Iron 101

Overview:

Iron is an essential bioelement for most forms of life, especially humans. Iron is a necessary building block of crucial aspects of our bodies, the transport of oxygen, and the production of ATP (our energy source.). As essential as it is, when our amount of iron falls out of homeostasis (balance), it also can become one of the most dangerous and toxic substances resulting in ROS (reactive oxygen species). ROS is one of the major causes of most modern diseases – metabolic dysfunction. The following is an overview of iron and how it is both essential while in balance and toxic when not.

Key Benefits of Iron:

  • Iron is necessary for most forms of life because of its ability to mediate electron transfer.
  • Iron is necessary for the biogenesis of mitochondria as well as ATP production itself.
  • Iron is necessary for red blood cells.
  • Iron is the only mineral that carries oxygen.
  • Iron is necessary for building structures in the body, including bones.

Key Risks of Iron:

  • Iron toxicity – leaking into fluids, tissues, and organs. Generally caused by excessive iron consumption.
  • Without enough bioavailable copper, iron builds up inside the mitochondria and thus inside the cells, which interferes with the mitochondria’s ability to make energy (Mg-ATP). (1) 
  • Dysregulated, unbound, excess iron is the most significant known source of oxidative stress and inflammation in the body.
  • Iron catalyzes ROS generation and promotes lipid oxidation, contributing to atherosclerotic plaque instability. (2) 
  • Too much iron can lead to osteoporosis.
  • Iron deficiency is associated with obesity, and iron overload increases diabetes risk by directly damaging pancreatic cells, as well as by increasing insulin resistance.
  • Iron’s ability to donate and accept electrons means that it can catalyze the conversion of hydrogen peroxide into free radicals. Free radicals can cause damage to a wide variety of cellular structures and ultimately kill the cell.
  • Excessive iron feeds bacteria. Thus many defenses deprive bacteria or make it harder for them to attain iron within the body.
  • ATP production can vary by at least 40% and as much as 96% if there’s too much iron in the cell and/or in the mitochondria.

Iron is a metallic chemical element with the symbol Fe and atomic number 26. It is the most common element on Earth, more common than oxygen. (3) 

Iron forms compounds mainly in the oxidation states +2 (iron(II), “ferrous”) and +3 (iron(III), “ferric”). Iron also occurs in higher oxidation states, e.g., the purple potassium ferrate (K2FeO4), which contains iron in its +6 oxidation state. Iron is by far the most reactive element in its group.

Iron’s ability to mediate electron transfer is key to iron’s importance. Iron acts as an electron donor in the ferrous state (Fe2+), while in the ferric state (Fe3+) it acts as an acceptor. Thus, iron plays a vital role in the catalysis of enzymatic reactions that involve electron transfer (reduction and oxidation, redox).

Iron is a crucial part of proteins and enzymes involved in numerous aspects of our life, from red blood cells down to our energy sources, the mitochondria. Our cells require iron to produce ATP via cellular respiration. Iron is essential to the transportation of oxygen. (4)  

Well-nourished people in industrialized countries have ~4 to 5 grams of iron in their bodies, mostly in hemoglobin and myoglobin (∼38 mg iron/kg body weight for women and ∼50 mg iron/kg body for men) (5) 

Ferritin complexes contain the majority of the body’s iron in all cells but are most common in bone marrow, liver, and spleen. The liver stores of ferritin are the body’s primary physiologic source of reserve iron. (6)

Reticuloendothelial System (RES)

The reticuloendothelial system is mainly comprised of monocytes and tissue macrophages (white blood cells). RES plays two major roles in iron metabolism: it recycles iron from senescent red blood cells, and it serves as a large storage depot for excess iron. The RES comprises ~95% of our body’s need for iron. (7)(8)

How do we absorb more iron? First, iron is absorbed by the gut via enterocytes. Second, iron is moved out of the enterocytes and into the bloodstream-is where the real challenge occurs. Iron must pass through that ferroportin (FPN) doorway for this to happen.

