Can Anemia Lead to Anxiety and Depression?

Anemia is the most common blood disorder, affecting more than three million Americans (42). Not only does anemia reduce energy levels, it can affect how you think and feel. A significant amount of research is emerging to suggest that anemia may be at the root of your anxiety and depression.

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Understanding Anemia

Red blood cells are donut-like shaped blood cells made in the bone marrow and released into the bloodstream. Their primary function is transporting oxygen from the lungs to the body's peripheral tissues and vital organs. After doing so, they carry carbon dioxide back to the lungs to be exhaled from the body. Hemoglobin, the central molecule of each red blood cell, allows these cells to perform these vital functions. (14) 

What Is Anemia?

Anemia is a blood condition characterized by a reduced number of red blood cells or a decreased ability of red blood cells to carry oxygen to the body's tissues. Anemia can occur when there is a deficiency in red blood cells, hemoglobin, or both. (6) 

Anemia can be characterized based on the size, shape, and color of red blood cells, which can be assessed by blood tests and peripheral blood smear examinations. These blood cell characteristics provide important clues about its underlying cause. Anemias are broadly categorized by size (microcytic, normocytic, or macrocytic) and color (hypochromic, normochromic, hyperchromic). (6, 36) 

What Causes Anemia?

The three leading causes of anemia include decreased red blood cell production, excessive red blood cell destruction, and blood loss (6). 

The body needs nutrients, notably iron, vitamin B12, and folic acid, to make enough red blood cells. Due to poor diet, surgical resection of the stomach or intestines, or changes to the stomach/intestinal lining, the body may not have enough of these nutrients to synthesize sufficient red blood cells. (16) 

Other possible causes of anemia include genetic variations, certain medications, chronic diseases, heavy menstrual bleeding, and pregnancy (2).

What Are the Symptoms of Anemia? 

The specific symptoms of anemia can vary depending on the underlying cause and the degree of anemia; however, common characteristics and manifestations of anemia include:

• Fatigue
• Weakness
• Pale skin
• Shortness of breath, especially during physical activity
• Rapid heartbeat (tachycardia)
• Dizziness or lightheadedness
• Cold hands and feet
• Brittle nails and hair
• Headaches
• Cognitive and behavioral changes, such as poor memory, difficulty concentrating, and changes in mood

The Link Between Anemia and Mental Health

Reduced oxygen levels, termed hypoxia, from anemia negatively impact the brain, causing cognitive and mental health symptoms. Research shows that the prevalence of anemia is higher in patients with chronic psychiatric conditions and that this coexistence increases the severity of the psychological condition in these patients. 

Studies have also linked anemia to the risk of cognitive decline, specifically in the context of dementia and Alzheimer's disease. One study found that all types of anemia were associated with cognitive impairment, as demonstrated by lower mini-mental status examination (MMSE) scores in those with low hemoglobin levels. Several theories help to explain this relationship. One theory suggests that low hemoglobin levels in anemia could lead to chronic brain cell hypoxia, beta-amyloid precipitation, and subsequent inflammation of neurons, all of which can result in declining brain function. Anemia may also cause inadequate blood flow to the brain, contributing to neurological deficiencies and ischemia. Additionally, anemia is linked to the progression of white matter hyperintensity and cortical brain atrophy. (15) 

Iron is required for central nervous system functioning and development, cellular replication and repair, nervous system myelination, and neurotransmitter signaling (26). A 2013 study concluded that iron deficiency, often associated with anemia, increases the risk of psychiatric disorders. Researchers hypothesize that this is likely due to a disruption in neuronal myelination and altered neurotransmitter systems during childhood development. 

Anemia's Effects on Anxiety and Depression

Anxiety disorders, characterized by feelings of apprehension or unease, are the most common mental health disorders, affecting nearly 30% of adults. Classic symptoms of anxiety include excessive worry, restlessness, difficulty concentrating, fatigue, body pain, digestive issues, and feelings of panic. A 2014 study linked these symptoms to low iron. Among other vitamins and minerals, iron is an essential cofactor for synthesizing serotonin, an important neurotransmitter that influences mood. Iron deficiency can reduce serotonin levels, a potential cause of panic attacks. 

