iron

Iron is a trace mineral that is essential for life and is found in virtually every cell of the human body. About 70% of the body's iron is bound within hemoglobin, a protein in red blood cells responsible for transporting oxygen from the lungs to tissues and organs. Another significant portion resides in myoglobin, a protein in muscle cells that stores and supplies oxygen during physical activity. Iron also forms part of various enzymes and proteins involved in energy metabolism, DNA synthesis, and immune function. Dietary iron exists in two forms: heme iron and non-heme iron. Heme iron, found in animal-derived foods such as red meat, poultry, and seafood, is bound within hemoglobin or myoglobin and is generally absorbed more efficiently by the body. Non-heme iron, found primarily in plant-based foods and fortified products, is not bound within these proteins and is less efficiently absorbed. Despite differences in absorption, both forms contribute importantly to total iron intake. Because the human body has limited mechanisms for excreting iron, most iron is conserved and recycled, particularly through macrophages that break down old red blood cells. Women of reproductive age, due to menstrual blood loss, along with pregnant women, infants and young children with rapid growth, and individuals following strict vegetarian or vegan diets, are at increased risk of inadequate iron intake or status. The deficiency can reduce the production of hemoglobin, leading to iron deficiency anemia and impairing oxygen delivery to tissues, resulting in fatigue, weakness, and impaired cognitive and immune function.

Iron has several critical biological roles. Its primary function is to support oxygen transport and storage. Hemoglobin, the iron-containing protein in red blood cells, binds oxygen in the lungs and releases it in tissues throughout the body. Without adequate iron, hemoglobin synthesis is reduced, impairing oxygen delivery and resulting in fatigue and decreased physical performance. In skeletal muscle, iron is part of myoglobin, which stores oxygen and makes it available during increased metabolic demand. Iron is also a cofactor for numerous enzymes involved in mitochondrial electron transport and energy production, including cytochromes in the electron transport chain. Beyond oxygen transport, iron plays roles in immune function. Iron-containing enzymes are involved in the generation of reactive oxygen species used by immune cells to kill pathogens. Iron is also required for DNA synthesis and repair, and for neurotransmitter synthesis, affecting cognitive function and mood. Several studies have examined the health benefits of iron supplementation in deficient populations. In adults with iron deficiency anemia, oral iron supplementation significantly increases hemoglobin levels and improves symptoms like fatigue and exercise tolerance, with effects seen in randomized controlled trials. In school-aged children, supplemental iron has been shown to improve hemoglobin levels and may improve cognition and attention, particularly in settings of iron-deficiency anemia. For certain clinical conditions like heart failure with iron deficiency, intravenous iron has been studied; meta-analyses suggest improved functional capacity and quality of life in these patients when iron deficiency is corrected. Emerging research also highlights the role of iron in pregnancy. Adequate iron status in pregnancy supports maternal red blood cell expansion and fetal growth. Severe deficiency increases the risk of preterm birth and low birth weight. Given the multifaceted roles of iron in oxygen transport, energy metabolism, and enzymatic reactions, ensuring adequate intake and status is vital for health across the lifespan.

Recommended intakes of iron vary by age, sex, and physiological status. Infants from birth to 6 months have an Adequate Intake (AI) of about 0.27 mg daily. From 7 to 12 months, the Recommended Dietary Allowance (RDA) is approximately 11 mg. Children aged 1–3 years need about 7 mg per day, while those aged 4–8 years need 10 mg. From ages 9 to 13 years, the RDA is 8 mg per day. Among teenagers, boys require about 11 mg while girls require about 15 mg due to menstrual losses. Adult men and women aged 19–50 have different needs: 8 mg per day for men and 18 mg for women to offset menstrual iron losses. After age 50, both men and women require about 8 mg daily. Pregnancy imposes a significant increase in iron requirements to support maternal blood volume expansion and fetal development, with an RDA of 27 mg. During lactation, iron needs decrease compared to pregnancy but remain higher than in non-pregnancy at 9–10 mg daily. Vegetarians and vegans may need nearly twice the RDA due to lower absorption of non-heme iron from plant foods. Factors that influence iron requirements include growth, blood loss, pregnancy, and any condition that increases erythropoiesis. Chronic blood donors, endurance athletes, and people with gastrointestinal disorders that impact absorption may also have higher requirements. Iron needs should be individualized based on dietary intake, bioavailability from food sources, and clinical status.

