A Functional Medicine Iron Deficiency Anemia Protocol: Comprehensive Testing, Therapeutic Diet, and Supplements

Approximately one-quarter of people worldwide have anemia. Iron deficiency, the most common cause of anemia, accounts for 50% of all anemias. While mild iron deficiency and iron deficiency anemia may not show symptoms, untreated and severe iron deficiency anemia may lead to serious complications, including chronic fatigue, restless legs syndrome, heart problems, pregnancy complications, and developmental delays. Therefore, early identification and management are important, especially in high-risk groups. (13) 

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What Is Iron Deficiency Anemia?

Iron deficiency anemia (IDA) occurs when there is an insufficient amount of iron in the body to produce adequate amounts of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to the rest of the body. Iron is an essential mineral that is necessary for the production of hemoglobin. When there is a lack of iron, the body cannot produce enough hemoglobin, resulting in a decreased ability to make sufficient red blood cells and carry oxygen. This can lead to various symptoms and health complications.

IDA progresses in three stages: 

1. Iron Depletion: In this initial stage, the body's circulating iron levels are low, but the hemoglobin levels in the blood remain normal. Laboratory tests may show slightly reduced levels of ferritin, a protein that stores iron. However, the body can still produce enough hemoglobin and red blood cells, and the patient usually does not experience any significant symptoms.
2. Iron-Deficient Erythropoiesis: In the second stage, the body's iron stores continue declining, and red blood cell production becomes impaired. The bone marrow, which is responsible for producing red blood cells, does not have enough iron to synthesize hemoglobin effectively. As a result, the red blood cells produced are smaller and paler than average (microcytic and hypochromic). Symptoms may appear, and laboratory tests may reveal low hemoglobin levels (anemia) and other signs of iron deficiency.
3. Iron Deficiency Anemia: In the final stage, the iron deficiency becomes severe, and anemia develops. Hemoglobin levels drop significantly, leading to a reduced capacity of the blood to carry oxygen. The red blood cells are small, pale, and insufficient in number. Symptoms become more pronounced, and laboratory tests will confirm the presence of anemia and show further evidence of iron deficiency.

Iron Deficiency Anemia Signs & Symptoms

The signs and symptoms of IDA intensify as the severity of the anemia worsens. Symptoms of IDA commonly include: 

• Fatigue
• Weakness
• Chest pain, fast heartbeat, or shortness of breath (especially with physical exertion) 
• Headache
• Dizziness or lightheadedness
• Cold hands and feet
• Brittle nails
• Unusual cravings for and indigestion of non-food items 

A physical exam will likely reveal paleness of the skin, particularly in the face, conjunctiva (inside the eyelids), mucous membranes, and nail beds. Nails may be spoon-shaped or have ridges or cracks. Resting tachycardia, a rapid heart rate, is also common.

What Causes Iron Deficiency Anemia?

Iron deficiency and IDA can result from insufficient dietary iron intake, decreased absorption, or blood loss (2). Women, infants and children, vegetarians, and frequent blood donors are at the highest risk of IDA (8). 

Insufficient consumption of iron-rich foods is a leading cause of iron deficiency anemia. Iron is predominantly obtained from dietary sources such as red meat, poultry, seafood, legumes, fortified cereals, and leafy green vegetables. Inadequate intake of these iron-rich foods can result from poor dietary choices, restrictive diets (e.g., vegetarian or vegan diets without proper iron supplementation), poor access to nutritious food, or increased systemic iron requirements (such as during pregnancy). (2, 3)

Iron absorption occurs primarily in the small intestine. Certain conditions can interfere with the body's ability to absorb iron effectively, leading to iron deficiency anemia. Examples of conditions that can impair iron absorption include celiac disease, Crohn's disease, H. pylori infection, hypochlorhydria, small intestinal bacterial overgrowth (SIBO), and gastric bypass surgery. (4) 

Chronic or acute blood loss can deplete the body's iron stores and lead to anemia. Menstrual bleeding in women, especially heavy or prolonged periods, can result in iron loss over time. Gastrointestinal bleeding from ulcers, tumors, hemorrhoids, or other conditions can also lead to iron deficiency anemia. Other potential sources of blood loss include trauma, surgery, or certain medical conditions that cause internal bleeding. (4) 

Functional Medicine Labs to Test for Root Cause of Iron Deficiency Anemia

Any patient with suspected IDA should have a CBC and complete iron panel ordered to confirm the diagnosis, differentiate between other types of anemia, and stratify the severity of the disease. The table below highlights the hallmark findings of iron deficiency anemia.

