Does anemia cause vitamin D deficiency? Unpacking the bidirectional relationship

October 14, 2025 •

5 min read

According to a systematic review published in 2025, vitamin D deficiency (VDD) and anemia are two common public health issues with a possible biological connection. Emerging evidence suggests a bidirectional relationship rather than one directly causing the other, complicating the question of whether anemia causes vitamin D deficiency.

Quick Summary

This article examines the complex and often bidirectional relationship between vitamin D and anemia. It details the physiological mechanisms involving hepcidin and erythropoiesis, explores shared risk factors, and discusses the challenges in establishing causality between these common deficiencies.

Key Points

Bidirectional Relationship: Evidence shows that vitamin D deficiency and anemia have a complex, two-way relationship, not a simple cause-and-effect.
Hepcidin Modulation: Vitamin D helps suppress hepcidin, a hormone that blocks iron absorption. Low vitamin D can therefore lead to iron-restricted anemia.
Erythropoiesis Support: Active vitamin D directly stimulates the production of red blood cells in the bone marrow, a process compromised by deficiency.
Iron's Role in Vitamin D Activation: Iron-containing enzymes are essential for converting inactive vitamin D into its active form, so iron deficiency can hinder this process.
Inflammation Connection: Vitamin D has anti-inflammatory effects that can counteract the inflammation-driven hepcidin overproduction, which is a major cause of anemia of chronic disease.
Risk Populations: Vulnerable groups, including pregnant women, older adults, and those with chronic illnesses, are at higher risk for co-occurring deficiencies.
Overlapping Symptoms: Both conditions share symptoms like fatigue, weakness, and reduced immunity, making correct diagnosis crucial.

For many years, researchers and clinicians have observed a frequent co-occurrence of anemia and vitamin D deficiency in populations worldwide. While the idea that one condition directly causes the other is simplistic, a growing body of evidence points to a sophisticated and reciprocal relationship. This interplay involves inflammation, hormonal signaling, and shared metabolic pathways, meaning a deficiency in one nutrient can indeed negatively impact the other. Understanding this connection is crucial for effective diagnosis and treatment, particularly in at-risk groups.

The Bidirectional Relationship Explained

The relationship between vitamin D deficiency and anemia is not a simple one-way street. Instead, it is best described as a bidirectional association where each condition can influence the development or severity of the other through different physiological mechanisms. For example, studies have shown that individuals with one deficiency are at a significantly higher risk of having the other. This is more complex than simply co-existing due to poor overall nutrition, as mechanistic studies reveal direct biological pathways linking them.

How Anemia Can Influence Vitamin D Status

Anemia, especially iron deficiency anemia (IDA), can indirectly lead to lower vitamin D levels through its effect on vitamin D metabolism. The process of converting vitamin D into its active, usable form requires certain iron-dependent enzymes known as cytochromes P450.

Role of Iron-Containing Enzymes: Both the liver and kidneys house these enzymes, which perform crucial hydroxylation steps in vitamin D activation. When iron is deficient, the activity of these enzymes decreases, impairing the body's ability to produce sufficient active vitamin D.
Impact on Absorption: Some evidence suggests that iron deficiency may also impair the intestinal absorption of fat-soluble vitamins, including vitamin D, though more research is needed to fully understand this link.

How Vitamin D Affects Iron and Red Blood Cell Production

On the other side of the coin, a deficiency in vitamin D can exacerbate or contribute to anemia through its influence on iron regulation and erythropoiesis—the production of red blood cells.

Modulation of Hepcidin: Vitamin D plays a crucial role in regulating hepcidin, a hormone produced by the liver that controls systemic iron homeostasis. High levels of hepcidin restrict iron from being released from storage cells and block its absorption from the gut. Active vitamin D (calcitriol) has been shown to suppress hepcidin production, helping to increase iron availability for red blood cell synthesis. Thus, low vitamin D levels can lead to high hepcidin, effectively trapping iron and causing anemia.
Anti-Inflammatory Effects: Vitamin D also has powerful anti-inflammatory properties. In cases of chronic inflammation (often seen in anemia of chronic disease), high levels of pro-inflammatory cytokines stimulate hepcidin production. By reducing these cytokines, vitamin D can indirectly lower hepcidin and restore proper iron recycling.
Direct Effect on Erythropoiesis: Vitamin D receptors (VDR) are present in the bone marrow, where red blood cells are made. Studies have shown that calcitriol, the active form of vitamin D, can directly promote the proliferation and differentiation of red blood cell precursors. A deficiency could therefore impair this process.

