Iron

Iron: A Comprehensive Encyclopedic Reference

1. Identity: Chemical Nature, Natural Sources, and Common Forms

Chemical Identity

Iron (chemical symbol: Fe; atomic number: 26; from the Latin ferrum) is an essential trace mineral and the fourth most abundant element in the earth's crust. After oxygen, silicon, and aluminum, iron is the fourth most abundant element in the earth's crust. In biological contexts, iron exists primarily in two oxidation states: ferrous (Fe²⁺) and ferric (Fe³⁺), a chemical duality that underpins both its physiological utility and its biochemical complexity. Iron is an essential trace element that is highly abundant in nature, predominantly in its poorly soluble ferric form. Because iron readily participates in oxidation and reduction chemistry, it has evolved to have an important role in oxygen transport (in hemoglobin), oxygen storage (in myoglobin), energy metabolism (cytochromes), and intermediary metabolism.

Natural Sources

Dietary iron is present in food in two main forms, heme and nonheme. Heme iron, as a component of hemoglobin and myoglobin, is found in animal foods such as meat, fish, seafood, and poultry. Nonheme iron is present in plant-based foods and iron-fortified foods (e.g., iron-fortified cereals). Notable plant sources of nonheme iron include legumes, dark leafy greens, tofu, seeds, and fortified grains. Animal sources supplying heme iron include beef, chicken liver, oysters, clams, and sardines.

Common Forms and Preparations

There are various types of oral iron supplements. The two major classes are ferrous (Fe²⁺) salts and ferric (Fe³⁺) complexes. Other types include carbonyl iron and heme iron polypeptide. The most common oral iron supplements are ferrous salts with sulfate, fumarate, or gluconate. Others include ferrous glycine sulfate, bisglycinate, ascorbate, carbonate, tartrate, iodine, chloride, sodium citrate, aspartate, or succinate.

Among the most widely used forms, ferrous sulfate is the most widely used iron supplement, providing 20% elemental iron. Ferrous fumarate contains 33% elemental iron, while ferrous gluconate contains approximately 12% elemental iron. Because dissolved Fe²⁺ is readily oxidized to insoluble Fe³⁺, a main challenge for liquid supplements is to maintain Fe²⁺ reduced; this is done with the addition of excipients such as sodium bisulfite. Slow-release (enteric-coated) ferrous salt formulations have also been designed with the aim of reducing gastrointestinal adverse effects, while preserving iron absorption.

Intravenous (IV) iron preparations — including iron sucrose, ferric carboxymaltose, ferric gluconate, and low-molecular-weight iron dextran — are available for clinical use when oral therapy is insufficient or poorly tolerated. Iron is available in many dietary supplements. Multivitamin/mineral supplements with iron, especially those designed for women, typically provide 18 mg iron, which is 100% of the Daily Value (DV). Multivitamin/mineral supplements for men or seniors frequently contain less or no iron. Iron-only supplements usually deliver more than the DV, with many providing 65 mg iron (360% of the DV).

2. Traditional and Historical Use

Ancient Civilizations

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia.

Among the earliest recorded medical uses, iron is mentioned in the Ebers Papyrus as an ingredient of a paste for the treatment of eye disease, while haematite in ox fat was applied to the eye by Babylonian physicians to alleviate photophobia. The Hippocratic writings described the use of iron salts to stem bleeding, possibly resulting from the belief that battle wounds were best healed by application of the agent that caused them.

Around 3500 B.C., ancient Egyptians used iron powder for baldness — a condition now described as non-scarring alopecia. Reflecting on the tradition of physical strength associated with Ares, Greeks used a mixture of wine and iron to treat male impotency.

Ayurvedic and South Asian Traditions

Iron is used in Ayurvedic, Siddha, and Unani systems of medicine. Ayaskruti and Lauha Rasayana are the primitive uses of iron, later refined to biologically produced nanoparticles as Iron bhasma. Makhika (Iron pyrite), Kasisa (Ferrous sulphate), and Gairika (Ochre) are iron-containing compounds extensively used in Ayurveda. A total of 293 formulations containing iron nanoparticles (Lauha Bhasma) have been identified, with 85 formulations used for 55 diseases. The maximum formulations of Lauha Bhasma are found for Jvara (Fever), Pandu (Anemia), Arsha (Piles), and Sotha (Inflammatory disorders).

