Approximately 25% of people worldwide have anemia, a blood disorder defined by low red blood cell counts and hemoglobin concentration. Iron deficiency, the most common nutritional deficiency, is responsible for causing 50% of all anemias. Iron is essential for the human body; it plays many roles, including physical growth and neurological development, hormone synthesis, cellular functioning, and hemoglobin synthesis. In iron-deficient states, microcytic anemia can occur along with symptoms such as fatigue, weakness, and poor exercise tolerance. (3, 4)
Because iron deficiency anemia is the most common type of anemia, it must be included in the differential diagnosis for anemia. This article will explain how iron deficiency anemia develops, clinical manifestations and laboratory findings that support the diagnosis, and an integrative approach to treatment.
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What is Iron Deficiency Anemia?
Iron deficiency anemia (IDA) is the most common microcytic anemia, characterized by small red blood cells (RBCs) due to the body's lack of hemoglobin. The healthy synthesis of hemoglobin, the oxygen-carrying protein in RBCs, requires iron. Iron deficiency progressively leads to IDA as the body cannot sustain normal hemoglobin and RBC production. (7)
Causes of iron deficiency include blood loss, insufficient dietary intake, and decreased absorption. The following groups are at the highest risk for developing IDA (1):
- People who have heavy menstrual periods, are pregnant, or are breastfeeding
- People who have undergone major surgery or physical trauma
- People with underlying gastrointestinal (GI) pathologies that impair iron absorption such as Celiac disease and inflammatory bowel disease (IBD)
- People with insufficient dietary intake of iron such as vegetarians and vegans
Other causes of IDA may include (7):
- Low stomach acid (hypochlorhydria)
- GI infections: Helicobacter pylori, small intestinal bacterial overgrowth (SIBO)
- Chronic GI bleeding caused by ulcers, hemorrhoids, frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs), and certain cancers
- Frequent blood donations
Iron Deficiency Anemia Symptoms
Symptoms of iron deficiency and IDA are the same, and symptom severity is usually proportional to the degree of deficiency and anemia. A poorly oxygenated state arising from IDA affects all body systems, leading to many vague symptoms that can be easily attributed to other causes (1):
- Anxiety
- Cold intolerance
- Depression
- Dizziness
- Exercise intolerance
- Fatigue
- Headaches
- Irritability
- Muscle weakness
- Pica (craving and ingestion of nonfood items)
- Restless legs syndrome (RLS)
Iron is involved in thyroid hormone synthesis, and hypothyroidism can result in the context of iron deficiency. Note that hypothyroidism and iron deficiency share many of the same symptoms:
- Brain fog
- Brittle nails
- Cold intolerance
- Constipation
- Depression
- Fatigue
- Hair loss
- Irregular periods
- Puffiness or fluid retention
- Weight gain
Iron also plays a role in collagen synthesis. In iron-deficient states, the following symptoms may appear:
- Brittle nails
- Cracked corners of the mouth
- Dry, pale skin
- Hair loss
- Inflamed tongue
Functional Medicine Labs to Diagnose Iron Deficiency Anemia
A complete blood count (CBC) is a panel that includes markers detailing the size, shape, and color of red blood cells. The table below summarizes the results that indicate microcytic anemia:
A complete iron panel includes multiple blood tests specific to iron. Analyzed together, these tests provide a comprehensive analysis of iron status and help to differentiate between different types of anemia.
- Serum iron measures the total circulating iron in the blood. It is low in iron deficiency and IDA.
- Ferritin is the protein that stores iron in the liver and is the most reliable marker to assess the body's iron stores. Low levels indicate a more progressed state of iron deficiency, as the body has run out of its stores in an attempt to maintain circulating blood levels.
- Transferrin is the protein that transports iron throughout the body to its intended destination; it has an inversely proportional relationship to serum iron and is increased in iron-deficient states.
- Transferrin saturation, also called iron saturation or % Sat, is the percent of transferrin that has iron bound to it. Transferrin saturation is decreased in IDA due to the lack of available iron.
- Total iron binding capacity (TIBC) is a marker of how much iron can be bound to transferrin and can act as an indirect measure of transferrin. In iron-deficient conditions, the relative amount of transferrin increases compared to available iron, and thus TIBC will be elevated.
- Unsaturated iron binding capacity (UIBC) is the remaining transferrin that is not bound to and transporting iron. It is increased in IDA.
The reticuloendothelial system (RES), or iron recycling system, is a complex system that serves to regulate iron homeostasis in the body. If the RES is not functioning correctly, even with normal serum iron and ferritin levels, the body will not be able to move iron where it needs to go to perform its functions. In states of vitamin A and copper deficiency, RES function is impaired, essentially leading to a state of iron deficiency. Measuring vitamin A and copper levels may be especially useful in cases where serum iron and ferritin are normal, but anemia symptoms are present, and labs show abnormal TIBC and % Sat levels. (8, 9)
Tests to Rule Out Root Cause of Iron Deficiency
Once IDA is diagnosed, the root cause of iron deficiency needs to be identified. A thorough medical history can aid in this process: a diet recall and a complete medication list can provide clues to lifestyle factors contributing to low iron status.