Comparing the Pathways Linking Anemia and Vitamin D Deficiency


Feature	Anemia affecting Vitamin D Status	Vitamin D affecting Anemia Status
Primary Mechanism	Affects the function of iron-dependent enzymes necessary for vitamin D conversion	Modulates the iron-regulating hormone hepcidin and reduces inflammation
Key Player	Iron-containing cytochrome P450 enzymes	Hepcidin, inflammatory cytokines, erythroid precursors
Effect on Vitamin D	Decreased conversion of inactive vitamin D to its active form (calcitriol)	Indirectly supports vitamin D's function by ensuring sufficient iron for proper metabolism
Effect on Anemia	Iron deficiency can contribute to reduced vitamin D levels, affecting its downstream functions	Deficiency can increase hepcidin, block iron absorption, and impair erythropoiesis
Evidence Level	Supported by mechanistic studies showing iron's role in metabolism	Strong epidemiological and mechanistic evidence, especially for anemia of inflammation

Populations at Higher Risk

Several groups are particularly vulnerable to this dual deficiency, and the interaction can be influenced by multiple factors.

Pregnant Women: They have an increased need for both iron and vitamin D. Studies show a significant association between low maternal vitamin D levels and a higher risk of anemia during pregnancy.
Children and Adolescents: Growing bodies require ample amounts of these nutrients. Research indicates that suboptimal vitamin D is associated with an increased risk of anemia in children, independent of iron status in some cases.
Older Adults: With aging comes a higher risk for both vitamin D insufficiency and anemia, along with confounding factors like malnutrition, chronic inflammation, and comorbidities like chronic kidney disease.
Individuals with Chronic Diseases: Chronic kidney disease (CKD) and inflammatory conditions can disrupt both vitamin D and iron metabolism, leading to a higher prevalence of both deficiencies.
Those with Limited Sun Exposure: Since sunlight is the primary source of vitamin D, people with minimal sun exposure (due to lifestyle, clothing, or geographic location) are at higher risk of deficiency.

Identifying the Overlap: Signs and Symptoms

Because the symptoms of anemia and vitamin D deficiency can overlap, it is important to pay attention to a combination of signs. Common symptoms include:

Persistent fatigue: Both conditions can cause overwhelming tiredness.
Weakness and lethargy: A general feeling of lack of energy.
Pale skin: A classic sign of anemia due to reduced red blood cells.
Hair loss: Can be a sign of iron deficiency anemia.
Bone or muscle pain: Directly related to low vitamin D levels.
Weakened immune system: Both conditions can impact immune function, leading to frequent illnesses.

Conclusion: Navigating a Complex Nutritional Interplay

The connection between anemia and vitamin D deficiency is a complex, bidirectional relationship rooted in shared metabolic pathways involving hepcidin, inflammation, and erythropoiesis. It is not a simple case of one causing the other, but rather an intricate interplay where each deficiency can worsen the other. This dynamic relationship is especially prevalent in vulnerable populations such as pregnant women, children, and those with chronic diseases. Due to this complexity, health strategies must consider both nutrients together, rather than in isolation, to effectively prevent and treat these common deficiencies. Future research, including larger-scale and interventional studies, is still needed to fully elucidate the optimal screening and treatment strategies for this common co-occurrence.

For more detailed information on vitamin D's role in anemia, read this scientific review.

Frequently Asked Questions

Not directly. While iron is needed for vitamin D metabolism, supplementing iron alone will not correct a vitamin D deficiency. Proper levels of both nutrients are required for optimal function.

Hepcidin is a hormone that regulates iron in the body. When vitamin D levels are sufficient, it helps to suppress hepcidin production, allowing more iron to be available for red blood cell production.

No, it does not. While improving vitamin D levels can support erythropoiesis and iron utilization, anemia is often multifactorial. Your healthcare provider will need to address all potential causes, such as iron, B12, or folate deficiencies, and underlying chronic conditions.

Yes. Pregnant women have increased nutritional needs, and studies consistently show a high prevalence of both vitamin D deficiency and anemia during pregnancy.

Chronic diseases often involve inflammation, which can increase hepcidin levels and lead to anemia of chronic disease. Since vitamin D has anti-inflammatory properties, a deficiency can worsen this inflammatory state and its effect on iron utilization.

Given the frequent overlap and bidirectional influence, testing for the other deficiency is often a good idea. This allows for a more comprehensive treatment plan that addresses both nutritional issues simultaneously.

You can address these deficiencies through a balanced diet rich in iron (e.g., red meat, beans) and vitamin D (e.g., fatty fish, fortified dairy), as well as safe sun exposure for vitamin D synthesis.