Yes, Patients Can Be Symptomatic with Low Ferritin and Normal Hemoglobin
Patients with low ferritin and normal hemoglobin—a condition called non-anaemic iron deficiency (NAID)—can absolutely experience symptoms, and these symptoms warrant recognition and treatment. 1
Understanding Non-Anaemic Iron Deficiency
Iron deficiency progresses through distinct stages before anemia develops:
- Stage 1 (NAID): Iron stores are depleted (low ferritin) but hemoglobin remains within normal range 1
- Stage 2: Hemoglobin begins to drop, typically when ferritin falls below 15 ng/mL 2
- Stage 3: Frank iron deficiency anemia develops with low hemoglobin 3
The British Society of Gastroenterology explicitly recognizes that "the development of anaemia from iron deficiency goes through an initial phase where body iron stores are depleted resulting in hypoferritinaemia, but the Hb concentration is still within the normal range." 1
Common Symptoms in NAID
Patients with low ferritin but normal hemoglobin frequently experience:
- Fatigue and exercise intolerance 3
- Difficulty concentrating and cognitive impairment 4, 3
- Irritability and depression 3
- Restless legs syndrome (32-40% of iron deficient patients) 3
- Pica (40-50% of cases) 3
- Dyspnea and lightheadedness 3
These symptoms occur because iron is essential not only for hemoglobin production but also as "a critical constituent of many enzymes" necessary for optimal cognitive function and physical performance. 4
Diagnostic Thresholds
For healthy adults >15 years, a ferritin cut-off of 30 μg/L is appropriate for diagnosing iron deficiency, even without anemia 4:
- Ferritin <15 μg/L indicates absolute iron deficiency with 99% specificity 1
- Ferritin <30 μg/L generally indicates low body iron stores 1, 4
- Ferritin <45 μg/L provides optimal sensitivity-specificity trade-off (92% specificity) 1
Important caveat: Ferritin is an acute-phase reactant, so inflammation can falsely elevate levels. Always check C-reactive protein to exclude false-negative results. 4 In inflammatory conditions, ferritin up to 100 μg/L may still represent iron deficiency. 1, 2
Clinical Implications for Treatment
Iron deficiency at all levels—including NAID—should be treated 4:
- The threshold for investigating NAID should be low in men, postmenopausal women, and those with GI symptoms or family history of GI pathology 1
- In premenopausal women without other concerning features, GI investigation is generally not warranted as menstrual blood loss is the likely cause 1
- First-line treatment is typically oral iron (ferrous sulfate 325 mg daily or on alternate days) 4, 3
- Intravenous iron is indicated for intolerance, malabsorption, chronic inflammatory conditions, or ongoing blood loss 3
Monitoring Response
Repeat basic blood tests (hemoglobin, ferritin, MCV, MCH) after 8-10 weeks to assess treatment response. 4 Patients with recurrent low ferritin benefit from intermittent oral supplementation and long-term monitoring every 6-12 months. 4
Critical warning: Long-term iron supplementation when ferritin is normal or high is not recommended and potentially harmful. 4, 5