Vitamin B12

Vitamin B12 and folate are separate tests often used in conjunction to detect deficiencies and to help diagnose the cause of certain anemias, such as pernicious anemia, an autoimmune disease that affects the absorption of B12.

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.)

B12 and folate tests may also be used to help evaluate an individual with an altered mental state or other behavioral changes, especially in the elderly. A B12 test may be ordered with folate, by itself, or with other screening laboratory tests such as a complete blood count (CBC), comprehensive metabolic panel (CMP), antinuclear antibody (ANA), C-reactive protein (CRP) and rheumatoid factor (RF) to help determine why a person shows signs and symptoms of a condition affecting nerves (neuropathy).

Additionally, B12 and folate tests may be used in conjunction with an assortment of other tests to help evaluate the general health and nutritional status of a person with signs and symptoms of significant malnutrition or dietary malabsorption. This may include people with, for example, alcoholism, liver disease, gastric cancer, or individuals with malabsorption conditions such as celiac disease, inflammatory bowel disease, or cystic fibrosis.

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:

• Diarrhea
• Dizziness
• Fatigue, muscle weakness
• Loss of appetite
• Pale skin
• 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
• Paranoia

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:
  • Pernicious anemia, the most common cause of B12 deficiency
  • Celiac disease
  • Inflammatory bowel disease, including Crohns disease and ulcerative colitis
  • Bacterial overgrowth or the presence of parasites, such as tapeworms, in the intestines
  • Reduced stomach acid production from long-term use of antacids or H2 proton pump inhibitors
  • Surgery that removes part of the stomach, such as gastric bypass, or the intestines may greatly decrease absorption.
  • Pancreatic insufficiency
• Heavy drinking or chronic alcoholism
• 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.
• Smoking

(For additional information, see the article Vitamin B12 and Folate Deficiencies.)

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.