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  • Macrocytic anemia.

  • Megaloblastic blood smear (macro-ovalocytes and hypersegmented neutrophils).

  • Reduced folic acid levels in RBCs or serum.

  • Normal serum vitamin B12 level.


“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 GI 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 GI 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.

Table 13–7.Causes of folic acid deficiency.


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 RBC folic acid level below 150 ng/mL (340 nmol/L) is diagnostic of folic acid deficiency. Whether to order a serum or a RBC 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, but it should always be measured when folic acid deficiency is suspected. In some instances, folic acid deficiency is a consequence of the GI mucosal atrophy 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 RBC (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 ...

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