Iron

Iron is an essential trace mineral that functions as a central component of hemoglobin (the oxygen-carrying protein in red blood cells) and myoglobin (the analogous protein in muscle cells), as well as a component of numerous enzymes involved in energy metabolism, DNA synthesis, and cellular respiration. Approximately two-thirds of the body's iron is contained in functional iron (primarily hemoglobin), with the remainder stored as ferritin and hemosiderin, primarily in the liver, spleen, and bone marrow.¹

Iron deficiency is the most common nutritional deficiency globally and the leading cause of anemia worldwide. It occurs when iron stores are depleted below levels adequate to support normal erythropoiesis and other iron-dependent functions. Causes include inadequate dietary intake, increased requirements (growth, pregnancy, lactation), malabsorption, and blood loss (the most common cause in adults in high-income countries). Iron deficiency exists on a spectrum: iron depletion (reduced ferritin without functional impairment) → iron-deficient erythropoiesis (reduced transferrin saturation) → iron deficiency anemia (reduced hemoglobin).¹

Dietary iron comes in two forms with different absorption characteristics: heme iron (from animal sources, absorbed at approximately 15–35% efficiency) and non-heme iron (from plant sources and iron supplements, absorbed at approximately 2–20% efficiency, highly variable depending on other dietary factors).¹

Iron supplementation is used for the prevention and treatment of iron deficiency and iron deficiency anemia, for meeting increased iron requirements during pregnancy, and increasingly for non-anemic iron deficiency in individuals with symptoms attributable to low iron stores (fatigue, reduced cognitive function, impaired exercise capacity) in the absence of frank anemia.¹

The NIH ODS notes that iron supplementation has been shown to improve iron status, reduce anemia, and improve outcomes in groups at high risk of deficiency including pregnant women, young children, female adolescents, and individuals with iron-related conditions. For non-anemic iron deficiency with functional symptoms, evidence for supplementation benefit is more limited but exists in some populations (e.g., female athletes with iron depletion and reduced exercise performance).¹

Recommended Dietary Allowances (RDA) for iron:¹

• Males 19–50 years: 8 mg/day
• Females 19–50 years: 18 mg/day (higher to account for menstrual losses)
• Pregnant individuals: 27 mg/day
• Postmenopausal females: 8 mg/day

For treatment of iron deficiency anemia, therapeutic doses are substantially higher — typically 150–200 mg of elemental iron per day in adults, divided across doses (for example, 50–65 mg elemental iron two to three times daily). Ferrous sulfate (325 mg tablet = approximately 65 mg elemental iron) is the most commonly used form.

Ferrous bisglycinate (also called iron bisglycinate, iron glycinate) is a chelated form of iron with better gastrointestinal tolerability and comparable absorption efficiency to ferrous sulfate at lower elemental doses; it is commonly used when ferrous sulfate is not tolerated.

The Tolerable Upper Intake Level for iron is 45 mg/day for adults from all sources. Therapeutic doses exceed the UL and are appropriate only under medical supervision with confirmed deficiency.

Oral (most supplement and many prescription forms). Intravenous iron (ferric carboxymaltose, iron sucrose, ferric gluconate) is used when oral supplementation is inadequate or not tolerated — typically in chronic kidney disease, inflammatory bowel disease, or significant malabsorption.

Store at room temperature. Keep away from moisture. Keep out of reach of children — iron overdose is a leading cause of fatal poisoning in young children. Iron supplement containers should have child-resistant caps.¹

Several important considerations apply to iron supplementation:¹

• Side effects: Gastrointestinal effects — constipation, nausea, dark stools, and upper abdominal discomfort — are the most common side effects of oral iron and the primary reason for poor adherence. These effects are dose-related. Ferrous bisglycinate and ferrous gluconate are generally better tolerated than ferrous sulfate. Taking iron with food reduces GI side effects but also reduces absorption by approximately 40%.
• Absorption enhancers and inhibitors: Vitamin C (ascorbic acid) significantly enhances non-heme iron absorption and is often co-administered. Calcium, coffee, tea (tannins), phytates (in whole grains, legumes), and some antacids inhibit non-heme iron absorption; these should be separated from iron supplementation by 1–2 hours.
• Drug interactions: Oral iron reduces absorption of levothyroxine, fluoroquinolone and tetracycline antibiotics, levodopa, and several other medications. Medications should be separated from iron supplements.
• Alternate-day dosing: Emerging research suggests that alternate-day dosing of iron supplements (every other day rather than daily) may improve total absorbed iron over time because of reduced hepcidin-mediated suppression of iron absorption after each dose.
• Iron overload: Iron supplementation without confirmed deficiency can lead to iron accumulation, particularly in individuals with hereditary hemochromatosis or other conditions affecting iron metabolism. Serum ferritin, transferrin saturation, and clinical context should be evaluated before initiating supplementation.
• Pregnancy: Iron needs increase substantially during pregnancy. All pregnant individuals should have iron status assessed, and supplementation is recommended for those with deficiency; universal supplementation during pregnancy is practiced in many clinical guidelines.