Iron deficiency

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Common nutritional deficiency caused by inadequate iron stores, with or without anemia

Iron deficiency
Synonyms Low iron, depleted iron stores, iron depletion, sideropenia
Pronounce N/A
Specialty Hematology, Primary care, Gastroenterology, Nutrition, Obstetrics
Symptoms Fatigue, weakness, pallor, reduced exercise tolerance, shortness of breath, dizziness, headache, brittle nails, hair loss, pica, restless legs
Complications Iron deficiency anemia, impaired cognitive development, adverse pregnancy outcomes, reduced work capacity, heart strain in severe anemia
Onset Usually gradual
Duration Variable; may be acute after blood loss or chronic with ongoing loss or poor intake
Types N/A
Causes Inadequate intake, increased requirement, blood loss, malabsorption, inflammation-related impaired iron use
Risks Pregnancy, heavy menstrual bleeding, gastrointestinal bleeding, infancy, adolescence, vegetarian or vegan diet without planning, celiac disease, inflammatory bowel disease, bariatric surgery, chronic kidney disease
Diagnosis Complete blood count, serum ferritin, transferrin saturation, serum iron, total iron-binding capacity, reticulocyte hemoglobin in selected cases
Differential diagnosis Anemia of inflammation, thalassemia trait, vitamin B12 deficiency, folate deficiency, chronic kidney disease, sideroblastic anemia, lead poisoning
Prevention Iron-rich diet, food fortification, supplementation in high-risk groups, treatment of blood loss, screening when indicated
Treatment Oral iron, intravenous iron, dietary optimization, treatment of underlying cause, blood transfusion only for selected severe cases
Medication Ferrous sulfate, ferrous fumarate, ferrous gluconate, ferric maltol, iron sucrose, ferric carboxymaltose, ferric derisomaltose, ferumoxytol, low-molecular-weight iron dextran
Prognosis Usually good when the cause is identified and treated
Frequency Very common worldwide
Deaths N/A


Koilonychia iron deficiency anemia
File:Iron-deficiency anaemia world map-Deaths per million persons-WHO2012.svg
Iron-deficiency anaemia world map-Deaths per million persons-WHO2012

Iron deficiency is a state of insufficient body iron stores to meet physiologic needs. It may occur with or without anemia. When iron deficiency becomes severe enough to reduce hemoglobin production, it causes iron deficiency anemia, the most common form of anemia worldwide. Iron deficiency can affect oxygen transport, energy metabolism, immune function, pregnancy outcomes, physical performance, cognition, and quality of life.Anaemia(link). World Health Organization.Iron: Fact Sheet for Health Professionals(link). National Institutes of Health Office of Dietary Supplements.

Iron deficiency is caused by inadequate intake, increased requirements, impaired absorption, chronic blood loss, or a combination of these factors. Common settings include heavy menstrual bleeding, pregnancy, rapid growth in infants and adolescents, gastrointestinal blood loss, celiac disease, inflammatory bowel disease, bariatric surgery, and chronic kidney disease."Iron-deficiency anemia".New England Journal of Medicine.2015;372(19)

1832-1843.doi:10.1056/NEJMra1401038.PMID:25946282.

Overview[edit]

Iron deficiency exists on a spectrum.

Iron deficiency can be missed if clinicians only look for anemia. Symptoms such as fatigue, restless legs, hair shedding, poor concentration, or reduced exercise capacity may occur before hemoglobin falls.

Physiology of iron[edit]

Iron is essential for many biologic processes.

  • Hemoglobin - Iron-containing protein in red blood cells that carries oxygen.
  • Myoglobin - Iron-containing protein that stores oxygen in muscle.
  • Heme - Iron-containing chemical group used in hemoglobin, myoglobin, cytochromes, and enzymes.
  • Cytochrome - Iron-containing proteins involved in cellular respiration.
  • Mitochondrion - Cellular organelle that depends on iron-containing enzymes for energy production.
  • Ferritin - Main intracellular iron storage protein; serum ferritin reflects iron stores in many clinical settings.
  • Transferrin - Blood protein that transports iron.
  • Transferrin saturation - Percentage of transferrin iron-binding sites occupied by iron.
  • Hepcidin - Liver-derived hormone that regulates iron absorption and release from stores.
  • Ferroportin - Iron export protein inhibited by hepcidin.
  • Duodenum - Main site of dietary iron absorption.
  • Macrophage - Recycles iron from old red blood cells.
  • Bone marrow - Uses iron to produce red blood cells.