Testing may also be necessary to identify the root cause:
- Serum hCG to rule out pregnancy
- A fecal occult blood test (FOBT) measures blood in the stool to rule out intestinal bleeds
- Blood tests that measure genetic and immune markers common in Celiac disease and IBD can help rule out inflammatory GI conditions causing malabsorption
- Hormonal imbalances can cause heavy menstrual bleeding. A urinary hormone panel can measure estrogen, progesterone, and testosterone levels. Progesterone deficiency and estrogen dominance, alone or in combination, are common causes of heavy periods.
- A comprehensive Helicoplyori pylori stool test can diagnose an H. pylori infection. It also includes virulence factors and antibiotic resistance testing that guide treatment recommendations.
- SIBO breath test
Imaging and endoscopic procedures are required to diagnose hypochlorhydria, Celiac disease, and IBD.
Functional Medicine Treatment for Iron Deficiency Anemia
Iron Repletion
The treatment of IDA requires addressing the underlying cause of iron deficiency while repleting iron stores through supplementation (4).
The dosage of elemental iron required to treat iron deficiency anemia in adults is 120 mg daily for at least three months. Follow-up with repeat CBC and iron testing is recommended after one month of treatment to confirm adequate response to treatment. Repletion therapy should be continued for one to three months after hemoglobin levels have normalized to replenish iron stores fully. (5)
There are various iron forms that you will find in oral iron supplements. The most common and affordable supplements contain iron salts like ferrous sulfate, but they often cause GI upset like abdominal pain and constipation. Functional practitioners often recommend an alternative, better-tolerated form of iron called ferrous (bis)glycinate to improve tolerance to therapy. (2)
There are various ways to enhance oral iron absorption (2, 6, 7):
- Take iron supplements between meals
- Avoid taking iron supplements with inhibitors of iron absorption: phytates (in bran), polyphenols (in certain vegetables), tannins (in tea and coffee), calcium-containing foods and supplements, soy, and oxalates (in spinach, beans, and nuts)
- Take iron supplements with ascorbic acid (vitamin C) to enhance absorption
There are now several studies supporting that taking oral iron every other day is just as or more effective than daily dosing at raising serum iron levels. This dosing regimen may better suit those who do not respond to oral iron repletion as expected or experience GI side effects.
Intravenous (IV) iron is more reliably and quickly distributed through circulation than oral supplementation. IV infusions may be the preferred course of treatment for those that are intolerant to oral iron, have a malabsorptive GI disease, or are not responding to oral iron as desired. (4, 6)
Blood transfusions may be required for severe IDA. There is no universally accepted guideline for ordering blood transfusions, but the patient's clinical condition and symptoms are important considerations in the decision. (5)
Nutrition
Dietary iron has two main forms: heme and nonheme. Heme iron, found in animal sources, is very well absorbed and functional in the body. Nonheme iron, found in plant-based and iron-fortified foods, is significantly less bioavailable to the body. Top animal sources of iron include red meat, oysters, liver, and chicken. Plant sources of iron include dark leafy greens, legumes, molasses, and tofu. (3)
Just as is the case with supplements, making smart decisions with cooking can boost iron absorption:
- Cook meals in cast iron pans
- Soaking beans and legumes in water before cooking can remove nutrients that impair iron absorption
- Pair iron-rich foods with a vitamin C source (e.g., citrus fruits, strawberries, bell peppers, cruciferous vegetables)
- Avoid eating iron-rich foods with calcium, tannins, phytates, polyphenols, and oxalates
Herbs & Supplements
Consider supplemental vitamin A and copper to support the iron recycling system, especially when deficiencies in either nutrient are identified.
This article will not extensively outline treatment protocols for specific conditions underlying IDA. Know that addressing these conditions is necessary for treating IDA and preventing iron deficiency recurrence. Functional medicine practitioners routinely implement integrative protocols specific to the health concern that include botanical herbs, nutritional supplements, dietary and lifestyle modifications, and pharmaceutical medications (when applicable).
Lifestyle Modifications
Endurance athletes are at increased risk for IDA. Intense exercise increases the body's iron requirements to compensate for excess iron lost through sweat, decreased intestinal absorption secondary to acute inflammatory responses activated during exercise, and increased destruction of RBCs by physical forces. Some research suggests that high-intensity and endurance exercise increases iron losses by as much as 70% compared to sedentary populations. Decreasing exercise intensity and frequency during active IDA therapy can improve response to iron repletion therapy. Athletes may be candidates for increased dietary and supplemental iron intake to satisfy increased demands. (10)
Summary
Iron is an essential mineral for the human body, partly for its involvement in hemoglobin and red blood cell synthesis. In iron-deficient states, microcytic anemia can occur, and impaired oxygenation of the body leads to symptoms associated with iron deficiency anemia. Functional medicine practitioners are trained to use a comprehensive testing strategy to understand iron status and metabolism. An integrative approach to treating iron deficiency anemia, utilizing nutritional therapy, dietary supplements, and lifestyle modifications, is effective in restoring the body's iron and red blood cell balance.
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