Iron Level Tests
Serum Iron (SI)
Iron contained in blood serum (or plasma) is normally bound to the protein transferrin. Each molecule of transferrin can transport two molecules 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. When body iron stores increase above these relatively normal ratios, proportionally greater amounts of iron are stored in non-blood tissue in ferritin molecules or 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) and Transferrin Saturation % (TS%)
Total iron binding capacity (TIBC) is often measured at the same time as 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 will no longer can efficiently harbor NTBI. Some of the iron will then bind to other molecules not have transferrin’s ability to protect its host from iron catalyzed lipid peroxidation and the formation of reactive oxygen species. Iron toxicity results when circulating iron exceeds the capacity of transferrin available to bind it. 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 is often above 50%, and sometimes even as high as 100%. The optimal range of TS % is generally 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.
Serum Ferritin (SF)
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 uses iron to supply oxygen and energy for everyday needs. Iron in excess of daily needs is stored in ferritin molecules, which hold up to 4,500 iron atoms each. Normally, dietary intake offsets daily loss iron loss (about 1 to 1.5 milligrams per day). Therefore, one gram of storage 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. The body routinely looses greater amounts of iron as a result of trauma or other conditions resulting in blood loss or through menstruation.
Iron lost through unknown causes can signal disease processes that often lead to anemia. Most harmful bacteria, fungi, parasites, and cancers need iron to grow. Viruses utilize iron to synthesize and spread viral particles. Iron deficiency can sometimes 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 normally sequester some potentially dangerous iron in ferritin molecules.
Safely bound iron stores are unavailable to feed 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 stored iron is actually stored in transferrin or 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 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 are close to these values. Approximately 95% of the population will fall within “normal” population range simply because ranges are calculated using standard statistical methodology. Except for the lower ends of these ranges, which can predict iron deficiency, 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, stroke, 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 and increased incidences of: atherosclerosis, type 2 diabetes, cancer, gout, and accelerated aging including osteoporosis and sarcopenia (muscle wasting) due to oxidative stress. 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.
Ferritin can elevated even when both serum iron and transferrin saturation percentages are at low-normal levels or below. High ferritin under these circumstances might not signal iron overload, but can result from a defense mechanism, sometimes called acute phase reaction. The body will synthesize 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 inflammatory response. 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.
Gamma Glutamyl transferase (GGT)
Gamma Glutamyl transferase or GGT is a liver enzyme that has traditionally been measured to detect liver health and function. In recent years, elevated GGT measurements have proved to be effective early warning signs of other health risks such as atherosclerosis, stroke, type 2 diabetes, kidney disease and even cancer. Large population studies conducted in the US and around the world have identified increased risks of metabolic syndrome, including cardio vascular disease and diabetes, as well as all-cause mortality in both men and women, when GGT concentrations exceeded the lowest 25% of normal population ranges. In other words, substantial numbers of people incurred increased disease risk when GGT was measured above the “low-normal” range. Medical researchers describe this phenomenon as a “dose-response relationship,” essentially, the higher the GGT concentration, the greater the risks of future diseases and premature mortality, even when GGT levels were within “normal” lab ranges.
The high end of normal GGT laboratory ranges are generally 65–70 U/L for men and 40 – 45 U/L for women. Although GGT correlates with other risk factors, most research has demonstrated that elevated GGT, independent of other risk factors, predicts increased disease and mortality. Researchers have concluded this by studying large, apparently healthy populations from which they analyzed data covering multiple known risk factors. Years later they compared outcome data gathered from health, hospital and death records. When the populations were stratified into smaller groups according to similar factors like age, sex, body mass index, smoking, cholesterol, alcohol consumption, diet, and exercise, the researchers were able to calculate that elevated GGT presented a significant additional risk, independent of those shared by individual with comparable risk and health profiles.
The mechanism behind these findings is generally described as follows: The normal biologic role of GGT is to reconstitute glutathione, the body’s master antioxidant. Glutathione provides natural protection against harmful oxidative stress. When GGT concentrations are above “low-normal” ranges, excess GGT can catabolize (break down) glutathione causing critical depletion of this very important antioxidant. When glutathione is depleted, and only insufficient amounts remain to protect the body’s organs from oxidative stress, damage starts to occur. Over time, this process can lead to a vicious cycle of irreversible cell, tissue and DNA damage, and ultimately to severe impairment of vital organ function.
Fortunately, an inexpensive blood test can determine GGT concentration. GGT levels can be lowered through a balanced diet that includes ample portions of grains, fruits, nuts and vegetables; this bolsters the body’s natural antioxidant defenses. Several studies have shown that phlebotomy reduces GGT and other enzymes often associated with liver diseases. Interestingly, moderate to high coffee consumption has been universally shown to reduce GGT; and by doing so, effectively enhance the protective antioxidant capabilities of glutathione. On the other hand, excessive alcohol and red meat consumption have been demonstrated to increase GGT, which depletes glutathione and impairs antioxidant protection.
For some people it might be important to test GGT periodically. An Austrian study of 76,000 people followed over seven years demonstrated that not only were the initial GGT testing levels important, but also, the direction and degree of change over time modified the initial risks significantly. Irrespective of the original GGT measurement, although lower initial GGT always indicated less risk than higher, individuals whose GGT concentrations increased over time were subject to heightened disease and mortality risk, while those whose GGT went down faced diminished risks. As in the studies based on one-time GGT measurements, the degree of change over time (up or down) also followed a “dose-response relationship.” An interesting common finding of almost all of the research in this area indicated the strength of these relationships, and therefore the risks, were significantly greater among men and women younger than 60 or 65 years of age than they were for older people.
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).
Koenig G, Seneff S. Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk. Dis Markers. 2015;2015:818570. doi:10.1155/2015/818570
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