Vitamin B12 and Folate
When you have large red blood cells, specifically when you have symptoms of anaemia and/or of neuropathy. When you are being treated for vitamin B12 or folate deficiency
A blood sample taken from a vein in your arm
Fasting is not required for a standard vitamin B12 test. Certain medicines and pregnancy may affect the test results; your heathcare professional will advise you on which ones to stop taking.
These tests measure the concentration of folate and vitamin B12 in the serum (liquid portion of the blood).
Vitamin B12 and folate are both part of the B complex of vitamins. Folate is found in leafy green vegetables, citrus fruits, dry beans and peas, liver, and yeast. Vitamin B12 is found in animal products such as red meat, fish, poultry, milk, and eggs. In recent years fortified cereals, breads, and other grain products has also become important dietary sources of folate (identified as "folic acid" on nutritional labels).
Both vitamin B12 and folate are necessary for normal red cell formation, tissue and cellular repair, and DNA synthesis. Vitamin B12 is also important for nerve health, while folate is necessary for cell division such as is seen in a foetus during pregnancy. A deficiency in either vitamin B12 or folate can lead to macrocytic anaemia, where red cells are reduced but macrocytic (abnormally large). Specifically a bone marrow test may show megaloblastic anaemia, where immature red cells called megaloblasts may be seen. It is usually unnecessary for a bone marrow test to be performed for diagnosis of vitamin B12 deficiency.
Vitamin B12 deficiency can also result in varying degrees of neuropathy, nerve damage that can cause tingling and numbness in the patient's hands and feet. In severe vitamin B12 deficiency, a more serious nerve damage may occur known as subacute combined degeneration of the cord or SACD, where severe weakness and incoordination may occur. Subtle deterioration in eyesight and mental ability may occur. Folate deficiency in early pregnancy can cause neural tube defects such as spina bifida in a growing foetus.
There are a variety of causes of vitamin B12 and/or folate deficiencies. They include:
The human body stores several years’ worth of vitamin B12 in the liver. Vitamin B12 is widely available in non-vegan foods, so a dietary deficiency of this vitamin is rare. 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 and breastfed infants of vegan vegetarians. Since they do not have the stores that adults do, deficiencies in children and infants show up fairly quickly. Vitamin B12 deficiency is extremely uncommon in children but can be rarely seen with genetic defects involving vitamin B12 metabolism.
Folate deficiency used to be common but with the advent of fortified cereals, breads, and grain products it is less so. Since folate is stored in tissue in smaller quantities than vitamin B12, folate must be consumed more regularly than vitamin B12.
Both vitamin B12 and folate deficiencies may be seen with conditions that interfere with their absorption in the small intestine. These may include:
- Coeliac disease (specifically folate deficiency)
- Bacterial overgrowth in the stomach and intestines
- Reduced stomach acid production (stomach acid is necessary to separate B12 from the protein in food)
- An autoimmune disorder called pernicious anaemia, the most common cause of vitamin B12 deficiency. Normally a molecule called intrinsic factor is made by parietal cells that line the stomach. B12 binds to intrinsic factor in the stomach, and the resulting complex is absorbed in the small intestines (ileum). With pernicious anaemia, antibodies attack parietal cells, reducing intrinsic factor production, or attack intrinsic factor, blocking its action, in either case preventing the efficient absorption of B12.
- Surgery that removes part of the stomach (and the parietal cells) or the intestines may greatly decrease absorption. This includes gastric banding procedures.
- Crohns disease affecting the end of the small intestine (ileum)
- the type 2 diabetes drug Metformin may affect B12 levels
- Alcoholism, with alcohol abuse less B12 and folate are absorbed and more are excreted from the kidneys
All pregnant women need increased amounts of folate for proper fetal development. If a woman has a folate deficiency prior to pregnancy, it will be intensified during gestation, and may lead to premature birth and neural tube defects in the child. Folic acid supplementation should be started pre-conception ideally and continued until 12 weeks pregnant (400 micrograms daily).
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
No special preparation for a standard vitamin B12 blood test.
How is it used?
Vitamin B12 and folate are primarily requested to help diagnose the cause of macrocytic anaemia. They can be requested as follow-up tests when large red cells and a decreased haemoglobin concentration are found during a FBC test. Folate and vitamin B12 may be used to help evaluate the 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 coeliac disease, Crohn's disease, and cystic fibrosis. Vitamin B12 may also be used to help diagnose the cause of mental or behavioural changes, especially in the elderly.
In patients with known vitamin B12 and folate deficiencies, these tests may be used occasionally to help monitor the effectiveness of treatment. This is especially true in patients who cannot absorb vitamin B12 and/or folate and must have lifelong treatment.
When is it requested?
Vitamin B12 and folate are primarily measured when a FBC, done routinely or as part of an evaluation of anaemia, indicates the presence of large red RBCs.
When a person, especially an elderly person, exhibits mental or behavioural changes such as irritability, confusion, depression and/or paranoia, vitamin B12 may be requested to help diagnose the underlying cause. They may also be used when a patient has physical symptoms that suggest 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, numbness or abnormal sensations in the toes or fingertips and weakness or clumsiness in the hands or feet, a vitamin B12 test may be requested to help diagnose the cause and to detect the presence of a vitamin B12 deficiency.
B12 and folate may sometimes be requested 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 vitamin B12 or folate deficiency, 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 vitamin B12 or folate deficiency, they 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.
What does the test result mean?
The doctor is looking for vitamin B12 and/or folate deficiency. If a symptomatic patient has decreased concentrations of vitamin B12 and/or folate, then it is likely that he has some degree of deficiency. The test results indicate the presence of deficiency, but do not necessarily reflect the severity of the anaemia or neuropathy associated with the deficiency.
It is possible to have low B12 or folate levels on blood tests without any clinical problems. In the case of B12 measurements, this partly reflects a weakness in the standard B12 blood test (also called serum cobalamin) which does not directly measure whether there is an actual deficiency of active vitamin B12 in the cells of the body. Second-line tests that might help determine true deficiency include plasma/serum methylmalonic acid and homocysteine. Serum holotranscobalamin (also referred to as ‘active’ B12) is an alternative first-line test, but some uncertainty may still exist. The availability of these second-line tests is currently limited.
If a patient with a vitamin B12 or folate deficiency is being treated with oral supplements (or with intramuscular B12 injections), then normal or elevated results indicate a response to treatment. It is not standard practice to monitor patients having regular B12 injections.
High levels of B12 and folate are not usually monitored. Increased B12 may be seen in conditions such as leukaemia or liver dysfunction. Increased folate may be seen with pernicious anaemia, vegetarian diets, or with a condition called bacterial overgrowth syndrome where bacteria multiply in the upper bowels.
Is there anything else I should know?
If a patient is deficient in both vitamin B12 and folate, but only takes folic acid supplements, the vitamin B12 deficiency may be masked. The anaemia associated with both may be resolved, but the underlying neuropathy (nerve damage) will persist and may deteriorate.
In the past the Schilling test was used to confirm a diagnosis of pernicious anaemia by demonstrating abnormal B12 absorption in the small intestine however it is no longer available. The Schilling test has been replaced, by the measurement of intrinsic factor binding antibodies although these may only be seen in about 50% of patients with pernicious anaemia.
B12 levels may be reduced in women taking oestrogen containing oral contraceptives and in pregnancy, however this does not necessarily reflect a true deficiency of the vitamin in the body, demonstrating that the standard B12 laboratory test can be unreliable under some circumstances.
Can taking too many vitamin B12 and folic acid supplements hurt me?
Is there a difference between folate and folic acid?