In this article, CARE will explain transferrin saturation to you in detail, covering its relevance, measurement, and the effects of low and high levels on your health.

Are you ready? Then, get ready to be an expert on transferrin saturation in a few minutes.

What Is Transferrin?

Before we explain transferrin saturation, it is first important to understand the protein transferrin and some other terms associated with this glycoprotein. A glycoprotein is a macromolecule consisting of a protein and one or more covalently bonded carbohydrate groups. [1]

Transferrin (Tf) is such a glycosylated protein that binds iron and is found in your blood plasma. It plays a critical role in your body's iron metabolism by binding and transporting iron.

Transferrin is capable of binding two iron ions, making it a key component for the iron metabolism in your body. [1]

Transferrin saturation is, in turn, an important value in the diagnosis of iron levels in the blood. In the context of transferrin saturation, ferritin, and TIBC are also commonly mentioned and determined in a blood analysis. Transferrin and ferritin sound almost the same – what is the difference between these two proteins?

The main difference between transferrin and ferritin is that transferrin is a protein that transports iron, while ferritin is a protein that stores iron.

In diagnostic blood tests to assess your iron metabolism, these two parameters are used along with other parameters such as TIBC (Total Iron-Binding Capacity) and Hb (Hemoglobin) levels to provide a comprehensive picture of your body's iron metabolism.

While transferrin provides information about the availability of iron for transport, ferritin indicates how much iron is already stored in your cells. This allows doctors to better understand and diagnose iron deficiency or iron overload conditions. The Hb levels are also relevant in the context of iron levels in the blood.

The hemoglobin level tells you how much iron is currently in your blood. However, it does not tell you anything about the amount of iron that is stored in your cells. Hb levels only drop once the iron stores are completely empty, and enough red blood cells can not be produced anymore. When this happens, you already suffer from a condition called anemia, which we will discuss later.

So, because the Hb levels do not provide information about an iron deficiency until it is already well advanced, transferrin saturation is so important.

What does a normal range of transferrin saturation look like?

Transferrin Saturation – Normal Range

Transferrin saturation indicates the ratio of serum iron circulating in blood plasma to total transferrin. It refers to the ratio of the serum iron concentration and the TIBC expressed as a percentage.

Transferrin saturation can, therefore, be calculated from the blood levels of iron and transferrin.

Normally, transferrin saturation ranges from about 16% to 45% in healthy men and women.

This range may vary slightly depending on laboratory standards and individual factors of a person. Laboratory values within the ranges listed below indicate a balanced iron metabolism. [1]

Normal Values for Women:
Hemoglobin: 12.3 - 15.3 g/dl
Ferritin: 15 - 150 µg/l

Normal Values for Men:
Hemoglobin: 14.0 - 17.5 g/dl
Ferritin: 30 - 400 µg/l

Normal Values for Women & Men:
Transferrin: 200 - 400 mg/dl
Transferrin-Saturation: 16 -45%
Soluble Transferrin-Receptors: 0.76 - 1.76 mg/dl

If your transferrin saturation is above or below these values, this can be due to a variety of reasons. [1]

Both low and high values can indicate different health problems or deficiencies. The causes of deviations from the norm can be many, from dietary habits to genetic factors. We will discuss possible causes of too high transferrin saturation or too low transferrin saturation later.

If a disorder of your iron metabolism is suspected due to your transferrin saturation, medical clarification should always be obtained to ensure the best possible treatment and to avoid possible sequela and complications.

It is especially important to evaluate transferrin saturation in conjunction with the other iron parameters such as ferritin, Hb levels, and the TIBC to make an accurate diagnosis.

And how is transferrin saturation actually tested?

How Is Transferrin Saturation Tested?

Transferrin saturation is usually determined through a blood analysis. Several biomarkers are measured in your blood: ferritin (serum iron), transferrin (transport of iron), hemoglobin levels (Hb levels), and TIBC (Total Iron Binding Capacity). [2]

We will consequently explain the two terms you don't know yet, ferritin and the TIBC, and once again clarify the difference between transferrin and ferritin:

Transferrin – Iron Transport

As you have already learned, transferrin is a protein circulating in the blood plasma that plays an important role in the transport of iron in your body. It serves as a carrier protein for iron by binding iron ions and transporting them in the blood into your cells.

