B12 and folate are primarily ordered to help diagnose the cause of macrocytic anemia. They are ordered as follow-up tests when large RBCs and a decreased hemoglobin concentration are found during a CBC test. Folate, B12, and an assortment of other tests may be ordered to help evaluate the general health and nutritional status of a patient with signs of significant malnutrition or malabsorption. This may include those with alcoholism and those with disorders associated with malabsorption such as celiac disease, Crohn’s disease, and cystic fibrosis. B12 and folate may also be ordered to help diagnose the cause of mental or behavioral changes, especially in the elderly.

B12 may be ordered with folate, by itself, or with other screening laboratory tests – such as a CMP (comprehensive metabolic panel) – to help diagnose the cause of neuropathy.

In patients with known B12 and folate deficiencies, these tests may be ordered occasionally to help monitor the effectiveness of treatment. This is especially true in patients who cannot absorb B12 and/or folate and must have lifelong treatment.

Either a serum or RBC folate test may be used to help detect a deficiency. Some doctors feel that the RBC folate test is more clinically relevant than serum folate but there is not widespread agreement on this.

B12 and folate are primarily measured when a CBC, done routinely or as part of an evaluation of anemia symptoms, indicates the presence of large RBCs.

When a person, especially an elderly person, exhibits mental or behavioral changes such as irritability, confusion, depression and/or paranoia, B12 and folate may be done to help diagnose the underlying cause. They may also be ordered when a patient has physical symptoms that suggest a B12 or folate deficiency, including dizziness, weakness, fatigue, or a sore mouth or tongue.

When a patient has symptoms suggesting nerve damage or impairment, such as, tingling, burning, or numbness in their hands, arms, legs, and or/feet, a B12 test may be requested to help diagnose the cause and detect the presence of a B12 deficiency. The B12 measurement may be ordered by itself, along with a folate level, and/or in conjunction with other tests such as a CMP.

A B12 and folate may sometimes be ordered as part of a general health evaluation when a patient shows signs of malnutrition or malabsorption or is known to have a disorder that affects nutrient absorption. When a breastfed infant has a B12 or folate deficiency, then the mother may also be tested to see if she has a deficiency that is affecting both her and her child.

When a patient is being treated for a B12 or folate deficiency, he may occasionally be monitored to evaluate the effectiveness of the treatment. In a person with a nutritional deficiency, this may be done as a follow-up to treatment. In a person with a condition causing a chronic deficiency, this may be part of a long term treatment plan.

The doctor is searching for B12 and/or folate deficiencies. If a symptomatic patient has decreased concentrations of B12 and/or folate, then it is likely that he has some degree of deficiency. The test results will indicate the presence of the deficiency, but they do not necessarily reflect the severity of the anemia or neuropathy associated with the deficiency or its underlying cause.

There are a variety of causes of B12 and/or folate deficiencies. They include:

Insufficient intake
The human body stores several years worth of B12 in the liver and it is readily available in the food supply, so a dietary deficiency of this vitamin is extremely rare in the U.S. It may be seen sometimes with general malnutrition, and in vegan vegetarians - those who do not consume any animal products including milk and eggs. It may also be seen in children of vegan vegetarians and breastfed infants. Since they do not have the stores that adults do, deficiencies in children and infants show up fairly quickly.

Folate used to be a common deficiency but with the advent of fortified cereals, breads, and grain products it is less common. Since folate is stored in tissue in smaller quantities than B12, folate must be consumed more regularly than B12.

Malabsorption
Both B12 and Folate deficiencies may be seen with conditions that interfere with their absorption in the small intestine. These may include:

• Celiac disease (an intolerance to wheat that causes inflammation and malabsorption)
• Bacterial overgrowth in the stomach and intestines
• Reduced stomach acid production (stomach acid is necessary tseparate B12 from the protein in food)
• Pernicious anemia, the most common cause of B12 deficiency. Normally a molecule called intrinsic factor is made by parietal cells that line the stomach. B12 binds tintrinsic factor in the stomach, then the resulting compound is absorbed in the intestines. With pernicious anemia, little or no intrinsic factor is produced, preventing the absorption of B12.
• Surgery that removes part of the stomach (and the parietal cells) or the intestines may greatly decrease absorption

Increased loss This may be seen with:

• Liver and kidney disease
• Alcoholism, with alcohol abuse less B12 and folate are absorbed and more are excreted from the kidneys
• Anti-seizure medications such as dilantin and phenytoin can decrease folate as can drugs such as metformin and methotrexate

Increased need All pregnant women need increased amounts of folate for proper fetal development. If a woman has a folate deficiency prior tpregnancy, it will be intensified during gestation, and may lead to premature birth and neural tube birth defects in the child.

If a patient with a B12 or folate deficiency is being treated with supplements (or with B12 injections), then normal or elevated results indicate a response ttreatment.

If a patient 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 (nerve damage) will persist.

The Schilling test was once ordered fairly routinely to confirm a diagnosis of pernicious anemia as the cause of a B12 deficiency. It is still ordered occasionally but 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.