Traditional Chinese and Japanese Medicine

Iron-containing minerals have been documented throughout East Asian medical traditions. The documentation and study of mineral medicines in ancient medical texts have been particularly prominent in Chinese-language literature. Over the past decade, numerous studies have examined historical Chinese medical texts such as Shi Yao Er Ya, Bencao Tujing, Treatise on Cold Damage (Shang Han Lun), Synopsis of the Golden Chamber (Jin Kui Yao Lue), and others. Gelatin-based traditional Chinese medicines have long been used to treat anemia.

Greco-Roman and Medieval European Traditions

Some iron-containing mineral treatments first recorded in the folklore traditions of ancient cultures (e.g., Roman folklore as recorded by Pliny the Elder in the first century AD) were then incorporated into mainstream medicine by authorities such as Galen in the second century AD. In medieval European folk medicine, iron-rich waters from mineral springs (known as "chalybeate" or "steel" waters) were prescribed for conditions characterized by weakness and pallor — conditions that would today be identified as iron-deficiency anemia.

3. Key Constituents, Active Compounds, and Mechanisms of Action

Iron as a Fundamental Biochemical Component

Iron is classified as a trace element and is an essential component of many proteins and enzymes including hemoglobin and myoglobin, the cytochromes, NADH dehydrogenase, lipooxygenases, superoxide dismutase, ribonucleotide reductase, fatty acid desaturases, and phosphatases. Its redox versatility — the ability to cycle between Fe²⁺ and Fe³⁺ — is what makes iron so indispensable to these molecular functions.

The body uses iron to make hemoglobin, a protein in red blood cells that carries oxygen from the lungs to all parts of the body, and myoglobin, a protein that provides oxygen to muscles. The body also needs iron to make some hormones.

Iron is a key functional component of oxygen-transporting and storage molecules (e.g., hemoglobin and myoglobin) and of many enzymes that catalyze the redox reactions required for the generation of energy (e.g., cytochromes), the production of various metabolic intermediates, and for host defense (e.g., nicotinamide adenine dinucleotide phosphate [NADPH] oxidase).

Absorption Mechanisms

The pathway by which iron enters the body depends heavily on its chemical form. Heme iron, sourced from animal foods, is actively absorbed intact into intestinal enterocytes. Heme iron bypasses dietary inhibitors to the enterocyte, where heme oxygenase releases ferrous iron (Fe²⁺). This is then exported into the bloodstream through ferroportin. Alternatively, non-heme iron, predominantly from synthetic or plant-based foods, often initially exists as ferric iron (Fe³⁺), requiring reduction to ferrous iron (Fe²⁺) by duodenal cytochrome B (DcytB) before transport across the enterocyte membrane.

Iron is absorbed as ferrous (Fe²⁺) iron via a divalent metal transporter 1 (DMT-1) located on the apical membrane of the enterocyte. Heme iron can also be absorbed by heme-carrier protein 1 on the apical membrane, after which iron is released by the action of lysosomal heme oxygenase.

Heme iron absorption is approximately 25%, whereas nonheme iron is less well and more variably absorbed. A number of dietary and physiological factors influence the efficiency of dietary nonheme iron absorption. Individuals with adequate body iron stores absorb less nonheme iron than individuals with insufficient body iron stores. Mean dietary iron absorption from Western-style diets is estimated to be around 15% to 18%.

Enhancers and Inhibitors of Absorption

Vitamin C enhances the absorption of non-heme iron due to its iron-chelating and reducing abilities, converting ferric iron to ferrous iron, which is more soluble. Vitamin C also counteracts iron absorption inhibitors, including phytates in grains and legumes, polyphenols in tea, coffee, and red wine, and calcium in dairy products.

Dietary components that influence nonheme iron absorption include animal muscle tissue and ascorbic acid. Inhibitors of nonheme absorption include phytates, polyphenols, and calcium. The heme iron in meats, fish, and poultry (called the "MFP factor") significantly increases iron absorption from non-heme sources such as fruits, vegetables, and grains when consumed together. One study demonstrated that adding chicken, beef, or fish to a meal increased non-heme iron absorption 2 to 3 fold.

The Hepcidin–Ferroportin Axis and Iron Homeostasis

The relatively recent identification of hepcidin and development of techniques to quantify concentrations have revealed that hepcidin is the main regulator of systemic iron homeostasis. Hepcidin has an important role in the development of anemia of inflammation or anemia of chronic disease that is associated with diverse conditions such as obesity, cancer, and infection.

