Iron Deficiency in Adults: A Review

Absolute iron deficiency, defined as low iron stores with or without anemia, affects approximately 2 billion people worldwide and 14% of adults in the US. Iron-deficiency anemia, defined as low hemoglobin due to low iron stores, affects approximately 1.2 billion people worldwide, including 10 million in the US.

Absolute iron deficiency progresses from low iron stores to iron-deficiency anemia. Individuals with nonanemic iron deficiency or iron-deficiency anemia may be asymptomatic or experience fatigue, irritability, depression, difficulty concentrating, restless legs syndrome (32%-40%), pica (40%-50%), dyspnea, lightheadedness, exercise intolerance, and worsening heart failure (HF). Symptom prevalences vary depending on age, comorbidities (eg, chronic kidney disease [CKD], HF), and severity and rate of development of iron deficiency. The most common causes of iron deficiency are bleeding (menstrual, gastrointestinal), impaired iron absorption (atrophic gastritis, celiac disease, bariatric surgical procedures), inadequate dietary iron intake, and pregnancy. In high-income countries, approximately 38% of nonpregnant, reproductive-age women have iron deficiency without anemia and about 13% have iron-deficiency anemia. During the third trimester of pregnancy, iron deficiency affects up to 84% of pregnant women, based on data from high-income countries. Additional risk factors include use of nonsteroidal anti-inflammatory drugs, inflammatory bowel disease (IBD [13%-90%]), and other chronic inflammatory conditions, such as CKD (24%-85%), HF (37%-61%), and cancer (18%-82%). Testing for iron deficiency is indicated for patients with anemia and/or symptoms of iron deficiency (fatigue, pica, or restless legs syndrome) and should be considered for those with risk factors such as heavy menstrual bleeding, pregnancy, or IBD. Iron deficiency is diagnosed by low serum ferritin (typically <30 ng/mL) in individuals without inflammatory conditions or by transferrin saturation (iron/total iron binding capacity × 100) less than 20%. Causes of iron deficiency should be identified and treated. Oral iron (ferrous sulfate 325 mg/d or on alternate days) is typically first-line therapy. Intravenous iron is indicated for patients with oral iron intolerance, poor absorption (celiac disease, post-bariatric surgical procedure), chronic inflammatory conditions (CKD, HF, IBD, cancer), ongoing blood loss, and during the second and third trimesters of pregnancy.

Iron deficiency and iron-deficiency anemia are common conditions that may cause symptoms such as fatigue, exercise intolerance, and difficulty concentrating. Ferritin and/or transferrin saturation are required for diagnosis and screening. Oral iron is first-line therapy for most patients. Intravenous iron is used for individuals who do not tolerate or have impaired absorption of oral iron, those with ongoing blood loss, certain chronic inflammatory conditions (IBD, CKD, HF, cancer), and during the second and third trimesters of pregnancy.