Iron

Why it happens in Crohn’s disease

Two mechanisms run simultaneously and need different treatments. The first is straightforward loss and malabsorption: ulcerated mucosa bleeds continuously, and iron is absorbed in the duodenum and proximal jejunum, which proximal Crohn’s disease can involve directly. The second is anaemia of inflammation. Inflammatory cytokines, especially IL-6, drive hepatic production of hepcidin, which degrades ferroportin — the only cellular iron exporter. Iron is then trapped inside enterocytes and macrophages: dietary and oral supplemental iron is absorbed poorly no matter how much is given, while stored iron cannot be mobilised for erythropoiesis. This is why oral iron underperforms in active Crohn’s disease in a way it does not in simple dietary deficiency.

Who is most at risk

• Active mucosal ulceration with ongoing occult blood loss
• Proximal small bowel (duodenal/jejunal) disease involvement
• High inflammatory burden with raised CRP, driving hepcidin
• Menstruating patients, who start from a lower reserve
• Restricted or low-residue diets adopted during flares

Symptoms of deficiency

• Fatigue that is disproportionate to disease activity — usually the earliest and most disabling symptom
• Breathlessness on exertion, palpitations, headache
• Pallor, brittle nails, hair shedding
• Restless legs syndrome
• Pica — craving ice, clay or starch
• Impaired concentration and measurably reduced quality of life even before anaemia develops

Many of these overlap with Crohn’s disease itself, which is exactly why deficiencies are missed. Fatigue attributed to active disease is frequently anaemia, and neuropathy attributed to medication is sometimes B12.

How it is tested

Ferritin alone is unreliable in Crohn’s because it is an acute phase reactant and rises with inflammation. Interpret it against CRP: without inflammation, ferritin below 30 µg/L indicates deficiency; with active inflammation, the threshold rises to 100 µg/L. Transferrin saturation below 20% supports the diagnosis, and soluble transferrin receptor is useful where the picture is ambiguous. ECCO guidance is to screen every 6–12 months in quiescent disease and at least every 3 months in active disease.

Replenishment protocols

Intravenous iron is first-line in active IBD, in anyone intolerant of oral iron, and where haemoglobin is below 100 g/L. Ferric carboxymaltose is the best-studied preparation in IBD and allows large single doses with a strong safety record. ECCO recommends a minimum of 500–1,000 mg of iron for symptomatic deficiency even without anaemia. Oral iron remains reasonable in quiescent disease with mild deficiency, but should be given at low dose — 40–60 mg of elemental iron every other day is better absorbed than daily high doses because it avoids the hepcidin spike that daily dosing provokes. Ferric maltol is an oral option designed for better GI tolerability in IBD. Unabsorbed luminal iron generates oxidative stress and shifts the microbiome, which is the mechanistic reason high-dose oral iron so often aggravates symptoms.

Amounts reflect what gastroenterology literature and guidelines describe. The right dose for you depends on your test results, absorption and surgical history, so test first and work with your care team to personalise it.

Medication interactions

Oral iron binds and reduces absorption of numerous drugs and should be separated from them by at least two hours. Proton pump inhibitors reduce oral iron absorption by raising gastric pH. None of the biologics — Humira, Remicade, Stelara, Skyrizi, Entyvio — interfere with iron directly, but by controlling inflammation they lower hepcidin and make iron therapy work better, which is why anaemia often resolves after successful escalation of Crohn’s therapy.

Sources

1. 1

   European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases

   Dignass AU, Gasche C, Bettenworth D, et al. · Journal of Crohn’s and Colitis (ECCO) · 2015 · PMID 25518052

2. 2

   Practical guidance for the management of iron deficiency in patients with inflammatory bowel disease

   Stein J, Aksan A, Farrag K, Dignass A, Radeke HH. · Therapeutic Advances in Gastroenterology · 2018

3. 3

   Safety and efficacy of ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease: a systematic review

   Systematic review of ferric carboxymaltose in IBD · Cureus · 2025