Depression is a mental health disorder characterized by persistent sadness, hopelessness, and a loss of interest or pleasure in previously enjoyable activities. A 2018 cross-sectional study found a direct relationship between anemia and depression, findings that were later corroborated by a large systematic review and meta-analysis in 2020. Researchers noted that anemia can cause depressive symptoms (e.g., fatigue, irritability, and poor concentration) and impair brain oxygenation and performance. Deficiencies in iron, folate, and vitamin B12 deficiency, common causes of anemia, have also been linked to depression. 

Functional Medicine Labs to Assess Anemia

Because of the strong link between anemia and mental health disorders, a diagnostic evaluation for anemia is a standard component of a functional medicine assessment of anxiety and depression.

Complete Blood Count (CBC)

A CBC is a standard blood test that provides important information about the components of your blood. It includes several measurements, and healthcare professionals pay close attention to specific parameters within the CBC when assessing for anemia. Low levels of total red blood cells, hemoglobin, and/or hematocrit are diagnostic for anemia. The mean corpuscular volume (MCV) measures the average size of red blood cells, which can further classify the type of anemia. Low MCV is diagnostic for microcytic anemia, whereas elevated MCV is diagnostic for macrocytic anemia. The mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) provide information about the average hemoglobin content in red blood cells and their concentration, respectively. They help to differentiate between hypo- and hyperchromic anemias. These differentiations aid in diagnosing anemia as they help narrow the differential diagnosis for potential causes of anemia and help determine the appropriate follow-up tests to order. (32) 

A CBC, especially if abnormal, may also be ordered alongside a reticulocyte count and peripheral blood smear. Reticulocytes are immature red blood cells and may be present in abnormal amounts in some types of anemia. A peripheral blood smear can be performed to visually examine the shape and characteristics of red blood cells, providing clues to the underlying cause of anemia.

Iron Panel

An iron panel is a set of blood tests that assess various aspects of iron metabolism in the body. It is often used to help diagnose and evaluate different types of anemia, particularly when the underlying cause is suspected iron deficiency. The typical components of an iron panel include measurements of serum iron, total iron-binding capacity (TIBC), transferrin saturation, and serum ferritin.

Functional Medicine Labs to Further Assess Anxiety and Depression

Anxiety and depression are multifactorial, complex health conditions. Many other potential underlying factors can contribute to the onset and severity of both of these conditions. Therefore, in addition to ruling out anemia, your functional medicine provider may also recommend ordering additional tests.

Thyroid Panel

Thyroid diseases can affect mood. With overactive thyroid (hyperthyroidism), mood symptoms can include anxiety, nervousness, and irritability. With underactive thyroid (hypothyroidism), mood symptoms may include depression and fatigue; up to 40% of patients with hypothyroidism will develop clinically significant depression. Therefore, screening for thyroid disease with a thyroid panel should be considered as part of routine assessment of mood disorders.

Blood Glucose

Research supports that good blood sugar control is critical for healthy mood, judgment, and cognitive function. Conversely, dysglycemia (encompassing high and low blood sugar) and insulin resistance increase the risk of anxiety, depression, and cognitive disturbances. Monitoring blood sugar control and screening for insulin resistance can be done through various methods, including a diabetes panel, oral glucose tolerance test (OGTT), or continuous glucose monitoring (CGM). (13) 

Reproductive Hormones

Fluctuations in female reproductive hormones, including estrogen, progesterone, LH, and FSH, can impact neurocognitive function, contributing to the higher rates of mental health conditions in the female population compared to men. Hormonal imbalances play a role in anxiety and depression in men, too; men with low testosterone levels report higher levels of depression and poorer quality of life. Therefore, serum testing to measure circulating levels of reproductive hormones can be important in evaluating mood disorders in male and female populations.

Organic Acids Test (OAT)

An OAT is a specialty urine test that measures a variety of organic acids, which are byproducts of cellular metabolism. This test can be a great diagnostic tool for providers wanting to cast a broad diagnostic net to screen for intestinal dysbiosis, vitamin deficiencies, neuroinflammation, and neurotransmitter imbalances. Abnormal results can help doctors initiate treatment protocols or may indicate the need for more in-depth functional medicine testing, such as a micronutrient panel, comprehensive stool test, and neurotransmitter panel. 

