Alerts and Notices
SynopsisFolate deficiency refers to a deficiency of vitamin B9. Folate is a water-soluble vitamin that is essential to DNA synthesis. It is naturally present in many foods, particularly leafy vegetables. Additionally, in many countries, foods are fortified with folate, such as pastas and flours. In the United States, folate deficiency is rare in the general population in the absence of underlying risk factors predisposing to gastrointestinal malabsorption (eg, celiac disease, inflammatory bowel disease, gastric bypass surgery) or dietary intake deficiency (eg, alcohol use disorder, restrictive eating disorder, vegan diet without supplementation). Incidence in the United States is estimated at approximately 0.056% in the general population.
Folate deficiency presents most commonly as a macrocytic anemia. In the United States, approximately 6% of macrocytic anemias are attributed to folate deficiency, which accounts for about 0.5% of all anemia. Pallor, fatigue, and oral ulcers are also observed in folate deficiency. In rare circumstances, folate deficiency can be associated with neuropathy, paresthesia, or neuropsychiatric symptoms. These are more typically seen in vitamin B12 deficiency, another cause of macrocytic anemia. Folate deficiency can develop quickly over a period of weeks to months as body stores are rapidly depleted with cell division and DNA synthesis.
Folate needs are increased in special populations and, if not proactively supplemented, folate deficiency can arise. These populations include patients with exfoliative skin disorders, hemodialysis dependence, or chronic hemolytic anemia, patients who are pregnant, and patients on certain medications (eg, methotrexate, sulfasalazine).
D52.9 – Folate deficiency anemia, unspecified
190633005 – Folic acid deficiency
Differential Diagnosis & Pitfalls
- Inflammatory bowel disease (particularly small bowel or gastric Crohn disease)
- Celiac disease
- Chronic parasitic infection
- Tropical sprue
- Protein-losing enteropathy
- Dietary vitamin B12 deficiency
- Pernicious anemia
- Familial selective vitamin B12 malabsorption disease (Imerslund-Grasbeck disease)
- Hereditary folate malabsorption
- Methylenetetrahydrofolate reductase deficiency
- Formiminotransferase deficiency
- Heat stroke (megaloblastic anemia)
- Uremic or hepatic encephalopathy
- Medication side effect (particularly methotrexate, trimethoprim-sulfasalazine, and antiepileptics including phenytoin, valproic acid, and carbamazepine)
- Systemic lupus erythematosus
- Copper deficiency
- Chronic hemolytic anemia
- Malignancy (particularly liquid tumors)
Drug Reaction DataBelow is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.