Author: Payal Bhandari, M.D.

Contributors: Amer Džanković, Hailey Chin, Vivi Chador, Nigella Umali Ruguian 

Key Insights

Iron panel blood tests check your body’s iron levels and how it uses and stores iron. These tests usually include:

• Iron: Measures iron in your blood.

• Ferritin: Shows stored iron in your organs.

• Total Iron Binding Capacity (TIBC): Measures how well blood proteins carry iron.

• Unsaturated Iron Binding Capacity (UIBC): Shows extra space on transferrin (a protein) for iron.

Low iron and ferritin levels mean iron deficiency. High levels mean too much iron (hemochromatosis). In iron deficiency, TIBC and UIBC go up because there’s more unused transferrin. In iron overload, they go down due to liver damage.

Unbalanced iron can cause anemia, inflammation, infections, or organ damage. Diet, stress, and medication affect iron levels.

What Is Iron? 

Iron (Fe) is a mineral the body needs to stay healthy. There are two types: heme and non-heme. Non-heme iron comes from plants like beans, grains, vegetables, and nuts. Heme iron comes from animal foods like meat, fish, and eggs, with red meat having the most. Heme iron is crucial because it makes up most of the iron the body uses. It helps the liver create proteins, like transferrin, which carry iron. In Western diets, heme iron is about two-thirds of the body’s total iron, even though it’s only one-third of what we eat.

Iron’s Role in the Body

1. Oxygen Transport:

Hemoglobin (Hb) is a protein in red blood cells (RBCs) that carries oxygen (O₂) from the lungs to the body and removes carbon dioxide (CO₂) when we exhale. RBCs act like cars, with hemoglobin as the driver picking up oxygen and delivering it to tissues. Most oxygen (98–99%) binds to hemoglobin because free oxygen in the blood can be harmful.

RBCs are made in the bone marrow and are packed with hemoglobin, which gives blood its red color. They don’t have a nucleus or mitochondria, so they don’t use oxygen themselves.

Figure 1:  Red blood cells (RBCs)’s main job is to carry oxygen (O2) to tissue and release the waste product, carbon dioxide (CO2), during exhalation. RBCs contain around 640 million hemoglobin molecules per cell. 

Vitamins B12 and B9 (folate) help hemoglobin bind oxygen to iron (Fe²⁺). Each hemoglobin molecule can carry up to four oxygen molecules. The stomach manages vitamins B12 and B9, while the small intestine absorbs iron.

Figure 2: Each hemoglobin structure comprises two alpha and two beta-globin protein chains with four heme groups (derived from porphyrin) in the center that each attaches to a single iron atom, Fe2+. 

Figure 3: Heme is a key part of hemoglobin, which carries oxygen in the blood. The process starts in cell mitochondria, where succinyl-CoA and glycine combine to make aminolevulinic acid (ALA) with the help of the enzyme ALA synthase. ALA changes into Protoporphyrin IX, and the enzyme ferrochelatase adds an iron atom to complete heme. Heme joins globin proteins to form hemoglobin. About 15% of hemoglobin is made in the liver, and 85% is made in the bone marrow.

2. Oxygen Storage

Skeletal muscles store oxygen as myoglobin, which helps produce energy during activity. In raw meat, iron in myoglobin is in the ferrous (Fe2+) state, making the meat red. When cooked, iron loses an electron, becoming ferric (Fe3+), which turns the meat brown.

3. Energy Production

Iron is involved in a series of reactions for harvesting energy (adenosine triphosphate; ATP) via cellular respiration. It involves a three-step process that generates the greatest amount of energy in the mitochondria of cells: 34 ATP + 2 ATP, each ATP derived from the breakdown of glucose (glycolysis) and the Krebs cycle. Iron plays a critical role in the electron transport chain.

Figure 4: Cellular respiration is a set of metabolic reactions that convert electrons from plants that do direct photosynthesis into high-energy, electron-carrying molecules like adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NADH), and flavin mononucleotide-FMN (FADH). The waste product CO2 is released and excreted during exhalation by the lungs. 

