The Mean Corpuscular Volume (MCV) is a measurement included in a standard complete blood count (CBC) that reflects the average size of your red blood cells. A high MCV indicates that the red blood cells are larger than normal, a condition called macrocytosis. This finding suggests that the cells produced in the bone marrow are not maturing or dividing correctly, or that the cell membranes have been altered. Macrocytosis is a laboratory finding, not a diagnosis, that points toward potential underlying health issues. While it can be associated with a form of anemia, it often requires follow-up testing to determine the specific cause.
Nutritional Deficiencies Causing High MCV
The most frequent causes of an elevated MCV are deficiencies in two B vitamins: Vitamin B12 (cobalamin) and Folate (Vitamin B9). Both nutrients are integral cofactors in DNA synthesis and cell division within the bone marrow. When either B12 or Folate is lacking, red blood cell precursors cannot complete their final stages of division.
This failure results in the formation of fewer but abnormally large, immature red blood cells, known as megaloblastic anemia. These enlarged cells, called macro-ovalocytes, also exhibit a shorter lifespan. Vitamin B12 deficiency is often caused by poor absorption, such as in pernicious anemia where the body fails to produce intrinsic factor necessary for B12 uptake. Severe B12 deficiency can also lead to neurological symptoms like tingling or numbness, which are not seen in folate deficiency.
Folate deficiency is usually related to insufficient dietary intake, though certain medical conditions or medications can interfere with its absorption. Folate and B12 work together in a metabolic pathway that ensures components for DNA are available. When this process stalls, the resulting macrocytosis typically sees the MCV rise into a higher range, often between 116 and 130 femtoliters (fL).
Non-Nutritional Medical Conditions
Other medical conditions can cause red blood cells to swell, resulting in non-megaloblastic macrocytosis. Chronic liver disease, particularly cirrhosis, frequently causes an elevated MCV due to alterations in the red blood cell membrane. Liver dysfunction impairs lipid metabolism, leading to excess cholesterol and fat molecules depositing on the red blood cell surface, which increases their volume. This type of macrocytosis usually presents with a milder MCV elevation, often in the 100 to 116 fL range.
Chronic alcohol consumption is another common cause, acting as a direct toxin to the bone marrow and suppressing healthy red blood cell production. Alcohol can also interfere with folate absorption, creating a combined effect. Macrocytosis caused by alcohol use may occur even before significant liver damage has developed. Hypothyroidism can slow the body’s overall metabolism, indirectly affecting the bone marrow’s ability to produce red blood cells.
Myelodysplastic Syndromes (MDS) are serious, less common disorders involving dysfunction within the bone marrow. Damaged stem cells produce structurally abnormal and ineffective cells, including large red blood cells. Certain medications, such as chemotherapy drugs and some antiviral agents, can also cause macrocytosis by interfering with DNA synthesis, similar to vitamin deficiencies.
What Happens After Macrocytosis is Detected
Detecting a high MCV on a complete blood count initiates an investigation to pinpoint the underlying cause. A physician will first conduct a thorough symptom review, asking about common indicators of anemia, such as fatigue, weakness, and shortness of breath. They will also inquire about diet, alcohol intake, and current medications, as these frequently contribute to macrocytosis.
Follow-up blood tests are then ordered to confirm or rule out common causes. These diagnostic tests include measuring the serum levels of Vitamin B12 and Folate. Further analysis may involve checking liver function tests (LFTs) to assess for liver disease and thyroid-stimulating hormone (TSH) to screen for hypothyroidism.
To confirm a functional B12 deficiency, even if serum levels are normal, doctors often order tests for Methylmalonic Acid (MMA) and Homocysteine. Since B12 is required to metabolize MMA, an elevated MMA level is a highly specific indicator of functional B12 deficiency. Treatment ranges from simple dietary supplements for a confirmed deficiency to managing chronic diseases or cessation of alcohol use.