Getting the right facts about Iron Deficiency
Red meat contains haem iron that is easier for the body to absorb.
Iron deficiency is the most common nutritional deficiency worldwide. The population group that is most at risk of iron deficiency is premenopausal women, but it can also affect people with low dietary iron intake or medical conditions such as inflammatory bowel diseases or chronic kidney disease.
Iron is needed for a multitude of functions within the body including transporting oxygen via haemoglobin that is part of red blood cells. Iron is also needed for cellular energy production via the electron transport chain which lives inside the mitochondria or power house of every cell. Other less known functions that iron is needed for include thyroid hormone production and dopamine, an essential neurotransmitter that plays an important role in mood and energy. It’s not hard to see why low iron results in symptoms such as fatigue, breathlessness and poor concentration.
Low iron is often the first thing that is thought of when someone reports feeling tired, and it can be tempting to reach for a bottle of supplemental iron with the view that it will fix the problem. Iron supplements are readily available in pharmacies, healthfood stores and even in some supermarkets. Doses and forms can vary and often there is little guidance about what is the best option. Although iron is a common nutrient and often part of a normal diet, it can be harmful when taken in large supplemental doses and for prolonged periods of time. That’s why it’s important to understand when iron supplementation is required, and how to take it for a beneficial outcome.
There is a difference between iron deficiency and iron deficiency anaemia, and this will affect how and when treatment is administered. Iron deficiency describes low iron stores (ferritin). Ferritin is the storage protein for iron that is found mostly in the liver, think of it like a bank account for iron. Ferritin levels are measured using a sample of blood. In Australia, iron deficiency is diagnosed when ferritin falls below 30 micrograms per litre of blood. Other markers of iron availability include transferrin, a protein that carries iron from the gut to the liver and other areas of the body (like a taxi), and transferrin saturation which measures how much iron is being carried by the taxi (transferrin). Iron deficiency will usually result in high transferrin, because the body makes more taxis, and low saturation because there’s not enough iron available for transport. In less common cases, there is low transferrin which may indicate chronic inflammation, or a genetic disposition to low iron stores due to poor transport availability.
Iron deficiency anaemia is diagnosed when low iron stores are depleted and haemoglobin levels fall below 130mg/dL for men, 120mg/dL for women and 110mg/dL for pregnant women. Haemoglobin is the iron containing part of red blood cells and its function is to transport oxygen around the body. There are some other markers that can provide clues about low iron, including mean cell haemoglobin (MCH), hematocrit (Hct) and red cell count (RCC).
Iron absorption
Iron that is consumed from the diet, or as a supplement, is absorbed in the gastrointestinal tract. Only small amounts of iron are absorbed at a time because large amounts can be dangerous for the body due to the oxidative nature of iron.
Dietary iron is either animal based (haem iron), or plant-based (non-haem iron). Haem iron is easier for the body to absorb and doesn’t contain some of the chemicals that block absorption, such as phytates and tannins that are found in non-haem iron. Once absorbed, iron is converted to a form that can be utilised by the body. Supplemental iron is bound to a molecule to help with absorption. There are a variety of forms including oxides, gycinates, amino acid chelates and citrates. Amino acid chelates, glycinates and citrates are more easily absorbed and are less likely to cause gastrointestinal side effects.
To protect the body from large amounts of iron, a protein called Hepcidin is produced by the liver. It works by blocking absorption in the gastrointestinal tract, reducing the amount of iron that ends up in circulation. Levels of hepcidin fluctuate throughout the day and will also increase in response to large doses of iron being consumed. Hepcidin is naturally lowered in iron deficiency anaemia when iron becomes very scarce. It is important to consider hepcidin levels when supplementing iron to achieve the best clinical outcomes.
Hepcidin will also increase when there is inflammation present, either due to an infection or in response to other factors including high cortisol or increased blood glucose. When chronic inflammation is present, ferritin levels can be falsely elevated.
Iron absorption can also be inhibited when gastrointestinal function is impaired. Iron is absorbed in the small intestine, and conditions such as coeliac disease, inflammatory bowel diseases as well as poor stomach acid production can reduce iron absorption.
Gut health
Gut health can play a role in iron absorption. Gut inflammation will reduce dietary and supplemental iron absorption by increasing hepcidin levels. Large doses of supplemental iron have also been found to cause changes to the gut microbiome which can also lead to inflammation and impaired absorption. Probiotic supplements, and in particular lactobacillus plantarum 299v have been shown to reduce gut inflammation and improve absorption. Soluble fibre such as partially hydrolysed guar gum (PHGG) can also improve iron absorption. Lactoferrin an iron binding glycoprotein, can also improve gastrointestinal absorption of iron.