Figure 5: In mitochondria of cells, oxygen (O2) acts as the final electron acceptor that pulls down electrons in the electron transport chain, creating a proton gradient that drives energy production. The proton gradient comprises protons and hydrogen ions (H+) that break off from other enzymes and require ATP to be transported. In the presence of iron (Fe2+) and O2, the electrons move downhill from carrier to carrier, losing their charge until ATP is harvested.

4. Enzyme Function

Iron helps enzymes work properly by keeping their structure intact and speeding up important body processes. These processes include metabolism, protecting cells from damage, making DNA, and fixing it. Enzymes often need helpers called cofactors, which can be metals like iron, organic molecules, or a mix of both.

Figure 6: Iron is a cofactor for many enzymatic reactions                   

Regulation of Iron, Ferritin, TIBC, and UIBC Blood Levels

Iron absorption is controlled by the type of iron in food. Heme iron from meat is absorbed more easily than non-heme iron. Peptides and amino acids from meat help absorb both types, raising iron levels in the blood.

Non-heme iron absorption is affected by vitamin C (which helps) and compounds like phytates and polyphenols (which block it). Too much iron in the blood, from red blood cell breakdown or too much meat, causes the liver to produce proteins like hepcidin, ferritin, and transferrin.

Transferrin carries iron in the blood and helps make red blood cells. Transferrin saturation shows iron levels. Hepcidin stops the release of stored iron and blocks its absorption. Ferritin stores extra iron in organs and muscles, which can cause problems like hemochromatosis if too much builds up.

Figure 7: Iron is needed for oxygen transport and energy. It comes in two forms: heme and non-heme iron. Heme iron is absorbed better, but vitamin C helps absorb non-heme iron, while calcium can block it. The body absorbs 1-2 mg of iron daily, which is carried to the bloodstream by transferrin. Some iron goes to muscles, and the rest makes hemoglobin and red blood cells. The liver stores extra iron and releases it when blood iron is low.

The body gets rid of extra iron through bleeding, menstruation, blood donation, urine, and shedding skin and gut cells. Ferritin stores and uses iron in skin cells. The kidneys filter 150-200 liters of blood daily, removing waste, salts, and water, and making 1-2 liters of urine. Most of the important substances, like iron, are reabsorbed into the blood. Inflammation can affect how iron is absorbed and used.

Figure 8: When red blood cells break down (hemolysis), the liver and immune cells produce proteins to remove harmful byproducts like hemoglobin and iron. Haptoglobin and hemopexin carry these byproducts to the liver and spleen to be broken down. Heme is turned into bilirubin in the liver, which is excreted in bile or urine. Iron is stored or recycled in the body. Globulin is reused by the liver to make new proteins.

Clinical Significance of Low Blood Levels of Iron and Ferritin and Elevated TIBC and UIBC (Anemia)

Anemia occurs when blood iron and ferritin are low. The liver reduces hepcidin and ferritin, while increasing transferrin to help absorb and move iron. This raises iron levels in the blood. Lower iron stores also increase TIBC and UIBC, which measure available iron-binding transferrin.

Anemia causes include:

• Low iron from plant-based foods and lack of vitamin C.

• Substances like polyphenols, phytates, and calcium blocking iron absorption.

• Dehydration.

Dehydration makes it harder for iron, vitamin B12, and folate to carry oxygen. It also causes cells to shrink, which leads to more concentrated urine.

Figure 9: Osmosis is the movement of water in and out of cells. In hypotonic conditions, water moves into the cell. In isotonic conditions, water moves in and out equally. In hypertonic conditions, water moves out of the cell. These changes affect the cell’s function.

Dehydration can happen due to:

• Burns

• Diarrhea

• Overuse of diuretics or laxatives

• Sweating from exercise or heat

• Not drinking enough water

• Low breast milk in newborns

• Heavy blood loss from:

  • Periods

  • Inflammation from conditions like autoimmune diseases, cancer, infections, or surgery

  • Frequent blood donations

Dehydration lowers blood flow to organs and harms gut bacteria. This slows digestion, waste removal, and can cause nutrient deficiencies.

