What causes iron deficiency?

Causes of Iron Deficiency

Iron deficiency develops from four primary mechanisms: blood loss (the most common cause in adults), inadequate dietary intake, impaired absorption, and increased physiological demands—with the specific etiology varying dramatically by age, sex, and clinical context. 1

Blood Loss

Blood loss is the predominant cause of iron deficiency in most adult populations:

Menstrual Blood Loss

• Menstruation is the leading cause of iron deficiency in premenopausal women, accounting for an average additional loss of 0.3-0.5 mg of iron daily during childbearing years. 2
• Heavy menstrual blood loss (≥80 mL/month) affects approximately 10% of women in the United States and represents a critical risk factor for iron deficiency anemia. 2
• Use of intrauterine devices increases menstrual blood loss and iron deficiency risk, while oral contraceptives decrease this risk. 2

Gastrointestinal Blood Loss

• In men and postmenopausal women, gastrointestinal bleeding is the most common cause of iron deficiency, often from peptic ulcer disease, inflammatory bowel disease, or bowel cancer. 2, 3
• Approximately 62% of adults with iron deficiency anemia have clinical evidence of gastrointestinal bleeding from lesions such as ulcers and tumors. 2
• Pathological gastrointestinal blood loss occurs in infants and children sensitive to cow's milk and in adults with peptic ulcer disease or inflammatory bowel syndrome. 2
• Use of nonsteroidal anti-inflammatory drugs increases risk of gastrointestinal bleeding and subsequent iron deficiency. 1

Inadequate Dietary Intake

Dietary insufficiency represents a significant but often overlooked cause:

• Only one-fourth of adolescent girls and women of childbearing age (12-49 years) meet the recommended dietary allowance for iron through diet alone. 2
• Limited access to food due to low family income, migrant or refugee status, or specialized diets increases risk in children over 36 months. 2
• Vegetarian diets may require almost twice as much iron intake because non-heme iron from plant sources is less well-absorbed than heme iron from meat. 2
• Early introduction of whole cow's milk before age 1 year and consumption of >24 oz daily after the first year are risk factors because cow's milk contains little iron, may replace iron-rich foods, and can cause occult gastrointestinal bleeding. 2

Impaired Absorption

Multiple gastrointestinal conditions interfere with iron absorption:

• Atrophic gastritis, celiac disease, and bariatric surgical procedures impair iron absorption and are common causes of iron deficiency in high-income countries. 1
• Inflammatory bowel disease affects 13-90% of patients with iron deficiency due to both malabsorption and chronic inflammation. 1
• Malabsorption can result from various gastrointestinal conditions that affect the duodenum and proximal jejunum where iron absorption primarily occurs. 4

Increased Physiological Demands

Certain life stages and conditions dramatically increase iron requirements:

Pregnancy

• Iron requirements increase threefold during the second and third trimesters to approximately 5.0 mg/day due to expansion of blood volume by 35% and growth of the fetus, placenta, and maternal tissues. 2
• Up to 84% of pregnant women in high-income countries develop iron deficiency during the third trimester. 1
• Most pregnant women who do not take iron supplements cannot maintain adequate iron stores, particularly during the second and third trimesters. 2

Infancy and Childhood

• Preterm or low-birthweight infants are born with low iron stores despite having the same ratio of total body iron to body weight as full-term infants. 2
• Rapid growth during infancy requires approximately 30% of iron from dietary sources (compared to only 5% in adults), making infants particularly vulnerable to deficiency. 2

Adolescence

• Iron requirements increase during adolescence due to rapid pubertal growth, with the risk subsiding in boys after peak growth but persisting in girls throughout childbearing years. 2

Chronic Inflammatory Conditions

Functional iron deficiency occurs when inflammation impairs iron mobilization:

• Chronic inflammation increases hepcidin production, which blocks iron absorption and impairs iron mobilization from storage sites despite adequate iron stores. 5
• Chronic heart failure affects 40-70% of patients with functional iron deficiency due to systemic inflammation and elevated hepcidin levels. 5
• Chronic kidney disease commonly causes functional iron deficiency in 24-85% of patients, particularly those undergoing dialysis and receiving erythropoiesis-stimulating agent therapy. 5, 1
• Cancer patients experience iron deficiency in 18-82% of cases due to chronic inflammation, treatment effects, and often concurrent bleeding. 1

Additional Risk Factors

Several other conditions warrant consideration:

• High parity and previous diagnosis of iron deficiency anemia increase risk in women of childbearing age. 2
• Hookworm infections, though uncommon in the United States, are associated with gastrointestinal blood loss and iron depletion. 2
• Pharmacological stimulation of erythropoiesis with agents like Epoetin can lead to functional iron deficiency by increasing iron demands beyond the body's ability to mobilize stores. 5