What Is Megaloblastic Anemia?

A Type of Anemia With Large Red Blood Cells

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Megaloblastic anemia is a type of blood cell deficiency with larger than normal red blood cells and enlarged and abnormal red blood cell precursors (megaloblasts) in the bone marrow.

This type of anemia often develops due to vitamin B12 (cobalamin) deficiency or vitamin B9 (folate) deficiency. These deficiencies can occur for different reasons, such as malnutrition or gastrointestinal conditions.

The symptoms can include fatigue, headaches, dizziness, and other effects. Treatment generally involves getting enough of these vitamins, either in the diet or with supplements. If the deficiency is caused by an illness, medical management of the underlying illness is necessary as well.

What to Know About Megaloblastic Anemia - Illustration by Danie Drankwalter

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Types 

Megaloblastic anemia is a type of macrocytic anemia. Macrocytic anemia includes all types of anemia with larger than normal red blood cells. They can be megaloblastic (with enlarged and unusual red blood cell precursors in the bone marrow) or non-megaloblastic, and the causes of each type differ.

The different types of megaloblastic anemia are categorized by the cause, which can be insufficient vitamins in the diet, poor absorption of vitamins, or a medical problem. 

What Are the Symptoms of Megaloblastic Anemia?

You can have symptoms that range from mild to severe with megaloblastic anemia. The symptoms often develop gradually and may be accompanied by other effects of vitamin B12 or folate deficiency. 

Common effects of megaloblastic anemia include:

  • General tiredness 
  • Sleepiness 
  • Low energy
  • Headaches 
  • Dizziness 
  • Difficulty concentrating 
  • Diarrhea 
  • Glossitis (swollen tongue) 
  • Pale skin 

You can have one or more of these effects, and they can come and go. However, overall, you might experience them more and more often as the anemia worsens. 

Associated symptoms that you can also experience due to vitamin deficiency include:

  • Numbness, tingling, pain, or diminished sensation of your hands or feet
  • Trouble with balance and coordination 
  • Personality or behavior changes 
  • Weakness of the body 
  • Weight loss 

These symptoms generally occur at later stages or when vitamin deficiency is severe. 

What Causes Megaloblastic Anemia?

Megaloblastic anemia develops due to vitamin B12 or folate deficiency. You can develop a deficiency of one or both vitamins for many reasons. 

Causes include:

  • Dietary deficiency of vitamin B12Vitamin B12 is provided by meat, chicken, eggs, dairy, and more.
  • Dietary deficiency of vitamin B9Vitamin B9 is present in green leafy vegetables, fruit, and more.
  • Medications: Several different medications, such as Glucophage (metformin), can interfere with the way your body absorbs or uses vitamin B12 or vitamin B9.
  • Malabsorption: Gastrointestinal conditions such as Crohn’s disease (an inflammatory bowel disease) can interfere with the proper absorption of your food. Any surgery that involves the removal of a portion of your digestive tract, including gastric bypass surgery, can prevent you from absorbing nutrients from the food you eat. 
  • Pernicious anemia: This rare condition affects proteins in the gastrointestinal system, making it difficult to absorb vitamin B12.

Infants can have megaloblastic anemia due to maternal nutritional deficiencies.

How Megaloblastic Anemia Develops 

Your red blood cells last for approximately four months before they are broken down and the materials are recycled. Your body is constantly renewing your red blood cells.

The process of new red blood cell formation involves the production of the cell’s membrane, enzymes, proteins, and genetic material. Megaloblastic anemia occurs due to a lack of folate or vitamin B12, which are needed to produce a red blood cell’s genetic material.

How Is Megaloblastic Anemia Diagnosed?  

Megaloblastic anemia is diagnosed with blood tests. Often, an evaluation to identify the cause relies on additional tests. 

If you have symptoms of anemia, you should see a healthcare provider. Your medical history may identify risk factors for megaloblastic anemia, such as your eating patterns or medications. People who have a vegan diet, for example, are at risk of vitamin B12 deficiency.

Your physical examination may show signs consistent with megaloblastic anemia, but there are often no apparent signs noticeable on a physical examination.

