Do we really want to be Iron Man?

Author: Jonine Moller

We all know iron to be one of the common metals in everyday life. Other than being used to strengthen buildings, this metal is also an essential element for our bodies.

Iron is a crucial “ingredient” in producing red blood cells, of which many millions are formed every day [1]. Red blood cell production takes place in the bone marrow.

A 70 kg male has a total of about 3,5 g of iron in his body. 65% of this is found in the hemoglobin of red blood cells. Hemoglobin (a protein) is the part of the red blood cells that is responsible for carrying oxygen to all the cells in the body. The rest of the body’s iron is found in the muscles, liver, and other tissue and cell components [1].

In addition to being needed to carry oxygen around, iron is also essential for mitochondrial function, synthesis and repair of DNA, and many enzyme reactions [2].

The balance of iron in the body is vital. It is crucial for cellular metabolism and aerobic energy production. Excessive amounts have toxic effects, though, and can lead to cell death [3].

The first portion of the small intestine plays a key role in regulating the iron levels in the body. It assumes the role of regulating the absorption [1, 4, 5]. Absorption rates depend on the iron levels within the body, overall oxygen levels, and the rate at which red blood cells are produced [1].

About 20 ml of blood is produced daily, containing 6 g hemoglobin, of which iron is 20 mg [2]. In other words, a healthy adult’s body uses about 20 - 30 g of iron per day (most of which is, of course, needed for red blood cell production), but less than 10% is from dietary consumption. The rest comes from internal “recycling” of the body’s iron stores.

Due to the internal recycling, iron from food only needs to contribute about 1- 2 g per day. This equals the amount lost each day [1, 4, 5, 6, 7]. Food iron content, however, needs to contain more because not all gets absorbed.

The recommended daily allowance for pregnant women is 27 mg, 11 mg, and 15 mg for teenage boys and girls, respectively, and 8 and 18 mg for men and women under 50 years of age. The recommended daily allowance for post-menopausal women drops to the same as for men (8 mg) [8].

Foods high in iron are lean meats and seafood. Nuts, beans, vegetables, and fortified grains are also good sources. The bioavailability of the iron found in meat is higher than that of plant sources. Supplements could aid in preventing dietary iron deficiency but should be limited to less than 20 mg/kg [8].

The tight regulation of iron absorption is needed because the body cannot get rid of excess iron [4]. This is why iron overload can occur and why we should take care to avoid it. Blood loss is the greatest source of iron loss.

The liver also plays a key role in the regulation of iron metabolism and storage thereof. Hepcidin, iron’s regulatory hormone, is secreted by the liver. This hormone organizes the transport and subsequent degradation of iron [6].

Disorders involving hepcidin production and conditions that cause inflammation (including cancers, infections, and liver disease) can either cause iron deficiency or overload.

Iron deficiency can cause anemia, otherwise known as red blood cell deficiency [4]. The result is that the body does not have adequate capacity to carry oxygen to all the body’s cells. Without enough oxygen, the body’s energy-production ability is limited.

Iron binds to the blood transport protein, transferrin. Transferrin should be roughly 30% saturated with iron in normal conditions. If it is less than 16% saturated, it is a sign of iron deficiency anemia. More than 45% saturation indicates iron overload [6].

The World Health Organization defines anemia as having hemoglobin levels of less than 130 g/L, 120 g/L, or 110 g/L in men, women, and pregnant women, respectively [9]. These thresholds are not set in stone, though.

Iron deficiency is better and more accurately defined by measuring ferritin levels in the blood, except during conditions of increased inflammation. Iron deficiency is confirmed if ferritin concentrations are below 12 - 15 𝜇g/L [9]. Ferritin is an iron-storing protein [10].

The symptoms of iron deficiency may include any of the following [9, 11]:

• Decreased physical and mental performance in adults
• Delayed physical and mental development in children
• Increased disease symptoms in the case of irritable bowel syndrome and chronic kidney disease
• Fatigue, abnormal shortness of breath
• Decreased immune response
• Impaired thermoregulation
• Restless legs syndrome
• Pale, dry, and rough skin
• Dry and damaged hair
• Nail abnormalities
• Rapid heartbeat or angina
• Fainting
• Headaches
• Vertigo

The following places you at risk for iron deficiency [9]:

• Increased demand:
  • Infants
  • Preschool children
  • Adolescents with growth spurts
  • Pregnancy (2nd and 3rd trimesters especially)
• Decreased intake:
  • Poverty and malnutrition
  • Iron-poor vegan or vegetarian diets
• Decreased absorption:
  • Increased intake of calcium
  • Increased intake of tannins (found in tea and coffee)
  • Diseases:
    • Helicobacter pylori infection
    • Coeliac disease
    • Atrophic gastritis
    • Inflammatory bowel disease
  • Chronic inflammation
• Chronic or large blood loss
• Being an endurance athlete
• Major surgery

Iron overload is just as detrimental as an iron deficiency - it can seriously affect organs such as the heart, liver, and pancreas [2]. These are the organs in which excess iron accumulates. Over time, this excess accumulation can cause the organs to fail [12].