The peptide hepcidin, produced by hepatocytes, helps regulate iron homeostasis. High iron levels in the body stimulate hepcidin production, which decreases iron absorption and promotes cellular iron sequestration, thereby preventing iron overload. Conversely, low iron levels or anemia reduce hepcidin production, thereby increasing dietary iron absorption and the release of stored iron into the circulation to meet the body's needs.

Unlike other minerals, there is no active physiologic process of excretion. This makes iron homeostasis almost entirely dependent on regulating absorption, not elimination, making the hepcidin system critically important.

Aberrantly increased hepcidin leads to systemic iron deficiency and/or iron-restricted erythropoiesis. Furthermore, insufficiently elevated hepcidin occurs in multiple diseases associated with iron overload. Abnormal iron metabolism as a consequence of hepcidin dysregulation is an underlying factor resulting in pathophysiology of multiple diseases, and several agents aimed at manipulating this pathway have been designed, with some already in clinical trials.

4. Scientific Evidence by Area of Use

4.1 Iron-Deficiency Anemia (IDA)

The strongest and most consistent body of evidence for iron supplementation pertains to the treatment and prevention of iron-deficiency anemia (IDA). If dietary iron intake is insufficient to meet iron requirements, body iron stores will become depleted. When a negative iron balance persists for a sufficient period of time, iron deficiency anemia develops.

Short- and long-term clinical consequences of iron deficiency anemia can include developmental delay, cognitive impairment, adverse pregnancy outcomes, and impaired physical performance and quality of life. These adverse outcomes may justify oral iron supplementation when diet alone is anticipated to be insufficient to provide requirements for erythropoiesis and tissue needs and rebuild depleted body iron stores within a reasonable period of time.

Oral supplementation is the standard first-line approach. Ingestion of ferrous sulfate (or other ferrous salts) is expected to promote a rapid surge in serum iron and effectively increase hemoglobinization and iron stores. Iron administered parenterally increases hemoglobin levels to a greater extent and is associated with fewer side effects than oral iron supplementation in patients with anemia of chronic disease.

The evidence for treatment of IDA is classified as strong, based on numerous RCTs and established clinical guidelines. The evidence base is sufficient that regulatory agencies and professional societies worldwide recommend iron supplementation as primary therapy for documented IDA.

4.2 Pregnancy and Maternal Iron Status

Negative pregnancy outcomes, such as increased maternal sickness, low birthweight, preterm birth, and intrauterine growth restriction, are linked to iron deficiency. The WHO currently recommends that 30–60 mg of elemental iron is given daily from as early as possible during pregnancy. This public health policy aims to improve pregnancy outcomes and to reduce maternal anaemia.

Maternal hepcidin expression is suppressed during pregnancy, which ensures increased dietary iron absorption and release of iron stores to ensure adequate iron delivery to the fetus. Maternal hepcidin is a key determinant of iron homeostasis in mouse embryos and placentas.

Evidence for maternal supplementation preventing IDA in pregnancy is well established. Evidence regarding effects on offspring neurodevelopment, however, is more limited. In non-anemic pregnant women, prenatal iron for prevention of IDA resulted in little to no difference in cognition at 40 days post-partum (1 RCT, 503 infants; very low certainty evidence). Similarly, the effect on the intelligence quotient at four years was very uncertain (2 RCTs, 509 children; very low certainty evidence). There is no evidence from upper-middle-income countries and insufficient evidence from high-income countries to support or refute benefits or harms of prophylactic or therapeutic prenatal iron supplementation on child neurodevelopment.

4.3 Cognitive Development in Children

Iron deficiency is associated with impaired cognitive and motor development in infants and school-age children, and supplementation studies have attempted to address whether iron reverses these deficits. Iron supplementation of school-age children is recommended in settings where anemia is prevalent, but the evidence regarding its effectiveness on cognitive development is limited. Iron supplementation improved hemoglobin concentration and reduced the incidence of anemia and iron deficiency in school-age children. Furthermore, iron supplementation was shown to be effective in improving cognition, safe in malaria settings, and had no gastrointestinal adverse effects in certain trials.

However, a systematic review searching through December 2009 found mixed results: none of 5 RCTs individually showed a beneficial effect of iron supplementation during early life on the Mental Developmental Index of the Bayley Scales of Infant Development at different ages throughout the first 18 months. Meta-analysis of 3 RCTs (n = 561) showed that, compared with placebo, supplementation with iron had no significant effect on children's Mental Developmental Index at approximately 12 months of age (weighted mean difference: 1.66; 95% CI: −0.14, 3.47). Three of 5 RCTs showed a beneficial effect of iron supplementation on the Psychomotor Development Index at some time points, whereas 2 did not.

