Iron (oral salts: sulfate, fumarate, gluconate, bisglycinate, polymaltose)

Iron preparations. Antianaemic agents

ATC code: B03AA-IRON-ORAL (Oral iron (generic salt group))

Brand names – drugs

Feosol, Ferro-Sequels

Brand names – supplements

Solgar Gentle Iron, Thorne Iron Bisglycinate

Supplements are not tested in clinical trials and are not registered as medications.

Mechanism of action

Iron is a structural component of haem in haemoglobin and myoglobin and a cofactor for respiratory enzymes. Absorbed mainly in the duodenum and proximal jejunum. Absorption is regulated by hepcidin, an acute-phase protein that reduces absorption in inflammation. Ferrous iron (Fe²⁺, sulphate, fumarate, bisglycinate) is absorbed more readily than ferric iron (Fe³⁺, polymaltose) in patients without inflammation, but ferric forms cause less dyspepsia.

Indications

Iron deficiency anemia

First line

Oral iron is first-line for mild-to-moderate iron deficiency anaemia. Starting daily dose is 60–100 mg elemental iron; alternate-day dosing is more effective than daily per RCTs (less hepcidin response, better bioavailability). Target haemoglobin rise is 10–20 g/L over 4 weeks. Total therapy duration is 3–6 months after haemoglobin normalises to replenish stores. Efficacy is supported by WHO, BSG, and the 2021 Lancet seminar.

In oral intolerance, severe anaemia (haemoglobin below 70 g/L), inflammatory bowel disease, or late pregnancy with anaemia, intravenous iron is used.

Sources

Iron supplementation in pregnancy

First line

Daily 30–60 mg elemental iron in all pregnant women from early pregnancy to delivery and for 6 weeks postpartum is WHO-recommended for prevention of iron deficiency anaemia and obstetric complications. The 2015 Cochrane review (61 RCTs, more than 44,000 women) confirmed a 70% reduction in term anaemia and an 8% reduction in low birth weight. Russian clinical guidelines support routine use in pregnancy from early gestation.

Sources

Iron deficiency without anaemia

Individual decision

In patients with ferritin below 30 µg/L and clinical symptoms (fatigue, reduced exercise tolerance, restless legs), iron therapy is justified. BSG 2021 supports 4–6 weeks of oral therapy with follow-up ferritin. In women with heavy menstrual bleeding and low ferritin without anaemia, it is common practice. In symptomatic patients with ferritin above 30 µg/L, the decision is individualised given other likely fatigue causes.

Sources

Chronic fatigue without a clinical diagnosis

Not recommended

In patients with normal ferritin, transferrin, and haemoglobin, iron therapy for chronic fatigue lacks evidence. Unnecessary iron administration without deficiency increases oxidative stress risk and can worsen concurrent inflammatory processes. “Iron for fatigue” without laboratory work-up is not recommended by any international guidelines.

Sources

Practical notes

Timing and administration

Take on an empty stomach 30–60 minutes before meals, with water or a vitamin C-containing drink (enhances absorption). If dyspepsia is intolerable, take with food, but absorption drops 2–3 fold. Alternate-day dosing (100–200 mg) in non-pregnant women is more effective than daily dosing per the Stoffel 2017 RCTs.

Dose titration

Elemental iron dose: 60–100 mg daily when given daily; 100–200 mg on alternate days. One Sorbifer Durules tablet contains 100 mg elemental iron, Maltofer syrup 10 mg/mL, Tot'hema ampoule 50 mg. Prophylactic pregnancy dose is 30–60 mg daily, treatment dose 100–200 mg daily.

Monitoring

At 2 weeks, check reticulocytes (should rise). At 4 weeks, check haemoglobin (expected rise 10–20 g/L). If no rise, reconsider the diagnosis: exclude ongoing bleeding, absorption problems, or a dosing error. After haemoglobin normalises, check ferritin every 2–3 months for a year – therapy continues until ferritin exceeds 50 µg/L.

Food and drinks

Reduce absorption: calcium (dairy, calcium supplements), tea, coffee, whole grains with phytates, antacids, proton pump inhibitors. Separate iron and these items by at least 2 hours. Quinolones, tetracyclines, levothyroxine, and levodopa form insoluble complexes with iron – separate by at least 4 hours.

Common myths

Myth: “all women need iron for energy”. Fact: with normal ferritin, iron has no effect on fatigue. Unwarranted use increases oxidative stress. Check ferritin and complete blood count before buying an iron supplement.

Myth: “Maltofer is safer than Sorbifer because it's ferric”. Fact: safety differences with oral use are minor. Ferrous iron (Sorbifer, Feosol) is more effective at correcting deficiency; ferric forms (Maltofer) irritate the gastrointestinal tract less. The choice is a matter of tolerance.

Myth: “pomegranate juice and buckwheat raise haemoglobin”. Fact: non-haem iron from plant sources (buckwheat, pomegranate, apples) is absorbed less efficiently than haem iron from animal sources (red meat, liver, shellfish). In established anaemia, dietary correction is adjunctive – iron preparations are the main therapy.

Drug–nutrient interactions

Calcium

Calcium reduces iron absorption by 40–60% at concurrent doses above 300 mg. Iron and calcium are separated by 2 hours. In long-term therapy with both, timing is planned to different parts of the day.

Source: BSG: British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults (2021)

Vitamin C (ascorbic acid)

Ascorbic acid 100–200 mg increases ferrous iron absorption by 10–15% by reducing Fe³⁺ to Fe²⁺. The effect is stronger with concurrent than separated dosing. In BSG guidance, vitamin C is optional with iron therapy – not considered mandatory.

Source: BSG: British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults (2021)

Safety

Contraindications

Haemochromatosis and other iron overload states
Haemolytic, aplastic, and sideroblastic anaemia
Iron absorption disorders (haemosiderosis, haemochromatosis)
Repeated transfusions without ferritin monitoring
Hypersensitivity to components

Serious adverse effects

Acute overdose in children under 6 – potentially fatal at more than 20 mg/kg elemental iron
Anaphylactic reactions with parenteral administration (not applicable to oral forms)

Common adverse effects

Nausea, epigastric discomfort
Constipation or diarrhoea
Dark stools (normal, not indicative of bleeding)
Metallic taste

Uncommon adverse effects

Tooth staining with liquid forms without a straw (reversible)
Skin rash, pruritus

PregnancyFDA A

Routine oral iron in pregnancy is encouraged by WHO. FDA category A at recommended doses. In severe anaemia with oral intolerance, intravenous iron is used after the first trimester.

Breastfeeding

Transfers into breast milk in minimal amounts. Breast milk iron content is independent of maternal intake at physiological doses. Infants over 6 months receive iron separately, regardless of maternal status.