Which Type of Anemia Is Caused by a B12 Deficiency?

November 16, 2025 •

4 min read

According to the National Institutes of Health, vitamin B12 deficiency is a common cause of megaloblastic anemia, affecting various populations worldwide. A vitamin B12 deficiency leads to a form of megaloblastic anemia, which can be further specified as pernicious anemia depending on its underlying cause.

Quick Summary

B12 deficiency primarily causes megaloblastic anemia, a blood disorder where red blood cells are abnormally large. This is often linked to an absorption issue like pernicious anemia, an autoimmune condition.

Key Points

Megaloblastic Anemia: The direct type of anemia caused by a B12 deficiency is megaloblastic anemia, characterized by abnormally large, immature red blood cells.
Pernicious Anemia: The most common cause of B12 deficiency is often pernicious anemia, an autoimmune condition that prevents the absorption of vitamin B12.
Impaired DNA Synthesis: The root cause of the abnormal red blood cell formation is a disruption of DNA synthesis caused by the lack of B12.
Neurological Complications: Untreated B12 deficiency can lead to serious and potentially irreversible neurological problems, including nerve damage, memory loss, and difficulty with balance.
Lifelong Treatment: Many cases, especially pernicious anemia, require lifelong treatment with B12 supplements, often via injections, to manage the condition effectively.
Diverse Causes: Beyond pernicious anemia, a B12 deficiency can also be caused by dietary choices (e.g., veganism), gastrointestinal surgery, or certain medications.

A deficiency in vitamin B12, also known as cobalamin, is a key factor in the development of megaloblastic anemia. This condition is characterized by the production of abnormally large, immature red blood cells, called megaloblasts, which cannot function correctly to transport oxygen throughout the body. While megaloblastic anemia is the broad classification, the most common specific cause is pernicious anemia, an autoimmune disorder.

Understanding Megaloblastic Anemia

Megaloblastic anemia stems from impaired DNA synthesis in red blood cells during their development in the bone marrow. Because DNA replication is halted, the cells continue to grow without dividing, resulting in unusually large and fragile cells that are released into the bloodstream. Not only are these cells inefficient at carrying oxygen, but they also have a shorter lifespan than healthy red blood cells.

Why B12 is Crucial

Vitamin B12 is an essential cofactor for several enzymatic reactions within the body, including the metabolism of homocysteine and methylmalonic acid (MMA). Without sufficient B12, these metabolic pathways are disrupted, leading to the accumulation of homocysteine and MMA. This metabolic imbalance is what ultimately impairs DNA synthesis and triggers the characteristic blood cell abnormalities seen in megaloblastic anemia. It is critical that a B12 deficiency is diagnosed correctly, as treating megaloblastic anemia with folic acid alone (which can be deficient at the same time) could mask the underlying B12 issue and allow irreversible neurological damage to continue.

The Role of Pernicious Anemia

Pernicious anemia is the most frequent specific reason for B12 deficiency, particularly in the UK and among certain populations. It is a condition where the body's immune system mistakenly attacks the cells in the stomach that produce intrinsic factor (IF). Intrinsic factor is a protein that is vital for the absorption of vitamin B12 in the small intestine. When IF production is inhibited, the body cannot absorb B12 from food, regardless of dietary intake. This leads to a gradual depletion of the body's B12 stores, which can take several years due to the liver's ability to store the vitamin.

Other Causes of B12 Deficiency Anemia

Dietary Factors: Though less common, dietary insufficiency can cause B12 deficiency. Since vitamin B12 is found almost exclusively in animal products, vegans and long-term vegetarians are at higher risk if they do not take supplements or consume fortified foods.
Gastrointestinal Conditions: Surgical procedures, such as gastric bypass or removal of part of the stomach or small intestine, can interfere with B12 absorption. Chronic conditions like Crohn's disease, celiac disease, and small intestinal bacterial overgrowth (SIBO) can also disrupt nutrient absorption.
Medications and Other Factors: Some medications, including proton pump inhibitors (PPIs) and metformin, can interfere with vitamin B12 levels over time. Excessive alcohol use can also hinder absorption.
Genetic Disorders: Rare inherited conditions can affect the body's ability to transport or absorb B12.