Limited available evidence suggests that iron supplementation in infants may positively influence children's psychomotor development, whereas it does not seem to alter their mental development or behavior. Overall, evidence in this area is preliminary and mixed, with effect magnitude and certainty depending heavily on baseline iron status and degree of deficiency in study populations.

4.4 Physical Performance and Athletic Exercise Capacity

Insufficient iron status, starting with iron deficiency non-anaemia, is associated with fatigue, which may present as lack of energy, tiredness, decreased work and training capacity, performance impairment, poorer competition results, impaired muscle function, and impaired stress management.

A systematic review and meta-analysis published in The Journal of Nutrition found that daily oral iron supplementation in women of reproductive age (WRA) improves both maximal and submaximal exercise performance. These benefits are clearest in iron-deficient and trained women.

However, a more recent 2025 meta-analysis reached more nuanced conclusions: iron supplementation did not improve exercise performance assessed during time-to-exhaustion (TTE; MD: 0.76 min; 95% CI: −0.13, 1.65; p = 0.067) or time trial (TT; MD: −1.78 min; 95% CI: −3.88, 0.333 min; p = 0.059) protocols. By combining TTE and TT studies in the same analysis, a non-significant effect on exercise performance was observed (SMD: 0.97; 95% CI: −0.49 to 2.44; p = 0.139). Moreover, although iron supplementation led to consistent improvements in hemoglobin and serum ferritin levels, its effects on cardiorespiratory fitness and exercise performance were mixed. A moderate and statistically significant improvement in VO₂max or VO₂peak was observed (SMD: 0.70; 95% CI: 0.08 to 1.31; p = 0.030).

In the athletic population, despite recent proposals for a refinement of treatment strategies for iron-deficient athletes, there is no general consensus regarding the actual efficiency, dosage, or optimal regimen of oral iron supplementation. Evidence is rated as moderate for improvements in iron biomarkers (hemoglobin, serum ferritin) and preliminary-to-moderate for performance outcomes in iron-deficient populations.

4.5 Chronic Kidney Disease (CKD) and Anemia

Chronic inflammatory conditions, including chronic kidney disease, heart failure, and inflammatory bowel disease, can impair iron absorption or utilization, often through mechanisms involving hepcidin, which sequesters iron and reduces its availability for erythropoiesis.

Clinical data for iron supplementation in CKD-related anemia exist. A prospective observational study in 132 patients with anemia and chronic kidney disease who were not on dialysis or ESAs found that oral supplements (130 mg/day elemental iron from ferrous sulfate twice daily) for 1 year resulted in a decline in hemoglobin of only 0.13 g/dL compared with a decline of 0.46 g/dL in the placebo group. Hepcidin-mediated iron restriction contributes to anemia of chronic kidney disease, along with impaired renal production of erythropoietin. Intravenous iron is often preferred in CKD patients because oral bioavailability is impaired by elevated hepcidin.

4.6 Heart Failure

Iron deficiency has emerged as one of the most important causes of anaemia in patients with heart failure, though other causes need to be excluded as well. The prevalence of anemia among individuals with HF varied between 35% and 70%, with an overall prevalence of 55.4% across reviewed studies. Intravenous iron (particularly ferric carboxymaltose) has been studied in several clinical trials of heart failure patients and has shown improvements in functional capacity and quality of life, though the evidence base for mortality benefit remains evolving and is an active area of research.

4.7 Cancer-Related Anemia

In a randomized trial of 100 patients with cancer-related anemia, taking oral iron supplements (equivalent to 200 mg/day elemental iron, form of iron not specified) once per week with an erythropoiesis-stimulating agent (ESA) resulted in a mean increase of 2.4 g/dL hemoglobin after 24 weeks compared with taking only oral supplements. This area of evidence is active but still developing; IV iron is increasingly studied as an adjunct to ESA therapy in oncology settings.

4.8 Iron Deficiency Without Anemia (IDWA)

Emerging evidence suggests that iron deficiency in the absence of overt anemia can still impair fatigue, cognitive function, and work capacity, though the clinical evidence base is smaller and more heterogeneous than for IDA. A 2003 double-blind, randomized, placebo-controlled trial (BMJ 2003;326:1124) examined iron supplementation for unexplained fatigue in non-anemic women and found benefit; however, the overall evidence base for this indication remains preliminary and requires further RCTs.