Transferrin helps transport iron to the various tissues and organs in your body, where it is needed for critical functions.

Transferrin saturation refers to the ratio of serum iron to total transferrin and provides information about the availability of iron for transport. It is an accurate value to determine your iron metabolism.

Ferritin – Stored Iron

Ferritin is an intracellular protein found in various tissues, particularly the liver, spleen, and bone marrow. It serves as a storage protein for iron, helping to store excess iron and release it in a controlled fashion when required. [2]

Ferritin levels in blood plasma usually correlate with iron reserves in the body. If ferritin levels are low, this may indicate iron deficiency, while elevated ferritin levels may indicate adequate iron supply or iron overload.

TIBC – Total Iron-Binding Capacity

TIBC measures the total capacity of transferrin to bind iron. A low TIBC value may indicate iron deficiency, while a high value indicates increased availability of iron to transferrin. [2]

Together with serum iron and ferritin levels, TIBC provides an accurate calculation of transferrin saturation.

What Does It Mean If Transferrin Saturation Is Low?

Did you find out that your transferrin saturation is too low? Low transferrin saturation, with values below the normal range, indicates a possible iron deficiency. [2]

Iron deficiency can have several causes and should be investigated further.

What exactly is iron deficiency anyway, and why are your iron levels important to your health?

Iron Deficiency

Iron deficiency is a condition in which your body does not have enough iron to perform important functions. This can lead to anemia, a blood disorder in which the blood cannot carry enough oxygen due to the lack of a sufficient amount of hemoglobin. [2]

However, iron deficiency can have more consequences than just anemia itself; it can also affect the immune system, cause cognitive problems, and lead to developmental delays in children. [2]

The long-term effects of untreated iron deficiency can also increase the risk of cardiovascular disease. It is, therefore, indispensable to detect and treat iron deficiency early on to minimize its consequences on your health.

However, one of the main consequences of iron deficiency remains anemia. At least half of all cases of anemia are caused by iron deficiency and can be diagnosed by measuring transferrin saturation. [2]

Often, there is no specific indication of the onset of iron deficiency, either in the form of specific symptoms or in the results of common tests such as the red blood count test (RBC). This is because, in the early stages of storage iron deficiency, your body may initially draw on its existing iron reserves, the stored iron, to produce sufficient hemoglobin, the oxygen-transporting pigment of your red blood cells. [1]

Iron deficiency can be divided into three stages. Why transferrin saturation is such a meaningful and important value in the diagnosis of iron deficiency is illustrated by those three stages. [1]

Stage 1 – Storage Iron Deficiency

In stage 1, hemoglobin levels are still within the normal range, and your body can still compensate for its iron deficiency. Ferritin is considered a measure of stored iron and indicates whether iron stores in the body are still full.

Serum ferritin circulates in the blood and is, therefore, easy to measure. Ferritin is – in healthy people – the most sensitive biomarker for testing for iron deficiency. This is because low serum ferritin can already indicate a possible iron deficiency at stage I, whereas hemoglobin levels do not indicate a problem at this stage. [1]

If the values in your blood serum are < 12 μg/l, it can be assumed that you have completely depleted iron storage. Transferrin saturation gives an even better overview of the available iron in your body. [1]

Stage 2 – Iron-deficient Erythropoiesis

In stage 2, you might experience first symptoms of iron deficiency, but the Hb levels are still often in the normal range.

Transferrin saturations indicate how much transferrin molecules are loaded with iron.

Therefore, they are a marker of iron-deficient erythropoiesis. If the saturation is < 15%, you already have an advanced stage II iron deficiency [1].

