What kind of anemia is vitamin B12 deficiency?

October 23, 2025 •

3 min read

According to the National Institutes of Health, vitamin B12 deficiency can lead to a specific condition known as megaloblastic anemia. This form of anemia is characterized by the bone marrow producing abnormally large, immature red blood cells that cannot function correctly, impairing oxygen delivery throughout the body.

Quick Summary

Vitamin B12 deficiency is a cause of megaloblastic anemia, where impaired DNA synthesis leads to the production of abnormally large, dysfunctional red blood cells. A common cause of this is pernicious anemia.

Key Points

Megaloblastic Anemia: Vitamin B12 deficiency primarily causes megaloblastic anemia, a type of macrocytic anemia characterized by abnormally large, immature red blood cells.
Impaired DNA Synthesis: The core issue is that a lack of B12 disrupts DNA synthesis, leading to defective red blood cell maturation in the bone marrow.
Pernicious Anemia: A common cause is pernicious anemia, an autoimmune disorder where the body cannot produce the intrinsic factor required for B12 absorption.
Neurological Symptoms: Untreated B12 deficiency can lead to severe and potentially irreversible neurological damage, such as nerve tingling, confusion, and memory loss.
Diverse Causes: Beyond pernicious anemia, causes include vegan diets, gastrointestinal surgeries, intestinal diseases, and certain medications.
Treatment is Critical: Diagnosis and prompt treatment with vitamin B12 injections or oral supplements are vital to correct the anemia and prevent long-term complications.

Understanding Megaloblastic Anemia

Vitamin B12 deficiency causes a condition known as megaloblastic anemia, a sub-type of macrocytic anemia. Megaloblastic anemia is characterized by impaired DNA synthesis, leading to the bone marrow producing large, immature, and fragile red blood cells called megaloblasts. Normal red blood cells are uniform in size and shape, but megaloblasts are oval and oversized. This defective cell division not only affects red blood cells but can also impact other rapidly multiplying cells in the body, such as those lining the gastrointestinal tract.

The Role of Vitamin B12 in Red Blood Cell Production

Vitamin B12 (cobalamin) is vital for DNA synthesis and metabolism. It is needed for enzymes that convert homocysteine to methionine and methylmalonic acid to succinyl-CoA. Low B12 disrupts these processes, slowing DNA synthesis and causing the large, inefficient red blood cells seen in megaloblastic anemia.

The Link Between Pernicious Anemia and B12 Deficiency

Pernicious anemia is a common cause of B12 deficiency, particularly in the UK. This autoimmune condition attacks stomach cells producing intrinsic factor (IF), a protein needed to absorb B12 in the small intestine. Lack of IF leads to B12 depletion and megaloblastic anemia.

Symptoms of Megaloblastic Anemia

Megaloblastic anemia symptoms appear gradually and can include:

Physical symptoms: Fatigue, pale skin, shortness of breath, fast heart rate, sore tongue, and weight loss.
Neurological symptoms: Numbness or tingling, memory issues, confusion, balance problems, vision changes, and irritability. Severe deficiency can cause permanent nerve damage.
Psychological symptoms: Mood changes and depression.

Other Causes of Vitamin B12 Deficiency

Besides pernicious anemia, B12 deficiency can result from:

Diet: Vegan or vegetarian diets without supplements or fortified foods.
Surgery: Procedures affecting the stomach or small intestine.
Illness: Conditions like Crohn's, celiac disease, or chronic pancreatitis.
Medications: Drugs such as metformin and proton pump inhibitors.
Alcohol: Heavy alcohol use.

Megaloblastic vs. Nonmegaloblastic Macrocytic Anemia

Both megaloblastic and nonmegaloblastic anemias have large red blood cells. The key difference is the cause. Megaloblastic anemia results from impaired DNA synthesis due to B12 or folate deficiency.


Feature	Megaloblastic Anemia	Nonmegaloblastic Anemia
Underlying Cause	Impaired DNA synthesis due to B12 or folate deficiency	Liver disease, alcohol use disorder, hypothyroidism, certain medications, or myelodysplastic syndrome
Red Blood Cell Shape	Oval-shaped (macro-ovalocytes) and enlarged	Typically round (round macrocytes) and enlarged
Neutrophil Appearance	Often feature hypersegmented neutrophils (more than 5 lobes)	Hypersegmented neutrophils are generally absent
Diagnosis	Blood tests show elevated MCV, plus elevated methylmalonic acid (MMA) and/or homocysteine	Blood tests show elevated MCV, but MMA and homocysteine levels are typically normal

Diagnosis and Treatment of B12 Deficiency Anemia

Diagnosing B12 deficiency involves a blood count showing high MCV, and a blood smear revealing macro-ovalocytes and hypersegmented neutrophils. Testing B12 levels and elevated MMA and homocysteine confirms the diagnosis. For suspected pernicious anemia, intrinsic factor antibody tests are used.

Treatment varies by cause and severity. Severe cases or those with absorption issues like pernicious anemia often start with B12 injections for rapid improvement. Less severe cases may use oral supplements. Dietary deficiencies are addressed with B12-rich foods or supplements. Many with absorption problems need lifelong treatment. Prompt treatment is vital to prevent serious neurological issues.

Conclusion

Vitamin B12 deficiency leads to megaloblastic anemia, a type of macrocytic anemia characterized by large, dysfunctional red blood cells due to impaired DNA synthesis. Pernicious anemia, an autoimmune condition preventing B12 absorption, is a primary cause. Other causes include diet, GI disorders, and certain medications. Timely diagnosis and treatment, usually with B12 supplementation, are crucial to avoid serious health problems, especially permanent nerve damage. Long-term management is often needed for chronic conditions or dietary restrictions. Identifying the cause is key to effective treatment.

Visit the National Institute of Health for more information on Vitamin B12.

Frequently Asked Questions

Macrocytic anemia is a general term for any anemia with abnormally large red blood cells. Megaloblastic anemia is a specific type of macrocytic anemia caused by impaired DNA synthesis, typically due to a deficiency in vitamin B12 or folate.

Early signs often include fatigue, weakness, pale or slightly yellowish skin, a sore red tongue, and digestive issues like diarrhea or weight loss. Neurological symptoms may develop later.

Diagnosis involves a blood test called a complete blood count (CBC), which reveals an elevated Mean Corpuscular Volume (MCV). Additional tests for serum B12, methylmalonic acid (MMA), and homocysteine are also performed.

No, pernicious anemia is a specific autoimmune disease that is a cause of vitamin B12 deficiency. It prevents the body from absorbing B12 from food, but other factors can also cause B12 deficiency.

Treatment varies based on the cause. For severe deficiency or malabsorption issues like pernicious anemia, intramuscular B12 injections are necessary. In other cases, high-dose oral supplements may be used.

If left untreated, severe B12 deficiency can cause lasting damage, particularly to the nervous system. While some symptoms may improve with treatment, nerve damage can be permanent.

Yes. Since vitamin B12 is primarily found in animal products, individuals on a strict vegan diet who do not take supplements or consume fortified foods are at a higher risk of developing a deficiency.

Besides anemia, B12 deficiency is linked to various neurological symptoms and complications like vision problems, memory loss, depression, and balance issues. In pregnant women, deficiency can increase the risk of birth defects.