Folate refers to a stable group of pharmaceutical and folate vitamins that comprise pterolylglutamic acid (PGA, folic acid). The subunits of folate include glutamic acid, pteridine, and p-aminobenzoic acid. Folate is naturally found in the family of B-group vitamins, which include legumes, liver, leafy vegetables, and yeast. Folic acid is better absorbed than natural folates, which makes it useful in the reduction of neural tube defects (NTDs) and oral clefts.
Numerous studies have been conducted on the benefits and risks of dietary folate and folic acid. One such study involving randomized controlled trials indicated that folic acid supplementation significantly reduced the risk of pregnancies with NTDs. A study on the high intake of folate also showed similar results in addition to reduced risk of cardiovascular disease, some cancers, and age related cognitive declines. An absence of folate in pregnant women results in lower de novo DNA biosynthesis.
“This insufficiency causes the destruction of cell replication “resulting in rapidly dividing cell-types including erythrocytes and other cells generated by the bone marrow, enterocytes and skin cells”. Consequently, patients suffer from megaloblastic and macrocytic anemia. An important consideration in the delivery of treatment for macrocytic megaloblastic anemia is that a deficiency of vitamin B12 also causes this condition. As such, this deficiency should be eliminated before the administration of folate treatment. In addition to pregnancy, deficiencies of folate also arise due to infection, malignant disease, alcoholism, malabsorption syndromes, restricted diets in old people, and as a side-effect of some drug treatments.
The use of folic acid in the treatment of NTDs is a safe procedure since patients can take up to 20 mg/day without experiencing negative effects. However, a study conducted on the administration of 15mg/day of folic acid on healthy individuals revealed adverse symptoms including gastrointestinal problems, mental changes and sleep disturbances.
Adverse reactions may also occur in the event of folic reversal of the hematological signs of vitamin B12 deficiency, causing the latter to go untreated, though this is often found in older people. Recent studies in this field have shown a correlation between the intake of high levels of folic acid and increased risk for colorectal cancer. Animal studies have shown that a high intake of folic acid prevents the development of neoplastic lesions in normal tissues while increasing the rate of malignant transformation of the present neoplasms.
This high intake has also been noted to accelerate cognitive decline with age, as well as the reduction of the efficacy of antifolate drugs including methotrexate, which are used in treatment of cancer, as well as drugs used in treatment of epilepsy.
A Randomized control trial (RCT) conducted to determine the effect of folic acid supplementation on the increased risk of colorectal cancer involved the administration of 1 and 5mg folic acid supplements for 2 to 3 years. This study revealed positive effects in the reduction of risk associated with adenoma, and no effect on colorectal adenoma recurrence. A follow up study revealed that folic acid supplementation with a daily intake of 1mg did not restrict the development of colorectal adenomas.
However, six years after, the results of another study revealed significantly elevated cases of adenomas resulting from folic acid supplementation. This was attributed to the mandatory folic acid food fortification procedure in the US that increased the dosage by an extra 200μg folic acid per day. As such, it was concluded that a daily intake of more than 1mg of folate significantly increased the risk of developing advanced adenomas after several years, and as such, increased the risk of cancer.
The tendency by various countries to increase the intake of folic acid supplements by pregnant women in order to reduce NTD cases is based on the positive results taken from randomized controlled trials and observations. These studies indicated reduced incidence of foetal NTDs as well as lower levels of homocysteine, owing to the supplementation of peri-conceptional folic acid at daily levels of up to 10mg for periods of several weeks.
Consequently, COMA suggested a daily intake of 0.40 mg folic acid supplement by pregnant women to prevent foetal NTDs, with women in high risk groups taking more, as a complementary action to the normal dietary intake of folate. Studies show that intake of folic acid supplements by expectant mothers helps reduce the prevalence of oral clefts. This result supports the measures taken by various countries to emphasize on the importance of taking multivitamin drugs during pregnancy. However, studies reveal that many women who have attained the child bearing age are unaware of the need for periconceptual folic acid supplementation. As such, healthcare providers should take an active role in advising and training women who are planning pregnancies to take folic acid.
Many nations have recommended the use of folic acid supplements in the diet for pregnant women, though studies show that promotions to enhance their intake have been unsuccessful both prior to and during the first weeks following conception. The United States and Canada, among other countries, have introduced the obligatory enrichment of staple foods such as flour using folic acid, in their efforts to curb NTDs. Consequently, the incidences of NTD affected pregnancies have significantly reduced by 28% and 46% in the US and Canada respectively.
Various nations in the European Union recommend that women who might become pregnant supplement their diet with 400μg of folic acid daily, though the duration of intake is dependent on individual nations. Intake can commence immediately after ceasing contraception to four weeks before conception. The user can then continue after eight to twelve weeks of pregnancy throughout pregnancy and lactation.
Mandatory food fortification has been noted to complement proper daily intake of folic acid in the prevention of NTDs in a majority of most industrial countries and a few developing countries. The practice of voluntary food fortification is also common in the European Union under the 1925/2006/EC regulation on the addition of vitamins and minerals, among other substances in foods. As such, all foods with the exception of unprocessed products and alcoholic beverages can be fortified, including fairy products, fruit juices and beverages. The maximum level of folic acid to foods is not defined in the European regulations, though it does not exceed 1000μg/100g.
The lack of standards for the addition of folic acid to foods makes it difficult to identify the impact of this approach in the reduction of NTDs, though studies associate the reduction in NTD prevalence In Ireland to the 30% increase in dietary folic acid through voluntary fortification. As such, it can be concluded that folate is a vital supplement in the production of pregnancy supplements.
References
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