The body has no active mechanism for excreting excess iron. Iron balance is controlled mainly by absorption from the intestine and recycling from red blood cells.

Dietary iron[edit]

Dietary iron occurs in two major forms.

  • Heme iron - Iron from animal foods such as meat, poultry, and fish; generally more readily absorbed.
  • Non-heme iron - Iron from plant foods, fortified foods, eggs, and supplements; absorption is more influenced by other dietary factors.
  • Iron-fortified food - Food with added iron, such as some cereals and grain products.
  • Bioavailability - Degree to which iron can be absorbed and used.
  • Ascorbic acid - Vitamin C, which can improve non-heme iron absorption.
  • Phytate - Compound in grains and legumes that can reduce non-heme iron absorption.
  • Calcium - Can inhibit iron absorption when taken at the same time in some settings.
  • Tannin - Tea and coffee compounds that can reduce non-heme iron absorption.

Iron-rich foods include red meat, poultry, fish, shellfish, beans, lentils, tofu, spinach, pumpkin seeds, iron-fortified cereals, and enriched grains.

Causes[edit]

Inadequate intake[edit]

  • Low intake of iron-rich foods.
  • Poorly planned vegetarian diet or vegan diet.
  • Food insecurity.
  • Restrictive eating patterns.
  • Infants fed unfortified cow's milk too early.
  • Low intake of iron-fortified foods.
  • Malnutrition.
  • Eating disorders.

Increased requirements[edit]

  • Pregnancy
  • Lactation
  • Infancy
  • Childhood growth
  • Adolescence
  • Menstruation
  • Endurance athletics
  • Recovery from blood loss
  • Treatment with erythropoiesis-stimulating agents

Blood loss[edit]

Chronic blood loss is a major cause of iron deficiency.

In adult men and postmenopausal women, iron deficiency anemia should prompt evaluation for gastrointestinal blood loss unless an obvious non-gastrointestinal cause is present. The American Gastroenterological Association recommends bidirectional endoscopy for asymptomatic postmenopausal women and men with iron deficiency anemia.Gastrointestinal evaluation of iron deficiency anemia(link). American Gastroenterological Association.

Malabsorption[edit]

Inflammation and functional iron deficiency[edit]

Inflammation can make iron unavailable even when stores are present.

Risk groups[edit]

  • Infants and toddlers.
  • Children with excessive cow's milk intake.
  • Adolescents, especially menstruating adolescents.
  • Pregnant people.
  • People with heavy menstrual bleeding.
  • Premenopausal women.
  • Postmenopausal women with occult blood loss.
  • Adult men with occult gastrointestinal bleeding.
  • Vegetarians and vegans without planned iron intake.
  • Endurance athletes.
  • Frequent blood donors.
  • People after bariatric surgery.
  • People with celiac disease or inflammatory bowel disease.
  • People with chronic kidney disease.
  • People with heart failure.
  • People with cancer.
  • Older adults.
  • People with low socioeconomic status or food insecurity.

Signs and symptoms[edit]

Iron deficiency may be asymptomatic, especially early. Symptoms become more likely as deficiency worsens or anemia develops.

General symptoms[edit]

  • Fatigue
  • Weakness
  • Reduced exercise tolerance
  • Shortness of breath
  • Dizziness
  • Lightheadedness
  • Headache
  • Palpitations
  • Poor concentration
  • Irritability
  • Cold intolerance
  • Sleep disturbance

Skin, hair, and nail findings[edit]

Neurologic and behavioral symptoms[edit]

  • Restless legs syndrome
  • Pica
  • Pagophagia - Craving or eating ice.
  • Poor attention
  • Reduced school performance
  • Developmental delay in severe childhood deficiency
  • Irritability in children
  • Breath-holding spells in some children

Symptoms of iron deficiency anemia[edit]

  • Worsening fatigue.
  • Exertional dyspnea.
  • Tachycardia.
  • Chest discomfort in susceptible patients.
  • Syncope or near-syncope.
  • Pale conjunctiva.
  • Reduced work capacity.
  • Heart failure symptoms in severe or prolonged anemia.

Complications[edit]

Untreated iron deficiency can lead to multiple complications.

  • Iron deficiency anemia
  • Impaired physical performance
  • Reduced work productivity
  • Impaired cognitive development in infants and children
  • Behavioral and learning problems
  • Restless legs syndrome
  • Adverse pregnancy outcomes
  • Premature birth
  • Low birth weight
  • Maternal fatigue and reduced quality of life
  • Increased transfusion risk around surgery or childbirth
  • Heart strain in severe anemia
  • Worsening symptoms in heart failure or chronic kidney disease
  • Reduced immune function in selected settings

Diagnosis[edit]

Diagnosis requires both confirmation of iron deficiency and identification of the cause.

