What Is Iron?
Iron is an essential trace mineral present in virtually every cell of the body — and one the body cannot synthesise itself. As the central atom of haemoglobin in red blood cells, iron carries oxygen from the lungs to all tissues. As a component of myoglobin, it stores oxygen in muscle tissue for use during physical exertion.
Iron is not an optional add-on but a biochemical cornerstone — with one critical distinction from most nutrients: both deficiency and excess are clinically harmful.
Iron Distribution in the Body
| Compartment | Share of body iron | Function |
|---|---|---|
| Haemoglobin (red blood cells) | ~65% | Oxygen transport |
| Ferritin / haemosiderin (stores) | ~25% | Iron reserve in liver, spleen, bone marrow |
| Myoglobin (muscle) | ~10% | Oxygen storage for muscle work |
| Enzymes, transport proteins | <1% | Cytochromes, transferrin |
Who Is at Risk of Iron Deficiency?
- Menstruating women — losses of ~15–20 mg per cycle
- Pregnant women — demand rises to ~27 mg/day
- Vegans and vegetarians — rely exclusively on non-haem iron with lower bioavailability
- Endurance athletes — haemolysis (foot-strike, intravascular) and sweat losses
- People with coeliac disease, Crohn’s disease, or other malabsorption conditions
- Frequent blood donors
Mechanism: Haem vs. Non-Haem Iron
Bioavailability is the central issue with iron — and it differs dramatically between dietary sources.
Two Dietary Forms
Haem iron (animal sources): Found as a haem complex in meat, fish, and poultry. Absorption rate: ~25% — largely independent of other dietary components.
Non-haem iron (plant sources): Present as Fe³⁺, which must first be reduced to Fe²⁺ in the gut before absorption. Absorption rate: ~2–20% — strongly modulated by dietary enhancers and inhibitors.
Key Absorption Modulators
| Factor | Effect | Mechanism |
|---|---|---|
| Vitamin C (50–100 mg) | +300–600% absorption | Reduces Fe³⁺ to Fe²⁺; chelates soluble complexes |
| Fermented grains | +2–3-fold | Phytate breakdown by phytases |
| Meat, fish | +2-fold (for non-haem) | “Meat factor” — mechanism not fully elucidated |
| Coffee, black tea | −60–90% | Polyphenols bind iron |
| Calcium | −50% when taken simultaneously | Competitive transport mechanism |
| Phytates (grains, legumes) | −30–80% | Chelation; reduced by soaking or fermentation |
Iron Regulation: Hepcidin
The body has no active iron excretion pathway — it regulates iron balance exclusively through absorption. The liver-produced peptide hepcidin is the master regulator: when iron stores are full, hepcidin rises and blocks intestinal absorption. During inflammation, hepcidin also rises — which is why lab values can be misleading during acute infection or chronic inflammatory disease.
Evidence
Deficiency Prevalence and Diagnosis
Looker et al. (PMID 23107545): In nationally representative US data, iron deficiency (ferritin <12 µg/L) affected ~9–11% of women of reproductive age and ~2% of men. Iron deficiency anaemia is the single most common nutrient-deficiency cause of anaemia worldwide.
Pasricha et al. 2021 (PMID 31174214): The classical ferritin threshold of <12 µg/L detects only overt deficiency. Functional iron deficiency — impaired erythropoiesis and fatigue without full anaemia — occurs already at ferritin <30 µg/L. Clinical recommendation: treat ferritin <30 µg/L as a relevant intervention threshold even in the absence of classical anaemia. Key limitation: during concurrent inflammation (elevated CRP), ferritin can be falsely elevated into the normal range. In these cases, transferrin saturation should be measured alongside.
Vegetarians and Vegans: Elevated Risk
Haider et al. 2018 (PMID 27880062): The most comprehensive systematic review on iron status in plant-based eaters. Key findings:
- Vegetarian women: mean ferritin ~20 µg/L vs. ~35 µg/L in omnivorous women
- Iron deficiency prevalence in vegetarian women: ~30–40% depending on the threshold used
- Iron deficiency anaemia: 2–3-fold more common in vegetarians
- Adaptive response: the body compensates with ~40% higher absorption rates compared to omnivores consuming meat
Practical implication: people on plant-based diets should monitor ferritin at least annually and supplement or adjust dietary strategies when ferritin falls below 30 µg/L.
Bioavailability of Plant Iron Sources
Hurrell & Egli 2010 (PMID 29155946): Foundational work on non-haem iron absorption. Key numbers:
- Non-haem iron absorption without enhancers: ~2–5%
- With 50 mg vitamin C co-ingested: ~15–20% (3–6-fold increase)
- Coffee or black tea with the same meal: absorption reduced by 60–90%
- Sourdough bread vs. yeast bread: +2–3-fold through phytate degradation
- Soaking legumes before cooking: ~25–50% phytate reduction
These figures explain why plant-based diets without deliberate dietary strategies structurally lead to lower iron status.
