What Are the Causes of Macrocytic Anemia?


Macrocytic anemia refers to the presence of enlarged red blood cells (RBCs) in a lab sample. This finding is often the only sign that a patient is experiencing a deficiency of B12 or folate, two important nutrients for the health of the nervous system. Macrocytic anemia is defined as a Mean Cell Volume greater than 95 cubic millimeters (each lab sets its own range, so this number may vary).

What Are the Causes of Macrocytic Anemia?
What Are the Causes of Macrocytic Anemia? (Image: Chad Baker/Photodisc/Getty Images)


Macrocytic anemia is a sign that the RBCs are not maturing properly. These cells lose their nucleus and decrease in size during the normal growth process. The normal RBC is shaped like a biconcave disc. Without the necessary nutrients, cells will not attain this shape. The most common cause of macrocytic anemia is a lack of Vitamin B12 or folate (another B vitamin). The condition can also be a side effect of chemotherapy drugs, and is a common consequence of heavy alcohol use.

B12 Vitamins
B12 Vitamins (Image: Jupiterimages/Comstock/Getty Images)

B12 Deficiency

Vitamin B12 is present in meat and animal foods. The vitamin is absorbed in the small intestine with the help of intrinsic factor, produced in the stomach lining. Deficiency occurs for two main reasons--lack of B12 in the diet and problems with absorbing B12.

There are other considerations to note when it comes to B12 deficiency. Diets without animal protein do not provide adequate amounts of B12. Vegans are at risk for macrocytic anemia, and should consider taking B12 supplements. Also, if intrinsic factor is not present, Vitamin B12 cannot be absorbed. This condition is known as pernicious anemia, and is treated with B12 injections. Finally, alcohol interferes with the absorption of B12, and chronic heavy drinkers are at increased risk for macrocytic anemia.

Egg on toast
Egg on toast (Image: Jupiterimages/Polka Dot/Getty Images)

Folate Deficiency

Folate is abundant in green leafy vegetables, liver and mushrooms. Food must be cooked to make folate available, but too much cooking destroys this vitamin. Absorption of folate takes place in the small intestine.

Deficiency occurs for four main reasons--lack of folate in the diet, problems absorbing folate, difficulty utilizing the vitamin and increased requirement.

Also, diets without fresh, gently cooked leafy vegetables do not provide enough folate. Patients with celiac disease have trouble absorbing folate because this disease damages the cells where absorption takes place. It is also important to note that several drugs interfere with absorption, including birth control pills.

Several chemotherapy drugs, including methotrexate, interfere with the body's use of folate. This prevents cancer cells from building DNA, and has the same effect on many of the body's cells, including RBCs and the cells of the digestive tract. Alcohol also interferes with the use of folate.

Finally, pregnant and breastfeeding women have an increased need for folate, because it is necessary to the formation of the spine and nervous system of the growing baby.

Mushrooms (Image: Photos.com/Photos.com/Getty Images)


Macrocytic anemia is an early sign of B12 and/or folate deficiency. B12 is necessary to the health of the nerves. Long-term deficiency can cause numbness and tingling in the fingers and toes. Over time, these symptoms will progress upwards, in a pattern known as "glove and stocking" distribution. Paranoia and confusion can occur in very advanced cases. Macrocytic anemia is often the first sign of B12 deficiency, appearing before the patient experiences nerve symptoms.

Also, folate is necessary to the developing nervous system. Lack of folate during pregnancy can result in neural tube defects such as spina bifida in the infant. Most adults have no obvious symptoms of folate deficiency, so a diagnosis of macrocytic anemia may be the only sign that a problem exists.

Woman with hand on arm
Woman with hand on arm (Image: Pixland/Pixland/Getty Images)


Macrocytic anemia can be prevented by eating a balanced diet, containing animal proteins (for B12) and green leafy vegetables (for folate).

People in the following categories should consider a B12 supplement--vegans and others who eat very few animal products and heavy drinkers; while people in the following categories should consider a folic acid supplement--those who don't eat enough green leafy vegetables, those with celiac disease heavy drinkers, pregnant and lactating women. It is recommended that all women of childbearing age take this supplement, as neural tube development happens early in pregnancy, before some women realize that they are pregnant.

Woman making salad
Woman making salad (Image: Stockbyte/Stockbyte/Getty Images)


Folic acid supplementation will mask the main sign of B12 deficiency by "curing" the macrocytic anemia. For this reason, it is wise to take a combined B12/folic acid supplement. Patients on methotrexate and other chemotherapy drugs should consult their doctors before supplementing with B12 and folic acid. Most multivitamins contain B12 and folic acid. Consult your healthcare practitioner to determine if the amount in your multivitamin is enough for your needs.

Man talking with doctor
Man talking with doctor (Image: Jupiterimages/Creatas/Getty Images)

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