Treatment and Management of Hypoferritinemia (Low Iron Levels)
All patients with confirmed iron deficiency should receive iron supplementation to correct the deficiency and replenish body stores, regardless of whether anemia is present. 1
Initial Assessment and Diagnosis
Before starting treatment, confirm iron deficiency with appropriate testing:
- Serum ferritin <30 μg/L indicates depleted iron stores in otherwise healthy individuals without inflammation 1, 2
- Ferritin <15 μg/L is highly specific for iron deficiency (specificity 0.99) 1
- In the presence of inflammation or chronic disease, ferritin <45 μg/L may warrant treatment 1
- Transferrin saturation <20% supports the diagnosis when ferritin is equivocal 2
Critical step: Exclude inflammation by checking C-reactive protein, as ferritin is an acute phase reactant and may be falsely elevated despite true iron deficiency 3
Investigation for Underlying Cause
The approach differs based on patient demographics:
Men and Postmenopausal Women
- Require gastrointestinal investigation including upper endoscopy with duodenal biopsy and colonoscopy, as GI blood loss is the most likely cause 1
- Screen for celiac disease (found in 3-5% of iron deficiency cases) 1
- Check urinalysis to exclude urinary tract bleeding 1
Premenopausal Women
- GI investigation generally not warranted unless there are GI symptoms, family history of GI pathology, or age >45 years 1
- Menstrual blood loss, pregnancy, and breastfeeding are the usual causes 1
- Lower threshold for investigation if non-anemic iron deficiency persists despite treatment 1
First-Line Treatment: Oral Iron Supplementation
Start with ferrous sulfate 200 mg twice daily (or 325 mg daily on alternate days), which is the most cost-effective approach 1, 2
Key Treatment Details:
- Each 200 mg ferrous sulfate tablet contains approximately 65 mg elemental iron 4
- Alternative formulations (ferrous gluconate, ferrous fumarate) are equally effective if ferrous sulfate is not tolerated 1
- Lower doses (28-50 mg elemental iron) may improve tolerability with similar efficacy 3
- Alternate-day dosing may be better tolerated than daily dosing 2
- Liquid preparations can be used when tablets are not tolerated 1
Enhancing Absorption:
- Co-administer with vitamin C (250-500 mg) to enhance absorption 1
- Avoid tea, coffee, and calcium-containing foods around dosing times as they impair absorption 1
- Take on an empty stomach when possible for optimal absorption 3
Duration:
- Continue for 3 months after correction of anemia to replenish iron stores 1
- For non-anemic iron deficiency, continue until ferritin normalizes, then for 3 additional months 1
When to Use Intravenous Iron
Parenteral iron is indicated when:
- Intolerance to at least two different oral iron preparations 1
- Malabsorption conditions (celiac disease, inflammatory bowel disease, post-bariatric surgery) 1, 2
- Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer) 2
- Ongoing blood loss that cannot be controlled 2
- Second and third trimesters of pregnancy 2
- Non-compliance with oral therapy 1
Important caveat: Intravenous iron carries risk of serious reactions (0.6-0.7% incidence) and requires resuscitation facilities available 1. It should not be used routinely when oral iron is tolerated.
Monitoring Response to Treatment
Expected Response:
- Hemoglobin should rise by 2 g/dL after 3-4 weeks of oral iron therapy 1
- Recheck complete blood count and ferritin at 8-10 weeks 3
If Response is Inadequate:
The most common reasons for treatment failure are:
- Non-compliance (most common) 1
- Continued blood loss 1
- Malabsorption 1
- Misdiagnosis (anemia of chronic disease, thalassemia) 1
- Concomitant folate or B12 deficiency 5
Long-Term Follow-Up
After successful correction:
- Monitor hemoglobin and ferritin every 3 months for the first year, then annually 1
- Resume oral iron if hemoglobin or ferritin falls below normal 1
- For patients with recurrent deficiency, consider intermittent oral supplementation and monitor every 6-12 months 3
Critical warning: Long-term iron supplementation when ferritin is normal or elevated is potentially harmful and should be avoided 3. Do not supplement iron prophylactically in the absence of documented deficiency.
Dietary Modifications
While diet alone cannot correct established iron deficiency, dietary counseling should accompany supplementation:
- Increase consumption of heme iron sources (red meat, seafood) which have higher bioavailability 1
- For vegetarians/vegans, combine non-heme iron sources with vitamin C-rich foods 1
- Limit tea and coffee consumption around meal times 1
Important note: Dietary modifications should not substitute for iron supplementation in established deficiency 1