Mechanism of Action; How iron is absorbed

mechanism of action

Iron is the second most abundant element in the earth’s core; yet deficiency of iron is the most common cause of anemia across the globe. A well- balanced diet can supply recommended daily doses of iron. Human body maintains a steady balance between iron intake and loss. The need and absorption rate of iron increases in special situations such as pregnancy, surgery, or heavy menstruation. Iron intake is mostly external (through diet or supplementation). Most of the dietary iron can be absorbed by the gut if:

  • Gut is healthy 
  • There is no external or internal agent to interrupt the absorption of iron 

Iron Metabolism:  

An average adult stores about 1-3 grams of iron in their body, most of which is stored in liver or immune cells (also known as reticuloendothelial cells).

A balanced diet contains about 10-20 mg of iron. Under normal circumstances, our body reabsorbs about 10% of this amount, which is sufficient to maintain all bodily functions. 

  • An average adult loses about 1mg of iron every day due to cell breakdown
  • Adult females in reproductive age group lose about 2mg of iron due to menstruation and cellular breakdown

The regulation of iron stores in the body is mostly maintained by dietary iron intake. There are two varieties of dietary iron, heme and non-heme. Heme Iron is obtained from animal protein sources and is more readily absorbed by the body, whereas non-heme iron is primarily obtained from plant sources. It is also noteworthy that the absorption of non-heme iron is poor and depends on a number of factors such as gut pH level of the gut, food composition amongst others. 

Absorption of Iron:

Most dietary iron is absorbed in the small intestine (upper jejunum and duodenum). The chemical state of iron greatly influences its absorption in the gut. When ingested as a non-heme iron supplement or from vegetarian food sources, non-heme iron is in the Ferric state (Fe3+) which is insoluble and cannot be readily absorbed by the gut. 

In order for your body to absorb non-heme iron, two conditions must be met:

  1. Iron has to be in the Ferrous state (Fe2). For this to happen, the pH of the stomach needs to be slightly acidic in order to convert the non-heme iron from the ferric state (in which it was ingested) into the ferrous state (which can now be absorbed).
  2. Ingestion of non-heme iron needs to be spaced apart from certain foods that hinder absorption (such as caffeinated drinks, dairy products, other calcium containing supplements).

To help with absorption of non-heme irons, taking acidic foods (such as orange juice or a vitamin C supplement) at the same time can help to increase the pH and facilitate this transition. The dietary Ferric form of non-heme iron must be converted into Ferrous form for absorption in the duodenum and upper jejunum. This transition is facilitated by the enzyme Ferric reductase. Be mindful though, as previously mentioned, some foods can actually hinder the absorption of non-heme iron:

  • Most leafy greens contain oxalic acid which binds with non-heme iron and blocks its absorption in the gut
  • Non-heme irons are absorbed by the Divalent Metal Transporter (DMT1). Unfortunately, various metal ions found in foods, such as calcium, magnesium, also use the same DMT1 transporter in the duodenum. So, taken at the same time, these ions compete with non-heme iron to use the transporter to be absorbed.
  • Changing the pH level of the gut to less acidic, thus interfering with the conversion of Ferric to Ferrous state of non-heme dietary iron. Any iron that is not absorbed in the duodenum, must leave the body through the bowels and can cause constipation among other GI side effects.

What if Dietary Iron is in Heme Form?

Absorption of dietary iron in the heme form follows a different path for absorption. It is absorbed by the Heme Carrier Protein 1(HCP1). The HCP1’s is only able to absorb heme iron, thus other metal ions that are ingested (such as calcium and magnesium), do not compete for this receptor.. Heme comes from animal sources and does not need to be converted, thus is readily absorbed as heme in the small intestine, independent of the pH level of the gut. In addition, heme absorption in the gut is independent of food and other biological factors which makes it more bioavailable for consumption and uptake in the body. 

What are some factors that may influence Iron Absorption?

The absorption of non-heme iron as discussed previously, largely depends on the acidity level of the gut. The acidic environment is needed to convert dietary non-heme iron from the ferric to ferrous form (Fe3 to Fe2). Any factors which affect the pH level of the gut can compromise the absorption of non-heme iron in the body. 

For instance:

Drugs that interfere with Duodenal pH level:

Proton Pump Inhibitors (also referred to as PPI) are drugs that treat acidity or Gastroesophageal Reflux Disease(GERD). This class of drug (common examples being Prilosec, Prevacid, Nexium) reduce the production of gastric acid. As a result, when non-heme iron is ingested, there is not always enough acidity to convert the iron from the ferric into the ferrous state, rendering the iron un-absorbable in the duodenum. As such, since the absorption of heme iron does not require the acidic environment, PPIs do not affect the absorption of heme iron. The use of PPIs do not affect heme iron. 

Vitamin C / ascorbic acid:

Citrus fruits or Vitamin C improves the absorption of iron as they chelate (or act as a binding agent) with iron and help transfer it to the small intestine and aid in digestion. Vitamin C also has an acidic pH that favors the conversion of non-heme iron to Ferrous state. 

Tannins and Plant phytates: 

Tannins are present in tea, coffee and chocolate, whereas phytates are present in leafy greens such as spinach. These compounds, if consumed with iron rich foods, inhibit the absorption of iron by tightly binding with iron and preventing its uptake by the DMT1 transporters. 

Other metals: 

Lead is another metal that inhibits the absorption of iron by competing for the same receptor spot as non heme iron (DMT). Individuals living in areas where soil/ water has high levels of lead have a higher risk of developing iron deficiency anemia. Besides Lead, all other metals (such as calcium and magnesium) compete with non-heme iron for DMT receptors. If too many metals are present in the gut, DMT receptors become saturated preventing iron from binding and being absorbed. This unabsorbed iron will leave the body through the bowels.

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