Iron deficiency progresses through stages. Initially, iron stores become depleted, indicated by reduced serum ferritin. As deficiency worsens, iron supply to the bone marrow diminishes, reducing hemoglobin synthesis and resulting in iron deficiency anemia (IDA). Symptoms often begin subtly. Early signs include fatigue, weakness, and reduced exercise tolerance. As anemia develops, individuals may experience shortness of breath, dizziness, headaches, pale skin and mucous membranes, cold extremities, and impaired concentration. Some people also report unusual cravings for non-food substances (pica), restless legs syndrome, and brittle nails. Children with iron deficiency may demonstrate poor growth, delayed developmental milestones, and impaired cognitive performance. Iron deficiency is common globally and in the United States. National health surveys indicate that approximately 14% of U.S. adults have absolute iron deficiency while about 15% have functional iron deficiency, even without overt anemia. Iron deficiency anemia specifically is estimated to affect a notable proportion of adolescent girls and women of reproductive age, reflecting menstrual blood losses and increased demands. Routine blood tests including hemoglobin, hematocrit, serum ferritin, and transferrin saturation are used clinically to diagnose iron deficiency and its severity. Because iron deficiency can exist without anemia, measures beyond hemoglobin alone may be necessary for accurate diagnosis.

Dietary iron comes from both animal and plant sources. Heme iron is found in animal products and is absorbed more efficiently. Rich sources include beef liver, oysters, clams, lean beef, turkey, and poultry. Non-heme iron is found in plant foods, fortified grains, beans, lentils, tofu, spinach, nuts, seeds, and certain dried fruits. Fortified breakfast cereals often provide particularly high amounts of iron per serving, with some varieties contributing over 15 mg per serving due to fortification. Legumes such as lentils and white beans provide substantial non-heme iron. Dark leafy greens like cooked spinach and kale provide iron along with other micronutrients, though non-heme iron absorption may be limited by phytates and oxalates. Combining plant iron sources with vitamin C-rich foods such as citrus fruits, peppers, or tomatoes can significantly enhance non-heme iron absorption. In addition to common foods like red meat and beans, lesser-known iron sources include mollusks like oysters and clams, which provide notable amounts of iron per serving. Dried fruits like apricots, raisins, and figs contribute plant iron and make convenient snacks. Nuts and seeds such as pumpkin seeds and almonds also add modest amounts of iron. Tofu and tempeh are valuable iron sources for vegetarians and vegans. Whole grains and enriched breads can help contribute to daily iron intake, particularly when part of balanced meals.

Iron absorption varies widely depending on the type of iron and the composition of the meal. Heme iron from animal foods is absorbed at higher rates than non-heme iron from plant sources. Factors that enhance non-heme iron absorption include concurrent intake of vitamin C and heme iron-containing foods. Vitamin C reduces ferric iron to the more soluble ferrous form and forms complexes that are more readily absorbed. Inhibitors of iron absorption include phytates present in grains and legumes, polyphenols in tea and coffee, and calcium from dairy products or supplements if consumed simultaneously with iron-rich meals. Oxalic acid in foods like spinach can bind iron and significantly reduce absorption, making the iron in spinach less bioavailable despite its high iron content. Cooking can reduce some inhibitors and concentrate iron content but does not eliminate all absorption barriers. The hormone hepcidin regulates iron absorption and distribution. High hepcidin levels, which can occur with inflammation or infection, reduce iron absorption and release from stores, contributing to functional iron deficiency. Therefore, both dietary and physiological factors affect how much dietary iron ultimately enters circulation and supports bodily functions.

