What causes iron deficiency?

Causes of Iron Deficiency

Iron deficiency results from an imbalance between iron requirements and iron availability, with the most common causes being gastrointestinal blood loss in men and postmenopausal women, menstrual blood loss in premenopausal women, and malabsorption disorders—particularly celiac disease. 1, 2

Primary Causes by Patient Population

In Men and Postmenopausal Women

• Gastrointestinal blood loss is the leading cause, accounting for pathology in approximately one-third of cases 2
• Sources include colorectal cancer, gastric cancer, peptic ulcer disease, and NSAID-induced mucosal damage 1, 2
• Dual pathology (disease in both upper and lower GI tract) occurs in 1-10% of cases 1

In Premenopausal Women

• Menstrual blood loss is the most common cause, requiring an average additional 0.3-0.5 mg of iron daily during childbearing years 1, 2
• Pregnancy dramatically increases requirements, averaging 3 mg daily over 280 days of gestation 1

In Pregnant Women

• Iron deficiency affects up to 84% of pregnant women during the third trimester in high-income countries 3
• Physiologically increased requirements combined with blood loss at delivery and postpartum drive deficiency 1

Malabsorption Disorders

• Celiac disease is found in 3-5% of all iron deficiency cases and must be screened in every patient with unexplained anemia 2, 4
• Previous gastrectomy, gastric atrophy, and chronic proton pump inhibitor therapy impair iron absorption 2
• Bariatric surgical procedures cause poor absorption and are an increasingly common cause 1, 3
• Bacterial overgrowth, gut resection or bypass, and small bowel tumors contribute to malabsorption 2

Medication-Induced Blood Loss

• NSAIDs are common and frequently unreported causes of occult gastrointestinal blood loss, even without overt bleeding symptoms 4
• Patients often don't consider over-the-counter NSAIDs worth mentioning—explicitly asking about all NSAID use is essential 4
• Anticoagulants and antiplatelet agents can unmask underlying vascular lesions like angiodysplasia 4

Inadequate Dietary Intake

• Poor dietary iron intake is particularly common in developing countries and comprises a real public health problem 5
• In developed countries, dietary deficiency is infrequent but can occur in individuals of lower socioeconomic status with limited access to iron-rich foods 4
• Dietary restrictions, such as in celiac disease, create additional risk 5

Chronic Inflammatory Conditions

• Inflammatory bowel disease causes iron deficiency in 13-90% of affected patients 3
• Chronic kidney disease results in iron deficiency in 24-85% of patients 3
• Heart failure causes iron deficiency in 37-61% of patients 3
• Cancer is associated with iron deficiency in 18-82% of cases 3
• Cystic fibrosis patients experience iron deficiency ranging from 11% in children to over half of stable adults, driven by malabsorption, chronic infection and inflammation, chronic blood loss, and inadequate intake 1

Other Blood Loss Sources

• Urinary tract bleeding, epistaxis, and frequent blood donation can contribute to iron deficiency 2, 4
• Pathological gastrointestinal blood loss occurs in infants and children sensitive to cow's milk 1
• Hookworm infections, though uncommon in the United States, are associated with gastrointestinal blood loss and iron depletion 1

Critical Diagnostic Considerations

Multiple Causes Often Coexist

• Finding one cause should not deter further investigation, as iron deficiency is often multifactorial 1, 2
• Approximately 1 mg of iron is lost daily through feces and desquamated mucosal and skin cells in adults, with additional losses from any pathological process 1

Common Pitfalls to Avoid

• Assuming all anemia in men must be from gastrointestinal bleeding misses treatable malabsorption and nutritional causes 4
• Failing to ask specifically about over-the-counter NSAID use leads to missed diagnoses 4
• Not screening for celiac disease results in missed diagnoses in 3-5% of cases 2, 4
• In new presentations of iron deficiency anemia, a history of GI or bariatric surgery should not preclude a search for other causes 1