Mighty Iron

Iron: a vital nutrient with many functions

 

Iron is best known as an essential component of haemoglobin – the molecule in red blood cells that is responsible for transporting oxygen around the body. However, iron also plays a role in many other metabolic processes, including growth and development, cellular respiration and DNA repair and synthesis. However, iron is efficiently recycled by the body when in good health and is not readily excreted. If it is present in excess (for example, through over-supplementation or in the genetic disorder haemochromatosis), it generates free radicals that cause inflammation and damage to tissues and organs. It can also fuel bacterial infection since most bacteria depend on iron for their growth and proliferation. 

 

A very common deficiency

 

Iron deficiency is one of the most common nutrient deficiencies worldwide. Over 1.2 billion people globally suffer from iron deficiency anaemia, and up to twice this many are iron deficient without symptoms of anaemia.

 

Common signs of iron deficiency anaemia include extreme tiredness, heart palpitations, shortness of breath and pale skin. Signs of iron deficiency without anaemia may not be so recognisable. They can include the eating disorder known as ‘pica’ – the urge to consume non-food substances, such as paper, soil or clay. Studies have also found that low iron can directly contribute to poor cognitive performance due to reduced oxygen supply to the brain, impaired development of neurons, and impaired neurotransmitter synthesis. In children, this may manifest as hyperactivity or reduced attention span. Difficulty swallowing (dysphagia) is another sign of possible iron deficiency. Iron status is closely linked to thyroid function. An underactive thyroid gland may become swollen, putting direct pressure on the oesophagus, and making it difficult to swallow. Frequent infections may also be a red flag for low iron status, as iron deficiency weakens the immune system.

 

Changing needs 

 

Functional iron deficiency may be caused by a greater need for iron at certain life stages: childhood, adolescence, pregnancy and menstruation are times when the demand for iron increases. 

 

Even when dietary iron intake is plentiful, deficiency may still occur due to poor iron absorption, blood loss, chronic illness or infection2. In every case of iron deficiency, it is vital to understand the underlying cause since they require different approaches to correct the imbalance. 

 

Let’s look at some of the drivers of iron deficiency in more detail.

 

Low dietary intake and factors impacting absorption

 

There are two forms of iron; haem iron is found in animal protein, especially red meat. This is the form that is the most readily absorbed by the body. Non-haem iron is found in vegetables, grains, pulses, nuts and seeds, but this form of iron is not easily absorbed if consumed alone. People who consume little or no red meat may be at increased risk of iron deficiency. 

 

Vitamin C enhances the absorption of non-haem iron from food by up to 300%, so consuming vitamin C-rich foods or a vitamin C supplement simultaneously as meat-free meals can improve iron uptake.

 

Adequate levels of synergistic vitamins – B1, B2, B3, B6, B12, A, C and E are all required to maintain optimal iron balance and metabolism in the body. Insufficiencies of nutrients rarely exist in isolation, and a shortage of one or more of these may contribute to a functional iron deficiency.4

 

Tea, coffee and dairy products all inhibit the absorption of iron.4  Certain compounds found in plants – oxalates, phytates, and polyphenols can all bind with iron to make it less available to the body.

 

Iron absorption is dependent on a sufficiently acidic environment in the stomach. Where stomach acid production is insufficient, or when an individual is on long-term medication that suppresses stomach acid production (such as antacids or proton pump inhibitors like Omeprazole), iron absorption in the small intestine can be significantly reduced. 

 

Gut health is key 

 

Good gut health is fundamental to iron absorption and regulation of iron levels.

Chronic bleeding or inflammation in the gastrointestinal tract, a feature of inflammatory bowel diseases such as Crohn’s and ulcerative colitis, can lead to reduced iron absorption and increased loss of iron in the blood. Patients with active gastrointestinal disease usually need supplemental iron, but it is important to address the root cause of iron depletion. Nutritional therapy can be of great benefit, with appropriate dietary and supplement interventions to minimise gastrointestinal inflammation, improve intestinal barrier function and modulate the immune response. 

 

It should be noted that iron deficiency may, on occasion, be the only presenting clinical indicator of coeliac disease. The primary reason for this is the reduced duodenal iron absorption due to reduced intestinal surface area (coeliac disease leads to the damage and destruction of the villi – tightly packed, tiny projections that line the small intestine). Other complications of celiac disease may also contribute to depleted iron levels. These include blood loss, ulceration, and modifications in synthesising proteins that regulate iron uptake. 

 

Iron and the gut microbiome

 

Since nearly all bacteria depend on iron for their growth and replication, it follows that the availability of iron in the gut influences the composition of the bacterial communities. Furthermore, a healthy microbiome can help maintain the correct balance of iron in the body, as it regulates the abundance of iron transporters in the small intestine, influencing how much iron is absorbed into the blood. 