Understanding the underlying cause of IDA is essential to guide the management strategy. For patients in which a comprehensive history is insufficient in determining the cause of IDA (e.g., pregnancy, restrictive diet, heavy menstrual periods), additional labs should be ordered, which may include the following:

Celiac Antibodies

Serum celiac serology, which measures antibodies associated with celiac disease, is generally the first line of testing recommended for patients to screen for the presence of celiac disease. Genetic markers like HLA-DQ2 and HLA-DQ8 may also be included in this panel, which increase the likelihood of disease if present. The patient should eat gluten-containing foods daily for at least four weeks before the blood draw to ensure testing accuracy. 

Comprehensive Stool Analysis

Preliminary stool tests, including fecal occult blood and calprotectin, are often ordered to assess for the presence of bleeding and inflammation in the gastrointestinal tract. A referral to a gastroenterologist is warranted for additional evaluation if either of these tests is positive.  

Functional medicine doctors will often recommend ordering a comprehensive stool analysis. In addition to both the biomarkers above, a comprehensive stool analysis also includes markers that assess overall gut health and screen for maldigestion and intestinal infections (e.g., parasites, H. pylori) that can contribute to iron deficiency. 

SIBO Breath Test

A SIBO breath test is performed at home by the patient and measures various gases exhaled through the lungs that indicate SIBO if elevated.

Hormone Testing

A comprehensive hormone panel can help identify estrogen, progesterone, testosterone, and cortisol imbalances that may contribute to heavy menstrual bleeding. 

Thyroid disease is also a common cause of heavy or irregular menstrual bleeding. A thyroid panel, including at least TSH, free T3, and free T4, can evaluate for hypo- and hyperthyroidism. 

Imaging

In some instances, your provider may refer you for gastrointestinal and/or uterine imaging in the workup of IDA. Endoscopy and colonoscopy visualize the upper and lower portions of the digestive tract. They are required for the definitive diagnosis of celiac and inflammatory bowel diseases and can identify the source of intestinal bleeding. Transvaginal ultrasound is the first-line imaging choice to screen for uterine pathologies contributing to heavy bleeding, such as uterine fibroids. (11) 

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Conventional Management for Iron Deficiency Anemia

Conventional management for iron deficiency anemia involves iron supplementation to increase iron levels while addressing the underlying cause of anemia. The oral dosing recommendation to manage iron deficiency anemia is 120 mg of elemental iron daily for adults and 3 mg/kg/day (up to 60 mg) for children. Oral therapy should be continued for three months after the anemia is corrected to allow iron stores to replenish. (11) 

Functional Medicine Management Protocol for Iron Deficiency Anemia

The goals of a functional management protocol for IDA are the same as the conventional ones; however, they often utilize a wider variety of complementary and integrative modalities to more efficiently and effectively manage and support iron deficiency anemia. While the rest of this article will discuss a functional medicine protocol for iron repletion, Rupa Magazine has a plethora of helpful information pertinent to addressing the underlying causes of IDA, including the following articles: 

• A Functional Medicine Celiac Disease Protocol: Specialty Testing, Nutrition, and Supplements
• A Functional Medicine Crohn's Disease Protocol: Specialty Testing, Nutrition, and Supplements
• A Functional Medicine Fibroid Protocol: Testing, Supplements, and Therapeutic Diet
• A Functional Medicine SIBO Protocol: Testing and Treatment
• An Integrative Medicine Approach to Menorrhagia     

Therapeutic Diet and Nutrition Considerations for Iron Deficiency Anemia

Functional medicine emphasizes the importance of a nutrient-dense diet that includes a variety of whole foods rich in iron and other essential nutrients that enhance iron absorption and support healthy red blood cells. 