People with megaloblastic anemia are more likely to have associated signs of vitamin deficiency that can be detected with a physical examination, such as peripheral neuropathy (damage to sensory nerves that may produce numbness, tingling, and odd sensations in the limbs). 

Blood tests and other procedures are used to diagnose the condition.

Complete blood count (CBC): Your CBC is a blood test that determines the relative number and size of different cells in your blood, including your white blood cells, red blood cells, and platelets. With megaloblastic anemia, you would have some abnormalities on your CBC, including:

  • Hematocrit (which measures the percentage of blood composed of blood cells): Less than 20% is considered low and suggests anemia.
  • Mean red blood cell volume, described as mean corpuscular volume (MCV): Higher than 100 femtoliters per cell (fL/cell) is consistent with enlarged red blood cells.
  • Increased red blood cell distribution width (RDW): This shows there are cells of different sizes present.

Blood smear: A blood smear is a microscopic examination of a blood sample. In megaloblastic anemia, your blood smear would show enlarged, oval-shaped red blood cells and increased variation in the shape and size of red blood cells. They may have small remnants of nuclei in them (Howell-Jolly bodies).

The white blood cells may also show increased nuclear segmentation in granulocytes (a type of white blood cell).

Your care team would consider all of these results when determining whether you have megaloblastic anemia. These tests can be used to diagnose megaloblastic anemia, but they don’t specifically identify the cause.

Tests that can identify the cause of megaloblastic anemia:

  • B12 level below 200 picograms per milliliter (pg/mL) is considered low.
  • Folate level below 2 nanograms per milliliter (ng/mL) is considered low.
  • Low levels of gastrin (a hormone that triggers the release of digestive juices) and the presence of intrinsic factor antibodies or parietal cell antibodies can occur with pernicious anemia.
  • A bone marrow biopsy may be needed if there is concern about blood cancer. In this test, a hollow needle is used to take a sample of bone marrow from the hip or a long bone, and it is analyzed in the lab.
  • An endoscopy (imaging using a flexible tube with a camera inserted through the mouth) or colonoscopy (imaging using a flexible tube with a camera inserted through the anus) may identify gastrointestinal system problems that interfere with vitamin absorption. 
  • Imaging tests may be needed if there is concern that you could have a change in your gastrointestinal system that is visible with an abdominal computerized tomography (CT) (detailed imaging using X-rays) or ultrasound (imaging using sound waves). 

You may have a speedy diagnosis within days, but sometimes it takes months or longer to determine the cause of megaloblastic anemia. 

How Megaloblastic Anemia Is Treated

Treatment for megaloblastic anemia involves correcting the vitamin deficiency. This can be done with diet and sometimes with oral supplements or injections. 

If you have a problem absorbing vitamins in your gastrointestinal tract, you will likely need an injection. You may need repeated injections scheduled at regular intervals so that you won’t develop a deficiency again. 

You may also need treatment for your underlying medical condition and/or supplementation for other nutritional deficiencies that you may have. 

Prognosis: What to Expect 

Megaloblastic anemia should improve with treatment. It takes weeks—possibly months—to notice an improvement of symptoms and for blood tests to reflect the changes. 

This is because red blood cells last for several months, and your body is constantly making new red blood cells to replace the older ones. As your body makes new, healthy red blood cells, the dysfunctional cells will make up a smaller proportion of your red blood cells. 

Megaloblastic anemia can recur. You might need consistent treatment to prevent a recurrence. 

Summary 

Megaloblastic anemia is a type of macrocytic anemia. This condition occurs when red blood cells are not properly formed due to vitamin B12 or folate deficiency. This type of anemia causes fatigue, pale skin, and an enlarged tongue. Other symptoms of vitamin B12 deficiency can develop too.

Generally, megaloblastic anemia can be treated with the replacement of deficient vitamins and treatment of the underlying cause. 

A Word From Verywell 

Anemia is not uncommon, and you might have anemia at some time in your life. If you are diagnosed with megaloblastic anemia or any other type of anemia, it’s important that you follow through with a comprehensive evaluation of the cause. Rest assured that most of the time, megaloblastic anemia can be treated, and your symptoms should improve with treatment. 

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