Iron

Iron is a natural essential mineral belonging to the supplement class.

Iron is also known as ferrous and ferric.

Iron is an essential mineral that is required for energy metabolism and the transportation of oxygen. It is also necessary for physical growth, neurological development and cellular functioning.

A deficiency of iron leads to iron deficiency anaemia. Symptoms like pale skin, fatigue, breathlessness, dizziness and cold hands and feet characterize anaemia.

Iron is found in the non-haem form, derived from plants and dairy products, including egg yolks, nuts, legumes, fruit, dried fruit, raisins, dark molasses, vegetables, beetroot, grains and tofu. In contrast, the haem form is derived from animal sources, including liver, lean red meat, poultry, fish, oysters, clams, shellfish, kidneys and heart.

Red blood cells are produced to distribute iron, which is predominantly absorbed in the small intestine and transferred via transferrin. Intestinal cell shedding eliminates excess after being stored in the liver.

The common side effects of iron include gastrointestinal effects like abdominal cramps, diarrhoea and nausea.

Iron is available in oral liquid solutions, tablets and injectable solutions.

Biochemical action of iron

Iron belonging to the supplement class helps in the growth and development of the body. Iron acts via the heme synthesis pathway.

Iron is incorporated into porphyrin rings to produce heme molecules in heme production. The haemoglobin and myoglobin are essential for oxygen transport, and tissue oxygenation is made up entirely of these heme molecules. The hepcidin receptor regulates cellular iron export, whereas the transferrin receptor enables iron entrance into cells and maintains iron homeostasis by interacting with ferroportin. The mitochondrial electron transport chain uses iron to produce ATP for cellular activities. Iron metabolism is carefully supervised by hepcidin-mediated mechanisms, which control absorption, transport, and storage to maintain homeostasis. Iron metabolism is systematically regulated through hepcidin-mediated mechanisms regulating iron uptake, transport, and storage.

Immunity: Iron is crucial for the proliferation of all cells, including those of the immune system.

Oxygen transport and storage: Iron primary function is to assist red blood cells with haemoglobin in carrying oxygen. When muscles contract, myoglobin, another protein containing iron, stores and releases oxygen.

Protein and enzyme systems: Iron forms a part of several protein syntheses and is a cofactor for many biochemical processes.

Iron is available in oral liquid solutions and tablets.

• Oral liquid solutions: To be taken by mouth, as applicable.
• Tablets: To be swallowed whole with water/liquid, as applicable.
• Injectable solutions: To be administered parenterally, as applicable.

Iron can be used as a supplement when the amount of iron taken in from the diet is not enough.

Iron supplement orally is used for preventing and treating iron deficiency like anemia, especially during pregnancy.

Adequate oral intake of iron supplements might help improve thinking, learning, and memory in children and adolescents with low iron levels.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Iron may be useful as a supplement for the following health benefits:

• Iron deficiency and iron-deficiency anaemia: Ferrous sulfate is a typical oral treatment for anaemia caused by iron deficiency. Daily therapy is beneficial; however, it is associated with side effects and low compliance. Higher dosages and resolving related defects are required for therapy effectiveness.
• Pregnant women: As a woman's blood volume increases during pregnancy, she needs more iron for herself and her growing baby. A woman's risk of iron deficiency anaemia increases during pregnancy, as does her infant's risk of low birth weight, early birth, and low iron levels. A mother's deficiency of iron may damage fetal brain development.
• Infants and toddlers: Anemia in childhood might result in delayed psychological development, social withdrawal, and decreased capacity to pay attention. Full-term newborns may become iron deficient by 6 to 9 months if they do not consume iron-enriched solid meals or iron-fortified formula.
• Elderly: The risk of developing iron-deficient anaemia increases with ageing. The elderly should take the lowest effective iron dose possible due to dose-related side effects. Iron supplementation is an effective and safe way to treat anaemia after surgery.
• Anaemia of chronic disease: Iron use is hindered by chronic illnesses such as rheumatoid arthritis, inflammatory bowel disease, and some cancers. Increasing dietary or supplementary iron does not usually help with chronic disease-related anaemia. The treatment of the underlying illness is essential.

Iron supplementation may be administered orally and parenterally.

Iron supplements are available as solutions, and tablets can be taken orally. It is best absorbed on an empty stomach, preferably one hour before or 2 hours after eating.

