What is megaloblastic anemia?

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

This type of anemia is usually caused by a vitamin B12 (cobalamin) deficiency or a vitamin B9 (folic acid) deficiency. These deficiencies can occur for different reasons, such as malnutrition or gastrointestinal disease.

Symptoms may include fatigue, headache, dizziness, and other effects. Treatment usually involves getting enough of these vitamins from diet or supplements. If the deficiency is caused by disease, medical management of the underlying disease is also required.

Types of

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

The different types of megaloblastic anemia are categorized by cause, which may be vitamin deficiencies in the diet, vitamin malabsorption, or medical problems.

What are the symptoms of megaloblastic anemia?

Symptoms of megaloblastic anemia range from mild to severe. Symptoms usually develop gradually and may be accompanied by other effects of vitamin B12 or folate deficiency.

Common effects of megaloblastic anemia include:

  • general tiredness
  • sleepy
  • low energy
  • headache
  • Dizziness
  • difficulty concentrating
  • diarrhea
  • glossitis (swelling of the tongue)
  • pale complexion

You can have one or more of these effects, and they can come and go. In general, however, as anemia worsens, you may experience them more and more frequently.

Symptoms you may also experience from a vitamin deficiency include:

  • Numbness, tingling, pain, or decreased sensation in the hands and feet
  • balance and coordination issues
  • personality or behavior changes
  • frail
  • lose weight

These symptoms usually occur later in life or when vitamin deficiencies are severe.

What causes megaloblastic anemia?

Megaloblastic anemia is caused by vitamin B12 or folic acid deficiency. You may be deficient in one or two vitamins for a variety of reasons.

Reasons include:

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  • Dietary deficiency of vitamin B12: Meat, chicken, eggs, dairy products, etc. can provide vitamin B12.
  • Dietary Deficiency of Vitamin B9: Vitamin B9 is found in green leafy vegetables, fruits, etc.
  • 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 disorders such as Crohn’s disease (an inflammatory bowel disease) can interfere with the normal absorption of food. Any surgery that involves removing part 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.

Babies may have megaloblastic anemia due to insufficient maternal nutrition.

How does megaloblastic anemia develop

Your red blood cells last about four months before being broken down and the material recycled. Your body is constantly renewing your red blood cells.

The process of new red blood cell formation involves the production of cell membranes, enzymes, proteins and genetic material. Megaloblastic anemia occurs due to a lack of folic acid or vitamin B12, which is required for the production of red blood cell genetic material.

How is megaloblastic anemia diagnosed?

Megaloblastic anemia is diagnosed by a blood test. Often, assessment to determine the cause relies on additional testing.

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 dietary habits or medications. For example, people on a vegan diet are at risk for vitamin B12 deficiency.

Your physical examination may show signs consistent with megaloblastic anemia, but physical examination usually has no obvious signs.

People with megaloblastic anemia are more likely to have symptoms associated with vitamin deficiencies that can be detected on a physical examination, such as peripheral neuropathy (damage to sensory nerves that can cause numbness, tingling, and strange sensations in the extremities).

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

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Complete blood count (CBC): Your CBC is a blood test that determines the relative numbers and sizes of different cells in your blood, including white blood cells, red blood cells, and platelets. With megaloblastic anemia, your CBC will show some abnormalities, including:

  • Hematocrit (measures the percentage of blood made up of blood cells): A level below 20% is considered low and indicates anemia.
  • Mean corpuscular volume, described as mean corpuscular volume (MCV): Greater than 100 femtoliters per cell (fL/cell) is consistent with enlarged erythrocytes.
  • Increased red blood cell distribution width (RDW): This indicates the presence of cells of different sizes.

What is the red blood cell index?

Blood smear: A blood smear is a microscopic examination of a blood sample. In megaloblastic anemia, your blood smear will show enlarged, oval-shaped red blood cells and increased changes in the shape and size of the red blood cells. There may be small amounts of nuclear residues (Howell-Jolly bodies) in them.

Leukocytes may also show increased nuclear segmentation in granulocytes, a type of white blood cell.

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

Tests that can determine the cause of megaloblastic anemia:

  • B12 levels below 200 picograms per milliliter (pg/mL) are considered low levels.
  • Folate levels below 2 nanograms per milliliter (ng/mL) are considered low.
  • The presence of low levels of gastrin (a hormone that triggers the release of digestive juices) and intrinsic factor or parietal cell antibodies may occur with pernicious anemia.
  • If there is concern about blood cancer, a bone marrow biopsy may be required. In this test, a bone marrow sample is taken from the hip or long bone using a hollow needle and analyzed in a laboratory.
  • Endoscopy (imaging using a tube inserted into the camera through the mouth) or colonoscopy (imaging using a tube inserted into the camera through the anus) can identify gastrointestinal problems that interfere with vitamin absorption.
  • Imaging tests may be needed if you are concerned about possible changes in your gastrointestinal system, which can be seen on computed tomography (CT) of the abdomen (detailed imaging using X-rays) or ultrasound (imaging using sound waves).

You may get a quick diagnosis within a few days, but sometimes it takes months or more to determine the cause of megaloblastic anemia.

How to treat megaloblastic anemia

Treatment of megaloblastic anemia includes correction of vitamin deficiencies. This can be done through diet and sometimes through oral supplements or injections.

If your gastrointestinal tract has trouble absorbing vitamins, you may need injections. You may need to repeat the injection on a regular basis to prevent the defect from recurring.

You may also need to treat your underlying medical condition and/or supplement other nutritional deficiencies you may have.

Prognosis: what to expect

Megaloblastic anemia should improve with treatment. It can take weeks (possibly months) to notice an improvement in symptoms and have blood tests to reflect these changes.

This is because red blood cells last for several months, and your body keeps making new red blood cells to replace old ones. When your body makes new, healthy red blood cells, dysfunctional cells make up a smaller percentage of your red blood cells.

Megaloblastic anemia can recur. You may need ongoing treatment to prevent recurrence.


Megaloblastic anemia is a type of macrocytic anemia. It occurs when red blood cells do not form properly due to vitamin B12 or folic acid deficiency. This type of anemia can cause fatigue, pale skin, and a swollen tongue. Other symptoms of vitamin B12 deficiency can also appear.

In general, megaloblastic anemia can be treated by supplementing the lack of vitamins and treating the underlying cause.

VigorTip words

Anemia is not uncommon, and you may have it at some point in your life. If you are diagnosed with megaloblastic anemia or any other type of anemia, it is important to have a thorough evaluation of the cause. Rest assured, megaloblastic anemia is treatable in most cases, and your symptoms should improve with treatment.