*The passage of iron requires bioavailable copper via the ferroxidase enzyme to facilitate the release of iron, the opening of the enterocytes pathways, and the incorporation of iron onto the transport protein transferrin.

The amount of iron absorbed compared to the amount ingested is typically low but may range from 5% to as much as 35%, depending on circumstances, source and type of iron. However, the inorganic iron filings being added to wheat flour and other processed foods are estimated to have a higher absorption rate of ~60%. Which can wreak havoc on our digestive tract.

Generally, the best absorbed forms of iron come from animal products. Absorption of dietary iron in iron salt form (as in most supplements) varies somewhat according to the body’s need for iron and is usually between 10% and 20% of iron intake. Absorption of iron from animal and some plant products is in the form of heme iron and is more efficient, allowing absorption of from 15% to 35% of intake.

For iron to be beneficial to health, it must be mobilized, meaning it needs to primarily be circulating in the body via the blood cells instead of becoming unbound from blood and building up in tissues and organs.

Many of the key enzymes needed for producing red blood cells and hemoglobin and transporting iron are copper-dependent, especially those needed to make energy (cytochrome oxidase) and clear exhaust (SOD, glutathione peroxidase, or catalase).(9) 

To give you an idea of the enormous amount of heme and red blood cells created daily.

  • 2-3 million RBCs are produced every second, thus,>200 billion every 24 hours
  • There are ~270 million hemoglobin in each RBC
  • There are four heme inside each hemoglobin
  • There are ~1 billion heme in each RBC

Interestingly copper is essential for heme and the production of red blood cells. Heme protein is a very foundational protein in the body, but our bodies cannot make heme and knit those four heme groups together without bioavailable copper. (9) (10)

Ceruloplasmin, acting through its ferroxidase enzyme, plays a pivotal role in keeping this iron balanced to maintain proper iron metabolism and homeostasis. At the same time, protecting against oxidation by converting toxic ferrous (Fe++) iron into its nontoxic ferric (Fe+++) form that can bind with proteins. In addition, the ferroxidase activity of ceruloplasmin helps keep iron mobilized so that it does not allow the iron to get stuck in the tissue. Learn more about copper here.

Iron is potentially toxic. Its ability to donate and accept electrons means that it can catalyze the conversion of hydrogen peroxide into free radicals. Free radicals can cause damage to a wide variety of cellular structures and ultimately kill the cell.

Overdoses of ingested iron can cause excessive levels of free iron in the blood. High blood levels of free ferrous iron react with peroxides to produce highly reactive free radicals that can damage DNA, proteins, lipids, and other cellular components. Iron toxicity occurs when the cell contains free iron, generally when iron levels exceed the availability of transferrin to bind the iron. Damage to the cells of the gastrointestinal tract can also prevent them from regulating iron absorption, leading to further increases in blood levels.

Hopefully, you can understand why iron supplements are harmful, especially in our foods. These iron filings are the most toxic form of iron you can add.(11)

References:

  1. https://pubmed.ncbi.nlm.nih.gov/12243126/
  2. https://pubs.rsc.org/en/content/articlehtml/2014/mt/c4mt00104d
  3. https://en.wikipedia.org/wiki/Iron
  4. https://en.wikipedia.org/wiki/Human_iron_metabolism
  5. (Gropper, Sareen S.; Smith, Jack L. (2013). Advanced Nutrition and Human Metabolism (6th ed.). Belmont, CA: Wadsworth. p. 481. ISBN 978-1133104056.)
  6. (Truswell, A. Stewart (2010-07-15). ABC of Nutrition. John Wiley & Sons. p. 52. ISBN 9781444314229.)
  7. https://pubmed.ncbi.nlm.nih.gov/12641343/
  8. https://pubs.rsc.org/en/content/articlehtml/2014/mt/c4mt00104d
  9. (Cartwright and Wintrobe, 1958; Ames et al, 2005).
  10. https://en.wikipedia.org/wiki/Ferrochelatase
  11. Jym Moon, PhD, 2008, IronL The Most Toxic Metal. George Ohsawa Macrobiotic Foundation.

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