Increased iron losses
As well as impaired iron absorption from the gut, iron deficiency can result from increased iron losses. The most common reason for this is heavy menstruation. Other causes can include gastrointestinal bleeding and clotting disorders.
Other causes of low iron
Other less common causes of chronic low iron include:
Thyroid disease that results in lowered iron absorption
Reduced ability to recycle iron from red blood cells
Iron Supplementation
Iron supplementation should only be commenced when iron deficiency or iron deficiency anaemia is diagnosed. As previously discussed, this is done via a blood test.
In the first instance, oral iron should be considered as a treatment to increase iron stores and haemoglobin. Supplementation will need to be undertaken for at least 3 months, at which time re-testing of iron markers including ferritin, transferrin and transferrin saturation as well as haemoblobin is recommended.
It has been shown that alternate day dosing is most effective for oral iron. This strategy reduces the inhibitory effect of hepcidin.
Iron supplement doses range from 5mg to 100mg depending on the type of supplement. Low dose iron is often found in multivitamins and prenatal supplements. Lower doses such as 24mg are found in supplements where the iron is bound to glycine, citrate or an amino acid chelate. Large doses of iron (80-100mg) are found in pharmacy only medicines where the form is an iron oxide, sulfate or a polymaltose. Regardless of the form of iron, the total dose is not absorbed by the gut, and large doses (greater than 60mg) result in increased hepcidin production which blocks absorption for 24 hours. A 2020 study on iron supplementation in iron deficient women, found that alternate day dosing with doses less than 60mg resulted in 30-50% more iron absorption. The study also reported that large doses of iron resulted in gastrointestinal inflammation, further impeding iron absorption.
Co-factors that support iron supplementation
There are a number of nutrients that work together to improve iron absorption and utilisation by the body. These include:
Vitamin A
Vitamin C
Copper
Magnesium
Vitamin D
Vitamin B12
Vitamin B2
Intravenous iron infusion
When there is a poor response to oral iron supplementation, or in some circumstances such as late stage pregnancy, intravenous iron is used to quickly increase iron levels. A large dose of iron is delivered into the blood which can lead to increased inflammation. Common side effects from intravenous iron include fatigue, nausea, headaches and joint pain. Some people can experience more serious side effects such as low blood pressure, dizziness and breathing difficulties, however, intravenous iron infusions are generally well tolerated but they should not be used as a regular treatment for iron deficiency. It is vital to understand the underlying cause of your low iron and address this as a priority.
Summary
Iron deficiency is the most common nutrient deficiency worldwide, particularly in premenopausal women.
Iron deficiency is diagnosed by low iron stores (ferritin) and iron deficiency anaemia is diagnosed by depleted iron stores and low haemoglobin.
Iron is absorbed in the small intestine of the gastrointestinal tract.
Dietary sources of iron are from animal (haem) sources and plant-based (non-haem)
It is harder for your body to absorb plant-based iron because of chemicals including phytates and tannins that bind the iron and prevent absorption.
Hepcidin is a protein that the body produces to protect from absorption of large doses of iron. It prevents absorption from the gastrointestinal tract. Hepcidin levels are highest in the middle of the day. The best time of day to take your supplement is with your breakfast or evening meal.
Large doses of supplemental iron cause levels of hepcidin to increase
Chronic inflammation impairs iron absorption.
Iron deficiency or iron deficiency anaemia can be caused by increased iron losses. The most common reason for this is heavy menstruation.
Alternate day dosing of iron less than 60mg has been shown to be the most beneficial for increasing iron levels.
The best form of iron for supplementation is gycinate, amino acid chelate or citrate.
Take iron supplements with cofactors including vitamin C, Vitamin B12, Vitamin D and Vitamin A.
Always consult with a healthcare professional before taking iron supplements.
Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020 May;105(5):1232-1239. doi: 10.3324/haematol.2019.220830. Epub 2019 Aug 14. PMID: 31413088; PMCID: PMC7193469.
Zhao X, Zhang X, Xu T, Luo J, Luo Y, An P. Comparative Effects between Oral Lactoferrin and Ferrous Sulfate Supplementation on Iron-Deficiency Anemia: A Comprehensive Review and Meta-Analysis of Clinical Trials. Nutrients. 2022 Jan 27;14(3):543. doi: 10.3390/nu14030543. PMID: 35276902; PMCID: PMC8838920.