by Dr. John Neustadt

Lab testing is part of many doctors’ appointments. The complete blood count (CBC) is a routine blood test that healthcare providers order on annual exams and as a general screening test for anemia. Despite the results of this test being normal, millions of women are walking around tired, with their hair falling out, depressed and struggling with brain fog because most doctors don’t order the most important test. 

According to the World Health Organization, more than 30% of the worldwide population has anemia.¹  Anemia hits low-income countries hardest, affecting one of every two pregnant women and preschool children in developing countries.² Although low-income countries have the highest rates of anemia, it’s a growing problem even in the United States. Rates of anemia nearly doubled from 2003 to 2011 in the United States to just over 7%.³ 

While there are many types of anemia, iron deficiency anemia is the most common. Iron deficiency anemia affects at least twice as many women as men. Globally, iron-deficiency anemia accounts for at least 50% of all cases of anemia,⁴ with an estimated 1.62 billion people suffering from the effects of iron deficiency.⁵  

Among its symptoms, iron deficiency can cause fatigue, shortness of breath, rapid heart rate, dizziness, depression, difficulty processing information (brain fog), decreased memory (forgetfulness) and feeling cold. Because these symptoms have many other possible causes, anemia often goes unrecognized. 

Along with reporting white blood cell and platelet counts, the results of the CBC show the number of immature red blood cells, the number of mature red blood cells, hemoglobin concentration and the size and shape of the red blood cells. Testing these parts of the blood shows if your blood is able to deliver enough oxygen to tissues and cells throughout your body. 

Two important indicators to understand on this test are hemoglobin and red blood cells. Hemoglobin is a protein inside red blood cells that carries oxygen from the lungs to the rest of the body. Oxygen is used in the cells’ mitochondria to produce cellular energy. During energy production, carbon dioxide is created as a waste product. When the hemoglobin drops off its oxygen, it then picks up carbon dioxide and carries it to the lungs where we expel it from our bodies when we exhale and breathe it out. 

In iron-deficiency anemia, when the amount of hemoglobin is lower than normal, tissues such as muscles and the brain become deprived of oxygen. This can result in shortness of breath, fatigue and brain fog. Testing hemoglobin can show whether your blood cells are able to carry enough oxygen, and low hemoglobin is one indicator of anemia.

Since red blood cells survive for less than four months, the amount of red blood cells circulating in the blood, and thus also the hemoglobin content in red blood cells, are in constant flux.⁶  Approximately two million cells are released from the bone marrow into circulation every second, and that same number of cells are recycled and replaced.⁶ The constant turnover of red blood cells means the body must have a steady supply of iron and other nutrients to produce healthy cells. 

The CBC test is an excellent screening tool for anemia that provides important information, but it is not the only test provides information about the iron status. An iron blood panel typically includes serum iron, total iron-binding capacity (TIBC), transferrin saturation and serum ferritin. 

Ferritin: The test you have to get

Among all the tests, serum ferritin is the most sensitive indicator and is considered the primary measure of iron status.^5,7,8 

In addition to being part of an iron panel, a serum ferritin test can be added onto a CBC test or can be ordered by itself. Ferritin is the storage form of iron in the body, storing up to 80% of the total amount of iron.⁹ The largest concentrations of ferritin are in the liver, spleen, bone marrow and skeletal muscles. However, some ferritin circulates in the blood, which is why it can be detected on a blood test. 

Since red blood cells live for months at a time, however, it means that the CBC test is not the most sensitive indicator for iron. A person’s ferritin could be declining and it wouldn’t show up on a CBC test for months after. And since iron is used for so many different processes in the body, people can experience symptoms of iron deficiency long before any changes appear on a CBC. A serum ferritin test is the most reliable screening test for iron status.¹⁰

However, while it’s the most sensitive indicator for iron, the reference ranges on a serum ferritin test are so large that most clinicians don’t understand how to appropriately interpret them. Reference ranges on tests provide the “normal” values. Anything outside of that range is considered “abnormal.”

By definition, “normal” is a range in which 95% of test results fall. Since by definition 95% of people automatically are within the normal range, there will always be 5% of people outside the normal range. And while reference ranges report what is “normal,” they don’t tell healthcare providers or patients what “optimal” results are. Your test result may be technically normal, but is it optimal for you and your health? 

Ferritin is a great example of this. Most data used to create standard laboratory reference ranges for serum ferritin are from studies conducted more than 30 years ago.¹¹ These reference ranges don’t reflect ethnic or geographic diversity and were performed in an era for which laboratory methods no longer reflect present practice.¹¹ 

One consequence of using reference ranges based on decades-old studies is that the “normal” range for ferritin test results is so broad as to be clinically irrelevant. Normal reference ranges can vary by lab, but serum ferritin levels from 12 to 200 nanograms per milliliter are often considered “normal.”¹² A ferritin level below 12 nanograms per milliliter is reported as iron deficiency. 

Experts agree, however, that iron deficiency is likely when the ferritin level falls below 50 nanograms per milliliter. A large study of nearly 200 women ages 18-53 years confirms that iron supplementation should begin long before a person’s serum ferritin drops below 12 nanograms per milliliter. Women were admitted into the study if they had normal CBC test results but levels of ferritin less than 50 and if they also complained of fatigue. In those women, taking iron supplementation for 12 weeks improved their energy by nearly 48%.¹³ Another study reported benefits from taking iron when ferritin was less than 50 nanograms per milliliter in people with restless leg syndrome (RLS).¹⁴ 

The standard reference range for ferritin also doesn’t apply well to the elderly or when inflammation is present. Low ferritin is an indicator of not having enough iron. But ferritin is released into the blood when the body reacts to inflammation. Thus, if you have a chronic inflammatory disease, your ferritin levels might be elevated, despite declining iron.⁵ 

This becomes especially important as people age, since their risk for chronic inflammatory diseases increases. Inflammatory diseases include arthritis, heart disease, many cancers, glomerulonephritis, hepatitis, inflammatory bowel disease (IBD, which includes Crohn’s Disease and Ulcerative Colitis), asthma and autoimmune diseases such as Systemic Lupus Erythematosus (SLE, Lupus) and Sjogren’s Syndrome. 

A study of nearly 250 elderly patients confirms this. Study volunteers were approximately 70 years old.  The results showed that serum ferritin of less than 100 nanograms per milliliter predicted iron deficiency. The researchers concluded, “These findings indicate that in elderly subjects, iron deficiency anemia may develop with higher levels of serum ferritin. Hence, the conventional cutoff of serum ferritin for the diagnosis of iron deficiency anemia in young adults is not appropriate for the elderly population.”¹⁵ 

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