Folate is an essential vitamin that is also known as folic acid and
folacin. The synthetic form of the vitamin (folic acid), pteroylglutamic
acid, is seldom found naturally in food. The folates found in nature
contain the core chemical structure of pteroylglutamic acid but vary in
their state of reduction, the single carbon moiety they bear and/or the
length of the glutamate chain attached. At least 50% of whole body folate
is stored in the liver.
The metabolic role of folate is as an acceptor and donor of one-carbon
units in a variety of reactions involved in amino acid and nucleotide
metabolism. The carbon can be carried as a methyl, methylene, formyl,
formimino or methenyl group. The coenzyme form of the vitamin is typically
fully reduced and poly-glutamylated. In the adult, folate is absorbed
primarily in the proximal one-third of the small intestine. It is also
conceivable that a portion of the large depot of bacterially synthesized
folate in the large intestine may be absorbed. A large portion of folate
delivered to the liver is secreted into bile and redistributed to
peripheral tissues. Polyglutamylation (addition of glutamic acids) of
folate is believed necessary to concentrate and store folates in tissues.
Deficiencies: Given the role that folate coenzymes
play in the synthesis of RNA, DNA and protein, it is not surprising that
the folate requirement and, consequently, the risk of deficiency is
elevated during periods of rapid growth and/or enhanced metabolic activity
(e.g. pregnancy, lactation). Overt symptoms of severe folate deficiency
such as depapillation of the tongue are uncommon. Megaloblastic anemia,
indistinguishable from megaloblastic anemia secondary to vitamin B12
deficiency, is a more frequently cited functional outcome. Less than
optimal maternal folate status has been implicated in a number of negative
maternal and fetal outcomes, including low infant birthweight, abruptio
placenta, cervical dysplasia and neural tube defects. Low folate intakes
also are correlated with high levels of serum homocysteine which are
associated with an increased risk of atherosclerosis and several forms of
vascular disease. However, it is unclear currently whether supplemental
folate lowers risk.
Clinical Uses: Recent public policy recommendations
suggest that women of child-bearing potential consume 400 µg/d of
folate to reduce the number of pregnancies affected by a neural tube
defect. Consumption of large amounts of folate may interfere with the
diagnosis of pernicious anemia, a condition not uncommon in the elderly
which may produce neurologic defects. Very high doses of folic acid may
counteract certain antiepileptic drugs. Because of the importance of
folate in the synthesis of nucleotides, which are required for cell
multiplication, antifolate drugs such as methotrexate are important in
cancer therapy. When methotrexate is used in arthritis therapy, folate
supplements often are used to lessen side effects.
Diet Recommendations: The Dietary Reference Intakes (DRIs)
for folate each day are 400 µg Dietary Folate Equivalents (DFE) for adults
and teenagers. Pregnant women need a greater amount, 600 µg DFE, for
building red blood cells; lactating women require 500 µg. For children,
DRIs are 65 µg for infants 0-0.5 yr. and 80 µg for infants 0.5-1 yr.; and
150 µg for ages 1-3 yr., 200 µg for ages 4-8 yr., and 300 µg for ages 9 -
13 yr.
Food Sources: The folate content of foods is
inherently variable and a large fraction of the folate consumed each day
comes from foods that are frequently ingested, but not particularly
concentrated, sources of the vitamin. Excellent food sources of folate
(>55 µg/d) include fortified cereals, citrus fruits and juices, asparagus,
Brussels sprouts, spinach, baked beans, chickpeas, kidney beans or
lentils.
Many cereal-grain foods (flour, rice, pasta, cornmeal) constitute
important sources because they are fortified with folic acid. Folate
bioavailability varies with food type and overall diet composition. In
general, added folic acid in fortified foods is absorbed more efficiently
than many forms of naturally-occurring folate.
Toxicity:Most reports of folate toxicity have involved
massive (nonphysiological) doses given by injection. Such massive doses
have produced evidence of neuro- and nephrotoxicity. The main concern of
large doses of dietary folate intakes and commonly available supplements
is that a large intake might mask a B12 deficiency by allowing some
synthesis of blood cells by temporarily relieving the block of nucleotide
synthesis. This possibility should be continually evaluated in populations
at risk, including the elderly individuals. Under conditions of typical
intake in the US population, the beneficial effects of improved folate
status currently outweigh this small potential risk.