Initial evaluation[edit]

  • Medical history.
  • Diet history.
  • Menstrual history.
  • Pregnancy history.
  • Medication review.
  • Blood donation history.
  • Gastrointestinal symptoms.
  • History of bariatric surgery.
  • Family history of anemia or thalassemia.
  • Physical examination.
  • Assessment for bleeding, malabsorption, inflammation, and chronic disease.

Laboratory tests[edit]

  • Complete blood count - Evaluates hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width.
  • Serum ferritin - Best single marker of iron stores in many patients.
  • Serum iron - Circulating iron level; varies with time and inflammation.
  • Total iron-binding capacity - Indirect measure of transferrin availability.
  • Transferrin saturation - Often low in iron deficiency.
  • C-reactive protein - Helps interpret ferritin in inflammatory states.
  • Reticulocyte hemoglobin content - Reflects recent iron availability for red blood cell production.
  • Soluble transferrin receptor - May help distinguish iron deficiency from anemia of inflammation.
  • Peripheral blood smear.
  • Vitamin B12 and folate when macrocytosis or mixed anemia is suspected.
  • Kidney function tests.
  • Liver function tests.
  • Stool occult blood testing in selected contexts.
  • Celiac serology when indicated.
  • H. pylori testing when indicated.

Typical laboratory pattern[edit]

Classic iron deficiency anemia may show:

  • Low hemoglobin.
  • Low hematocrit.
  • Low mean corpuscular volume.
  • Low mean corpuscular hemoglobin.
  • High red cell distribution width.
  • Low serum ferritin.
  • Low serum iron.
  • High total iron-binding capacity.
  • Low transferrin saturation.
  • Reactive thrombocytosis in some cases.

Ferritin is an acute-phase reactant and may be falsely normal or elevated during inflammation, infection, liver disease, kidney disease, cancer, or obesity. In these settings, transferrin saturation, CRP, soluble transferrin receptor, reticulocyte hemoglobin, and clinical context become more important.

Ferritin thresholds[edit]

Ferritin interpretation depends on clinical context.

  • Very low ferritin is highly specific for iron deficiency.
  • Ferritin below 30 micrograms/L often suggests iron deficiency in many adults.
  • In patients with anemia, AGA recommends a ferritin cutoff of 45 ng/mL rather than 15 ng/mL for diagnosing iron deficiency.
  • In inflammatory disease, chronic kidney disease, or heart failure, iron deficiency may exist at higher ferritin levels if transferrin saturation is low.
  • WHO provides ferritin thresholds for assessing iron status in individuals and populations, with adjustments for inflammation.WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations(link). World Health Organization, NCBI Bookshelf.

Evaluation for underlying cause[edit]

Treatment should not stop at iron replacement. The cause must be identified when possible.

Premenopausal women[edit]

Common causes include heavy menstrual bleeding, pregnancy, dietary deficiency, and gastrointestinal disease. Evaluation depends on age, severity, symptoms, bleeding pattern, response to iron, and risk factors.

Men and postmenopausal women[edit]

Iron deficiency anemia in men and postmenopausal women is gastrointestinal blood loss until proven otherwise in many cases. Endoscopic evaluation is often recommended.

Children[edit]

Evaluation focuses on diet, cow's milk intake, growth, prematurity, lead exposure, chronic disease, gastrointestinal symptoms, and blood loss.

Pregnancy[edit]

Evaluation includes hemoglobin, ferritin when indicated, diet, supplementation history, gestational age, and obstetric risk.

After bariatric surgery[edit]

Iron deficiency is common after gastric bypass and other bariatric procedures because of reduced intake, reduced acid, bypassed absorption sites, and intolerance of iron-rich foods.

Differential diagnosis[edit]

Treatment[edit]

Treatment has two goals: replenish iron and correct the underlying cause.

Dietary treatment[edit]

Diet alone may help prevent deficiency and support recovery, but established iron deficiency often requires supplementation.

  • Increase heme iron foods such as meat, poultry, and fish when acceptable.
  • Increase non-heme iron foods such as beans, lentils, tofu, spinach, pumpkin seeds, fortified cereals, and enriched grains.
  • Pair non-heme iron with vitamin C-rich foods such as citrus, berries, peppers, or tomatoes.
  • Avoid taking iron supplements with tea, coffee, calcium supplements, or high-calcium meals.
  • Address food insecurity and dietary restrictions.
  • Use culturally appropriate nutrition counseling.

