Iron As a Micronutrient

 MICRO-MINERALS 

Minerals are indispensable part of a complete diet of humans, animals and plants  nutrition. They are inorganic elements that are found in all body tissues and fluids.  These minerals yield no energy but they have vital roles in many activities occurring in  the body. The body needs many minerals, called Essential minerals. They are divided  up into major minerals (macrominerals) and trace minerals (microminerals). These two  groups of minerals are equally important, but trace minerals are needed in smaller amounts usually in microgram quantities (less than 100 mg quantities). 

IRON (Fe) 

INTRODUCTION 

Iron is a chemical element with symbol Fe (from Latin: ferrum) and its  atomic number is 26. Iron (Fe) belongs to the first transition series and group 8 of the  periodic table. The Earth’s crust is made up of about 5% of iron. After oxygen, silicon,  and aluminum, iron is the fourth abundant element. 

Iron is an essential mineral to all cells of the human body. It is needed for  both physical and mental health because every cell in the body needs iron to produce  energy. It is present mainly in heme of hemoglobin, myoglobin, and cytochromes & in  iron storage proteins ferritin & hemosidrin.

SOURCES FOR IRON 

Sources of iron include: liver, cereals, flour, egg-yolk, fish and shellfish, red meat, beans (such as red kidney beans, edamame beans and chickpeas), nuts, dried fruit  (such as dried apricots), lentils, soy foods, green leafy vegetables, and raisins. Milk is  very low in iron content. Iron utensils also increases iron content of food.

In Foods, iron found in its two forms:

1. Heme Iron: derived from the hemoglobin and myoglobin animal food sources (meat, seafood, and poultry). Heme iron is the most easily absorbable form (15% to 35%) and accounts for 10% or more of our total absorbed iron.

2. Non-Heme Iron: Non-heme iron is obtained from plants  (such as cereals, legumes, fruits and vegetables) and iron fortified meals. It is not well absorbed as heme iron. (Lucia K et al., 2021).

Distribution of Iron in the Body

An adult human has approximately 4 grams of iron in his body. This amount is  available in two forms:

1: Functional forms: 

 About (75%) of iron is present in its functional form as:

a- Hemoglobin (67%) b- Myoglobin (7.5%) c- Respiratory enzymes (0.5%) as cytochromes etc.

2: Non-functional forms: 

About (25%) of iron is present in its non-functional form. Free iron is very toxic.  So, iron is bound to proteins (non-hememetaloproteins) that allows it to be transported  & stored in non-toxic forms.

1- Transferrin (0.1%): for transport of iron in blood. 

2- Ferritin & hemosiderin (24.9%): for storage of iron in tissues.

Storage of Iron in the body 

 A human body can store iron as a reserve. An individual’s iron level falls on a range (ranging from replete to depleted iron  stores) which is attributed to iron deficiency and iron toxicity. 

Hemoglobin: More than 65% of the body’s iron is present in the blood in the form of  hemoglobin, which is a protein in red blood  cells that transports oxygen to tissues in the body. Hemoglobin contains 3.4mg iron/gm.

Myoglobin: Smaller amounts of iron are found in myoglobin, a protein that helps  supply oxygen to muscle cells, and in enzymes that assist biochemical reactions in  cells. 

Ferritin: It is the chief storage form of iron in tissues. Iron is primarily stored in the liver,  spleen, bone marrow & intestinal mucosal epithelium in the form of ferritin. This form of storage is composed of a protein shell with a core containing iron as ferric form. Binding sites of ferritin saturated by 23% with iron.

Hemosiderin: It is almost similar to ferritin in its composition but its binding sites  saturated by 35% iron, thus stores more iron in it. 

Transferrin: A transport protein, which carries or binds to two iron molecules. This  protein is synthesized in the liver & runs with the b-globulin. Only 30% of transferrin  is saturated with iron (called Total Iron Binding capacity, TIBC).  

DIGESTION AND ABSORPTION OF IRON 

Iron is required for many metabolic processes in humans, such as DNA  synthesis, electron transport, and oxygen transport. In contrast to other minerals, iron  levels in the human body are solely controlled by absorption. 

      The majority of dietary iron is absorbed in the duodenum and proximal jejunum  and is heavily dependent on the physical state of the iron atom. 

           At physiological pH, iron occurs in the oxidized, ferric (Fe3+) form. Iron must be in  the ferrous (Fe2+) form or bonded by a protein such as heme to be absorbed (Ems T et  al., 2021).

FACTORS ENHANCES IRON ABSORPTION

 Individual's dietary inhibitory and enhancing factors exert profound influences  on iron absorption. 

• Eating foods containing vitamin C, vitamin A, meat, fish and poultry enhances iron  absorption. 

• Iron is best absorbed in ferrous form. 

• Gastric juice helps in the absorption of iron. 

• Chlorophyll and bile pigments increases iron absorption. 

• Increase amount of iron in diet, increase amount absorbed. 

• Condition associated with increased rate of erythrpoiesis effects iron absorption. 

