Iron Absorption Inhibition – Causes and Treatment

What is Iron Absorption Inhibition?

Iron absorption inhibition describes the reduced uptake of dietary iron through the intestinal mucosa into the bloodstream. Iron is an essential trace element required for the production of haemoglobin (the red blood pigment), oxygen transport, and numerous metabolic processes. When iron absorption is chronically impaired, it can lead to iron deficiency and, consequently, iron deficiency anaemia.

Mechanism of Iron Absorption

Dietary iron exists in two forms: haem iron (from animal sources such as meat) and non-haem iron (from plant-based foods). Haem iron is absorbed directly and efficiently in the small intestine. Non-haem iron must first be converted to its divalent form (Fe²⁺) by the enzyme ferrireductase before it can enter intestinal cells via the transporter DMT1 (Divalent Metal Transporter 1). This process is more susceptible to inhibition by various dietary components and medical conditions.

Causes of Iron Absorption Inhibition

Dietary Inhibitors

• Phytates (phytic acid): Found in whole grains, legumes, and nuts. Phytates bind iron in the gut, making it insoluble and unavailable for absorption.
• Polyphenols and tannins: Present in tea, coffee, red wine, and certain vegetables. They form insoluble complexes with iron, significantly reducing its uptake.
• Calcium: High calcium intake (e.g., from dairy products or calcium supplements) can impair the absorption of both haem and non-haem iron.
• Oxalates: Found in spinach, rhubarb, and cocoa; they bind iron and reduce its bioavailability.
• Phosphates: Phosphate additives in processed foods and soft drinks can inhibit iron absorption.

Medications as Inhibitors

• Proton pump inhibitors (PPIs) and antacids: These drugs reduce stomach acid, which is necessary for converting Fe³⁺ to Fe²⁺, thereby impairing iron uptake.
• Tetracyclines and fluoroquinolones: These antibiotics form chelate complexes with iron that are neither absorbed nor therapeutically active.
• Levothyroxine: When taken together with iron supplements, thyroid hormone preparations can mutually inhibit each other's absorption.

Diseases as Causes

• Coeliac disease: Chronic inflammation and villous atrophy in the small intestine significantly reduce the absorptive surface area.
• Crohn's disease and ulcerative colitis: Chronic inflammatory bowel diseases impair the absorptive capacity of the intestine.
• Helicobacter pylori infection: Can affect gastric acid production and thereby inhibit iron absorption.
• Elevated hepcidin levels: The liver hormone hepcidin regulates iron metabolism. During inflammation or chronic disease, increased hepcidin production blocks the release of iron from cells and inhibits intestinal absorption.

Symptoms of Chronic Iron Absorption Inhibition

If iron absorption inhibition goes unrecognised and untreated, it can lead to significant iron deficiency. Common symptoms include:

• Fatigue and exhaustion
• Pale skin and mucous membranes
• Shortness of breath and palpitations during exertion
• Difficulty concentrating and headaches
• Brittle nails and hair loss
• Angular cheilitis (cracks at the corners of the mouth)
• Restless legs syndrome

Diagnosis

Diagnosing impaired iron absorption involves a combination of medical history, blood tests, and further investigations where necessary:

• Full blood count: Detection of microcytic, hypochromic anaemia
• Serum ferritin: The most important marker of iron stores; reduced in iron deficiency
• Transferrin saturation and serum iron: Provide information on current iron transport in the blood
• Hepcidin measurement: Can be useful when functional iron absorption disorder is suspected
• Intestinal diagnostics: In cases of suspected underlying conditions such as coeliac disease or inflammatory bowel disease (endoscopy, biopsy, serological tests)

Treatment and Management

Dietary Optimisation

Targeted dietary adjustments can improve iron absorption. Key measures include:

• Taking vitamin C (ascorbic acid) alongside iron-rich meals, as it reduces Fe³⁺ to Fe²⁺ and increases iron solubility.
• Avoiding tea and coffee immediately before or after meals (allow at least 1 hour between consumption and iron intake).
• Separating calcium supplements from iron-rich meals or iron supplements by several hours.
• Reducing phytate content in legumes and grains through soaking, sprouting, or fermentation.

Supplementation

In confirmed iron deficiency, oral iron supplements (e.g., ferrous sulphate, ferrous gluconate) are used. These should be taken on an empty stomach with a glass of water or orange juice to maximise absorption. In cases of severe malabsorption or intolerance, intravenous iron therapy may be necessary.

Treatment of Underlying Conditions

Where an underlying condition such as coeliac disease or inflammatory bowel disease is identified, its treatment is essential for achieving long-term improvement in iron absorption.

At-Risk Groups

Certain groups of people are at increased risk of iron absorption inhibition and its consequences:

• Vegetarians and vegans (higher proportion of non-haem iron in the diet)
• Pregnant and breastfeeding women
• Infants and toddlers during growth phases
• Older adults
• Individuals with chronic inflammatory bowel disease or following gastric surgery
• People taking proton pump inhibitors long-term

References

1. Löffler, G. et al. - Biochemie und Pathobiochemie. Springer Verlag, 9th edition (2014).
2. World Health Organization (WHO) - Iron Deficiency Anaemia: Assessment, Prevention, and Control. WHO, Geneva (2001). Available at: https://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf
3. Tolkien, Z. et al. - Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS ONE, 10(2): e0117383 (2015). Available at: https://pubmed.ncbi.nlm.nih.gov/25700159/