Rethinking iron

Iron gets a lot of attention in the medical and nutrition space. We are frequently told that we need to make sure we are getting enough iron, and as soon as blood iron is low, we are diagnosed with ‘iron anemia’ and often told to take iron supplements or have an iron transfusion with no considerations as to the reasons why iron is low in the first place.

While iron plays an important role in many physiological processes such as oxygen transport and mitochondrial energy production, more iron is not necessarily a good thing. It is important to note that low iron in the blood does not always mean low iron in the body. Iron can accumulate in the tissues, and it is possible to have iron overload even when blood iron is low. It is not possible to know exactly how much iron is stored in your body without taking a liver biopsy. While there is a chance that someone has a true iron deficiency, it can be helpful to first rule out the considerations outlined below before supplementing. Taking iron supplements can end up driving iron accumulation further, which can increase your chance of almost every disease [1].

There are many reasons blood iron values could be low, including very low bioavailable iron intake in the diet, a lack of iron co-factors in the diet such as copper and retinol, poor thyroid function, or poor gut health. Our bodies can recycle around 24mg of iron a day if our Iron Recycling System (called the Reticuloendothelial System) is functionally optimally. This means that we only need an additional 1-2mg of iron each day absorbed from our food. Since we absorb around 5-30% of our ingested iron, this equates to consuming about 10-15mg of iron each day, which is easily attainable through a well-balanced diet. The reductionist thinking that isolates one nutrient, while ignoring its antagonists and agonists, is often misleading. If you have been told that you have iron anemia, it is important to investigate the underlying root cause before jumping into supplementation. Taking iron supplements can help you feel better initially, but if there is an underlying root cause that is not addressed, your symptoms will persistently reappear and iron accumulation in tissues could occur.

If the following points have all been addressed and iron levels still remain low in the blood, then only should iron supplementation be considered.

Identifying the root cause of Iron Anemia

Here are some factors that can be addressed to improve your iron status before resorting to supplementation.

1. Are you getting iron in the most bioavailable form in your diet? Heme-iron (found in animal foods) is far more absorbable than non-heme iron (found in plants) [2]. Eating an adequate intake of red meat, organ meat, and shellfish will ensure you are meeting your daily iron requirement and that the iron is absorbed efficiently.

2. Are you getting enough preformed vitamin A (retinol) in your diet? Retinol has a well-documented relationship with iron metabolism. There is a critical interplay between these two nutrients. Retinol plays an important role in the iron recycling system. Working with its metabolic partner, copper, retinol guarantees the effective circulation of iron around our bodies [3] [4] [5]. The best sources of retinol include liver, good quality dairy, butter, eggs, and fatty fish.

3. Are you getting enough copper in your diet? Copper helps to mobilize stored iron out of the tissues. Our livers produce a copper-carrying enzyme called ceruloplasmin which plays an important role in iron metabolism. Without sufficient copper in the diet, we are more likely to store too much iron in our tissues [6]. The best sources of copper include liver, oysters, and other shellfish.

4. Are you getting enough B-vitamins in your diet? Vitamin B2 in particular is an important regulator of iron and a deficiency can result in poor iron absorption [7]. Good sources of vitamin B2 include liver, eggs, dairy, and lean meats.

5. Are you hypothyroid? Low thyroid hormone levels suppress the activity of bone marrow, the tissue that makes red blood cells. This lowers the production of red blood cells and triggers anemia. Studies suggest that many people with hypothyroidism also have iron-deficiency anemia [8]. Supporting metabolic function and thyroid health can improve iron regulation.

6. How is your gut health? Poor intestinal health can lead to poor absorption of iron. Most of the iron taken in by food is absorbed in the upper small intestine. Abnormalities in the gastrointestinal tract can alter iron absorption. Bacteria also feed on iron. Supporting gut health through a gut-supporting diet can play an important role in managing your body’s uptake of iron [9].

7. What is your stress level? When cortisol is high, more iron is absorbed into the tissues. Therefore, stress can create an anemic state because it is placing iron in the wrong places [10].

In summary, regulating iron status is not as simple as taking a supplement. Addressing nutrition and lifestyle health practices at a holistic level is important to ensure optimal intake, uptake, retention, and use of iron.

Assessing iron status

Assessing true iron status is not simply a matter of testing serum iron and ferritin. In fact, serum iron and ferritin alone are poor indicators of true iron status [11] [12]. When going for a blood test, it is recommended to get a ‘Full Monty Iron Panel’ to get a true reflection of your iron status and understand the root cause of low iron in the blood.

A Full Monty iron panel looks at the following blood markers:

• Magnesium RBC

• Copper

• Zinc

• Ceruloplasmin

• Iron & TIBC

• Ferritin

• Transferrin

• Hemoglobin

• Vitamin A (retinol)

Getting a full thyroid panel and tracking thyroid health through temperature and pulse tracking can also be an informative tool in assessing your thyroid function and identifying the root cause of your iron dysregulation.

Getting rid of excess iron in the body

It is very possible that many people are actually at risk for iron overload rather than iron deficiency, due to iron getting stored in the tissues. As we get older, we tend to accumulate iron in our tissues more and more. The accumulation of iron can lead to oxidative stress in the body and has been implicated in the development of several chronic diseases, including diabetes [13] and heart disease [14].