• Taking ascorbic acid, succinic acid, fructose and sorbitol along with iron enhances  its absorption.

• Pathological conditions Hemochromatosis, Cirrhosis of liver, pancreatic insufficiency. 

Vitamin C Improves Non-Heme Iron Absorption: 

A scorbic acid (vitamin C) is  the most important iron absorption enhancer. Vitamin-C forms a chelate with ferric (Fe3+) iron in the low pH of the stomach, which persists and remains soluble in the alkaline environment of the duodenum. There is a dose-related effect of iron absorption; the more vitamin C in a meal, the greater the iron absorption.

FACTORS INHIBITING IRON ABSORPTION

• Malabsorption syndrome: These syndromes, including steatrorrhea, sprue and celiac  disease, impaired iron absorption. In steatrorrhea, fatty acids forms non-absorbable iron  soaps. 

• Diarrheal disease: The time for iron absorption decreases under such condition.

• Phytic acid, oxalates and phosphatase: Phytic acid which is present in cereals and oxalic acid which is abundant in leafy  vegetables form insoluble complexes with iron, so making iron nonabsorbable. Vegetable food have a lot of phosphates  which decrease iron absorption. 

• Subtotal Gastrectomy: Gastrectomy impairs iron absorption by impairing the Fe+3 reduction occurring in stomach or by decreasing HCl and transit time through the  duodenum. 

• Food Intake Along with Iron: When we ingested iron supplements along with  foods like eggs, tea they form insoluble iron complexes and causes less absorption of  medicinal iron.

• Antacid Therapy: Antacid makes an unfavorable environment for iron absorption as it reduces acidity of stomach or they binds to iron, preventing iron  absorption. 

• Surgical Removal of Upper Small Intestine: A large amount of iron is normally  absorbed on the surface of small intestine. In patients with partial or total surgical  removal of intestine, there is a loss of surface concerned with iron absorption. 

REGULATION AND HOMEOSTASIS OF IRON  ABSORPTION 

 A protein named Hepcidin (25 amino acid peptide hormone) is a key iron  regulatory hormone which regulates iron by negative regulation of Ferroportin  (iron’s cognate receptor). This hormone is synthesized by hepatocytes and causes  internalization and degradation of ferroportin. Hepcidin prevents transfer of iron into  blood.  

• It prevent normal iron level by reducing the transport of iron into the gut mucosa.

• Hepcidin regulates iron receptor ferroportin by post translational regulation. 

• It also regulates iron transporters present on duodenal enterocyte’s basolateral  membrane, placental syncytiotrophoblast and hepatocytes, thereby preventing the  release of iron into circulation. 

• Hepcidin denatures microphagous ferroportin in an autocrine manner thus making  retention of iron in macrophages locally.  

Thus in short hepcidin controls ferroportin concentration on different  cells that export cell like duodenal enterocytes, recycling of liver, spleen and  hepatocytes macrophages.

Figure showing regulation of iron absorption

Expression of Hepcidin:

Hepcidin synthesis is regulated by many stimuli at  transcriptional level.

• Inflammation IL-6 induces hepcidin. 

• STAT-3 dependent transcription 

• Stimulation through microbes also show hepcidin. 

MODE OF ACTION OF IRON 

• Oxygen carrier: In the red blood cells a protein called  hemoglobin binds iron with  itself. Upon breathing oxygen  in our lungs combines with  iron present in hemoglobin,  making it oxyhemoglobin.  Thus RBCs facilitate oxygen  transport from lungs around  the body via arteries. 

• Energy Production: Iron is involved in the production of energy by blood sugar  conversion or by other process as it is a constituent of many enzymes like iron  catalase, peroxidase and cytochrome enzyme. 

• Brain development: Iron develop brain along with folic acid. It myelinates neuron  as it is a cofactor part of ribonucleotide reductase. 

• Thermo regulator: Iron regulates body temperature. 

• Muscle movement: Iron is also a part of muscle protein myoglobin thus facilitate  oxygen use and storage as same as hemoglobin. 

• Production of enzymes: Iron indirectly involved in the production of new cells,  amino acids, hormones neurotransmitter and collagen as iron is a component of  enzymes or the production of these enzymes depends on iron. 

• Maintain healthy immune system: Iron is also needed for proper immune function  as iron is necessary for activation, maturation and proliferation of immune cells. It  also negatively effects the pathogens.

EXCRETION OF IRON  

 Human body does not have any specific mechanism for iron excretion thus  iron levels in body are regulated by regulating iron absorption and iron loss .The  human body requires a daily intake of iron to perform many functions. The daily  excretion of iron is about 0.9mg/day. Excretion of iron from the body is takes place by  following means:

1: In feces (90 – 95%): Fecal iron is unabsorbed iron.

2: In urine & sweat (5 – 10%): Daily loss of iron is about 0.5 -1 mg of iron 3: In menstruation & milk (5 – 10%): About 15 -30 mg of iron (in the form of  hemoglobin) is lost in menstruation per month. Lactation leads to a loss of 0.5- 1 mg  of iron per day.