Diagnosing and Treating a B12 Deficiency

Diagnosis typically involves a blood test to check for low levels of vitamin B12 and to measure the mean corpuscular volume (MCV), which will be high in megaloblastic anemia. If B12 levels are borderline, additional tests for methylmalonic acid (MMA) and homocysteine may be performed, as these accumulate in cases of B12 deficiency. Antibodies against intrinsic factor can be tested to confirm pernicious anemia.

Treatment varies based on the cause and severity. High-dose oral supplements may be effective, but if malabsorption is the issue, regular vitamin B12 injections are often necessary. Lifelong supplementation is typically required for those with pernicious anemia.

Symptoms and Complications

Symptoms of megaloblastic anemia can be subtle at first and progress slowly. Common signs include fatigue, weakness, pale skin, and shortness of breath. Neurological symptoms, such as numbness or tingling in the hands and feet, memory problems, and changes in balance, are characteristic of B12 deficiency and can become permanent if left untreated. Severe or prolonged deficiency can also increase the risk of heart conditions and, in the case of pernicious anemia, stomach cancer. Early diagnosis is crucial to prevent irreversible damage.

Comparison Table: B12 Deficiency vs. Iron Deficiency Anemia


Feature	B12 Deficiency Anemia (Megaloblastic)	Iron Deficiency Anemia
Cause	Lack of Vitamin B12 due to poor intake or malabsorption.	Lack of Iron due to poor intake, malabsorption, or blood loss.
Red Blood Cell Size	Abnormally large (Macrocytic).	Abnormally small (Microcytic) and pale.
Associated Symptoms	Neurological issues like tingling, numbness, and memory problems.	Restless legs syndrome, brittle nails, unusual food cravings (pica).
Diagnosis	Blood tests show high MCV; high MMA/homocysteine.	Blood tests show low MCV; low ferritin/serum iron.
Treatment	Vitamin B12 supplements (oral or injections).	Iron supplements and treating the underlying cause.

Conclusion

A deficiency in vitamin B12 leads to megaloblastic anemia, a condition marked by the production of oversized and dysfunctional red blood cells. The most common form is pernicious anemia, an autoimmune disorder that prevents B12 absorption. Prompt diagnosis through blood tests and early treatment with B12 supplements are essential to manage symptoms and prevent long-term complications, particularly neurological damage. Individuals with risk factors, such as those on a vegan diet or who have undergone certain surgeries, should be aware of the signs and seek medical advice. It is important to treat the specific deficiency, whether dietary or due to an underlying condition, to restore healthy red blood cell production.

Frequently Asked Questions

Megaloblastic anemia is a type of blood disorder where the bone marrow produces abnormally large, immature, and nonfunctional red blood cells due to impaired DNA synthesis.

Megaloblastic anemia is the broad term for the condition caused by B12 or folate deficiency. Pernicious anemia is a specific type of megaloblastic anemia caused by an autoimmune disorder that prevents the absorption of vitamin B12.

Vitamin B12 is essential for DNA synthesis during the formation of red blood cells. Without it, the cells grow too large and do not divide properly, leading to fewer, abnormal red blood cells.

Common symptoms include fatigue, weakness, pale skin, shortness of breath, a sore tongue, and neurological issues like numbness, tingling, and memory problems.

Diagnosis involves blood tests to check vitamin B12 levels and measure the size of red blood cells (MCV). Further tests, such as checking for intrinsic factor antibodies, can confirm the specific cause.

Treatment involves supplementing the missing vitamin, typically with oral tablets or vitamin B12 injections. The treatment plan depends on the cause of the deficiency.

For those with pernicious anemia, prevention is not possible, but management with lifelong B12 treatment is effective. For dietary-based deficiencies, eating B12-rich foods or supplements can prevent the condition.