Iron-Rich Foods

Consuming a diet rich in iron is essential for replenishing iron stores. Heme iron and non-heme iron are two forms of iron found in foods, and they differ in their structure and absorption rates in the body. Heme iron is predominantly found in animal-based foods, particularly red meat, poultry, and seafood. Non-heme iron is present in plant- and animal-based foods but is primarily found in plant sources such as legumes, fortified cereals, spinach, kale, and dried fruits. Heme iron is more easily absorbed by the body than non-heme iron and contributes a significant portion of the total iron absorbed from the diet. (4) 

Vitamin C

Pairing iron-rich foods with sources of vitamin C can enhance iron absorption. Vitamin C-rich foods like citrus fruits, strawberries, bell peppers, and tomatoes can be incorporated into meals and snacks to optimize iron absorption.

Iron Inhibitors

Some substances can inhibit iron absorption. For individuals with iron deficiency anemia, limiting the consumption of iron inhibitors such as tea, coffee, calcium-rich foods, and foods high in phytates (e.g., whole grains and legumes) is advisable. These can interfere with iron absorption and should be consumed separately from iron-rich meals. (2) 

Supplements Protocol for Iron Deficiency Anemia

Iron supplements are available in several forms. It is best to avoid taking antacids or consuming dairy or calcium-rich foods within two hours of iron supplements. Taking iron supplements with food can decrease absorption by approximately 40%, so it is best to take iron supplements on an empty stomach if possible. However, it is common to experience adverse gastrointestinal side effects with common supplemental forms of iron, and taking iron supplements with a meal can reduce these effects. (16) 

Iron Bisglycinate

The most common and affordable iron supplements include ferrous sulfate, gluconate, and fumarate. These forms commonly cause gastrointestinal side effects, especially constipation. Because of this, functional medicine providers often recommend iron bisglycinate as a well-absorbed and better-tolerated option. (2) 

As discussed above, the recommended oral dose of iron for managing IDA in adults is 120 mg of elemental iron daily in divided doses. However, newer evidence suggests that lower single daily doses and every-other-day dosing of iron can improve the absorption and tolerability of oral therapy. (9)

Dose: 60 mg every other day, taken in between meals if possible

Duration: continue until three months after IDA has been corrected

Vitamin C

The effect of vitamin C increases the absorption of iron when both nutrients are consumed together in a dose-dependent fashion. Studies have reported increased rates of iron absorption from 0.8% to 7.1% when increasing the dose of ascorbic acid (vitamin C) from 25 mg to 1,000 mg. (10) 

Dose: 100-1,000 mg every other day, taken with oral iron 

Duration: continue until three months after IDA has been corrected 

Betaine HCl

Medications and factors that induce reduced stomach acid secretions are associated with reduced absorption of dietary iron and iron tablets (11). Supplemental hydrochloric acid replaces stomach acid to support the healthy digestion of iron-rich foods and enhance dietary and supplemental iron.

Dose: 500-1,000 mg with each meal

Duration: Ongoing, until the underlying cause of maldigestion and digestive enzyme insufficiency has been addressed

When to Retest Labs

Patients should have their CBC and iron panel repeated one month after initiating oral iron therapy to monitor their response to management. An increase in hemoglobin of 1 g/dL one month after treatment shows an adequate response to management (11). Oral iron therapy is often required for at least 3-6 months to normalize iron status and replete ferritin levels (9). 

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Summary

Iron deficiency anemia is a common condition that can significantly impact overall health and well-being. This article discusses various approaches for addressing iron deficiency anemia, which encompasses managing iron deficiency and its underlying cause(s). A therapeutic diet, including consuming iron-rich foods, enhancing iron absorption with vitamin C, and avoiding iron inhibitors, should be emphasized in addition to supplemental iron.