Injectable iron supplements are administered either intravascularly or intramuscularly.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Oral solution: 15mg elemental Fe/mL, 220mg (44mg Fe)/5mL
• Oral liquid drops: 75mg (15mg Fe)/mL
• Tablet: 45mg Fe, 200mg (65mg Fe), 300 mg (60mg Fe), 325mg (65mg Fe)
• Tablet, delayed release: 325mg (65mg Fe)
• Tablet, extended release: 160mg (50mg Fe), 142mg (45 mg Fe), 140mg (45 mg Fe)

• Injectable solution: 20mg (Fe)/mL, 50mg(Fe) /mL 

Dosage Adjustment for Adult Patients

Iron Deficiency Anemia

Treatment is expressed as elemental iron

100-200 mg oral divided q12hr; may administer extended-release form once daily

Prophylaxis expressed as elemental iron

60 mg PO once daily.

Iron is available in oral liquid solutions, tablets and injectable solutions.

Iron should be used as supplement support for maintaining strong bones along with appropriate dietary restrictions.

• Limit the consumption of drinks that include caffeine, such as coffee, dairy products, eggs, chocolate, and alcoholic beverages, as this substance could hinder iron absorption.
• Herbs with significant tannin content, like green tea, bilberry and raspberry leaf as it, can bind to iron and reduce its absorption.
• People with insulin resistance may need to reduce heme-rich meat meals due to a potential relation to a high risk of cancer caused by excess iron in these populations.
• Stay within your daily calorie needs.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

For men, the RDA approximates 16 to 18 mg/day and 12 mg/day for women.

Upper Tolerable Intake (UTL):

The UTL set for iron is 45 mg/day.

Iron supplementation may be contraindicated in the following conditions:

• Hypersensitivity; sensitive to iron elements.
• Hemochromatosis, hemolytic anemia.
• Iron supplements should not be used in haemosiderosis or iron-loading anaemias (thalassaemia, sideroblastic anaemia).
• Peptic ulcer disease
• Ulcerative colitis
• Patients receiving frequent blood transfusions

When the child's iron status is uncertain, caution should be taken when giving iron supplements to newborns or children with apparently average growth.

Iron supplementation should be cautiously prescribed based on biological criteria and not on the assumption of anaemia alone, as unnecessary iron supplementation can result in adverse effects.

For individuals on hemodialysis, iron from supplements might not be absorbed well in people.

In women with type 2 diabetes, high iron intake in the diet may raise the risk of heart disease.

Iron supplements should be given cautiously to preterm children with low blood vitamin E levels, as they may cause serious effects.

Caution is advised when consuming alcohol with iron.

It is excreted in breastmilk; Safe to use during breastfeeding.

Limit the consumption of foods and beverages that include caffeine, such as coffee, tea, chocolate, and alcoholic beverages, as this substance could hinder iron absorption.

Iron is generally well-tolerated.

The adverse reactions related to iron can be categorized as-

• Common: Constipation, nausea, decreased appetite, upset stomach, and darkening of stools.
• Less Common: Abdominal pain, heartburn, or vomiting.
• Rare: Allergic reactions, severe stomach pain, or black/tarry stools.

The clinically relevant drug interactions of iron are briefly summarized here:

• Levodopa and carbidopa: May reduce the bioavailability of carbidopa and l-dopa- separate doses by 2 hr.
• Angiotensin-converting enzyme (ACE) inhibitors: Oral iron supplementation with ferrous sulfate 200 mg may suppress cough induced by ACE inhibitors through an effect on nitric oxide generation.
• Antacids: Reduces the effect and absorption of iron- Separate doses by at least 2 h.
• Ascorbic acid: Increases the effect and absorption of iron — caution in haemochromatosis.
• Cholestyramine and colestipol: In vitro investigations have shown that cholestyramine and colestipol bind iron citrate, reducing their effect- Separate doses by 4 h. Increased iron intake may be required with long-term therapy.
• Cimetidine: Iron can bind cimetidine in the gastrointestinal tract and reduce its absorption-Separate doses by at least 2 hr.
• L-Thyroxine: Taking iron with levothyroxine can reduce this medication’s effectiveness-separate doses by at least 2–4 hr.
• Proton pump inhibitors: The amount of nonheme iron the body receives from meals may be decreased due to the decrease in stomach acid.
• Calcium: Calcium might interfere with iron absorption- should at different times of the day to prevent this interaction.
• Haloperidol: It may cause decreased blood levels of iron. Avoid concurrent use or increased iron intake may be required with long-term therapy.
• Sulfasalazine: May bind together, decreasing drug and iron effect-Separate doses by at least 2 hr.
• Penicillamine: Reduced drug and iron absorption-Separate doses by at least 2 h.
• Tetracycline antibiotics: when used concurrently, may reduce the effect of the drug.Separate doses by 4 hr.
• H2-receptor antagonists (antiulcer drugs): Iron absorption depends upon gastric pH; therefore, medications that affect gastric pH may interfere with iron absorption. Avoid concurrent use.
• Penicillamine: Iron and penicillamine should be used cautiously as sudden withdrawal of iron has been linked to penicillamine toxicity and renal impairment

The common side of iron includes the following:

• Constipation
• Nausea
• Upset stomach
• Diarrhoea
• Darkening of stools.
• Heartburn

The use of iron should be prudent in the following group of special populations.

