Folate 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).