Researchers first documented an association between pregnant women’s folate levels and neural tube defects (NTD) in newborns in the 1960s. Today, low folate is a well-established risk factor for NTDs, and in 1998, the Food and Drug Administration mandated fortification of cereal grain products in the U.S. to ensure that women who are unaware of their pregnancies do not compromise their fetuses during the critical stage when the neural tube closes. The primary driving force behind this policy was the recognition that periconceptional folate supplementation, in addition to normal dietary folate intake, significantly reduces the incidence of NTDs. In fact, many countries now have either mandatory or voluntary flour fortification regulations to reduce the risk of NTDs in newborns.
Since the fortification of grains with folate began, there has been a substantial rise in folate concentration in the general population. So much so that low folate levels are now rare. Although folate levels in pregnant women are critical to the health of newborns, the majority of laboratory test orders for folate are made to investigate anemia along with vitamin B12 deficiency in nonpregnant patients.
This article will describe the metabolism of folate, the causes, clinical effects and prevalence of folate deficiency, as well as evidence about diagnostic thresholds and the clinical utility of folate testing.
Folic acid (pteroylmonoglutamate) acts as a carrier of one-carbon units in a variety of metabolic reactions (Figure 1). This class of vitamins is essential for the synthesis of nucleic acids, thymidylate, neurotransmitters, phospholipids, and hormones. Folate is also integral to the de-novo generation of methionine, which is required for genomic and nongenomic methylation reactions.
Humans lack the enzymes to synthesize folate, so dietary intake is necessary. Nutritionists estimate that the body stores 10–100 mg of folate, with 5–10 mg sufficient for about 4 months of normal metabolism.
Rich sources of dietary folate include green leafy vegetables, fruits, dairy products, cereals, yeast, and animal proteins. Cooking, however, destroys most folate in food. The dietary reference intake (DRI) recommendation for adults in the U.S. is 400 µg/day, and other countries have similar recommendations. For children, the recommended DRI is lower, but higher amounts are recommended for women during pregnancy and lactation. Natural folate is 50% bioavailable compared to 85% in fortified foods and almost 100% when taken as a supplement.
FOLATE METABOLISM-
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