Figure 10:  Healthy gut bacteria help with digestion, nutrient absorption, and waste removal. Dysbiosis is when the balance of bacteria is off, allowing harmful microbes to grow, which can disrupt metabolism and the immune system.

Dysbiosis causes several reactions in the body:

• Excess undigested food and toxins make it harder for red blood cells (RBCs) to carry oxygen. RBCs get damaged, releasing iron and hemoglobin into the bloodstream. The liver produces proteins like hepcidin to remove or store these toxins.

• Low oxygen levels reduce the liver’s ability to make heme, which lowers iron and hemoglobin production. The kidneys release hormones to make more RBCs and increase iron absorption, but long-term oxygen shortages can damage the kidneys and worsen anemia.

• The body changes metabolism to prioritize energy use, reducing the production of important digestive proteins. Undigested food, especially proteins, fats, and extra carbs, is stored as fat, leading to muscle breakdown. This causes fat to build up in organs and blood vessels, producing reactive oxygen species (ROS). ROS damage cells, change genes, and disrupt healthy cell growth. The protein leptin increases hepcidin, trapping iron in storage and lowering blood iron levels. This cycle damages cells and hinders growth.

Atherosclerosis-Induced Vascular Inflammation

Low blood iron causes tissue damage and bleeding. Inflammation breaks down red blood cells (RBCs) and increases iron in the liver and other organs. Iron helps repair wounds. Oxygen released from damaged RBCs attaches to LDL cholesterol and acts as an antioxidant. LDL is important for cell function, but when oxygen levels are low, LDL sticks to damaged blood vessels, causing blood clots, scar tissue, and new blood vessels. This leads to atherosclerosis, a process that controls bleeding and repairs damage.

Figure 11: Chronic dehydration and gut imbalance can cause tissue damage, leading to anemia and atherosclerosis. The diagram shows how fat, plaque, and blood clots thicken artery walls. Low oxygen triggers immune cells to clear debris, heal wounds, and grow new blood vessels. Atherosclerosis also raises blood pressure, reduces blood flow, and causes organs to enlarge and lose function.

Autoimmune Disorders, Infections, and Cancers

Chronic inflammation from atherosclerosis over activates immune cells, which shifts important nutrients away from fighting infections and repairing damage. This makes it harder for the immune system to fight harmful invaders like bacteria, cancer cells, and undigested food. Immune cells also start attacking the body’s own tissue.

Free iron can activate hidden pathogens and raise levels of hepcidin, a protein that blocks iron release and worsens iron deficiency anemia. This response, meant to stop infections, can support the growth of cancer and infections instead.

Lower iron absorption and higher levels of hepcidin and inflammation proteins are linked to a higher risk of conditions like diabetes, obesity, autoimmune diseases, atherosclerosis, infections, cancer, and organ damage.

Figure 12: Anemia of chronic inflammation increases white blood cells (leukocytes) and platelets (thrombocytes) to help fight infections and tumors, stop bleeding, and heal wounds. Platelets help tumors and pathogens grow by collecting hemin and iron, which they need to reproduce and spread. Neutrophils help protect blood vessels by releasing proteins that support blood vessel health and promote new blood vessel growth (angiogenesis). However, natural killer (NK) cells are prevented from attacking tumors and pathogens. The cytokines released allow pathogens to damage red blood cells, steal nutrients like iron and oxygen, and cause infections and tumor growth.

Clinical Significance of High Blood Levels of Iron and Ferritin and Low TIBC and UIBC 

Hyperferritinemia is when blood iron and ferritin levels are too high. Ferritin measures iron overload, like in hemochromatosis. Too much iron can damage the liver, lowering proteins like ferritin and transferrin that help manage iron. This causes high transferrin saturation, low TIBC and UIBC, and more free iron in the blood.

With fewer proteins, hemoglobin struggles to carry oxygen, harming tissues and energy levels. Bleeding removes extra iron, so the liver makes more proteins to capture free iron from damaged red blood cells. However, low oxygen worsens iron buildup and liver damage. Extra iron harms cells, genes, and processes, leading to heart disease, genetic issues, and cancer.

