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For further information, see CMDT Part 13-07: Folic Acid Deficiency

Key Features

  • Folic acid present in most fruits and vegetables (especially citrus fruits and green leafy vegetables)

  • Daily requirements of 50–100 mcg/day usually met in the diet

  • Total body stores of folate are enough to supply requirements for 2–3 mo

  • Most common cause of folate deficiency is inadequate dietary intake, which occurs in

    • Persons with alcohol use disorder

    • Anorectic patients

    • Persons who do not eat fresh fruits and vegetables

    • Those who overcook food

  • Other causes

    • Decreased absorption due to

      • Medications, eg, phenytoin, sulfasalazine, trimethoprim-sulfamethoxazole

      • Gastrointestinal mucosal atrophy

    • Increased requirement (chronic hemolytic anemia, pregnancy, exfoliative skin disease)

    • Loss (dialysis)

    • Inhibition of reduction to active form (methotrexate therapy)

Clinical Findings

  • Megaloblastic anemia, which may be severe

  • Glossitis and vague GI disturbances (eg, anorexia, diarrhea)

  • No neurologic abnormalities, unlike vitamin B12 deficiency


  • Megaloblastic anemia identical to that in vitamin B12 deficiency (eg, macro-ovalocytes, hypersegmented neutrophils (see Vitamin B12 Deficiency)

  • Red blood cell folate level < 150 ng/mL

  • Serum vitamin B12 level normal

  • Distinguish from vitamin B12 deficiency as well as from pure anemia of liver disease (macrocytic anemia with target cells but no megaloblastic changes)


  • Folic acid, 1 mg orally once daily, for patients with folic acid deficiency or increased folic acid requirements

  • Rapid improvement in sense of well-being, reticulocytosis in 5–7 days, and total correction of hematologic abnormalities within 2 months

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