Anemia is a blood disorder in which the number of red blood cells (RBCs) is lower than usual. Megaloblastic anemia is characterized by RBCs that are larger than typical. There also aren’t enough of them.

RBCs transport oxygen through the body. When your body doesn’t have enough RBCs, your tissues and organs don’t get enough oxygen. There are many types of anemia with different causes and characteristics.

When RBCs aren’t produced properly, it results in megaloblastic anemia. Because the blood cells are too large, they may be unable to exit the bone marrow to enter the bloodstream and deliver oxygen.

The two most common causes of megaloblastic anemia are deficiencies of vitamin B12 and folate.

These two nutrients are necessary for producing healthy RBCs. When you don’t get enough of them, it affects the makeup of your RBCs. This leads to cells that don’t divide and reproduce the way they should.

Vitamin B12 deficiency

Vitamin B12 is a nutrient found in foods and drinks such as:

Some people can’t absorb enough vitamin B12 from their diet, leading to megaloblastic anemia. Megaloblastic anemia caused by vitamin B12 deficiency is known as vitamin B12 deficiency anemia.

One rare type of vitamin B12 deficiency anemia is pernicious anemia. Pernicious anemia is an autoimmune condition and is due to the lack of a protein in the stomach called intrinsic factor. Without intrinsic factor, vitamin B12 can’t be absorbed, regardless of how much is consumed.

It’s possible to develop vitamin B12 deficiency anemia because there simply isn’t enough vitamin B12 in your diet. Since B12 isn’t naturally found in any plant-based products, vitamin B12 deficiency is common in people following a vegetarian or vegan diet.

You can also develop vitamin B12 deficiency anemia if you take medications that deplete vitamin B12, such as proton pump inhibitors and metformin (Fortamet, Glumetza). Having certain types of surgery, including bariatric surgery, can also result in an inability to absorb vitamin B12.

Folate deficiency

Folate is another nutrient that’s important for the development of healthy RBCs. Folate is found in foods such as:

Folate is often mixed up with folic acid. Technically, folic acid is the artificial form of folate. You can find folic acid in supplements as well as fortified cereals and foods.

Your diet is an important factor in whether you have enough folate. Folate deficiency can also be caused by alcohol misuse, since alcohol interferes with the body’s ability to absorb folate and folic acid.

Pregnant people are more likely to have folate deficiency because of the high amounts of folate needed by the developing fetus.

Other names for megaloblastic anemia

Depending on its cause, megaloblastic anemia may also be referred to as:

The most common symptom of megaloblastic anemia is fatigue.

Symptoms can vary from person to person. Other common symptoms include:

One test used to diagnose anemia is a complete blood count (CBC). This test measures the different parts of your blood. As part of the CBC, a healthcare professional can check the number and appearance of your RBCs. They’ll appear larger and underdeveloped if you have megaloblastic anemia.

Your doctor will also gather your medical history and perform a physical exam to rule out other causes of your symptoms.

Your doctor will need to order more blood tests to figure out if vitamin deficiency is causing your anemia. These tests will also help them find out whether a vitamin B12 or folate deficiency is causing your condition.

Schilling test

Another test that your doctor may use to help with diagnosis is the Schilling test. The Schilling test is a blood test that evaluates your ability to absorb vitamin B12.

After you take a small supplement of radioactive vitamin B12, you’ll:

  • collect a urine sample for your doctor to analyze
  • take the same radioactive supplement in combination with the intrinsic factor protein that your body needs to be able to absorb vitamin B12
  • provide another urine sample for comparison with the first one

If the urine samples show that you only absorbed the B12 after consuming it along with the intrinsic factor, it’s a sign that you don’t produce intrinsic factor on your own. This means that you’re unable to absorb vitamin B12 naturally.

Did you know?

Folate is also known as vitamin B9, while vitamin B12 is also known as cobalamin.

How you and your doctor decide to treat megaloblastic anemia depends on what’s causing it. Your treatment plan can also depend on your age and overall health as well as your response to treatments and how severe your disease is.

Treatment to manage anemia is often ongoing.

Vitamin B12 deficiency

In the case of megaloblastic anemia caused by vitamin B12 deficiency, you may need monthly injections of vitamin B12. You may also be given oral supplements.

Adding more foods with vitamin B12 to your diet can help. Additional foods that have vitamin B12 in them include:

Some individuals have a genetic mutation on the methylenetetrahydrofolate reductase (MTHFR) gene. This gene is responsible for the conversion of certain B vitamins, including B12 and folate, into their usable forms within the body.

Supplemental methylcobalamin is recommended for individuals with the MTHFR mutation.

Regular intake of vitamin B12-rich foods, vitamins, or fortified products isn’t likely to prevent deficiency or its health consequences in those with this genetic mutation.

Folate deficiency

Megaloblastic anemia caused by a lack of folate may be treated with oral or intravenous folic acid supplements. Dietary changes also help boost folate levels.

More foods to incorporate into your diet include:

As with vitamin B12, individuals with the MTHFR mutation are encouraged to take methylfolate to prevent a folate deficiency and its complications.

In the past, megaloblastic anemia was difficult to treat. Today, people with megaloblastic anemia due to either vitamin B12 or folate deficiency can manage their symptoms and feel better with ongoing treatment and dietary supplements.

Vitamin B12 deficiency can lead to other problems. These can include nerve damage, neurological problems, and digestive tract problems. These complications can be reversed with early diagnosis and treatment.

Genetic testing is available to determine if you have the MTHFR genetic mutation. People who have pernicious anemia may also be at higher risk of stomach cancer and reduced bone strength. For these reasons, it’s important to catch megaloblastic anemia early.

Talk with your doctor if you notice any symptoms of anemia. You and your doctor can come up with a treatment plan and help prevent any permanent damage.


What are the differences between microcytic anemia and macrocytic anemia?

Anonymous reader


There are three types of anemia: microcytic anemia, macrocytic anemia, and normocytic anemia. Each type has its own causes.

In microcytic anemia, red blood cells (RBCs) are smaller than normal. In macrocytic anemia, RBCs are larger than normal. Making this distinction in the size of RBCs will help doctors figure out the cause of a person’s anemia.

Alana Biggers, MD, MPHAnswers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.
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