In the bone marrow, stem cells make fewer red blood cells and platelets, shortening RBC life and increasing destruction. White blood cells may attack the body, causing autoimmune diseases. Some megakaryocytes (platelet precursors) move to the lungs and turn into platelets to heal injury. To control platelet levels and prevent atherosclerosis, the lungs produce hormones that destroy these cells, raising free iron and ferritin levels.

Figure 13: Low oxygen (hypoxia) destroys red blood cells (RBCs), prompting the liver and kidneys to release hormones that boost RBC and platelet production. If the cause isn’t treated, it damages organs, increasing RBC breakdown and iron levels. The kidneys make erythropoietin (EPO) and help the liver produce thrombopoietin (TPO) to support RBC and platelet production. In some types of anemia, harmful molecules damage organs, reducing RBC and platelet production. Sometimes, platelets get trapped in the lungs and become active when oxygen levels rise. The lungs then release TPO and CFU-meg to clear platelets, lowering iron and platelet levels.

Elevated iron and ferritin levels with reduced TIBC and UIBC can lead to several health problems, including:

• Metabolic disorders (e.g., type 1 and 2 diabetes, obesity, fatty liver disease, and certain skin conditions like psoriasis)

• Hormonal imbalances (e.g., Addison’s disease, PCOS, chronic fatigue, and thyroid issues)

• Autoimmune diseases (e.g., rheumatoid arthritis, lupus, and inflammatory bowel disease)

• Vascular diseases caused by atherosclerosis

• Infections (e.g., viral hepatitis and malaria)

• Cancer growth and spread

• Organ damage

Top reasons for hyperferritinemia:

1. Excess Iron Intake: Eating too many heme-iron-rich foods (like red meat) or taking iron supplements can cause too much iron to be absorbed into the body.

2. Frequent Blood Transfusions: Blood transfusions contain iron. Multiple transfusions can increase iron in the bloodstream and damage organs.

3. Alcohol and Toxins: Heavy drinking can damage the liver, reducing the production of key proteins that help regulate iron levels, leading to iron overload.

4. Excess Vitamin C: Too much Vitamin C can increase the absorption of iron from plant-based foods, raising blood iron levels, especially when combined with a high-iron diet.

5. Hormone Replacement Therapy: Testosterone or thyroid hormone treatments can increase blood iron levels by affecting iron absorption and storage in the body.

Prevalence and Statistics on Abnormal Iron, Ferritin, TIBC, and UIBC Levels

Iron deficiency anemia (IDA) and iron overload (hemochromatosis) are conditions that affect iron levels in the body, leading to low oxygen and tissue damage. IDA is the most common nutritional deficiency worldwide, affecting 30% of people. It causes half of all anemia cases, especially in young women, infants, pregnant women, and those with chronic diseases.

A U.S. study found 40% of young women had low iron, and 6% had IDA. Causes include poor diet, heavy periods, dehydration, and poverty.

The World Health Organization (WHO) reports 37% of pregnant women have anemia, mainly from IDA. Screening and good nutrition are key for mother and baby health. Half of children under five are iron deficient, with dairy as the main cause. The WHO and American Academy of Pediatrics recommend screening children at 12 months.

Iron overload affects 1 in 300-500 people, mostly of Northern European descent. It can also result from frequent blood transfusions, which are rising due to an aging population and chronic diseases.

Conclusion

Iron panel tests check your body’s iron levels and help diagnose related conditions. The iron test shows available iron, ferritin measures iron overload and inflammation, TIBC checks how well the liver produces iron-transport proteins, and UIBC shows how well transferrin binds to iron. Abnormal levels can affect oxygen flow and energy production. To fix iron issues, changes in diet, lifestyle, and avoiding drugs are key. Severe anemia may need supplements or transfusions, while iron overload may need treatment. Poor diet, dehydration, lack of sleep, drug use, and stress can reduce iron use and cause serious health problems. A healthy diet, good sleep, hydration, and stress control help keep iron levels balanced.

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