Why is Iron Deficiency Important?

Iron is required for good mental and physical health, to maintain energy levels and to ensure a healthy immune system.1–4 Without sufficient iron, patients may feel exhausted, lethargic and apathetic, and can exhibit a range of other symptoms which highlight the various systemic effects of low iron levels. Clinical studies have also shown that low iron levels can have a negative impact on an individual’s quality of life, both socially and economically.3 Iron deficiency can be diagnosed as a comorbidity with underlying chronic conditions and can be an indicator of a negative future outlook  for the patient’s health.5–7


Iron Metabolism

Iron is an essential nutrient that is required for many processes within the human body. It is primarily required for the production of haemoglobin, which carries oxygen within the red blood cells (erythrocytes) from the lungs to the rest of the body.8 Iron is also used in many enzymatic reactions, for example in energy metabolism and DNA synthesis,9 and is required for a healthy immune system.4 The majority of the iron in the body is present within haemoglobin, with substantial amounts also found in macrophages and the myoglobin of muscles. Excess iron is mainly stored in the liver but can also be stored as ferritin in other tissues.9,10

Iron is absorbed, mostly within the duodenum, from both plant and meat/fish sources (haem and non-haem sources, respectively).11 The balance of iron within the body is regulated by the intake of iron-containing foods and by the tight control of dietary iron absorption in the duodenum.9 Iron excretion is not regulated by the body.9 In healthy individuals, iron is only lost through the shedding of mucosal or skin cells or through bleeding.9

Iron is transported in the blood plasma via the iron transport protein transferrin, and is taken to the bone marrow for erythropoiesis.12 Erythropoiesis is stimulated by the hormone erythropoietin that is released from the kidneys. Iron is first incorporated into a haem group which is capable of binding oxygen, and then combines with other protein components to form haemoglobin within the red blood cells.12

At the end of their lifespan, red blood cells are engulfed and digested by the macrophages of the liver and spleen, and iron is released to be recycled or stored within the hepatocytes of the liver.8,9,13

About iron deficiency, with and without anaemia

Iron supply and demands can easily become imbalanced, leading to iron deficiency.

Iron deficiency without anaemia occurs when the iron stores in the body are reduced (serum ferritin concentration <15 µg/L) but haemoglobin levels are still above the cut off value for anaemia (Hb>12 g/dL). Over time iron deficiency can lead to iron deficiency anaemia where iron stores are depleted (serum ferritin concentration <15 µg/L), and haemoglobin levels drop below healthy values (Hb<12 g/dL).10

Iron deficiency is the most common nutritional deficiency in the world14 and between two and three percent of people in the United States are iron deficient.15,16 Women and children are more at risk of iron deficiency than men because of the increased iron demands from menstrual bleeding and growth.17,18

Functional and absolute iron deficiency

Iron deficiency can be divided into two categories, functional iron deficiency and absolute iron deficiency.10

In absolute iron deficiency iron stores are reduced or depleted and that iron transfer is low, meaning that insufficient iron is available for erythropoiesis.19 Absolute iron deficiency can be caused by:

  • An inadequate intake of absorbable iron in the diet
    • This can occur in vegetarians and vegans15
  • Inadequate absorption of iron in the gastrointestinal tract
    • This can be caused by inflammation of the gut mucosa, which can occur in conditions such as coeliac disease or inflammatory bowel disease20,21
  • Blood loss, for example as a result of:
    • Heavy periods15
    • Gastro-intestinal bleeding20
    • Frequent blood donation15
    • Traumatic injuries,22,23 or
    • Surgery24
  • Increased demand for red blood cells or oxygen in the body, for example as a result of:
    • Intense exercise25   
    • Growth and development in infants, children and adolescents, or11
    • Pregnancy15
  • Some other medical conditions and/or therapies, such as haemodialysis.

Absolute iron deficiency can be determined by a serum ferritin level below 15 µg/ L.10

In functional iron deficiency, the body contains adequate iron stores but the iron cannot be mobilised fast enough to the bone marrow for red blood cell production.10  This could be due to:

  • The use of erythropoietin stimulating agents (ESAs) that rapidly use up the iron circulating in the body26 
  • Recent blood donation27
  • Chronic inflammation in diseases such as inflammatory bowel disease or rheumatoid arthritis (this is also known as the anaemia of chronic disease)28
  • Malignant diseases10

If a patient has functional iron deficiency, they may have a normal or elevated serum ferritin value, but have more erythrocytes with a lower concentration of haemoglobin and/or a reduced haemoglobin content of  immature red blood cells (reticulocytes).10

Why is it important to treat iron deficiency? 

Recognising iron deficiency and treating it appropriately can greatly improve your patient’s quality of life by relieving symptoms of fatigue and other signs associated with iron deficiency. This can increase your patients’ productivity at work, improve their social lives and help them to feel happier and healthier.29–31

In addition to general improvements, the status of the patient’s comorbidities can also improve. For example, one study suggests that the long-term outlook for patients with chronic heart failure is more positive for non-anaemic patients than anaemic patients7 and another showed that non-anaemic cancer patients can feel stronger and more able to undergo further rounds of cancer treatments than anaemic patients.32