5. Body Systems and Health Areas

• Hematopoietic system: Essential for erythropoiesis; incorporated into hemoglobin in red blood cells; deficiency leads to microcytic, hypochromic anemia.
• Musculoskeletal system: Provides oxygen to muscles via myoglobin. Deficiency impairs muscle energy metabolism and exercise tolerance.
• Neurological system: Iron is needed to keep the immune system healthy and help brain cells work normally. Iron is required for myelination, neurotransmitter synthesis, and dopaminergic pathway function.
• Immune system: Iron is a cofactor for immune-cell enzymes including NADPH oxidase; both deficiency and excess impair immune competence.
• Endocrine system: The body also needs iron to make some hormones. Iron is a cofactor for thyroid peroxidase, required for thyroid hormone synthesis.
• Cardiovascular system: Iron-deficiency anemia increases cardiac workload and is associated with adverse cardiovascular outcomes, particularly in heart failure.
• Energy metabolism: Iron forms the core of molecules required for the generation of ATP in all cells, including cytochromes in the mitochondrial electron transport chain.
• Reproductive and perinatal health: Critical for fetal development, placental function, and maternal erythropoiesis during pregnancy.

6. Dosage: Recommended Intakes and Amounts Used in Studies

Recommended Dietary Allowances (RDAs)

The RDA for healthy men of all ages (≥19 years of age) is 8 mg daily. The RDA for healthy women 19–50 years of age is 18 mg daily, and the RDA for healthy women ≥51 years of age is 8 mg daily.

The requirement for iron is 1.8 times higher for people who follow vegetarian diets than those who include animal products in their diet. This is because heme iron from meat is more bioavailable than nonheme iron from plant-based foods.

Supplemental Dosage Forms and Amounts Used in Research

• Iron-deficiency anemia treatment: Oral supplements of 130 mg/day elemental iron (from ferrous sulfate twice daily) for 1 year were studied in CKD patients with anemia.
• Cancer-related anemia: Oral iron equivalent to 200 mg/day elemental iron was used once per week alongside ESA therapy in a trial of 100 cancer patients.
• Pregnancy supplementation (WHO guidance): 30–60 mg of elemental iron daily from as early as possible during pregnancy.
• Athletic populations: 100 mg of FeSO₄ (approximately 20 mg of elemental iron) was shown to be effective in one RCT in active women.
• Elderly patients with IDA (dose-finding study): Rimon et al. compared three doses of oral iron — 15 mg, 50 mg, and 150 mg — and showed that supplementation at the level of the RDA (15 mg of elemental iron) already led to significant increases in iron status. The doses of 50 mg and 150 mg did not show further benefit but had significantly more side effects, particularly in the highest-dose group.
• Multivitamin/mineral supplements: Those designed for women typically provide 18 mg iron (100% of the Daily Value).
• High-dose therapeutic supplements: Over-the-counter high-dosage iron supplements prescribed for those with iron-deficiency anemia or who are at high risk for it may contain 65 mg or more.

The Food and Nutrition Board (FNB) has established Tolerable Upper Intake Levels (ULs) for iron from food and supplements based on amounts of iron associated with gastrointestinal effects following supplemental intakes of iron salts. The ULs apply to healthy infants, children, and adults. Physicians sometimes prescribe intakes higher than the UL, such as when people with IDA need higher doses to replenish their iron stores.

Established ULs from the NIH: Birth to 12 months: 40 mg; Children 1–13 years: 40 mg; Teens 14–18 years: 45 mg; Adults 19+ years: 45 mg.

In a 2024 scientific opinion, the EFSA Panel established a safe level of intake for iron of 40 mg/day for adults (including pregnant and lactating women), based on interventions in which black stools did not occur at supplemental iron intakes of 20–25 mg/day added to a background intake of 15 mg/day. Using allometric scaling, this value was scaled down to children and adolescents, with safe levels of intake between 10 mg/day (1–3 years) and 35 mg/day (15–17 years).

7. Safety Considerations and Interactions

Gastrointestinal Adverse Effects

Commonly reported side effects of using high-dosage iron supplements include constipation and nausea. Gastrointestinal intolerance — including nausea, abdominal pain, constipation, and dark stools — is among the most frequently cited reasons for poor compliance with oral iron supplementation. It is established that systemic iron overload leads to organ toxicity, but no formal UL could be established by EFSA based on these endpoints. The only indicator for which a dose–response could be established was black stools, which reflect the presence of large amounts of unabsorbed iron in the gut. This is a conservative endpoint among the chain of events that may lead to systemic iron overload, but is not adverse per se.

