Definition:

• Iron is an essential component of hundreds of proteins and enzymes that support essential biological functions, such as oxygen transport, energy production, and DNA synthesis. Hemoglobin, myoglobin, cytochromes, and peroxidases require iron-containing heme as a prosthetic group for their biological activities.
• Because the body excretes very little iron, iron metabolism is tightly regulated. In particular, the iron regulatory hormone, hepcidin, blocks dietary iron absorption, promotes cellular iron sequestration, and reduces iron bioavailability when body iron stores are sufficient to meet requirements.
• Iron status can be assessed in healthy men and nonpregnant women using laboratory tests that measure serum ferritin (iron-storage protein), serum iron, total iron binding capacity, saturation of transferrin (the main iron carrier in blood), and soluble transferrin receptor.
• Iron deficiency results from an inadequate supply of iron to cells following depletion of the body’s reserves. Microcytic anemia occurs when body iron stores are so low that hemoglobin synthesis and red blood cell formation are severely impaired.
• Iron deficiency is the most common nutritional deficiency worldwide, affecting primarily children, women of childbearing age, pregnant women, frequent blood donors, and individuals with certain medical conditions.
• Much of our iron requirement is met through recycling iron from senescent red blood cells. The recommended dietary allowance (RDA) for iron is 8 mg/day for men and postmenopausal women, 18 mg/day for premenopausal women, and 27 mg/day for pregnant women.
• Iron deficiency with or without anemia in children has been associated with poor cognitive development, poor school achievement, and abnormal behavior patterns. Limited evidence suggests that iron supplementation has no effect on the psychomotor development and cognitive function of anemic iron-deficient infants younger than three years but may improve attention and concentration in older children, adolescents, and women with anemia and/or iron deficiency.
• Heme iron comes from hemoglobin and myoglobin in animal food sources and represents 10%-15% of the total dietary iron intake of meat eaters. Yet, because it is much better absorbed than nonheme iron found in both plant and animal food sources, heme iron contributes up to 40% of total absorbed iron.
• Toxic iron deposition in vital organs in patients affected by hereditary hemochromatosis has been associated with numerous chronic conditions, including liver cancer and type 2 diabetes mellitus. Increased heme iron intake and/or loss of iron homeostasis might also increase the risk of chronic disease in individuals free of genetic disorders.
• Iron supplementation may cause gastrointestinal irritation, nausea, vomiting, diarrhea, or constipation, and interfere with the absorption and efficacy of certain medications, including antibiotics and drugs used to treat osteoporosis, hypothyroidism, or Parkinson’s disease symptoms.

Drug interactions

• Acid-suppressive therapy: Treatment with drugs that suppress gastric acid secretion may decrease the absorption of nonheme iron.
• Angiotensin-converting enzyme (ACE) inhibitors: Iron supplementation (256 mg/day of ferrous sulfate for 4 weeks) reduced the severity of angiotensin-converting enzyme (ACE) inhibitor-induced cough. However, ingestion of iron at the same time as captopril decreased the absorption of unconjugated captopril (the active form of the drug), apparently because of a chemical interaction between ferric ions and captopril in the gastrointestinal tract.
• Fluoroquinolone antibiotics: Iron and other minerals can bind to fluoroquinolones (such as ciprofloxacin, norfloxacin, levofloxacin, and gemifloxacin) and markedly reduce their absorption. It is recommended that mineral-containing supplements not be taken within 1–2 hours before or 2–6 hours after taking fluoroquinolones (recommendations vary according to the drug being used).
• Levodopa/carbidopa: Iron forms chemical complexes with levodopa and carbidopa. Administration of 325 mg of ferrous sulfate along with levodopa/carbidopa reduced the bio-availability of levodopa by 30% and the bioavailability of carbidopa by more than 75
• Iron has been shown to inhibit the absorption of levothyroxine, apparently by forming a complex with it. It is recommended that levothyroxine be taken at least 1 hour before or 2–4 hours after iron supplements.
• Iron decreases the absorption of penicillamine by chelating it in the intestinal tract.
• Concurrent administration of iron with tetracyclines (including minocycline) may interfere with the absorption of the drugs.

Dosage and administration

• Common dosage recommendation for patients with iron deficiency is 50–60 mg of elemental iron twice a day with food. This regimen frequently causes gastrointestinal side effects. A dosage of 30 mg 3 times per day with food may be better tolerated and is said to be sufficient to correct iron deficiency in most cases. Taking vitamin C with iron enhances iron absorption, but taking iron as a component of a multivitamin-multimineral preparation appears to decrease the bioavailability of iron. In patients with iron deficiency, laboratory indicators of iron status may improve after 6–12 weeks of supplementation, but longer treatment periods may be necessary to achieve adequate iron stores.