Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key component of the hemoglobin protein, acting as a transport medium for electrons within the cells in the form of cytochromes, and facilitating oxygen enzyme reactions in various tissues. Too little iron can interfere with these vital functions and lead to morbidity and death.
Total body iron averages approximately 3.8 g in men and 2.3 g in women. In blood plasma, iron is carried tightly bound to the protein transferrin. Several mechanisms control iron metabolism and safeguard against iron deficiency. The main regulatory mechanism is situated in the gastrointestinal tract. Most iron absorption occurs in the duodenum, the first section of the small intestine. Several dietary factors may affect iron absorption. Iron deficiency develops when iron loss is not sufficiently compensated by the intake of iron from the diet. When this state is uncorrected, it leads to iron-deficiency anemia, a common type of anemia. Before anemia occurs, the medical condition of iron deficiency without anemia is called latent iron deficiency (LID).
Anemia is a condition characterized by inadequate red blood cells (erythrocytes) or hemoglobin. When the body lacks sufficient amounts of iron, the production of the protein hemoglobin is reduced. Hemoglobin binds to oxygen, enabling red blood cells to supply oxygenated blood throughout the body. Women of childbearing age, children, and people with poor diet are most susceptible to the disease. A primary cause of iron deficiency in non-pregnant women is menstrual bleeding, which accounts for their comparatively higher risk than men. Alongside physical symptoms such as dizziness and shortness of breath, women with iron deficiency may also experience anxiety, depression, and restless leg syndrome.
Most cases of iron deficiency anemia are mild, but if not treated, it can cause problems like an irregular heartbeat, pregnancy complications, and delayed growth in infants and children that could affect their cognitive development and behavior.
Signs and symptoms
Symptoms of iron deficiency can occur even before the condition has progressed to iron deficiency anemia.
Symptoms of iron deficiency are not unique to iron deficiency (i.e., not pathognomonic). Iron is needed for many enzymes to function normally, so a wide range of symptoms may eventually emerge, either as a secondary result of anemia or as other primary results of iron deficiency. Common symptoms of iron deficiency include: fatigue pallor headache shortness of breath Less common symptoms of iron deficiency include: hair loss twitches irritability weakness pica tinnitus brittle or grooved nails hair thinning Plummer–Vinson syndrome: painful atrophy of the mucous membrane covering the tongue, the pharynx and the esophagus impaired immune function pagophagia desiderosmia restless legs syndrome in chronic cases, increase in blood pressure
Continued iron deficiency may progress to anemia and progressive fatigue. Iron deficiency can also cause an elevated platelet count (thrombocytosis). Low iron levels in the blood may make some people ineligible to donate blood.
Signs and symptoms in children Iron deficiency in children can progress slowly, and the signs and symptoms may not be obvious. The most common symptom in children is appearing tired and pale. pale skin fatigue slowed growth and development poor appetite decrease in the size of the testes behavioral problems abnormal, rapid breathing frequent infection
Iron requirements in young children to teenagers Age groupRecommended dailyamount of iron7–12 months11 mg1–3 years7 mg4–8 years10 mg9–13 years8 mg14–18 years, girls15 mg14–18 years, boys11 mg
Causes Many factors and health conditions can cause iron deficiency, and in many cases, it can be treated with iron supplements. In women, blood loss from heavy periods is a common cause of iron deficiency. Pregnant women are at risk of iron deficiency. Internal bleeding, such as from an ulcer in the stomach or intestines, is another common cause. Blood loss from donating blood can contribute to iron deficiency. There are also other factors that put people at risk, including: blood loss (hemoglobin contains iron) donation excessive menstrual bleeding non-menstrual bleeding bleeding from the gastrointestinal tract (ulcers, hemorrhoids, ulcerative colitis, stomach or colon cancer, etc.) rarely, laryngeal bleeding or bleeding from the respiratory tract cancer Diet: inadequate iron intake substances (in diet or drugs) interfering with iron absorption Fluoroquinolone antibiotics malabsorption syndromes inflammation where it is adaptive to limit bacterial growth in infection, but is also present in many other chronic diseases such as inflammatory bowel disease and rheumatoid arthritis parasitic infection A 2024 review examined iron metabolism and its interactions with calcium, magnesium, and selected trace elements (copper, zinc, lead, cadmium, mercury, and nickel), as well as their roles in certain diseases.
A 2008 study by researchers at Harvard Medical School identified mutations in the TMPRSS6 gene—encoding the enzyme matriptase-2—as the cause of iron-refractory iron deficiency anemia (IRIDA), a rare autosomal recessive disorder characterized by iron deficiency unresponsive to oral iron supplementation.
