Underlying Conditions Associated with Iron Deficiency

Many underlying conditions and lifestyle factors can affect the balance of iron demand and supply in the body. The balance of iron in the body can be disrupted by several factors.

  • Blood loss, and therefore iron loss. This could be due to, for example, heavy menstrual bleeding1 or internal bleeding from gastrointestinal conditions.2,3
  • Malabsorption and inflammation. Malabsorption may occur in many chronic conditions due to inflammation of the intestines, where iron uptake occurs.4,5 Other inflammation associated with chronic conditions can cause the anaemia of chronic disease, where an elevation in hepcidin causes both a decrease in dietary iron absorption and an increase in iron retention within the macrophages.6,7
  • Increased iron needs. This could be due to, for example,  adolescence,8,9 pregnancy,8 or intense physical training.10,11
  • Malnutrition, for example due to a restricted diet1 or bariatric surgery.12 Dietary restrictions either due to personal choice or medical conditions can mean that insufficient iron is available for the body’s needs. 

Chronic heart failure (CHF)

Inflammation and malabsorption. Chronic heart failure can affect multiple organs, including the gastrointestinal tract, which has altered morphology, permeability and absorption in patients with chronic heart failure.13 This may be due to an altered regulatory mechanism of duodenal iron transportation.14 Approximately 50% of heart failure patients have some form of iron deficiency, with or without anaemia.15

Malnutrition. Oedema in the stomach and intestines of heart failure patients can lead to hypomobility of the gastrointestinal tract.16 This hypomobility can lead to a loss of appetite, which in turn can cause malnutrition.16 In addition to this, malnutrition can occur via drug-induced anorexia.16

It is important to monitor for iron deficiency in chronic heart failure since iron deficiency is associated with reduced quality of life,17 impaired exercise capacity,18 and an increased risk of mortality in patients with chronic heart failure.15

Inflammatory Bowel Disease (IBD)

Blood loss. IBD refers to ulcerative colitis and Crohn’s disease, two autoimmune conditions that cause inflammation of the gastrointestinal tract. Ulcerative colitis mainly affects the colon (large intestine), whereas Crohn’s disease may affect any portion of the gastrointestinal tract from mouth to anus.19 A major symptom of IBD is intestinal bleeding.20 In ulcerative colitis the blood loss may be visible as rectal bleeding and loose bloody stools, but in Crohn’s disease it typically occurs as occult blood loss. Blood loss can also occur in Crohn’s disease due to anal fissures, which are a common complication.21 Multiple prevalence studies have shown that 36%–76% of people with IBD experience iron deficiency anaemia.2,22

Malabsorption and inflammation. The inflammation of the mucosa in the duodenum and upper jejunum of patients with IBD can reduce the absorption of iron from food or other oral iron sources.4

Malnutrition. IBD patients may avoid certain iron-rich foods such as leafy green vegetables if they have found that they increase abdominal symptoms.4

Coeliac disease

Blood loss. Bleeding due to any cause within the gastrointestinal tract can lead to iron deficiency.23 One possible cause of gastrointestinal bleeding is coeliac disease , also known as gluten-sensitive enteropathy, an autoimmune inflammatory disease of the small intestines.24 In patients with coeliac disease, the ingestion of gluten can cause chronic inflammation within the small intestine which results in villous atrophy and the flattening of mucosa.25 One study showed that the villous atrophy can cause occult blood loss from the gastrointestinal tract in between 25% and 54% of patients with coeliac disease.26 The prevalence of iron deficiency anaemia for those with coeliac disease is approximately 10-15%.27

Malabsorption and inflammation. The intestinal mucosal inflammation and villous atrophy caused by the immune response of coeliacs to gluten can reduce the absorption of iron from food as well as other nutrients such as folic acid and vitamin B12.28

Patients who have had bariatric surgery 

Bariatric surgery is weight-loss surgery for obese individuals. There are multiple variations of bariatric surgery such as gastric banding, gastric bypass, biliopancreatic diversion and duodenal switch.29 Each type of gastric surgery has a different risk of iron deficiency. Generally, gastric bypasses procedures are more likely to lead to iron deficiency than gastric bands.29

Malabsorption and inflammation. Gastric bands and gastric bypasses can decrease the amount of iron absorbed from the diet by both reducing the production of gastric acid that is required to break down the food and convert iron into an absorbable form12 and, in the case of gastric bypass procedures, also by malabsorption.12 Gastric bypass procedures prevent food from passing through the regions of the small intestine where iron absorption would normally occur.30 Overall 50% of people who have had bariatric surgery are iron deficient within one year of surgery. This rises to up to 62% over a 4-12 year period after surgery.31

Malnutrition. Following bariatric surgery, patients may need to reduce their intake of some iron-rich foods, especially red meat, due to no longer being able to tolerate them.12

Other gastrointestinal bleeding disorders

Blood loss. Any other causes of internal bleeding within the gastrointestinal tract can also lead to iron deficiency. For example, peptic ulceration including duodenal ulcers, gastric ulcers and anastomotic ulcers may be found in patients with iron deficiency anaemia.3 Angiodysplasia is a further cause of gastrointestinal bleeding.32

Chronic Kidney Disease (CKD) 