• Pregnancy: More iron is required to nourish the developing foetus and placenta and improve the mother's red cell mass.

The RDA for iron in pregnant women is 27 mg/day.

• Paediatrics: Iron plays an important role in the paediatric population's brain development, fighting infections and growth.

Iron supplements are the best way to help children get enough iron daily.

The RDA for iron in paediatrics ranges from 0.27-15 mg/day.

Dosage Adjustment for Paediatric Patients

Iron Deficiency Anemia

Treatment is expressed as elemental iron

3-6 mg Fe/kg/day orally divided q8hr

Prophylaxis is expressed as elemental iron

More than 4 months older receiving human milk as only nutritional source or more than 50% as a source of nutrition: 1 mg/kg/day orally.

6 months to 2 years in areas where anaemia prevalence is >40% and iron fortified food is not available: 2 mg/kg/day

2 to 5 years in areas where anaemia prevalence >40%: 2 mg/kg/day oral but not to exceed 30 mg/day

More than 5 years in areas where the prevalence of anaemia>40%: 30 mg/day with folic acid

Adolescents in areas where anaemia prevalence is >40%: 60 mg/day with folic acid.

• Geriatrics: Iron is essential in the elderly for physical activity, immunity, cognitive development and function, thermoregulation, and thyroid metabolism.

The RDA for iron in geriatrics is 8 mg/day.

• Lactating mothers: Iron supports proper neurological development during infancy and early childhood. Intake of iron during breastfeeding is generally acceptable, and clinical studies have shown no evidence of fetal risk.

The RDA for iron in lactating mothers is 9-10 mg/day.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of iron. Overdosing on Iron supplements may cause nausea, vomiting, abdominal pain, and in severe cases, shock or organ failure.

There is no specific antidote or treatment for excessive intake of supplemental iron. If an overdose occurs, one should stop taking iron supplements immediately and eliminate unabsorbed iron as soon as possible. Chelating medications like deferoxamine are used to lower iron levels in severe circumstances. Supportive and physical therapy can be provided, if necessary.

Biochemistry profile of iron

In biological systems, iron appears in oxidation states ranging from -2 to +6, chiefly in the ferrous (+2), ferric (+3), and ferryl (+4) forms. These conditions facilitate reversible ligand binding and electron transfers. As typical biological ligands, iron forms complexes with oxygen, nitrogen, and sulphur atoms.

Heme proteins (haemoglobin, myoglobin, cytochromes), iron-sulfur enzymes (flavoproteins, heme flavoproteins), transport/storage proteins (transferrin, lactoferrin, ferritin, hemosiderin), and other iron-related enzymes are the four types of iron-containing proteins found in mammalian systems. Iron sulphur enzymes (Fe-S, 2Fe-2S, 4Fe-4S, and 3Fe-4S proteins) adopt Fe-S configurations. In humans, protoporphyrin-IX is predominant. Heme proteins bind iron to porphyrin rings with various side chains. Iron plays crucial roles in several biological processes according to its variable states and binding affinities.

Kinetic profile:

• Absorption: With the help of stomach acid, iron is absorbed primarily in the small intestine, mainly in its ferrous form (+2).
• Distribution: It attaches to the transport protein transferrin and is sent to cells, where it gets integrated into haemoglobin, myoglobin, and enzymes. Iron promotes the erythropoiesis process, which produces red blood cells.
• Metabolism: The liver's role in iron metabolism involves storing excess iron as ferritin and releasing it when needed. A hormone called hepcidin regulates the absorption and release of iron to maintain the proper equilibrium. When macrophages phagocytose aged red blood cells, iron is released for reuse, facilitating iron recycling.
• Elimination: Iron is eliminated mainly by shedding intestinal cells that have absorbed iron. Iron deposition can occur in organs and cause harm in excessive iron levels or pathological situations.

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2. https://www.ncbi.nlm.nih.gov/books/NBK222309/
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