 

Bacterial infection 

 

Chronic bacterial infection can lead to ‘infectious anaemia’. When the body is fighting a bacterial infection, it sequesters iron from the blood into storage tissues, including the bones, spleen, liver and lymphatic tissue. This is a protective strategy: it renders iron unavailable to bacteria, as bacteria can use iron to grow and proliferate. While it is an effective defence against acute infections, if infection becomes chronic, iron is locked away long-term and is not available to be integrated into red blood cells, so anaemia develops. In this circumstance, simply supplementing iron will be ineffective at addressing anaemia. The key is to resolve the infection. An elevated iron: copper ratio in a hair mineral analysis may be indicative of chronic infection.

 

Identifying the cause of iron deficiency 

 

Alongside assessing a patient’s clinical presentation, medical and functional tests can shed light on the root cause of iron deficiency. A reputable functional medicine practitioner or nutritional therapist can help guide you on which tests are most appropriate to help establish the cause(s) of your iron deficiency and the most appropriate interventions to redress it. 

 

Challenges of supplementation

 

Elevated levels of free iron in the gut can cause the proliferation of potentially pathogenic bacteria. It also drives inflammation and intestinal permeability. So in inflammatory bowel diseases, where absorption of iron is poor, supplementing iron orally, rather than combating anaemia, can instead be a driver of the disease process.

 

However, we can select better forms of iron to take as supplements. Research has shown that iron bisglycinate is not only 4-5 times more bioavailable than more commonly prescribed ferrous sulphate, but it also positively impacts the gut microbiome composition, reduces the production of free radicals, and increases glutathione production.

 

Lactoferrin is a compound that can work well alongside supplementary iron. Promising studies in animal models show that lactoferrin binds to free iron in the gastrointestinal tract, carrying it across the intestinal lining, improving absorption, and also denying the availability of iron to pathogenic bacteria.

 

The importance of immune status

 

In cases of dysregulated immune function (for example, autoimmune disease or mast cell activation), with evidence of iron deficiency, supplementation can become even more complex. We may conclude that low iron is driving poor immune function. But in this instance, supplementing iron may lead to the ‘Fenton reaction’ – the production of free radicals that drive inflammation mentioned previously in this article. This in turn, depletes the body’s reserves of the master antioxidant, glutathione, which is used to neutralise free radicals and limit damage to tissues. Depleted glutathione renders individuals more susceptible to infections and increased immune dysregulation. 

 

Supporting an immune-compromised individual with supplementary glutathione before adding iron can help to prevent the build-up of free radicals and short-circuit this vicious cycle.

 

Conclusion

 

Iron plays an essential role in multiple metabolic processes. Many factors influence the absorption and metabolism of iron, and functional deficiency can arise from digestive insufficiency, chronic infections and compromised gut health. Supplementing iron to redress deficiencies is complex, and it is vital to establish the root cause of poor iron status to understand how to improve it. 

References

1. Kohgo, Y., Ikuta, K., Ohtake, T. et al., 2008. Body iron metabolism and pathophysiology of iron overload. Int J Hematol, 88, 7–15. https://doi.org/10.1007/s12185-008-0120-5
2. Camaschella, C., 2019. Iron deficiency. Blood, 133 (1): 30–39. doi: https://doi.org/10.1182/blood-2018-05-815944
3. https://www.nhs.uk/conditions/iron-deficiency-anaemia/
4. Watts, D., 2015. “Iron” in Trace Elements and Other Essential Nutrients (7th ed.) Writer’s B-L-O-C-K
5. National Academies of Sciences, Engineering, and Medicine, 2001. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc, Washington, DC: The National Academies Press. https://doi.org/10.17226/10026.
6. Yilmaz B, Li H., 2018. Gut Microbiota and Iron: The Crucial Actors in Health and Disease. Pharmaceuticals, 11(4):98. doi: 10.3390/ph11040098. PMID: 30301142; PMCID: PMC6315993.
7. Freeman, H. J., 2015. Iron deficiency anaemia in celiac disease. World Journal of Gastroenterology, 21 (31), 9233-9238. https://doi.org/10.3748/wjg.v21.i31.9233
8. Milman, N., 2020. A review of nutrients and compounds which promote or inhibit intestinal iron absorption: making a platform for dietary measures that can reduce iron uptake in patients with genetic haemochromatosis, Journal of Nutrition and Metabolism, vol. 2020, Article ID 7373498. https://doi.org/10.1155/2020/7373498
9. https://cogenceimmunology.com/clinical-pearls-iron-and-glutathione/
10. Dong Z, Zhang D, Wu X, Yin Y, Wan D., 2022. Ferrous Bisglycinate Supplementation Modulates Intestinal Antioxidant Capacity via the AMPK/FOXO Pathway and Reconstitutes Gut Microbiota and Bile Acid Profiles in Pigs. J Agric Food Chem, 70( 16): 4942-4951. doi: 10.1021/acs.jafc.2c00138. Epub 2022 Apr 14. PMID: 35420025.