Folates are compounds of pteroylglutamic acid (PGA)
that function as coenzymes in metabolic reactions involving the transfer
of single-carbon units from a donor to a recipient compound. Folate,
with vitamin B12, is essential for DNA synthesis, which is required for normal red blood cell maturation.2 Humans obtain folate from dietary sources including fruits, green and leafy vegetables, yeast, and organ meats.3 Folate is absorbed through the small intestine and stored in the liver.
Low
folate intake, malabsorption as a result of gastrointestinal diseases,
pregnancy, and drugs such as phenytoin are causes of folate deficiency.4 Folate deficiency is also associated with chronic alcoholism.5 Folate and vitamin B12
deficiency impair DNA synthesis, causing macrocytic anemias. These
anemias are characterized by abnormal maturation of red blood cell
precursors in the bone marrow, the presence of megaloblasts, and
decreased red blood cell survival.2
Since both folate and vitamin B12
deficiency can cause macrocytic anemia, appropriate treatment depends
on the differential diagnosis of the deficiency. A serum folate
concentration <3 ng/mL is considered to represent clinical deficiency
by the World Health Organization and numerous subsequent clinical
studies.6,7 Serum folate measurement provides an early index of folate status3;
however, folate is much more concentrated in red blood cells than in
serum so the red blood cell folate measurement more closely reflects
tissue stores.5,8 Erythrocytes incorporate folate as they
are formed, and levels remain constant throughout the life span of the
cell. RBC folate levels are less sensitive to short-term dietary effects
than are serum folate levels. Red blood cell folate concentration is
considered the most reliable indicator of folate status.3
Low serum folate during pregnancy has been associated with neural tube defects in the fetus.9,10
In
the 1990s mandatory increased fortification of enriched cereal-grain
products along with the requirement of folate-related health and
nutrient content claims on food and dietary supplement products
significantly increased the folic acid content of the US food supply.11-13
Several reports have shown that serum folate concentrations have
increased in the general US population since these measures were
implemented.11-13