Oral iron therapy[edit]

Oral iron is usually first-line therapy when absorption is adequate and symptoms are not severe.

Modern practice often uses lower-dose oral iron once daily or every other day to improve absorption and tolerability. British Society of Gastroenterology guidance recommends initial treatment with one tablet per day of ferrous sulfate, fumarate, or gluconate; if not tolerated, a reduced dose every other day, alternative oral preparations, or parenteral iron may be considered."British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults".Gut.2021;70(11)

2030-2051.doi:10.1136/gutjnl-2021-325210.PMID:34497146.PMC:8515119.

Oral iron side effects[edit]

  • Nausea
  • Constipation
  • Diarrhea
  • Abdominal pain
  • Metallic taste
  • Dark stools
  • Heartburn
  • Poor adherence due to gastrointestinal intolerance

Side effects may improve with lower dose, alternate-day dosing, different formulation, taking with a small amount of food, or switching to IV iron when appropriate.

Intravenous iron[edit]

IV iron is used when oral iron is ineffective, not tolerated, too slow, or unlikely to be absorbed.

Common indications include:

  • Severe iron deficiency anemia requiring rapid correction.
  • Malabsorption.
  • Inflammatory bowel disease with active inflammation.
  • Chronic kidney disease.
  • Heart failure with iron deficiency.
  • Post-bariatric surgery iron deficiency.
  • Ongoing blood loss exceeding oral replacement.
  • Late pregnancy when rapid correction is needed.
  • Intolerance to oral iron.
  • Poor response to oral iron.
  • Need to optimize hemoglobin before surgery.

IV iron preparations include:

Potential risks include infusion reactions, hypersensitivity, hypotension, and hypophosphatemia with some formulations. Patients should be monitored according to local protocols.

Blood transfusion[edit]

Blood transfusion is not a routine treatment for uncomplicated iron deficiency. It may be needed for severe symptomatic anemia, hemodynamic instability, active major bleeding, or urgent clinical circumstances. Iron replacement is still needed after transfusion unless iron overload is present.

Monitoring response[edit]

Response to treatment should be monitored.

  • Reticulocyte response may begin within about a week.
  • Hemoglobin often rises over several weeks if treatment is effective.
  • Anemia may correct in 1 to 3 months depending on severity and ongoing losses.
  • Iron therapy is often continued for several months after hemoglobin correction to replenish stores.
  • Ferritin and transferrin saturation can be rechecked to confirm repletion.
  • Lack of response should prompt assessment of adherence, dose, absorption, ongoing bleeding, incorrect diagnosis, inflammation, or mixed deficiency.

Iron deficiency in pregnancy[edit]

Iron requirements increase substantially during pregnancy because of maternal red cell expansion, fetal growth, placental development, and blood loss at delivery.

  • Screening is commonly performed during prenatal care.
  • Iron deficiency may occur even before anemia develops.
  • Oral iron is commonly used.
  • IV iron may be used in selected patients, especially when oral iron is not tolerated, malabsorption is present, anemia is moderate to severe, or rapid correction is needed later in pregnancy.
  • Severe untreated iron deficiency anemia is associated with maternal fatigue, transfusion risk, preterm birth, and low birth weight.

Iron deficiency in infants and children[edit]

Children are vulnerable because of rapid growth and dietary transitions.

  • Premature infants have lower iron stores.
  • Exclusively breastfed infants may need iron supplementation after early infancy depending on local guidelines.
  • Iron-fortified formula and cereals can prevent deficiency.
  • Excess cow's milk intake can displace iron-rich foods and cause intestinal blood loss in some toddlers.
  • Iron deficiency can impair neurodevelopment.
  • Pediatric dosing and evaluation should be supervised by a clinician.

Iron deficiency in chronic disease[edit]

Chronic kidney disease[edit]

Iron deficiency is common in chronic kidney disease because of inflammation, reduced erythropoietin, blood loss, dialysis, and treatment with erythropoiesis-stimulating agents.

Heart failure[edit]

Iron deficiency can worsen exercise capacity and quality of life in heart failure, even without anemia. Some guidelines support IV iron in selected patients with heart failure and iron deficiency.

Inflammatory bowel disease[edit]

Iron deficiency may result from intestinal blood loss, inflammation, poor intake, and malabsorption. IV iron is often preferred when disease is active or oral iron is not tolerated.

