Macrocytosis Is a Condition of Enlarged Red Blood Cells (2023)

Macrocytosis is when a person's red blood cells (RBCs) are larger than normal and not functioning as they should. Macrocytosis is also called megalocytosis or macrocythemia.

Macrocytosis is usually caused by low vitamin B12 or folate levels. It can also occur with other conditions, including liver disease and cancer, or from taking certain medications.

This article discusses the symptoms and causes of macrocytosis. It also looks at how this condition is diagnosed and treated.

Macrocytosis Is a Condition of Enlarged Red Blood Cells (1)

What Are the Symptoms of Macrocytosis?

Generally, macrocytosis is associated with anemia (macrocytic anemia), which is diminished RBC count. The condition causes a decrease in oxygen delivered to the body’s tissues. Usually, the symptoms are mild to moderate, but sometimes the effects can be severe.

Common symptoms of macrocytosis include:

  • Fatigue
  • Headaches
  • Difficulty concentrating
  • Lightheadedness or dizziness
  • Pale skin

These symptoms can wax and wane in severity, and they may linger for months or longer before you feel the need to see a healthcare provider.

For example, you might feel energetic when you wake up from sleeping but then become more tired than usual as the day goes on. Or you may have some days of feeling more worn out than others. And illnesses, such as the common cold, can make you especially tired when you have macrocytosis.

What Is Macrocytic Anemia?

Associated Symptoms

Often macrocytosis is accompanied by other symptoms related to its cause.Some of these include:

  • Diarrhea, which can be a sign of malabsorption, can make you deficient in vitamin B12 and other nutrients
  • Enlarged tongue (glossitis) can develop due to vitamin B12 deficiency
  • Peripheral neuropathy causes numbness of the fingers and toes and can result from a vitamin B12 deficiency or alcoholism
  • Weakness can develop from an iron deficiency
  • Bruising or bleeding can occur due to leukemia, cancer of the blood and bone marrow
  • Enlarged abdomen due to splenomegaly (enlarged spleen) can occur with RBC breakdown
  • Jaundice (yellow skin and whites of the eyes) can result from liver failure

If you have these symptoms along with fatigue or other direct signs of macrocytosis, let your healthcare provider know so you can get the right diagnostic testing.

What Causes Macrocytosis?

There are several causes of macrocytosis. The most common cause is a deficiency in vitamin B12 and folate (vitamin B9). These two vitamins cannot be produced in the body and must come from your diet.

There are several potential causes of vitamin B12 deficiency, including:

  • Insufficient amounts in your diet (dietary sources include liver, beef, chicken, fish, dairy products, eggs, food fortified with vitamin B12)
  • Malabsorption from the intestine, such as from infection, celiac disease (an immune reaction from eating gluten, a protein in wheat, barley and rye), or inflammation
  • Pernicious anemia, an uncommon condition in which the absorption of vitamin B12 is impaired due to a lack of intrinsic factor, a protein that is needed to absorb this vitamin

Potential causes of folate deficiency include:

  • Insufficient folic acid in the diet (sources include leafy green vegetables, fruit, meat, and fortified cereals)
  • Drinking too much alcohol
  • Conditions affecting the lower digestive tract
  • Cancer
  • Some medications
  • Pregnancy

Other causes of macrocytosis include:

  • Alcoholism
  • Liver disease
  • Hypothyroidism (underactive thyroid)
  • Leukemia
  • Bone marrow disease
  • Myelodysplastic syndrome (MDS), a condition in which the blood cells do not develop normally
  • Some medications, including those used in chemotherapy
  • Hemolysis (breakdown of RBCs), resulting in rapid production of RBCs
  • Lesch-Nyhan syndrome, an inherited metabolic disorder characterized by overproduction of uric acid


The red blood cells in the body can be large for several reasons. Without vitamin B12 and folate, RBCs remain in an immature stage of development, which is larger than their mature size.

With some metabolic problems, such as those caused by alcoholism or liver disease, fat can accumulate in the RBCs, causing them to be enlarged. Problems with the bone marrow or problems that result from chemotherapy can prevent the RBCs from maturing properly as they form.

How Is Macrocytosis Diagnosed?

Macrocytosis is generally detected with a complete blood count test, which may be ordered to evaluate symptoms or as a routine screening. If you are found to have enlarged RBCs, you may also need to have diagnostic tests to determine the cause.

Generally, macrocytosis results from anemia, but macrocytosis without anemia also can occur. Either way, you may need the same diagnostic tests to determine the cause.

Blood measurements that can identify macrocytosis include the following, which are commonly reported as part of the complete blood count (CBC):

  • Mean corpuscular volume (MCV) measures the average size of the RBCs, which is usually greater than 100 femtoliter (fL) in macrocytosis
  • Red cell distribution width (RDW) measures the variation in size of the RBCs; a normal range for RDW is 11.8%–14.6%, and it is expected to be high in macrocytosis due to the variation in RBC size

Red Blood Cell Indices: Types, Uses, Results

Depending on your other symptoms or medical conditions, your healthcare provider may order additional tests to identify the cause of your macrocytosis. These include looking at the white blood cell count, which is commonly part of the CBC.

Tests you might have:

  • Vitamin B12 level
  • Liver function tests
  • Bone marrow biopsy

How Is Macrocytosis Treated?

The treatment of macrocytosis centers on correcting the cause, when possible. Oftentimes, vitamin B12 and/or folate supplementation will correct the problem. If you cannot absorb vitamin B12 adequately due to gastrointestinal issues, you may need to get B12 injections rather than taking a supplement by mouth.

Your healthcare provider may prescribe another treatment if your macrocytosis has a different cause.

Vitamin B12 Deficiency: Symptoms, Causes, Risks


Preventing macrocytosis generally involves making sure you get adequate nutrients in your diet. Having regular medical checkups is important as well. Your healthcare provider may detect early signs of the condition and initiate treatment before it begins to affect your quality of life.

If you have a medical condition that could predispose you to macrocytosis, it’s especially important that you have regular medical evaluations so that problems such as macrocytosis can be identified and treated at early stages.


Macrocytosis means that your red blood cells are larger than normal. It is associated with anemia, when you also have insufficient numbers of properly functioning red blood cells.

Macrocytosis is usually caused by low vitamin B12 or folate levels, but there are other reasons it develops, including liver disease, alcoholism, and from taking certain medications. Treatment will depend on the underlying cause and may include taking in additional vitamin B12 and folate.

6 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

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  2. Pawlak R. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians? Am J Prev Med. 2015;48(6):e11-26. doi:10.1016/j.amepre.2015.02.009

  3. Toprak B, Yalcın HZ, Colak A. Vitamin B12 and folate deficiency: should we use a different cutoff value for hematologic disorders? Int J Lab Hematol. 2014;36(4):409-14. doi:10.1111/ijlh.12158

  4. Johns Hopkins Medicine. Folate-deficiency anemia.

  5. Nagao T, Hirokawa M. Diagnosis and treatment of macrocytic anemias in adults. J Gen Fam Med. 2017;18(5):200-204. doi:10.1002/jgf2.31

  6. Cakmakli HF, Torres RJ, Menendez A, et al. Macrocytic anemia in Lesch-Nyhan disease and its variants. Genet Med. 2019;21(2):353-360. doi:10.1038/s41436-018-0053-1

Macrocytosis Is a Condition of Enlarged Red Blood Cells (2)

By Heidi Moawad, MD
Heidi Moawad is a neurologist and expert in the field of brain health and neurological disorders. Dr. Moawad regularly writes and edits health and career content for medical books and publications.

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