Supplement Forms: Bisglycinate vs. Sulfate
Iron supplements differ meaningfully in tolerability and bioavailability:
Iron bisglycinate (chelated): Iron bound to two glycine molecules. Absorbed via a different transporter (peptide transporter PepT1), less affected by dietary inhibitors. Multiple trials show comparable or superior absorption to sulfate with significantly fewer gastrointestinal side effects. Better compliance for long-term supplementation.
Iron sulfate: The most studied and cost-effective form. Effective but associated with higher rates of constipation, nausea, and dark stool — particularly at therapeutic doses ≥100 mg/day.
Iron fumarate, gluconate: Intermediate tolerability; less data than sulfate.
For maintenance supplementation (14–20 mg/day) and anyone with a sensitive gut, bisglycinate is the preferred choice.
What Is Not Supported by Evidence
- Iron supplementation at normal ferritin levels for more energy: No RCT evidence; excess iron is oxidatively harmful
- Performance enhancement in healthy athletes without deficiency: Not evidence-based
- Preventive supplementation without diagnostics: Contraindicated — can harm HFE mutation carriers
- Iron as a general anti-fatigue supplement: Iron helps only iron-deficiency-related fatigue; many other causes exist
Dosing and Timing
| Parameter | Evidence / Practice |
|---|---|
| RDA (EU/US) | 8–18 mg/day (women 18 mg; men 8 mg; pregnancy 27 mg) |
| Therapeutic dose for deficiency | 50–200 mg elemental iron/day, divided doses |
| Maintenance dose | 14–20 mg/day (preventive in at-risk groups) |
| Preferred forms | Iron bisglycinate (best tolerability), iron sulfate (cost-effective) |
| Timing | Fasting or with vitamin C — not with coffee, tea, calcium, or antacids |
| Monitoring | Check ferritin before starting and ~8–12 weeks after |
Alternate-day dosing: Emerging evidence suggests that taking iron every other day (rather than daily) may increase absorption per dose, because daily supplementation raises hepcidin and blunts next-day absorption. Discuss with a physician for therapeutic courses.
EFSA Status
Iron has multiple approved EFSA health claims under Regulation (EC) 1924/2006:
- “Iron contributes to normal cognitive function” ✓
- “Iron contributes to normal formation of red blood cells and haemoglobin” ✓
- “Iron contributes to normal oxygen transport in the body” ✓
- “Iron contributes to normal energy-yielding metabolism” ✓
- “Iron contributes to the normal function of the immune system” ✓
- “Iron contributes to the reduction of tiredness and fatigue” ✓
These claims are scientifically valid — but refer specifically to correction of deficiency, not to supplementation in iron-replete individuals.
Safety and Interactions
Iron is one of the few supplements where overdose is clinically dangerous.
Common side effects during supplementation:
- Constipation, dark stool (expected; not a warning sign)
- Nausea, gastric discomfort (more frequent with sulfate)
- Metallic aftertaste
Serious risks:
- Oxidative stress: Free (non-transferrin-bound) iron catalyses reactive oxygen species via the Fenton reaction — oxidative damage to DNA, lipids, and proteins
- Hereditary haemochromatosis: ~1 in 200–400 people in Northern Europe are homozygous HFE mutation carriers; unsupervised iron supplementation can cause liver, cardiac, and pancreatic damage
- Acute poisoning in children: Iron supplements are a leading cause of accidental poisoning in young children — store securely
Drug interactions:
- Calcium: Inhibits iron absorption — separate by at least 2 hours
- Antacids, PPIs: Reduce gastric acid → impaired iron absorption (iron requires acidic environment)
- Tetracyclines, quinolones: Form insoluble chelates with iron → both less effective; take iron ≥2 hours apart
- Levothyroxine: Separate by at least 2–4 hours
Pregnancy
Iron demand increases substantially during pregnancy — from ~18 mg/day to ~27 mg/day — to support foetal red blood cell production and expanded maternal blood volume. Iron deficiency anaemia in pregnancy is associated with preterm birth, low birth weight, and impaired neonatal development. Routine screening and supplementation (typically 30–60 mg/day) is recommended by WHO in populations with high deficiency prevalence. In Europe, supplementation is individualised based on ferritin testing.
Conclusion
Iron is essential — and targeted supplementation makes a real, measurable difference when deficiency is confirmed: ferritin rises, fatigue resolves, cognitive function improves. The evidence is solid.
But iron is not a wellness supplement for everyone. Supplementing without lab diagnostics (ferritin, ideally with CRP and transferrin saturation) is not merely pointless — it can actively harm individuals with haemochromatosis or those with chronic inflammatory conditions. The principle applies here with unusual force: test first, then supplement.
High-risk groups — menstruating women, vegans, pregnant women, endurance athletes — should check ferritin at least once a year.