Blood loss. Patients with CKD often have gastrointestinal blood loss require frequent blood tests and therefore regularly lose iron.33 If the patient is undergoing haemodialysis for their condition, further iron losses can occur from blood retention in the dialysis filter and line, access bleeding and, if applicable, from surgical blood loss.33 Up to half of patients with CKD stages 2-5 have some form of iron deficiency.34

Malabsorption and inflammation. Patients with CKD may have impaired dietary iron absorption from the intestines.35 This could be due to an excess of the hormone hepcidin, which is responsible for maintaining systemic iron homeostasis.7 The production of hepcidin is upregulated due to inflammation in many chronic conditions.7 In addition to reducing iron uptake from the diet, hepcidin can also block the mobilization of iron from the patient’s iron stores.7 CKD patients may also eat a diet low in iron.36

Increased demand for iron due to use of erythropoiesis-stimulating agents (ESAs ). ESA may be prescribed for patients with CKD since their kidneys are less able to produce sufficient erythropoietin.7 ESAs stimulate erythropoiesis, increasing the demand for iron and reducing the pool of circulating iron.  Iron deficiency is the primary reason for hyporesponse to ESA,37 therefore, iron therapy is often required concomitantly.7

Cancer and cancer treatments 

Blood loss. Gastrointestinal or colorectal cancer can cause internal bleeding,38 and some gynaecological cancers such as ovarian or cervical cancer, can also lead to greater than normal blood loss, putting patients at higher risk of iron deficiency anaemia. Across all cancer types, approximately 30-45% of patients experience iron deficiency.38

Increased demand for iron due to use of erythropoiesis stimulating agents (ESAs). Patients undergoing myelosuppressive chemotherapy may be given ESAs.39 ESAs reduce the pool of circulating iron by increasing erythropoiesis, and iron supplementation may be required concomitantly.7

Rheumatoid arthritis (RA)

Blood loss. Patients with rheumatoid arthritis can experience chronic blood loss from intestinal bleeding if they are being treated with non-steroidal anti-inflammatory drugs (NSAIDs).40,41

Malabsorption and inflammation. Patients with active rheumatoid arthritis can have impaired absorption of iron within the small intestine.42 Anaemia of chronic disease (ACD) also contributes to the anaemia burden in RA and affects 30-70% of patients with RA.43

Restless leg syndrome (RLS)

Restless leg syndrome is a sleep-related disorder where the patient may experience unpleasant creeping, tingling or burning feeling in their limbs, especially their legs, when resting.44 This can create an urge for the person to move their legs since often the unpleasant sensations can be relieved or partially relieved by movement.45 Because the symptoms of restless leg syndrome are often experienced during the night,44 sleep can be disturbed, leading to daytime weariness and reduced well-being.45 Around 2-15% of the population experience restless leg syndrome across all age groups, however the syndrome is around twice as prevalent in women than in men.45

The direct cause of RLS is unclear, however a role for dopamine has been implicated.45 Restless leg syndrome is also associated with iron deficiency.46 People who have an increased risk of iron deficiency such as pregnant women,  people with chronic kidney disease (CKD)44, those who undergo haemodialysis47 and people with coeliac disease48 are also more likely to have RLS. Iron deficiency is not sufficient or necessary for the development of RLS.45

Malnutrition


Vegetarians and vegans

Haem iron derived from animal sources is more easily absorbed than non-haem iron from plant sources. In addition, the bioavailability of non-haem iron can be reduced when tea, coffee and dairy products are also consumed.5 Since vegetarians rely on non-haem sources of iron, it is possible that they do not obtain sufficient dietary iron to meet requirements and may need dietary advice and/or supplemental iron.  Ascorbic acid (vitamin C)-rich foods enhance non-haem iron absorption.5

Obese patients

One study has shown that overweight American children are twice as likely to be iron deficient than their normal weight counterparts49 and further studies comparing obese and non-obese adults have confirmed that excess adiposity may negatively affect iron status.50–52

Despite adequate calorific intake, consumption of energy-dense, nutrient poor foods can lead to nutrient deficiencies.52 The individual’s diet may be limited in iron content and the enhancers of iron absorption (vitamin C containing foods), but rich in foods that contain inhibitors of iron absorption such as tannins present in tea or calcium present in dairy products.53

In overweight and obese patients iron absorption is also be reduced.52 This may be due to inflammation increasing with body mass index (BMI) so that obese patients may have some form of chronic inflammation.52 Chronic inflammation leads to an increased release of hepcidin, which in turn can reduce iron absorption.52

Patients who have had bariatric surgery

Following weight loss surgery, such as a gastric band or a gastric bypass, patients may need to reduce their intake of some iron-rich foods, especially red meat, due to no longer being able to tolerate them.12

Elderly

Various studies have indicated that the prevalence of anaemia in elderly populations is 10-45%.54 There are multiple causes for anaemia in elderly individuals, which can include one or more long-term conditions including chronic kidney disease.54 A large proportion of this anaemia (approximately 34%) could be due to nutritional deficiencies such as deficiencies in iron, folic acid, and vitamin B12.54

  • One study of 259 elderly patients indicated an iron deficiency prevalence of 36%.55
  • A small study of 63 individuals over 80 years of age with a diagnosis of anaemia found that 49 of 63 (78%) of the patients had IDA.56
  • In a larger study of 1,388 patients over 65 years of age, 106 had iron deficiency (30.5% of the patients with anaemia).57