Introduction
Iron deficiency anaemia is the most common cause of anaemia, affecting more than one billion people worldwide. Iron is essential for the formation of haemoglobin, a protein found in red blood cells that helps to transport oxygen from the lungs to the rest of the body. Iron also plays important roles in energy production, the oxygen storage capacity of muscles, and the proper functioning of the immune system.
On average, our body needs to absorb around 1mg of iron for adult males and 1.5mg for menstruating females each day in order to stay healthy. However, much of the iron we ingest is not absorbed. The Australian Recommended Dietary Intake (RDI) for iron per day based on different age groups and life stages are shown in Table 1.
Table 1. Australian RDI for iron for different age groups
|
Age groups and life stages |
Recommended dietary iron intakes per day |
| Infants 0-6 months | 0.2 mg for breastfed infants* |
| Infants aged 7-12 months | 11mg |
| Girls and boys aged 1-3 years | 9mg |
| Girls and boys aged 4-8 years | 10mg |
| Girls and boys aged 9-13 years | 8mg |
| Boys aged 14-18 years | 11mg |
| Girls aged 14-18 years | 15mg |
| Men aged 19 years and over | 8mg |
| Women aged 19-50 years | 18mg |
| Pregnant women | 27mg |
| Lactating women 14-18 years | 10mg |
| Lactating women 19-50 years | 9mg |
| Women aged 51 years and over | 8mg |
* The bioavailability of iron in formula is much lower than breast milk, so the recommended intake is significantly higher for formula-fed infants
Symptoms of iron deficiency include fatigue, lethargy, and pale skin. It can also cause dizziness, hair loss, and breathlessness during physical exertion.
Anaemia may be first identified by a full blood examination (FBE) test. Additional tests are then required to determine the cause and severity of the anaemia. Serum ferritin levels are commonly included in iron studies to diagnose iron deficiency. Ferritin is an intracellular protein with the ability to store up to 4,000 iron atoms. Under normal conditions, serum ferritin levels correlate well with the amount of total iron stored in the body. However, serum ferritin levels can be increased in the presence of inflammation or chronic disease. In these cases, serum ferritin is not a good marker of total body iron stores. A low serum ferritin level (< 15-30mcg/L in adults or < 10-12mcg/L in children) is almost exclusively seen in iron deficiency anaemia.
Iron deficiency can be corrected in a number of ways depending on the severity of the anaemia and patient comorbidities. Options range from increasing dietary iron intake, oral or parenteral iron therapy, and blood transfusions. Dietary sources of iron include haem iron from animal sources (e.g. red meat and liver) and non-haem iron from plant-based sources (e.g. dried beans, dark green leafy vegetables, iron-fortified bread and cereals).
In general, iron from plant sources is not as well absorbed as the iron from animal sources. However, some foods can increase or inhibit iron absorption as shown in Table 2.
Table 2. Foods that affect iron absorption
| Foods that increase iron absorption | Foods that decrease iron absorption |
| Vitamin C | Soy proteins can reduce iron absorption from plant sources |
| Cooking plant-based sources of iron may increase the amount of iron absorbed (e.g. the body absorbs 6% of the iron from raw broccoli compared to 30% from cooked broccoli) | Avoid consuming tea, coffee and wine; tannins from tea can bind to iron and impair iron absorption |
| Animal protein boosts iron absorption from plant sources | Calcium and phosphorus reduce the absorption of plant-sourced iron |
While optimisation of dietary intake is key in the primary prevention of iron deficiency, oral iron therapy can be used to correct anaemia and replenish iron stores. For the prevention of iron deficiency anaemia, the recommended dose is 1mg/kg daily for breastfed infants, 1-2mg/kg daily for children over 12 months, and 60-120mg daily for pregnant women. The dose is usually given as a single daily dose. Higher doses are required for the treatment of iron deficiency. In this case, the recommended oral daily dose for adults is 100-200mg daily, while children should receive 3-6mg/kg daily up to a maximum of 100-200mg daily. These higher amounts can be given in divided doses to improve gastrointestinal tolerance.