One of the more common causes of iron overload is hereditary hemochromatosis [10, 13]. This is a condition in which the liver iron content is very high. There are different types of hereditary hemochromatosis, due to different genes [13].

Symptoms of iron overload and acute supplement overload may include [8, 12, 14]:

• Arrhythmias
• Fatigue
• Joint pain
• Loss of libido
• Gastrointestinal upset, abdominal pain, and constipation
• Nausea and vomiting
• Feeling faint and weak

Dietary supplementation with iron should only be undertaken in treating iron deficiency anemia to prevent overload. It is very important to know your genetic predisposition to iron deficiency or overload. Either can develop relatively easily and unknowingly, especially if you are not specifically conscious of your dietary intake.

By doing a simple DNA test, you can greatly decrease your iron deficiency and overload risk. Fatigue, for example, is a very common symptom that can be due to either iron deficiency or overload.

Knowing your genetic predisposition towards either deficiency or overload will greatly aid in determining your need for iron supplements. With adequate knowledge and subsequent consciousness, you can majorly impact your health and quality of life.

References:

[1] Muñoz, M., Villar, I., & García-Erce, J. A. (2009). An update on iron physiology. World Journal of Gastroenterology, 15(37), 4617–4626. https://doi.org/10.3748/wjg.15.4617

[2] Muckenthaler, M. U., Rivella, S., Hentze, M. W., & Galy, B. (2017). A Red Carpet for Iron Metabolism. Cell, 168(3), 344–361. https://doi.org/10.1016/j.cell.2016.12.034

[3] Muñoz, M., García-Erce, J. A., & Remacha, Á. F. (2011). Disorders of iron metabolism. Part II: Iron deficiency and iron overload. Journal of Clinical Pathology, 64(4), 287–296. https://doi.org/10.1136/jcp.2010.086991

[4] Duck, K. A., & Connor, J. R. (2016). Iron uptake and transport across physiological barriers. BioMetals, 29(4), 573–591. https://doi.org/10.1007/s10534-016-9952-2

[5] Zhang, D. L., Ghosh, M. C., & Rouault, T. A. (2014). The physiological functions of iron regulatory proteins in iron homeostasis - an update. Frontiers in Pharmacology, 5 JUN(June), 1–12. https://doi.org/10.3389/fphar.2014.00124

[6] Hentze, M. W., Muckenthaler, M. U., Galy, B., & Camaschella, C. (2010). Two to Tango: Regulation of Mammalian Iron Metabolism. Cell, 142(1), 24–38. https://doi.org/10.1016/j.cell.2010.06.028

[7] Waldvogel-Abramowski, S., Waeber, G., Gassner, C., Buser, A., Frey, B. M., Favrat, B., & Tissot, J. D. (2014). Physiology of iron metabolism. Transfusion Medicine and Hemotherapy, 41(3), 213–221. https://doi.org/10.1159/000362888

[8] NIH. (2021). Iron. Fact sheet for Health Professionals. Dietary Supplement Fact Sheets. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

[9] Cappellini, M. D., Musallam, K. M., & Taher, A. T. (2020). Iron deficiency anaemia revisited. Journal of Internal Medicine, 287(2), 153–170. https://doi.org/10.1111/joim.13004

[10] Milic, S., Mikolasevic, I., Orlic, L., Devcic, E., Starcevic-Cizmarevic, N., Stimac, D., Kapovic, M., & Ristic, S. (2016). The role of iron and iron overload in chronic liver disease. Medical Science Monitor, 22, 2144–2151. https://doi.org/10.12659/MSM.896494

[11] Oppenheimer, S. J. (2001). Iron-deficiency anemia: reexamining the nature and magnitude of the public health problem. The Journal of Nutrition, 131, 616–635.

[12] Kotze, M. J., van Velden, D. P., van Rensburg, S. J., & Erasmus, R. (2009). Pathogenic Mechanisms Underlying Iron Deficiency and Iron Overload: New Insights for Clinical Application. Ejifcc, 20(2), 108–123. http://www.ncbi.nlm.nih.gov/pubmed/27683335%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4975278

[13] Batts, K. P. (2007). Iron overload syndromes and the liver. Modern Pathology, 20(1), 31–39. https://doi.org/10.1038/modpathol.3800715

[14] Piperno, A., Pelucchi, S., & Mariani, R. (2020). Inherited iron overload disorders. Translational Gastroenterology and Hepatology, 5, 1–23. https://doi.org/10.21037/TGH.2019.11.15