Written by Babatunde Carew
Spoon Feed
This review outlines our current understanding of iron deficiency—with or without anemia—focusing on screening, accurate diagnosis, and treatment.
Ironing out the details
Iron deficiency is the most common nutritional deficiency and a leading cause of anemia, often signaling underlying issues like GI malignancy or chronic blood loss. According to the American Gastroenterological Association, it affects 1%–4% of men, ≥39% of premenopausal women, and 8% of postmenopausal women, with anemia seen in 4%–17% of women. Identification of iron deficiency guides appropriate treatment and evaluation, potentially leading to the diagnosis of otherwise missed conditions.
Etiology
Iron deficiency results from blood loss, inadequate dietary intake, or impaired iron absorption.
- Blood loss: menstruation, GI bleeding (gastritis, IBD, colorectal cancer), blood donations
- Reduced absorption: bariatric procedures, celiac disease, IBD, H. pylori infection, chronic PPI
- Chronic inflammation: cancer, CKD, rheumatologic disease, IBD
Signs and symptoms of iron deficiency
Individuals with iron deficiency with or without anemia can be asymptomatic or have multiple symptoms and are more often symptomatic if also anemic.
- Symptoms
- Fatigue
- Decreased exercise tolerance
- Restless legs syndrome (RLS)
- Pica (especially pagophagia – ice craving)
- Difficulty concentrating (“brain fog”)
- Irritability or depression
- Physical exam findings:
- Pallor (skin, conjunctiva)
- Tachycardia (in severe anemia)
- Flow murmur
- Glossitis or depapillated tongue
- Cheilosis (cracked lips)
- Koilonychia (spoon nails)
- Diffuse nonscarring alopecia
Diagnosis
All patients with symptoms of iron deficiency, unexplained anemia, or unexplained microcytosis (MCV <80) should be tested.
- Ferritin <30 ng/mL → diagnostic for iron deficiency
- Transferrin saturation (TSAT) <20% → used to assist with diagnosis if there is concern inflammation may falsely elevate ferritin.
- Though not discussed in this review, soluble transferrin receptor may be able to aid diagnosis when anemia of chronic disease vs. iron deficiency is in question.
- Remember that normal Hgb/MCV does not rule out iron deficiency.
- In patients with confirmed iron deficiency, determine the underlying cause:
- Consider etiologies such as celiac disease, heavy menses, etc.
- Patients with uncertain cause of iron deficiency after initial evaluation should typically undergo EGD and colonoscopy.
Screening
Screening recommendations for iron deficiency in asymptomatic individuals vary across professional guidelines. Consider screening:
- Menstruating or pregnant individuals
- Patients with chronic conditions (e.g. CKD, HF, IBD)
- Bariatric surgery patients
- Vegetarians/vegans, older adults, frequent blood donors
- Patients on anticoagulants
Treatment
Consider using the Ganzoni equation to determine total body iron deficit.
Oral iron (first-line):
- Ferrous sulfate 325 mg every other day or daily (alternate day dosing has similar efficacy, fewer GI side effects).
- Avoid calcium, tea/coffee around dose of oral iron.
- Consider adding vitamin C or meat protein to enhance absorption.
- Continue treatment until Hgb and ferritin are in normal range.
IV Iron may be indicated if there is:
- Oral iron intolerance
- Poor absorption (bariatric surgery, IBD, etc.)
- Ongoing blood loss (GI bleeding or heavy menses)
- Inflammatory diseases (CKD, IBD, cancer, HF, etc.)
- Hgb, ferritin, and TSAT should be checked 4 weeks after IV iron infusion; if there is insufficient repletion, additional IV iron should be administered.
Source
Iron Deficiency in Adults: A Review. JAMA. 2025 May 27;333(20):1813-1823. doi: 10.1001/jama.2025.0452. PMID: 40159291
