13-07: Folic Acid Deficiency

“Folic acid” is the term commonly used for pteroylmonoglutamic acid. Folic acid is present in most fruits and vegetables (especially citrus fruits and green leafy vegetables). Daily dietary requirements are 50–100 mcg. Total body stores of folic acid are approximately 5 mg, enough to supply requirements for 2–3 months.

The most common cause of folic acid deficiency is inadequate dietary intake (Table 13–7). Alcoholic or anorectic patients, persons who do not eat fresh fruits and vegetables, and those who overcook their food are candidates for folic acid deficiency. Reduced folic acid absorption is rarely seen, since absorption occurs from the entire gastrointestinal tract. However, medications such as phenytoin, trimethoprim-sulfamethoxazole, or sulfasalazine may interfere with its absorption. Folic acid absorption is poor in some patients with vitamin B₁₂ deficiency due to gastrointestinal mucosal atrophy. Folic acid requirements are increased in pregnancy, hemolytic anemia, and exfoliative skin disease, and in these cases the increased requirements (5–10 times normal) may not be met by a normal diet.

A. Symptoms and Signs

The clinical features are similar to those of vitamin B₁₂ deficiency. However, isolated folic acid deficiency does not result in neurologic abnormalities.

B. Laboratory Findings

Megaloblastic anemia is identical to anemia resulting from vitamin B₁₂ deficiency. A red blood cell folic acid level below 150 ng/mL (340 nmol/L) is diagnostic of folic acid deficiency. Whether to order a serum or a red blood cell folate level remains unsettled since there are few, if any, data to support one test over the other. Usually the serum vitamin B₁₂ level is normal, and it should always be measured when folic acid deficiency is suspected. In some instances, folic acid deficiency is a consequence of the gastrointestinal mucosal megaloblastosis from vitamin B₁₂ deficiency.

The megaloblastic anemia of folic acid deficiency should be differentiated from vitamin B₁₂ deficiency by the finding of a normal vitamin B₁₂ level and a reduced red blood cell (or serum) folic acid level. Alcoholic patients, who often have nutritional deficiency, may also have anemia of liver disease. Pure anemia of liver disease causes a macrocytic anemia but does not produce megaloblastic morphologic changes in the peripheral blood; rather, target cells are present. Hypothyroidism is associated with mild macrocytosis and also with pernicious anemia.

Folic acid deficiency is treated with daily oral folic acid (1 mg). The response is similar to that seen in the treatment of vitamin B₁₂ deficiency, with rapid improvement and a sense of well-being, reticulocytosis in 5–7 days, and total correction of hematologic abnormalities within 2 months. Large doses of folic acid may produce hematologic responses in cases of vitamin B₁₂ deficiency, but permit neurologic damage to progress; hence, obtaining a serum vitamin B₁₂ level in suspected folic acid deficiency is paramount.

Referral to a hematologist is not usually necessary.