Stage 3 – Iron-Deficiency Anemia

It is only at this stage that the Hb levels drop and are below the normal values. By now, you suffer from clear symptoms of iron deficiency. The Hb levels only drop after the iron stores have been emptied, and a sufficient amount of red blood cells can no longer be produced. Your blood lacks hemoglobin for the transport of oxygen, which leads to various symptoms of anemia.

From this point on, we speak of stage III iron deficiency and iron deficiency anemia, which means that you require therapy to restore a healthy iron metabolism and the necessary levels of hemoglobin and red blood cells. [1]

The causes and symptoms of iron-deficiency anemia can be broad.

Causes of Iron Deficiency

There are several reasons why your transferrin saturation may be low, indicating iron deficiency:

Insufficient Iron Intake – Vegetarians Beware

An unbalanced diet with too few iron-rich foods can lead to iron deficiency. Iron-rich foods are an important source for maintaining balanced iron levels in your body. [3]

Iron is found in foods in two forms: heme iron, which comes from animal sources, and non-heme iron, which is found in plant foods. Your body absorbs iron from animal sources (heme iron) more efficiently than from plant sources (non-heme iron).

To increase the absorption of non-heme iron, you can combine these food sources with foods rich in vitamin C since vitamin C promotes iron absorption.

For example, if you steam some spinach, which is a great source of non-heme iron, you can drizzle some freshly squeezed citrus juice on top of it to improve your iron absorption of the heme-iron.

Malabsorption of Iron – Diseases or Iron-Compromising Foods

Certain gastrointestinal conditions, such as celiac disease or Crohn's disease, can impair the absorption of iron from your diet. Excessive consumption of coffee, tea, or foods containing calcium can, for example, reduce iron absorption. [3]

People who eat a purely plant-based diet often also have lower iron absorption because plant iron (non-heme iron) is absorbed less efficiently than animal iron (heme iron).

Blood Loss – Menstruation

Heavy menstrual bleeding, stomach ulcers, or chronic bleeding can lead to iron loss. Particularly in women, heavy or prolonged menstrual bleeding can lead to increased iron requirements. Still, just a normal period can lead to insufficient iron levels and women should be conscious about their iron intake during menstruation. [3]

Pregnancy And Lactation

Women who are pregnant or breastfeeding have increased iron requirements and are more susceptible to developing an iron deficiency. [4]

During pregnancy, a woman's body needs to produce extra blood for the growing baby. The placenta needs an increased iron supply to pass them on to the baby. This means more iron is required because iron is an essential component of hemoglobin, the protein in red blood cells that carries oxygen. [4]

In addition, bleeding occurs during childbirth and in the postpartum period, the puerperium, resulting in additional loss of blood and, consequently, iron.

Chronic Diseases

Inflammatory diseases, such as rheumatoid arthritis, can cause or exacerbate iron deficiency. [3]

Increased Needs of Athletes

Athletes or people who are exposed to severe physical stress may also have an increased need for iron. [5]

It's always important to determine the exact cause of an iron deficiency, as your treatment will depend on it.

Aside from your blood work, what are the actual symptoms of an iron deficiency?

Symptoms of Anemia – Iron-Deficiency Anemia

Anemia caused by iron deficiency can cause a variety of symptoms and signs – especially if it's already more advanced. [3] [1]

Symptoms of iron deficiency anemia can vary from person to person in severity, depending on how advanced the iron deficiency is.

Fatigue & Weakness

Being tired and feeling weak are the most common symptoms of iron deficiency. These symptoms can also occur at an early stage of iron deficiency. Affected individuals often feel persistently tired and exhausted, even after adequate sleep. They feel low in energy and lethargic. [3]

Pallor/Paleness

Pallor of the skin and mucous membranes, especially of the tongue and gums, occurs due to low hemoglobin levels. This is often a symptom of advanced iron deficiency. [3]

Shortness of Breath

People with iron-deficiency anemia may feel short of breath, even with little physical exertion. Hemoglobin binds and transports oxygen in your body.

Since iron deficiency leads to a decrease in hemoglobin production, resulting in a lower oxygen binding and transport capacity in the blood, this can, in turn, lead to shortness of breath and lack of oxygen in the body. [3]

Racing Heart – Palpitations (Tachycardia)

Do you feel like your heart is racing?

