Most (two-thirds) of the iron that we have in our body is bound up in heme i.e. hemoglobin or myoglobin. Remember that hemoglobin carries oxygen in the blood and myoglobin takes oxygen from the red blood cells and carries it to tissues that need it.  

Therefore, iron is very important as an oxygen carrier when in the heme form. As a component of cytochrome, an electron carrier in the electron transfer chain, iron allows us to produce energy (ATP). Iron is also a part of many enzyme systems involved in various metabolic reactions including DNA synthesis. 

How is Iron Regulated?

Excess iron can cause toxicity, and can act as a prooxidant (opposite of antioxidant) to promote free radical damage. Therefore, the amount of iron in our blood must be carefully regulated. The absorption of iron depends on various factors.  

  1. Amount in the diet: If iron content is high, absorption will be low and vice versa
  2. Type of iron: There are two types of iron i.e. heme iron (iron bound to heme) and non-heme iron (iron that is not bound to heme). Non-heme iron typically makes up 85-90% of our diet. We can get both of these types of iron from animals, but plants only have non-heme iron since they don’t have hemoglobin or myoglobin. Heme iron is more absorbable than non-heme iron. 
  3. Amount of stomach acid: Stomach acid reduce iron from its ferric (Fe3+) to its ferrous (Fe2+) form which is more absorbable. Therefore, people with low production of HCl in the stomach such as the elderly, and those taking medications to reduce stomach acid will have difficulty absorbing iron
  4. Dietary factors: (i) Consumption of vitamin C (ascorbic acid) with iron enhances iron absorption. This is because vitamin C reduces ferric (Fe3+) to the more absorbable ferrous form (Fe2+) as explained above, plus it forms a soluble vitamin C-Iron complex that is easier to absorb. (ii) Consumption of meat, fish or poultry along with plant foods enhance the absorption of non-heme iron. This is due to the presence of meat, fish, poultry (MFP) factor. (iii) If your diet has high amounts of minerals in the divalent action form, this can reduce absorption. Example of these minerals include Zn2+, Mn2+ and Ca2+. (iv) The presence of antinutrients such as phytates, polyphenols and oxalates in plant foods can reduce iron absorption.  
  5. Iron status: If your body is iron deficient you will have increased absorption of iron, but less will be absorbed if you have adequate iron in your body

How is Iron Transported and Stored?

Heme and iron in its ferric and ferrous form are directly absorbed into the enterocytes (cells that line the small intestine). Once in the enterocytes, it can be stored there in the ferric form as ferritin or hemosiderin if there is an iron overload. These stores are called upon later, when iron status is low. If iron is needed right away, it is carried across the membrane of the enterocytes to the blood using ferroportin protein shuttle. In the blood, iron is converted from its ferrous form to ferric form using another protein called ceruloplasmin. Ferrous iron may also be converted to its ferric form in the basolateral membrane of the enterocytes (membrane at the base of the enterocyte) by hephaestin protein. A transfer protein called transferrin takes iron in the blood to wherever it is needed in the body. Apart from the enterocytes, iron may also be stored in the liver, bone marrow and spleen. In general, men store more iron than women. Women are at greater risk of iron deficiency due to loss of blood in the menses and the extra demand during pregnancy. 

Iron absorption and storage 

How is Iron Excreted and Recycled? 

Iron is excreted through the loss of enterocytes which we lose every 3-6 days. As they are excreted in the feces, the iron stored in them are also lost. Iron in hemoglobin however, it not excreted but is recycled after red blood cells die. Remember that red blood cells die after every 120 days. This process is important since heme is the body’s main source of iron. You get 20 times more iron from heme than you get from your food. Iron is also lost in the menses, sweat, semen, when you get a cut, or donate blood. 

Iron Toxicity and Deficiency

Iron toxicity can be caused by taking too much iron tablets. Parents must keep an eye on their kids carefully and keep supplements properly locked away. Some supplements can be particularly inviting for kids, especially the ones formulated in the form of gummy bears. Toxicity may also be caused by a genetic disorder called hemochromatosis which is caused by unusually high rates of iron absorption. This condition is often treated by using chelating drugs to bind iron and hence reduce its absorption. The chelated iron instead excreted in the urine. Blood removal may also be done to reduce iron levels. This blood is not reused but discarded. 

Iron deficiency is the most common nutrient deficiency in the world. It is associated with premature birth, low birth weight, increased risk of infections, and impaired cognitive performance. Iron deficiency progress in three stages:

  1. Stage 1 (Iron depletion): Ferritin levels in blood is low. Earlier you learned that ferritin is stored in the enterocytes. This is correct, but a small amount is also stored in the blood. Your doctor can test ferratin levels in the blood and use the result to correlate with how much is available in your enterocytes. Low ferritin indicates iron deficiency. At this stage, there will be less iron to help drive metabolism and various enzyme function. However, red blood cells are not yet affected. 
  2. Stage 2 (Iron deficiency erythropoiesis): Transferrin; the shuttle that transports iron in the blood starts having empty iron receptors. This can be compared to a train traveling with very few passengers. This makes transferrin more eager or more receptive to fill those empty seats. This “eagerness” is reflected by an increase in total iron-binding capacity (TIBC) which can be measured in a lab. Therefore, if your TIBC is high, you are iron-deficient. At stage 2 you will have less iron available to make red blood cells, causing their numbers to drop (erythropoiesis). 
  3. Stage 3: The quantity of red blood cells become so low that the remaining ones are not able to adequately supply oxygen. We call this condition anemia

Role of Other Nutrients (Summary)

Zinc: Acts as a coenzyme in the synthesis of the heme structure in hemoglobin

Copper: Part of a protein called ceruloplasmin (or ferroxidase I) that is used to enable oxidation of ferrous iron to ferric iron. Recall that iron must be in the ferric form to be transported by transferrin

Vitamin K: Acts as a coenzyme in the synthesis of proteins used for blood coagulation including prothrombin and procoagulation factors VII, IX, and X

Vitamin B6 (pyridoxine): Needed for the synthesis of the porphyrin ring that makes up the heme complex 

Vitamin B9 (folate): Needed for synthesis of DNA and amino acids that are needed for making and growing healthy red blood cells. Deficiency results in red blood cells that are abnormally large (macrocytic) yet having insufficient hemoglobin (macrocytic anemia).

Vitamin B12 (cobalamin): Assists in DNA synthesis needed for proper formation of red blood cells. Like folate deficiency, B12 deficiency also leads to macrocytic anemia. This type of anemia associated with B12 deficiency is called pernicious anemia

Reference: Thompson,&  J., Manore, M., Vaughan, L. (2020). The science of nutrition (5th ed.). New York. Pearson

Courtney Simons
Courtney Simons is a food science professor. He holds a BS degree in food science and a PhD in cereal science from North Dakota State University.
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