There are several oral iron preparations available in Australia as displayed in Table 3. Many of these preparations contain different salt forms of iron. The approximate equivalencies of these agents is as follows:
- 1 mg elemental iron is equivalent to 3mg of ferrous fumarate;
- 1 mg elemental iron is equivalent to 3mg of ferrous sulfate (dried); and
- 1 mg elemental iron is equivalent to 5mg of ferrous sulfate (non-dried, heptahydrate).
For example, the Therapeutic Guidelines suggests ferrous sulfate at a dose of 325-650mg daily which is equivalent to 105-210mg of elemental iron.
Table 3. Common iron preparations available in Australia
| Formulation | Brand name |
Elemental iron content |
| Ferrous sulfate 325mg Controlled-release tablets | Ferro-Gradumet® | 105mg |
| Ferrous sulfate 325mg Vitamin C 500mg Controlled-release tablets |
Ferrograd C® | 105mg |
|
Ferrous sulfate 250mg |
FGF® | 80mg |
| Ferrous sulfate 270mg Folic acid 300mcg Controlled-release capsules |
Fefol® | 87.4mg |
| Ferrous sulfate 30mg/ml | Ferro-liquid® | 6mg/ml |
| Ferrous fumarate 200mg | Ferro-tab® | 65.7mg |
| Ferrous fumarate 310mg Folic acid 350mcg |
Ferro-F-tab® | 100mg |
| Iron polymaltose 370mg | Maltofer® | 100mg |
The most common side effect of oral iron supplements is dark coloured or black stools. Other common side effects include abdominal pain, nausea, vomiting, constipation, and diarrhoea which are all dose-related. Oral liquid can also cause temporary black discolouration of the teeth. To prevent teeth discolouration, oral liquids may be diluted with water or sipped through a straw, followed with a drink of plain water. Iron supplements should be taken on an empty stomach for better absorption. However, they can be taken with food or shortly after food to prevent stomach upset and thereby increase compliance. Controlled-released formulations may reduce gastrointestinal adverse effects, although their bioavailability may be lower. Gastrointestinal adverse effects can be reduced by starting at a low dose and gradually increasing the dose or dividing the daily dose into smaller doses. The recommended treatment duration is normally three to six months.
Iron is toxic in overdose. It is therefore important to keep oral iron products out of reach and sight of children and ensure bottles are kept tightly closed.
Parenteral iron therapy can rapidly increase iron stores, and it is often indicated when oral therapy has failed, or the patient requires rapid iron replenishment. There are several intravenous iron preparations available in Australia.
Table 4. Intravenous iron preparations
| Compound | Brand name |
Maximum single dose | Duration of infusion |
| Ferric carboxymaltose | Ferinject® | 1000mg | 15 minutes |
| Iron polymaltose | Ferrosig® | 1000-2500mg | Approximately 5 hours |
|
Iron sucrose |
Venofer® | 100mg during dialysis 3 times per week | 15 minutes minimum |
Iron polymaltose can be given as an intramuscular injection. However, this is usually avoided as it can be painful and can permanently stain the skin. Slow intravenous infusion is usually preferred, although its use is limited outside of hospitals by its lengthy duration of administration of up to five hours. In contrast, ferric carboxymaltose may be administered over 15 minutes. It is therefore suitable in ambulatory settings and general practices. The maximum single dose is up to 1gm which may be repeated a week later. Side effects from intravenous infusion are pain at the injection site, headache, nausea, and vomiting. There is a risk of anaphylactic reactions which can be fatal, although this is rare. Parenteral iron is safe to use during pregnancy. However, manufacturers contraindicate its use in the first trimester. It is safe to use while breastfeeding.
References:
- Baird-Gunning J, Bromley J. Correcting iron deficiency. Aust Prescr. 2016; 39:(66): DOI: 10.18773.
- Nutrition Australia. Iron. Carlton: Nutrition Australia Vic Division; 2017.
- Rossi S (ed). Australian Medicines Handbook 2017. Melbourne: AMH; 2017.