The heart rate increases with iron deficiency and anemia because your body is trying to carry oxygen more efficiently. It pumps faster in an attempt to carry more oxygen, and this results in heart palpitations. [3]

Headache

Do you often have a dreadful headache that just doesn't go away?

A persistent lack of oxygen to the brain due to iron deficiency can cause headaches. [3]

Cold Hands and Feet

An iron deficiency can affect blood flow, which can lead to cold extremities and the sensation of chilly hands and feet. So if you feel like you have cold hands and feet all the time, you should have your iron levels checked through the transferrin saturation in your blood. [3]

Brittle Nails and Hair Loss

As if it is not enough to be pale and without energy, an iron deficiency can also lead to hair loss and brittle nails. A decreased supply of oxygen to the hair follicles and nails affects hair growth and nail formation. [3]

In addition, iron deficiency influences the production of collagen, which impacts the elasticity and strength of your hair and nails. This explains the symptoms of hair breakage and brittle nails when one suffers from iron-deficiency anemia. [3]

Restless Legs Syndrome (RLS)

An uncomfortable tingling or twitching sensation in the legs, especially when you are actually sitting or lying still, is seen in some people with iron-deficiency anemia. Iron plays a role in the regulation of dopamine in the brain. An imbalance of this neurotransmitter can cause the Restless Legs Syndrome, shortly referred to as RLS. [3]

Has this information been of no interest to you so far because you don't have a low transferrin saturation but too high a transferrin saturation in your blood? Do not worry, we have got you covered and can provide you with information about a transferrin saturation that is too high.

What Does It Mean If the Transferrin Saturation Is High?

Is your transferrin saturation too high? Elevated transferrin saturation can indicate several conditions and diseases or be a result of an excessive diet. [2]

Firstly, a high transferrin saturation means that there is a lot of free iron in your blood that can be bound to transferrin. This may indicate an iron overload.

Hemochromatosis

A common cause of high transferrin saturation is hemochromatosis, a genetic disorder in which the body absorbs excess iron from food and accumulates it in tissues, especially in the pancreas, heart, and liver. This can lead to serious health problems, including organ damage, diabetes, heart disease, and liver disease. [2]

There are two forms of hemochromatosis:

Primary Hemochromatosis

Primary hemochromatosis is the most common form and is usually the result of genetic mutations that affect the regulation of iron absorption in the intestine.

The most common genetic cause for this is the HFE mutation. Primary hemochromatosis is inherited in an autosomal recessive manner, meaning that both parents must carry the mutated gene for the disease to develop. The first symptoms usually only appear in midlife. [2]

Secondary Hemochromatosis

Secondary hemochromatosis is a rare form of the disease and occurs in response to other health conditions that affect iron absorption or distribution in your body. It is not inherited.

This form of hemochromatosis can be caused by frequent blood transfusions for certain conditions, liver disease, or hemolysis (destroyed red blood cells). [2]

Liver Disease

Liver disease, such as cirrhosis, can lead to elevated transferrin saturation levels because the liver plays an important role in iron metabolism. Liver cirrhosis leads to impaired production of transferrin in the liver, which is critical for your iron metabolism. [2]

At the same time, liver dysfunction can impact the production of hepcidin, a hormone that regulates iron. The combination of reduced transferrin and impaired hepcidin production can lead to an increase in transferrin saturation, indicating altered iron metabolism in the body. [2]

Iron Poisoning

Acute or chronic iron poisoning can also lead to high transferrin saturation levels. This can occur from accidental ingestion of iron tablets in large quantities or from other causes. [2]

For example, even a swallowed iron coin could cause iron poisoning. So don't swallow coins – either way.

Thalassemia

Thalassemia is a hereditary disorder in which the formation of hemoglobin is disturbed. This can also lead to impaired iron regulation and manifest as increased transferrin saturation. [2]

Now, you know a lot about iron metabolism, transferrin saturation, and the different biomarkers in your blood.