Preventing Anemia and Promoting Mental Well-Being

Now that we've established that anemia can cause depression and anxiety, let's discuss how to prevent and treat it with an integrative and holistic treatment protocol for optimizing mental health. Functional medicine doctors are well-trained in various non-invasive modalities that can fortify the synthesis and health of red blood cells and optimize psychoemotional aspects of health. 

Dietary Recommendations to Prevent Anemia

Deficiencies in iron, folate, and vitamin B12 are the most common nutrient deficiencies related to anemia. Fortunately, diet is a great way to optimize nutritional status. Patients with pathological digestive conditions leading to malabsorption and nutrient deficiencies may require an individualized elimination diet. For example, patients with celiac disease (often manifesting with iron deficiency at diagnosis) require a strict gluten-free diet as part of their treatment protocol. 

For most patients, though, nutritional treatment protocols will emphasize incorporating nutrient-dense foods into the diet to ensure the consumption of foods rich in iron and B vitamins. Dietary iron has two forms: heme and nonheme. Heme iron, found in animal sources like red meat, oysters, and liver, is very well absorbed by the body. Nonheme iron, found in plant-based and iron-fortified foods like legumes, molasses, and tofu, is significantly less bioavailable to the body. Pairing nonheme-rich iron foods with vitamin C sources can help improve dietary absorption. (7) 

Animal products, including meat, fish, poultry, dairy, eggs, B12-fortified cereals, and nutritional yeast products, contain bioavailable vitamin B12. Folate and folic acid are found in green vegetables, legumes, liver, and fortified grains. 

Supplements to Treat and Prevent Anemia

The supplements used to treat or prevent anemia should be decided upon based on the type of anemia present and individual patient risk factors. 

Sometimes, diet alone is insufficient in treating anemias caused by nutrient deficiencies, so supplemental nutrients can be added to expedite the optimization of nutritional status. Per a Cochrane review, daily iron supplementation raises hemoglobin and iron stores, effectively reducing the prevalence of anemia and iron deficiency. Likewise, vitamin B12 and folate supplementation can treat vitamin B12 and folate-deficient anemias. Patients with gastrointestinal pathologies, a history of gastric surgery, or those who eat restricted diets (e.g., vegetarian or vegan) are at higher risk for vitamin deficiency anemia and may benefit from supplementation. 

Anemia of chronic disease is the second most common type of anemia worldwide, caused by a reduced production of red blood cells in the presence of chronic inflammatory conditions. In this instance, anti-inflammatory herbs proven to reduce systemic inflammation and manage inflammatory health conditions can help treat and reduce anemic symptoms. These include but are not limited to Boswellia, curcumin, ginger, resveratrol, and rosemary. (10)  

Lifestyle Changes for Overall Mental Health

In addition to a healthy diet, the importance of regular physical activity and exercise for mental health cannot be overstated. Exercise has been shown to help improve anxiety and depression for several reasons. Exercise triggers the release of endorphins, which act as natural mood lifters and pain reducers. Physical activity improves the functioning of the hypothalamus-pituitary-adrenal axis, reducing the production of stress hormones, like cortisol, linked to feelings of stress and anxiety. Finally, exercise can help restore and maintain a healthy balance of neurotransmitters in the brain. (28) 

A number of complementary and integrative medicine approaches have been documented as effective in improving anxiety and depression. Mind-body techniques, such as yoga, meditation, and biofeedback, help the body adapt to stress by increasing vagal tone and improving heart rate variability. Chiropractic adjustments, acupuncture, massage, aromatherapy, and music therapy have also been shown to improve blood flow and increase parasympathetic tone to support mood and well-being. (4, 21) 

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Summary

The intricate connection between anemia and mental health, specifically anxiety and depression, underscores the importance of a comprehensive approach to healthcare. While anemia's impact on cognitive function and emotional well-being is increasingly recognized, its effects are often modifiable through early detection and appropriate intervention. By addressing the underlying causes of anemia and supporting mental health through therapy, lifestyle modifications, and, when necessary, medication, healthcare providers can contribute to not only the physical vitality of their patients but also their mental and emotional well-being. A holistic approach that considers both hematological and psychological aspects of health is essential in providing comprehensive care to individuals affected by anemia and its potential repercussions on mental health.