Folate Deficiency

The most common causes of folate deficiency are

Deficiency can also result from inadequate bioavailability and increased excretion (see table ).

Prolonged cooking destroys folate, predisposing to inadequate intake. Intake is sometimes barely adequate (eg, in people with alcohol use disorder). Liver stores provide only a several-month supply.

Alcohol interferes with folate absorption, metabolism, renal excretion, and enterohepatic reabsorption and reduces healthy food intake. 5-Fluorouracil, metformin, methotrexate, phenobarbital, phenytoin, triamterene, and trimethoprim impair folate metabolism.

In the US and Canada, many dietary staples (eg, cereals, grain products) are routinely enriched with folate, tending to reduce risk of deficiency.

Folate deficiency may cause glossitis, diarrhea, depression, and confusion. Anemia may develop insidiously and, because of compensatory mechanisms, be more severe than symptoms suggest.

Folate deficiency during pregnancy increases the risk of fetal neural tube defects Overview of Congenital Neurologic Anomalies Congenital brain anomalies cause a spectrum of neurologic deficits; although some may be barely noticeable, others may be fatal. Some of the most serious neurologic anomalies (eg, anencephaly... read more and perhaps other brain defects.

Complete blood count may indicate megaloblastic anemia Megaloblastic Macrocytic Anemias Megaloblastic anemias result most often from deficiencies of vitamin B12 and folate. Ineffective hematopoiesis affects all cell lines but particularly red blood cells. Diagnosis is usually based... read more indistinguishable from that of vitamin B12 deficiency Vitamin B12 Deficiency Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic anemia, damage... read more .

If serum folate is < 3 mcg/L or ng/mL (< 7 nmol/L), deficiency is likely. Serum folate reflects folate status unless intake has recently increased or decreased. If intake has changed, erythrocyte (red blood cell) folate level better reflects tissue stores. A level of < 140 mcg/L or ng/mL (< 305 nmol/L) indicates inadequate status.

Also, an increase in the homocysteine level suggests tissue folate deficiency (but the level is also affected by vitamin B12 and vitamin B6 levels, renal insufficiency, and genetic factors). A normal methylmalonic acid (MMA) level may differentiate folate deficiency from vitamin B12 deficiency, because MMA levels rise in vitamin B12 deficiency but not in folate deficiency.

Folate 400 to 1000 mcg orally once a day replenishes tissues and is usually successful even if deficiency has resulted from malabsorption. The normal requirement is 400 mcg/day. (CAUTION: In patients with megaloblastic anemia, vitamin B12 deficiency must be ruled out before treating with folate. If vitamin B12 deficiency is present, folate supplementation can alleviate the anemia but does not reverse, and may even worsen, neurologic deficits.)

For pregnant women, the recommended daily allowance (RDA) is 600 mcg/day. For women who have had a fetus or infant with a neural tube defect, the recommended dose is 4000 mcg/day, started 1 month before conception (if possible) and continued until 3 months after conception.