Treatment of Iron Deficiency Without Anemia
Yes, treat iron deficiency without anemia in specific high-risk populations (inflammatory bowel disease, pregnancy, heart failure), but not routinely in otherwise healthy asymptomatic adults. 1
Clinical Context Determines Treatment Decision
The approach differs dramatically based on the underlying condition:
Treat Iron Deficiency Without Anemia In:
Inflammatory bowel disease patients with ferritin <30 ng/mL or transferrin saturation <20%, as iron deficiency can cause symptoms and impair quality of life even without anemia, including reduced physical performance, cognitive dysfunction, fatigue, headache, sleeping disorders, and restless legs syndrome 2
Pregnant women during second and third trimesters regardless of anemia status 1
Heart failure patients, where evidence supports treatment even without anemia 1
Symptomatic patients with fatigue, restless legs syndrome, or other iron deficiency symptoms, particularly in at-risk populations (adolescents, heavy menstruation, high-performance athletes, vegetarian/vegan diet) 3
Do Not Routinely Treat In:
Otherwise healthy asymptomatic adults, as evidence for benefit is lacking and the British Society of Gastroenterology identified this as a priority research gap 2, 1
Men and postmenopausal women without symptoms, where the primary concern is identifying the underlying cause (particularly gastrointestinal malignancy) rather than empiric supplementation 2
Diagnostic Thresholds
Without inflammation: Ferritin <30 ng/mL confirms iron deficiency 1, 3
With inflammation or chronic disease: Ferritin 30-100 ng/mL with transferrin saturation <20% suggests combined iron deficiency and anemia of chronic disease 1
In children: Use age-appropriate cut-offs (15 µg/L for ages 6-12 years, 20 µg/L for ages 12-15 years) 3
Treatment Protocol When Indicated
First-line oral therapy:
- Ferrous sulfate 200 mg (65 mg elemental iron) once daily - this is the most cost-effective option and improves tolerance compared to multiple daily doses 1
- Add vitamin C 500 mg with each dose to enhance absorption 1
- Preparations with 28-50 mg elemental iron content are appropriate to minimize gastrointestinal side effects 3
Monitoring:
- Recheck ferritin at 3-month intervals during treatment 1
- If no improvement after 3 months of compliant therapy, reassess for malabsorption, ongoing blood loss, or consider IV iron 1
- Continue until ferritin normalizes (typically >30 ng/mL) 1
Intravenous iron indications:
- Intolerance to oral iron 1
- Malabsorption conditions 4
- Need for rapid repletion 4
- Inflammatory bowel disease (where IV iron prevents anemia recurrence better than oral therapy, with hazard ratio 0.62 for developing anemia) 2
Critical Pitfalls to Avoid
Do not treat without identifying the underlying cause - particularly in men and postmenopausal women where gastrointestinal malignancy must be excluded 2, 1
Do not prescribe multiple daily doses of oral iron, as this increases side effects without improving efficacy 1
Do not supplement patients with normal ferritin levels - preventative iron administration in those with normal stores is inefficient, has side effects, and appears harmful 3
Do not overlook vitamin C supplementation when oral iron response is suboptimal 1
Do not assume elevated ferritin excludes iron deficiency - check C-reactive protein to exclude acute phase reaction that falsely elevates ferritin 3
Special Consideration for IBD Patients
The European Crohn's and Colitis Organisation provides the strongest evidence for treating iron deficiency without anemia, noting that iron deficiency commonly presents as the only sign of disease activity in IBD patients 2. The FERGImain study demonstrated that proactive IV iron treatment (ferric carboxymaltose 500 mg when ferritin fell below 100 µg/L) in non-anemic IBD patients reduced progression to anemia (27% vs 40% in placebo, HR 0.62) and was associated with fewer GI symptoms and IBD flares 2.