Observed genes

Polygenic score

Influential genes: HFE,HBS1L,ERFE

The HFE gene influences iron absorption by modulating the expression of hepcidin, the main controller of iron homeostasis​

A genetic variant located in the intergenic region between HBS1L and MYB has been linked to a higher susceptibility to iron overload.

ERFE is the an erythroid regulator of hepcidin, the homeostatic hormone controlling plasma iron levels and total body iron.

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Summary

Iron is an essential mineral our body uses for many functions. We can get iron from various animal and plant sources. Iron deficiency can lead to anemia, but iron excess can also have harmful effects. 

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Overview 

Iron is an essential mineral our body uses for many functions, like oxygen transport, synthesis of collagen, and certain neurotransmitters. Iron is found in various products, like meat, poultry, seafood, beans, nuts, and fortified cereal. If you don’t have enough of this mineral, you can develop iron deficiency anemia. Iron excess can also lead to adverse health effects. However, you should always remember that It’s important to consult your healthcare provider before taking any supplements. 

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The importance of iron in the body  

Iron is an essential mineral that our body uses for many functions, but it is toxic to humans in its free form, so it is bound to various proteins. 

Around 70% of iron in our body is bound to proteins, hemoglobin, and myoglobin. Hemoglobin is a protein found in red blood cells that carries oxygen from the lungs throughout the body. Myoglobin, in its turn, is found in muscles and is used for oxygen storage.

About 25% of iron is stored in a protein complex called ferritin, found in all tissues throughout the body, mainly in the liver, bone marrow, and skeletal muscles. 

Around 6% of iron is a component of various proteins used for metabolism and respiration; and a part of enzymes used for synthesizing collagen and certain neurotransmitters. 

Another protein, transferrin, is responsible for transporting iron in the bloodstream to storage places. Iron absorption and distribution are regulated by a hormone called hepcidin.^[1]

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Iron types, sources, and requirements

The daily iron requirements vary based on factors such as age, gender, and dietary choices. Iron is naturally present in a diverse range of foods and is added to certain fortified products. There are two primary forms of iron: heme iron and non-heme iron. Animal-derived foods such as meat, poultry, liver, and seafood provide both heme and non-heme iron. On the other hand, plant-based sources and iron-fortified products exclusively offer non-heme iron, which is less readily absorbed by the body.

Consequently, individuals who follow a vegetarian diet, thus excluding animal products, may require nearly twice the amount of dietary iron. Notable sources of iron in plant-based foods encompass beans, nuts, dried fruits, fortified cereals, and more. Your body absorbs iron from plants better when you eat it with meat, poultry, seafood, or foods high in vitamin C, like citrus fruit, strawberries, tomatoes, broccoli, etc.^[2]

The recommended daily intake of iron is listed in the table below^[2]:

Iron supplements should only be taken after consulting a healthcare provider. 

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Iron deficiency 

Your body stores iron, so not having enough in the short term doesn't show noticeable signs. But, once the iron storage is used up, you might get iron deficiency anemia (IDA), a condition characterized by small red blood cells with less hemoglobin that leads to insufficient oxygen transport throughout the body. IDA symptoms include upset stomach, tiredness, headaches, dizziness, trouble focusing, looking pale, weak nails, and getting sick easily. Pregnant women, infants and toddlers, women with heavy menstruation, people on a vegetarian diet, people with GI disorders and cancer, as well as frequent blood donors are all at a higher risk of developing IDA.^[3]

Iron deficiency can be diagnosed through blood tests and is usually treated with iron supplements. Consult your GP if you experience signs and symptoms of IDA for an appropriate treatment.

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Iron excess

Iron in large quantities can be harmful. Iron absorption is well controlled in healthy individuals, so you can’t get iron overdose from food sources. However, taking high doses of iron supplements can lead to gastric upset, constipation, nausea, abdominal pain, vomiting, and diarrhea, as well as reduce zinc absorption. Really high doses can even cause gastritis and ulcers.^[4]

An inherited autosomal recessive disorder called primary hemochromatosis leads to increased iron absorption from dietary sources. People suffering from this disease have really high levels of iron that are deposited in various tissues in the body. This iron build-up can cause serious health problems, including cirrhosis, liver cancer, diabetes, joint pain, and heart diseases.^[5]

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Genetics

Genetic factors can affect the body's iron status by influencing the way the body absorbs, transfers, and uses iron. Mutations in certain genes can lead to conditions such as hereditary hemochromatosis, where the body absorbs too much iron, or iron deficiency anemia, where the body does not get enough iron. Other factors, such as diet and lifestyle, can also affect iron levels.^[6]

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Iron metabolism is a complex process that involves the regulation of iron absorption, its transport, storage, and utilization. Several genes have been identified to play a role in these processes, including the HFE and TMPRSS6 genes. Mutations in the HFE gene are associated with hereditary hemochromatosis, leading to iron overload and damage to organs such as the liver, heart, and pancreas.^[6,7]

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On the other hand, mutations in the TMPRSS6 gene have been linked to iron-deficiency anemia. Mutations in the TMPRSS6 gene cause hepcidin overexpression, reducing dietary iron absorption and leading to decreased serum iron and transferrin saturation.^[8]

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Researchers continue to investigate the genetic factors that influence iron metabolism and how they interact with environmental factors such as diet and lifestyle. Understanding the complex molecular pathways and mechanisms involved in iron metabolism is important for the development of new treatments for iron-related disorders.^[9]

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In Macromo, we use polygenic risk scores and causative evidence-based genetic variants for evaluation. The polygenic risk score (PRS) represents the total number of genetic variants that increase an individual's risk of developing a particular disease or trait. All variants across their genome are summed and ranked according to their effect on disease development. 

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Recommendations

• Ensure you're meeting the recommended daily intake of iron based on your age, gender, and life stage. 
• Incorporate a variety of iron-rich foods into your diet. Animal-derived foods like meat, poultry, liver, and seafood provide both heme and non-heme iron. Plant-based sources such as beans, nuts, dried fruits, fortified cereals, and vegetables offer only non-heme iron.
• Enhance iron absorption from plant-based sources by consuming them with foods high in vitamin C, such as citrus fruits, strawberries, tomatoes, and broccoli. Vitamin C helps improve the absorption of non-heme iron.
• If you suspect an iron deficiency or have specific health conditions that put you at risk, consult a healthcare provider before taking iron supplements. Excessive iron intake, especially from supplements, can lead to adverse effects and should be managed under medical guidance.
• Avoid taking iron supplements without medical guidance. While iron is essential, excessive intake can lead to adverse health effects.
• Be aware of the genetic disorder called primary hemochromatosis.
• Regularly monitor your health. Health checkups can help detect any abnormalities early and ensure timely intervention.

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