Folate deficiency
Folate deficiency is a megaloblastic, macrocytic anemia caused by impaired DNA synthesis from inadequate vitamin B9, most often from alcohol use disorder, malabsorption, or increased demand such as pregnancy. It resembles vitamin B12 deficiency hematologically but causes no neurologic findings. Diagnosis rests on a compatible macrocytic anemia plus a low folate level or, when equivocal, an elevated serum homocysteine with a normal methylmalonic acid. First-line treatment is oral folic acid 1 to 5 mg daily, after excluding concurrent vitamin B12 deficiency.
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What this article covers
- Overview
What it is: folate (vitamin B9) deficiency is a nutritional megaloblastic anemia caused by impaired DNA synthesis in rapidly dividing hematopoietic precursors.
- Epidemiology
Population affected: dietary folate deficiency is uncommon where grain products are fortified with folic acid and is concentrated in malnutrition, alcohol use disorder, pregnancy, and malabsorptive disease.
- Risk factors
Alcohol use disorder: reduced dietary intake combined with impaired jejunal absorption of folate.
- Pathophysiology
Absorption: dietary folate is absorbed in the jejunum and converted to its active circulating form, 5-methyltetrahydrofolate.
- Clinical features
Onset: symptoms develop gradually over weeks to months as marrow folate reserves are exhausted.
- Differential diagnosis
Vitamin B12 (cobalamin) deficiency: produces an identical megaloblastic, macrocytic anemia, but neurologic findings, paresthesias, gait disturbance, impaired vibration sense, are present, and…
- Diagnosis
What establishes the diagnosis: the diagnosis is confirmed by a low serum or red cell folate level in a patient with macrocytic anemia, or, when the serum folate is equivocal, by an elevated serum…
- Management
First, exclude vitamin B12 deficiency, then start oral replacement: folic acid 1 mg to 5 mg PO once daily for 1 to 4 months or until the hemoglobin normalizes and folate stores are replete, continuing longer if the underlying cause persists.
- Complications
Pancytopenia: severe, prolonged folate deficiency can suppress all three cell lines through ineffective hematopoiesis, occasionally severe enough to warrant transfusion before the reticulocyte response begins.
- Prognosis
Rapid hematologic response: the reticulocyte count begins to rise within days of starting oral folic acid, with the hemoglobin typically normalizing over the following weeks once the cause is controlled.
- Prevention
Food fortification: folic acid fortification of grain products in the United States has made dietary folate deficiency uncommon outside malnutrition, alcohol use disorder, and malabsorptive states.
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