Iron supplements are commonly used to treat or prevent iron deficiency and iron deficiency anemia. They are particularly recommended in individuals diagnosed with low iron status, those with significant blood loss, pregnant women with increased needs, and individuals unable to meet requirements through diet alone. Typical supplement forms include ferrous sulfate, ferrous gluconate, ferrous fumarate, and newer formulations such as ferric citrate or iron bisglycinate. When supplementation is indicated, clinicians often tailor dosing to individual needs, balancing efficacy and gastrointestinal tolerability. Evidence from clinical studies demonstrates that oral iron supplementation increases hemoglobin and ferritin levels in iron-deficient individuals, improving symptoms like fatigue and exercise intolerance. Some randomized controlled trials have compared daily vs alternate-day dosing, suggesting alternate-day regimens may offer similar efficacy with improved tolerability, though evidence varies. In certain chronic conditions such as heart failure with iron deficiency, intravenous iron has been studied and shows benefits on functional status and quality of life in patients with documented deficiency. Supplements should be taken with medical guidance because excess iron can be harmful. Taking iron on an empty stomach can enhance absorption but may increase gastrointestinal side effects; some individuals tolerate iron better with food despite slightly reduced absorption. The addition of vitamin C does not consistently show a large benefit in all cases, and spacing iron from calcium or antacid supplements can improve absorption. Iron supplements are essential tools for managing deficiency when diet alone is insufficient but should be monitored through blood tests.

Although iron is essential, excess iron can be harmful because the body lacks a regulated pathway to excrete excess amounts. The tolerable upper intake level for adults is generally set at 45 mg per day; exceeding this significantly through supplements increases the risk of adverse effects. Acute iron toxicity most commonly occurs from accidental ingestion of high-dose supplements, particularly in children, and can lead to nausea, vomiting, abdominal pain, metabolic acidosis, and even organ failure. Chronic iron overload can occur in genetic conditions like hereditary hemochromatosis or with excessive supplementation over time. Iron overload leads to increased deposition of iron in organs such as the liver, heart, and pancreas, contributing to conditions including liver disease, cardiomyopathy, diabetes, and joint disorders. Monitoring iron status is crucial during long-term supplementation to prevent toxicity. Symptoms of chronic iron overload may be subtle initially but can include fatigue, arthralgias, and skin hyperpigmentation. Special populations with predispositions to iron accumulation should avoid unnecessary supplementation.

Iron interacts with several medications and nutrients that can affect absorption or therapeutic efficacy. Antacids and proton pump inhibitors (e.g., omeprazole, lansoprazole) decrease gastric acidity, reducing non-heme iron absorption when taken concurrently. Calcium supplements and dairy products can inhibit both heme and non-heme iron absorption if consumed at the same time as iron-rich meals or supplements. Certain antibiotics like tetracyclines and fluoroquinolones can chelate with iron, impairing absorption of both the iron and the antibiotic, necessitating spacing doses by several hours. Additionally, iron can reduce the effectiveness of levothyroxine by binding to it in the gastrointestinal tract, requiring careful timing of ingestion. Iron supplements can interact with other minerals such as zinc and copper, affecting their absorption when taken together in high doses. Clinicians often advise separating iron supplements from these medications and nutrients by at least 2–4 hours to minimize interactions and maximize absorption.

Common Forms: Ferrous sulfate, Ferrous gluconate, Ferrous fumarate, Ferric citrate, Iron bisglycinate

Typical Doses: 30–60 mg elemental iron for deficiency treatment unless otherwise directed

When to Take: On an empty stomach if tolerated, or with food to reduce GI side effects

Best Form: Heme iron or ferrous salts (e.g., ferrous sulfate)

⚠️ Interactions: Antacids, Proton pump inhibitors, Calcium supplements, Antibiotics like tetracycline