This relationship is often difficult to assess due to similar effects reported for vitamin B12 deficiency, and potential masking effect each of these has upon the other. This is not to suggest that folate supplementation functions as a mood enhancer, only that certain biochemical processes required for proper neurological function are folate dependent. The direct relationship between this vitamin and normal mental function is difficult to assess at best, and a great deal more work in this area will likely be forthcoming.

      Dietary fiber intake. It has been suggested that dietary fiber intake, particularly at higher levels, has an inhibitory effect on dietary folate absorption and utilization. Over all, the experimental data do not support this contention. One report did indicate that certain forms of fiber (e.g., wheat bran) may affect the utilization of certain forms of folate under some conditions, but this appears to be an isolated case, not a general rule.