Cancer[edit]

Cancer-related iron deficiency may be due to blood loss, inflammation, poor intake, treatment effects, or surgery. Management depends on cancer type, treatment plan, anemia severity, and goals of care.

Prevention[edit]

Prevention depends on risk group and cause.

  • Iron-rich diet.
  • Iron-fortified foods.
  • Prenatal vitamins or iron supplementation during pregnancy when recommended.
  • Screening high-risk infants and children.
  • Avoiding excessive cow's milk in toddlers.
  • Treating heavy menstrual bleeding.
  • Investigating gastrointestinal blood loss.
  • Iron replacement after bariatric surgery when indicated.
  • Monitoring frequent blood donors.
  • Deworming and malaria control in endemic regions when appropriate.
  • Food fortification programs.
  • Public health nutrition programs.
  • Education on iron absorption enhancers and inhibitors.

Public health[edit]

Iron deficiency is the most common nutritional deficiency globally and the leading nutritional cause of anemia. It contributes to maternal morbidity, impaired child development, reduced productivity, and health inequities. Strategies to reduce burden include food fortification, supplementation for high-risk groups, infection control, reproductive health care, poverty reduction, and improved access to diagnosis and treatment.

WHO states that iron deficiency is the most common nutritional deficiency leading to anemia, though anemia can also result from deficiencies of folate, vitamin B12, vitamin A, infections, inflammation, inherited blood disorders, and other causes.Anaemia(link). World Health Organization.

Prognosis[edit]

The prognosis is usually good when iron deficiency is recognized, treated, and the underlying cause is corrected. Recurrence is common when the cause persists, such as heavy menstrual bleeding, gastrointestinal blood loss, malabsorption, chronic kidney disease, or inadequate dietary intake.

Patient education[edit]

  • Iron deficiency can occur without anemia.
  • Fatigue, pica, restless legs, hair shedding, or poor exercise tolerance may be clues.
  • Do not ignore iron deficiency in adult men or postmenopausal women because gastrointestinal bleeding must often be excluded.
  • Take oral iron as directed; more frequent dosing is not always better.
  • Keep iron supplements away from children because overdose can be dangerous.
  • Vitamin C can improve absorption of plant-based iron and supplements.
  • Tea, coffee, calcium, and some antacids can reduce iron absorption when taken with iron.
  • Report black tarry stools, blood in stool, vomiting blood, heavy periods, unexplained weight loss, or persistent abdominal pain.
  • Follow-up blood tests are important to confirm recovery.
  • Treating the cause is as important as replacing iron.

When to seek medical care[edit]

  • Severe fatigue or shortness of breath.
  • Chest pain or fainting.
  • Rapid heartbeat.
  • Pregnancy with symptoms of anemia.
  • Heavy menstrual bleeding.
  • Blood in stool or black tarry stools.
  • Vomiting blood.
  • Unexplained weight loss.
  • Persistent abdominal pain.
  • New iron deficiency in an adult man.
  • New iron deficiency after menopause.
  • Failure to respond to oral iron.
  • Symptoms of celiac disease or inflammatory bowel disease.
  • Child with poor growth, pica, developmental concerns, or excessive cow's milk intake.
  • Restless legs symptoms with fatigue or low ferritin.
  • Recurrent iron deficiency after prior treatment.

See also[edit]

Further reading[edit]

  • Anaemia(link). World Health Organization.
  • WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations(link). World Health Organization, NCBI Bookshelf.
  • Guideline on haemoglobin cutoffs to define anaemia in individuals and populations(link). World Health Organization.
  • Iron: Fact Sheet for Health Professionals(link). National Institutes of Health Office of Dietary Supplements.
  • Gastrointestinal evaluation of iron deficiency anemia(link). American Gastroenterological Association.
  • "AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia".Gastroenterology.2020;159(3)
1085-1094.doi:10.1053/j.gastro.2020.06.046.PMID:32810434.
  • "British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults".Gut.2021;70(11)
2030-2051.doi:10.1136/gutjnl-2021-325210.PMID:34497146.PMC:8515119.
  • "Iron-deficiency anemia".New England Journal of Medicine.2015;372(19)
1832-1843.doi:10.1056/NEJMra1401038.PMID:25946282.
  • "Oral iron treatment in adult iron deficiency".European Journal of Haematology.2022;PMC:9949769.
  • "Recommendations for diagnosis, treatment, and prevention of iron deficiency and iron deficiency anemia".HemaSphere.2024;PMC:11247274.

External links[edit]



Nutrition information of Iron deficiency[edit]


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