B12 and folate are two vitamins that cannot be produced in the body and must be supplied by the diet. They are required for normal red blood cell (RBC) formation, repair of tissues and cells, and synthesis of DNA, the genetic material in cells. B12 is essential for proper nerve function. (For more, see the "What is being tested?" section.)
In those treated for known B12 and folate deficiencies, testing may be used to monitor the effectiveness of treatment. This is especially true for those who cannot properly absorb B12 and/or folate and must have lifelong treatment.
Folate levels in the liquid portion of blood (serum) can vary based on a person's recent diet. Because red blood cells store 95% of circulating folate, a test to measure the folate level within RBCs may be used in addition to or instead of the serum test. Some health practitioners feel that the RBC folate test is a better indicator of long-term folate status and is more clinically relevant than serum folate, but there is not widespread agreement on this.
Other laboratory tests that may be used to help detect B12 and folate deficiencies include homocysteine and methylmelonic acid (MMA). Homocysteine and MMA are elevated in B12 deficiency while only homocysteine, and not MMA, is elevated in folate deficiency. This distinction is important because giving folate to some who is B12-deficient will treat the anemia but does not treat the neurologic damage, which may be irreversible.
B12 and folate levels may be ordered when a complete blood count (CBC) and/or blood smear, done as part of a health checkup or an evaluation for anemia, indicates a low red blood cell (RBC) count with the presence of large RBCs. Specifically, a high mean corpuscular volume (MCV) indicates that the RBCs are enlarged.
Testing for B12 and folate levels may be appropriate when a person has signs and symptoms of a deficiency, such as:
Fatigue, muscle weakness
Loss of appetite
Rapid heart rate, irregular heartbeats
Shortness of breath
Sore tongue and mouth
Tingling, numbness, and/or burning in the feet, hands, arms, and legs (with B12 deficiency)
Confusion or forgetfulness
B12 and folate testing may sometimes be ordered when a person is at risk of a deficiency, such as people with a history of malnutrition or a condition related to malabsorption.
These tests may be ordered on a regular basis for individuals being treated for malnutrition or a B12 or folate deficiency to evaluate the effectiveness of their treatments. For individuals with a condition causing a chronic deficiency, this may be part of a long-term treatment plan.
Normal B12 and folate levels may indicate that a person does not have a deficiency and that the signs and symptoms are likely due to another cause. However, normal levels may reflect the fact that a person's stored B12 and/or folate has not yet been fully depleted.
When a B12 level is normal but a deficiency is still suspected, a health practitioner may order a methylmalonic acid (MMA) test as an early indicator of B12 deficiency.
A low B12 and/or folate level in a person with signs and symptoms indicates that the person has a deficiency but does not necessarily reflect the severity of the anemia or associated neuropathy. Additional tests are usually done to investigate the underlying cause of the deficiency. Some causes of low B12 or folate include:
Dietary deficiency of folate or B12—this is uncommon in the U.S. It may be seen with general malnutrition and in vegans who do not consume any animal products. With the introduction of fortified cereals, breads, and other grain products, folate deficiency is very rare.
Malabsorption—both B12 and folate deficiencies may be seen with conditions that interfere with their absorption in the small intestine. These may include:
Use of some drugs such as metformin, omeprazole, methotrexate or anti-seizure medications such as phenytoin
Increased need—all pregnant women need increased amounts of folate for proper fetal development and are recommended to take 400 micrograms of folic acid per day. People with cancer that has spread (metastasized) or with chronic hemolytic anemia have increased need for folate.
If a person with a B12 or folate deficiency is being treated with supplements (or with B12 injections), then normal or elevated results indicate a response to treatment.
High levels of B12 are uncommon and not usually clinically monitored. However, if someone has a condition such as chronic myeloproliferative neoplasm, diabetes, heart failure, obesity, AIDS, or severe liver disease, then that person may have an increased vitamin B12 level. Ingesting estrogens, vitamin C or vitamin A can also cause high B12 levels.
If a person is deficient in both B12 and folate but only takes folic acid supplements, the B12 deficiency may be masked. The anemia associated with both may be resolved, but the underlying neuropathy will persist.
Intrinsic factor antibodies can interfere with the vitamin B12 test, producing falsely elevated results. If a person has these antibodies in their blood, the results of their B12 test must be interpreted with caution.
The Schilling test was once ordered fairly routinely to confirm a diagnosis of pernicious anemia as the cause of a B12 deficiency. It is rarely, if ever, ordered and has fallen from favor because it involves the administration of radioactive B12. The Schilling test has been replaced, in part, by the measurement of intrinsic factor binding antibodies and parietal cell antibodies, and gastrin.
Since folate deficiency is rarely seen in the U.S., some laboratories no longer offer the folate test.
This article was last reviewed on April 24, 2015. | This article was last modified on April 24, 2015.
The review date indicates when the article was last reviewed from beginning to end to ensure that it reflects the most current science. A review may not require any modifications to the article, so the two dates may not always agree.
The modified date indicates that one or more changes were made to the article. Such changes may or may not result from a full review of the article, so the two dates may not always agree.