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Iron contained in blood serum (or plasma) is normally bound to the protein transferrin. Each molecule of transferrin can transport two atoms of iron to areas of the body that need this element. Most of the body’s iron (about 60%) is contained in hemoglobin, which is the essential oxygen carrying protein of the blood. Another 30% is stored in ferritin, a protein found throughout the body (although this percentage can be significantly higher or lower in cases of iron overload or deficiency), and a few percent in myoglobin, a protein specifically utilized by muscle cells. In cases in which body iron stores increase above these relatively normal ratios, proportionally greater amounts of iron are stored in non-blood tissue in a complex called hemosiderin.
Generally men have higher levels of serum iron than women. Although laboratory ranges vary, most provide male ranges of around 65 to 176 µg/dL and female ranges of 50 to 170 µg/dL. When laboratories test for SI, they are testing iron contained in plasma that is generally bound to transferrin. In most people, about 25–35% of the transferrin contained in the serum is used to bind iron in transport. When laboratories measure serum iron they often also measure transferrin and calculate the percentage of transferrin molecules that are used to bind iron.
Total iron binding capacity (TIBC) is often measured along with serum iron. This measurement indicates the potential capacity of transferrin molecules to bind with serum iron. Laboratory ranges for men and women are generally in the about 240-450 μg/dL; but there can be significant variances between laboratories. When TIBC is at or below the low end of a laboratory range, it is an indication that there is limited capacity for transferrin molecules to accept additional iron. If that occurs in combination with a relatively high measure of serum iron, it is likely that the ability of transferrin to safely bind serum iron is impaired. Iron in the plasma that is not bound to transferrin is often called non-transferrin bound iron (NTBI). This is a potentially toxic form of iron that can damage most all body systems.
Generally, with minor variances based on blood PH, when 40% or less of transferrin molecules are used, iron is considered safely bound. Much above that, transferrin becomes saturated and it binding capacity drops to a point where it can no longer efficiently harbor NTBI. Some of the iron will then bind to other molecules that can not protect the body from iron catalyzed lipid peroxidation and the formation of reactive oxygen species. Iron toxicity results when circulating iron exceeds the binding capacity of transferrin. This causes oxidative stress, a process that if not countered by the body’s antioxidant defenses, will over time result in cell, tissue and DNA damage.
Transferrin saturation percentage (TS %) is calculated by dividing serum iron by TIBC, then multiplying by 100. The resulting number is referred to as transferrin saturation percentage (TS %). In people with undiagnosed hemochromatosis, this number will often be above 50%, and sometimes even as high as 100%. The optimal range of TS % is generally described as being between 25–35%. When the percentage is calculated to be less that about 17% or higher than 45%, a condition of either iron deficiency or iron overload is possible. In either case, further investigation is warranted including ferritin testing. Very low or very high ferritin in combination with low or high TS % can help a physician confirm a diagnosis of either iron deficiency or iron overload.
Ferritin is a protein synthesized by the body that is mainly utilized to store iron for future use. The body requires iron to make hemoglobin for blood and myoglobin for muscles. Each of these proteins use iron to supply oxygen and energy for everyday needs. Iron in excess of daily needs is sequestered in ferritin molecules, which hold up to 4,500 iron atoms each. Normally, dietary intake offsets the daily loss of body iron. Therefore, one gram of iron (1,000 milligrams) is usually adequate to meet all foreseeable needs. Only small amounts of iron are lost each day through urine and body sweat, or as skin cells slough off. This amounts to about 1 to 1.5 milligrams per day. The body routinely loses greater amounts of iron only as a result of trauma, other conditions resulting in blood loss, or through menstruation.
Iron lost through unknown causes can signal disease processes that often lead to anemia. Unwanted bacteria, fungi and parasites and cancers also need iron to grow. Iron deficiency can indicate these pathogens have successfully invaded and are competing with your body for iron to enable colonization, infection and disease progression. Fortunately, the body can safely sequester excessive amounts of iron in ferritin molecules.
When bound in ferritin, most iron stores are withheld from invaders. However, much more than one gram of storage iron can stress the body’s ability to provide a safe harbor for this potentially toxic metal. With a few exceptions, including events of inflammation or anemia of chronic disease, a blood test measuring SF can provide an accurate surrogate measure of iron stored in organs and non-blood tissue throughout the body. Only a very small fraction of the body’s sequestered iron is actually stored in ferritin molecules circulating in the bloodstream. However, in otherwise healthy individuals, the relative amount of ferritin found in serum is an accurate surrogate measure for the addition and potentially harmful iron stored in body organs.
Serum ferritin measurements range from about 15–200 ng/ml for women and 20–300 ng/ml for men. Although laboratory ranges vary, most align closely with these values. Approximately 95% of the population will fall within the “normal” population range simply because ranges are calculated using standard statistical methodology. Except for the lower ends of these ranges, which can predict anemia or iron deficiency anemia, the ranges per se do not define optimal or even healthy iron levels. Optimal SF ranges for men and women are 25–75 ng/ml. Individuals with risk factors for diabetes, cardiovascular diseases, stoke, liver diseases and cancer face amplified risks proportional to the amount of stored body iron over and above the optimal range.
Numerous medical research studies have demonstrated that serum ferritin above 100 ng/ml has been associated with decreased cardio vascular fitness, increased incidences of atherosclerosis, type 2 diabetes, cancer and accelerated aging, which is evidenced in conditions like osteoporosis and sarcopenia (muscle wasting). Excess iron can catalyze oxidative stress and results in the formation of Reactive Oxygen Species (ROS). This leads to cell and DNA damage see IRON Science Library. Fortunately this does not pertain to everyone; ferritin levels and stored iron can remain safely contained, even when ferritin exceeds 150 ng/ml, if the body’s natural antioxidant defenses are working properly see GGT Science Library.
Ferritin can be elevated even when both serum iron and transferrin saturation percentages are at low-normal levels or below. High ferritin under these circumstances does not generally signal iron overload, but rather is functioning as a defense mechanism, sometimes called an acute phase reaction. The body synthesizes ferritin in response to an evasion of many pathogens. The resulting conditions are sometimes referred to as the anemia of chronic disease, or more commonly today, anemia of inflammation. These are often temporary conditions that cause the body to sequester iron that would otherwise be available to assist invading pathogens and worsen infection, tissue damage or other disease conditions.
Hemoglobin is a protein in red blood cells that carries oxygen. Normal values are 13.8 to 17.2 gm/dL for males and 12.1 to 15.1 for females. Low or high measures of hemoglobin are not good indications of either iron overload or iron deficiency. Hemoglobin is frequently part of a complete blood count (CBC), which is most useful in assessing general health status and to screen for and monitor a variety of disorders, such as anemia. When hemoglobin is above upper range values, a condition called polycythemia vera (PV) could exist. PV is a bone marrow disease that leads to an increase in the number of blood cells (primarily red blood cells).