The human body has no controlled mechanisms for the excretion of iron. So, for some people that may need to reduce iron overload (if blood iron levels are too high), here are some considerations

• Donate blood. Blood donation has been shown to be beneficial to the health of the donor in many ways [15][16].

• Phlebotomy. If you cannot donate blood for whatever reason, you can get a phlebotomy treatment.

• Natural iron chelators. The use of iron chelators can help lower the absorption of iron to help lower the risk of iron overload. Natural iron chelators include coffee and milk.

• Lower stress. Since excess cortisol promotes iron storage in the tissues, it is essential to lower sources of stress in your life to reduce the risk of iron accumulation.
  

In summary

Health is extremely multi-faceted. Looking at one symptom, one blood test, and using one supplement is an extremely reductionist approach that ignores the fact that the systems of the human body do not operate in isolation. Healing takes a holistic approach where nutrition, lifestyle, and environmental factors all come into consideration. No single supplement is ever going to be the answer to your symptoms. If you are stressed and undernourished, symptoms will likely persistently reappear until you start focusing on improving your health at a root cause level.

Further reading

In addition to the references below, here are some great resources to get a better understanding of iron anemia and how you can get to the root cause of addressing it:

• Iron’s Dangers, article by Ray Peat

• Cu-re your fatigue, book by Morley Robbins

• Iron toxicity posts, by Morley Robbins

References:

[1] D. B. Kell, “Iron behaving badly: Inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases,” BMC Med. Genomics, vol. 2, 2009, doi: 10.1186/1755-8794-2-2.

[2] R. Hurrell and I. Egli, “Iron bioavailability and dietary reference values,” American Journal of Clinical Nutrition, vol. 91, no. 5. 2010, doi: 10.3945/ajcn.2010.28674F.

[3] M. W. Bloem, “Interdependence of vitamin A and iron: an important association for programmes of anaemia control,” Proc. Nutr. Soc., vol. 54, no. 2, 1995, doi: 10.1079/pns19950018.

[4] M. S. B. da Cunha, E. M. A. Siqueira, L. S. Trindade, and S. F. Arruda, “Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis,” J. Nutr. Biochem., vol. 25, no. 10, 2014, doi: 10.1016/j.jnutbio.2014.05.005.

[5] S. Jiang, C. xu Wang, L. Lan, and D. Zhao, “Vitamin A deficiency aggravates iron deficiency by upregulating the expression of iron regulatory protein-2,” Nutrition, vol. 28, no. 3, 2012, doi: 10.1016/j.nut.2011.08.015.

[6] D. M. Williams, D. Loukopoulos, G. R. Lee, and G. E. Cartwright, “Role of copper in mitochondrial iron metabolism,” Blood, vol. 48, no. 1, 1976, doi: 10.1182/blood.v48.1.77.77.

[7] S. Mosegaard, G. Dipace, P. Bross, J. Carlsen, N. Gregersen, and R. K. J. Olsen, “Riboflavin deficiency—implications for general human health and inborn errors of metabolism,” International Journal of Molecular Sciences, vol. 21, no. 11. 2020, doi: 10.3390/ijms21113847.

[8] E. Mehmet, K. Aybike, S. Ganidagli, and K. Mustafa, “Characteristics of anemia in subclinical and overt hypothyroid patients,” Endocr. J., vol. 59, no. 3, 2012, doi: 10.1507/endocrj.EJ11-0096.

[9] N. K. Das et al., “Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis,” Cell Metab., vol. 31, no. 1, 2020, doi: 10.1016/j.cmet.2019.10.005.

[10] M. Zhao et al., “Psychological stress leads to hepatic iron accumulation and disturbs iron homeostasis,” J. Chem. Pharm. Res., vol. 6, no. 5, 2014.

[11] F. Firkin and B. Rush, “Abnormal laboratory results: Interpretation of biochemical tests for iron deficiency: Diagnostic difficulties related to limitations of individual tests,” Aust. Prescr., vol. 20, no. 3, 1997, doi: 10.18773/austprescr.1997.063.

[12] A. Dignass, K. Farrag, and J. Stein, “Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions,” Int. J. Chronic Dis., vol. 2018, 2018, doi: 10.1155/2018/9394060.

[13] J. A. Simcox and D. A. McClain, “Iron and diabetes risk,” Cell Metabolism, vol. 17, no. 3. 2013, doi: 10.1016/j.cmet.2013.02.007.

[14] A. Pourmoghaddas, H. Sanei, M. Garakyaraghi, F. Esteki-Ghashghaei, and M. Gharaati, “The relation between body iron store and ferritin, and coronary artery disease,” ARYA Atheroscler., vol. 10, no. 1, 2014.

[15] A. Bukar et al., “The inconspicuous health benefit of blood donation,” Glob. J. Transfus. Med., vol. 5, no. 1, 2020, doi: 10.4103/gjtm.gjtm_14_20.

[16] M. Yunce, H. Erdamar, N. A. Bayram, and S. Gok, “One more health benefit of blood donation: Reduces acute-phase reactants, oxidants and increases antioxidant capacity,” J. Basic Clin. Physiol. Pharmacol., vol. 27, no. 6, 2016, doi: 10.1515/jbcpp-2015-0111.