Iron Overload and Toxicity

Iron toxicity occurs only with excess supplement consumption, including accidental ingestions, and in genetic conditions causing iron overload, such as hemochromatosis.

Without treatment by periodic chelation or phlebotomy, people with hereditary hemochromatosis typically develop signs of iron toxicity by their 30s. These effects can include liver cirrhosis, hepatocellular carcinoma, heart disease, and impaired pancreatic function. The American Association for the Study of Liver Diseases recommends that treatment of hemochromatosis include the avoidance of iron and vitamin C supplements.

There is evidence that oral iron loading increases circulating hepcidin; the recommended dosage of oral iron should not be too high.

Populations Requiring Special Caution

Patients with iron-overloaded states such as hereditary hemochromatosis, hemosiderosis, or a history of hemolytic anemia should not use iron supplements without medical supervision. Iron-deficiency anemia can also occur during periods of increased iron demand, such as pregnancy, infancy, and adolescence, when the body's need for iron surpasses intake or absorption. Conditions that decrease iron absorption, such as celiac disease, atrophic gastritis, and post-bariatric surgery, can also contribute to this condition.

Drug Interactions

The major mechanism of iron-drug interactions is the formation of iron-drug complexes (chelation or binding of iron by the involved drug). A large number of other important and commonly used drugs such as thyroxine, captopril, and folic acid have been demonstrated to form stable complexes with iron.

Key clinically significant interactions include:

• Levodopa (Parkinson's disease): Iron salts can interfere with the absorption of levodopa, decreasing peak levels by 55% and area under the curve by 51%.
• Levothyroxine (thyroid hormone replacement): A total of 107 articles with 128 studies documented drug interactions involving calcium and iron supplements, proton pump inhibitors, bile acid sequestrants, phosphate binders, sex hormones, anticonvulsants, and other drugs. Some food and beverages could also induce malabsorption. Iron and levothyroxine should be separated by at least four hours.
• Tetracycline and fluoroquinolone antibiotics: Concurrent ingestion of iron causes marked decreases in the bioavailability of a number of drugs. The affected drugs include tetracycline, tetracycline derivatives (doxycycline, methacycline, and oxytetracycline), penicillamine, methyldopa, levodopa, carbidopa, and ciprofloxacin. Doses should be separated by at least two hours.
• Proton pump inhibitors (PPIs) and antacids: Medications that reduce stomach acid, such as antacids (like Tums) and proton pump inhibitors (like omeprazole), can significantly impair iron absorption. The clinical relevance of this interaction is confirmed by a prospective study showing suboptimal response to ferrous sulfate in iron-deficient patients taking omeprazole.
• Calcium: Calcium might interfere with the absorption of iron, although this effect has not been definitively established. For this reason, experts suggest that people take individual calcium and iron supplements at different times of the day.
• Bisphosphonates: Iron reduces the absorption of bisphosphonates (e.g., alendronate), making them less effective at strengthening bones. Doses should be separated by at least two hours.
• Methyldopa: Iron can cause worsening of hypertension in patients taking methyldopa, and concomitant administration is not recommended.

Administration Considerations

It is generally recommended to administer oral iron between meals (e.g., 1 hour before or 2 hours after a meal) for optimal absorption, though this must be balanced against gastrointestinal tolerability, as food may reduce side effects at the cost of reduced absorption. Dietary iron intake is not directly related to body iron levels because of the wide variability in nonheme iron absorption, which complicates the derivation of Dietary Reference Intakes and has necessitated the use of dietary bioavailability algorithms to predict absorption.

Diagnostic Considerations

Hemoglobin and hematocrit are the most commonly used measures to screen patients for iron deficiency, although they are neither sensitive nor specific. Serum ferritin concentration, which is a measure of the body's iron stores, is also used, but it can be affected by inflammation. Often, health care providers will use multiple measurements to diagnose iron deficiency.

Global Burden

Worldwide, iron deficiency is considered to be the most common nutritional deficiency disorder. According to the WHO, iron deficiency is the most pervasive nutritional deficiency globally. In the 2021 Global Burden of Disease Study, the global prevalence of anemia was found to be 24.3% (1.92 billion people), with iron deficiency contributing to 66.2% of all anemia cases and affecting 825 million women and 444 million men globally.

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