Folic acid is the synthetic form of folate a water-soluble vitamin found in vitamins and supplements. When folic acid is consumed as a supplement and without food, it is nearly 100% bioavailable, consumed with food as in fortified cereal grains, absorption is slightly reduced. Doctors recommend adding folic acid supplements in addition to daily folate intake during situations where one may require increased folate, as in pregnancy, and also in situations where one may become deficient, as in chronic alcoholism. The liver changes the absorbed monoglutamate form of folate to the polyglutamate form. Alcohol interferes with the liver’s capacity to create a usable form of folate from the folate we ingest which is one reason alcoholics often become folate deficient. It is also for this reason alcohol during pregnancy can cause such detrimental effects.
Initiation of Folic Acid
The initiation of folic acid supplementation is crucial during the first trimester and especially during the first month of pregnancy to prevent neural tube defects. At this time period most women just realizing they are pregnant or are still unaware. For this reason, it is recommended all women of childbearing age take folic acid supplementation. Women who are not on supplementation are advised to start daily folic acid supplementation at least one month prior to becoming pregnant or as soon as they become aware they are pregnant.
Folic Acid and the Risk for Premature Delivery
One study showed that women who took folic acid for at least a year before getting pregnant cut their chances of delivering early by 50% or more. On the contrary, the Norwegian Mother and Child Cohort Study (MoBa) released data on more than 106,000 pregnancies suggesting the initiation of folic acid more than 8 weeks preconception was associated with increased risk of spontaneous preterm delivery, while folic acid supplementation prior to 8 weeks preconception was not associated with an increased risk.
Although the data by the MoBa cohort requires further investigating, the information provided should be considered with women who are already at high risk for preterm delivery as in diabetics, women with high blood pressure, women pregnant with more than one baby, being either obese or underweight, tobacco smokers, and women under psychological stress.
The CDC still recommends that women start taking folic acid every day for at least a month before becoming pregnant, and every day while pregnant as well.
Why is Folate and Folic Acid Important?
Humans cannot synthesize folate, therefore, it must be extracted from the food, vitamins, and supplements that pass through the small intestine. The recommended daily allowance (RDA) for folate for adults, especially women of childbearing age, is 0.4 mg/day and for pregnant women 0.6 mg/day, as is the daily value used on food and supplement labels. This is based on the amount needed to maintain red blood cell folate, control blood homocysteine and maintain normal blood folate concentrations.
Adequate levels of dietary folate are important during early pregnancy to support rapid cell growth, replication, cell division, and nucleotide synthesis for fetal and placental development. It is also needed for maternal erythropoiesis, mainly during the second and third trimesters. For these reasons, alcohol is not recommended during any stage of pregnancy but it can be detrimental during the first trimester, in particular, the first month of pregnancy. The recommended upper limit of folate intake is 1mg/day, however, it may be required for pregnant women to reach and on occasion surpass this amount to prevent neural tube defects in high-risk pregnancies. Excess folic acid can mask vitamin b12 deficiencies, for this reason, it is not recommended for prolonged periods of time.
Folate deficiency can result from a low intake, inadequate absorption which is often associated with alcoholism, increased requirement as in during pregnancy, compromised utilization typically associated with vitamin B-12 deficiency, use of certain chemotherapy medications and excessive excretion linked to long-standing diarrhea.
A deficiency in folate first affects cell types that are actively synthesizing DNA, such cells have a short lifespan and rapid turnover rate. Thus, one of the major folate deficiency signs is changes in the early phases of red blood cell synthesis, as these cells turn over every 120 days. Without folate, the precursor cells cannot divide normally to become mature red blood cells because they cannot form new DNA. These cells grow larger because there is a continuous formation of RNA, leading to increased synthesis of protein and other cell components to make new cells. Hemoglobin synthesis also intensifies, however, when it is time for the cells to divide, they lack sufficient DNA for normal division and thus remain in a large, immature form in the bone marrow, known as megaloblasts. Unlike normal, mature red blood cells, megaloblasts retain their nuclei and once they enter the blood stream they are called macrocytes. This results in a form of anemia called megaloblastic anemia. White blood cell synthesis also is disrupted by a folate deficiency because these cells are made in rapid bursts during immune challenges like infections. The GI tract is also impaired, leading to decreased absorptive capacity and persistent diarrhea.
Neural Tube Defects
Neural tube defects account for the largest proportion of congenital anomalies of the CNS resulting from a failure of the neural tube to close spontaneously between the 3rd and 4th week on in utero development. Neural tube defects including spina bifida and anencephaly can be easily avoided with adequate folate in most cases. Spina bifida may exhibit paralysis, incontinence, hydrocephalus, and learning disabilities while children with anencephaly die shortly after birth. The neural tube closure begins 21 days after conception and is completed by day 28 before or around the time when most women are realizing they are pregnant. As many as 70% of defects could be avoided with adequate folate ingestion and therefore, adequate folate is crucial for all women of childbearing years.
Hispanic women have highest rates of neural tube defects while lowest rates found in African American and Asian women. Women who have had a previous pregnancy with a neural tube defect or who are personally affected by a neural tube defect are at a higher risk for having an offspring with a neural tube defect in a subsequent pregnancy. Other factors include siblings with a neural tube defect, maternal diabetes and antiseizure medications such as valproic acid or carbamazepine. A higher risk of a neural tube defect is also associated with increased maternal weight. However, 95% of children with neural tube defects are born to couples without any family history of neural tube defects.
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