Athletics Possible reasons that athletics may contribute to lower iron levels include mechanical hemolysis (destruction of red blood cells from physical impact), loss of iron through sweat and urine, gastrointestinal blood loss, and haematuria (presence of blood in urine). Although small amounts of iron are excreted in sweat and urine, these losses can generally be seen as insignificant even with increased sweat and urine production, especially considering that athletes' bodies appear to become conditioned to retain iron better. Mechanical hemolysis is most likely to occur in high-impact sports, especially among long-distance runners who experience "foot-strike hemolysis" from the repeated impact of their feet with the ground. Exercise-induced gastrointestinal bleeding is most likely to occur in endurance athletes. Haematuria in athletes is most likely to occur in those who undergo repetitive impacts on the body, particularly affecting the feet (such as running on a hard road, or Kendo) and hands (e.g., Conga or Candombe drumming). Additionally, athletes in sports that emphasize weight loss (e.g. ballet, gymnastics, marathon running, and cycling) as well as sports that emphasize high-carbohydrate, low-fat diets, may be at an increased risk for iron deficiency.
Inadequate dietary intake A U.S. federal food consumption survey found that for women and men over 19, average iron consumption from foods and beverages was 13.1 and 18.0 mg/day, respectively. For women, 16% in the age range 14–50 years consumed less than the Estimated Average Requirement (EAR), and for men aged 19 and up, fewer than 3%. Consumption data were updated in a 2014 U.S. government survey and reported that for men and women ages 20 and older the average iron intakes were, respectively, 16.6 and 12.6 mg/day. People in the U.S. usually obtain adequate amounts of iron from their diets. However, subgroups like infants, young children, teenage girls, pregnant women, and premenopausal women are at risk of obtaining less than the EAR. Socio-economic and racial differences further affect the rates of iron deficiency.
Bioavailability Iron is needed for bacterial growth, making its bioavailability an important factor in controlling infection. Blood plasma as a result carries iron tightly bound to transferrin, which is taken up by cells by endocytosing transferrin, thus preventing its access to bacteria. Between 15 and 20 percent of the protein content in human milk consists of lactoferrin that binds iron. Lactoferrin is also concentrated in tears, saliva, and wounds to bind iron to limit bacterial growth. Egg white contains 12% conalbumin to withhold it from bacteria that get through the eggshell (for this reason, before antibiotics, egg white was used to treat infections).
To reduce bacterial growth, plasma concentrations of iron are lowered in a variety of systemic inflammatory states due to increased production of hepcidin, which is mainly released by the liver in response to increased production of pro-inflammatory cytokines such as interleukin-6. This functional iron deficiency will resolve once the source of inflammation is rectified; however, if not resolved, it can progress to anemia of chronic inflammation. The underlying inflammation can be caused by fever, inflammatory bowel disease, infections, chronic heart failure (CHF), carcinomas, or following surgery.
Reflecting this link between iron bioavailability and bacterial growth, taking oral iron supplements over 200 mg/day causes a relative overabundance of iron that can alter the types of bacteria present within the gut. There have been concerns regarding parenteral iron being administered whilst bacteremia is present, although this has not been borne out in clinical practice. A moderate iron deficiency, in contrast, can protect against acute infection, especially against organisms that reside within hepatocytes and macrophages, such as malaria and tuberculosis. This is mainly beneficial in regions with a high prevalence of these diseases and where standard treatment is unavailable.
Diagnosis A complete blood count can reveal microcytic anemia, although this is not always present—even when iron deficiency progresses to iron-deficiency anemia. Low serum ferritin (see below) Low serum iron High TIBC (total iron binding capacity), although this can be elevated in cases of anemia of chronic inflammation. It is possible that the fecal occult blood test might be positive if iron deficiency is the result of gastrointestinal bleeding; although the sensitivity of the test may mean that in some cases it will be negative even with enteral blood loss.
As always, laboratory values must be interpreted with the lab's reference values in mind and considering all aspects of the individual clinical situation.
Serum ferritin can be elevated in inflammatory conditions; so a normal serum ferritin may not always exclude iron deficiency, and the utility is improved by taking a concurrent C-reactive protein (CRP). The serum ferritin level viewed as "high" depends on the condition. For example, in inflammatory bowel disease the threshold is 100, whereas in chronic heart failure (CHF) the levels are 200.
Treatment Before commencing treatment, there should be a definitive diagnosis of the underlying cause of iron deficiency. This is particularly the case in older patients, who are most susceptible to colorectal cancer and the gastrointestinal bleeding it often causes. In adults, 60% of patients with iron-deficiency anemia may have underlying gastrointestinal disorders leading to chronic blood loss. It is likely that the cause of the iron deficiency will need treatment as well.
Upon diagnosis, the condition can be treated with iron supplements. The choice of the supplement will depend upon both the severity of the condition, the required speed of improvement (e.g., if awaiting elective surgery), and the likelihood of treatment being effective (e.g., if the patient has underlying inflammatory bowel disease (IBD), is undergoing dialysis, or is having erythropoiesis-stimulating agent (ESA) therapy).
Commonly-used forms of oral iron are ferrous sulfate, ferrous gluconate, or amino acid chelate tablets. Recent research suggests the replacement dose of iron, at least in the elderly with iron deficiency, may be as little as 15 mg per day of elemental iron.