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This article waslast modified on 10 January 2020.
What is it?

B12 and folate are B complex vitamins that are necessary for normal red blood cell formation, tissue and cellular repair, and DNA synthesis. A B12 and/or folate deficiency reflects a chronic shortage of one or both of these vitamins. Since the body stores 3 to 5 years’ worth of B12 and several months’ supply of folate in the liver, deficiencies and their associated symptoms can take months to years to manifest in adults. Infants and children, however, will show signs of deficiency more rapidly as they have not yet established extensive reserves.

Over time, a deficiency in either B12 or folate can lead to macrocytic ('large cell') anaemia, a condition characterised by the production of fewer, but larger red blood cells resulting in a decreased ability to carry oxygen. Due to the anaemia, patients may be weak, light-headed, tired and short of breath. A deficiency in B12 can also result in varying degrees of neuropathy (nerve damage that can cause tingling and numbness in the patient’s hands and feet) and mental changes that range from confusion and irritability to severe dementia.

Pregnant women need increased amounts of folate for proper development of the baby. If a woman has a folate deficiency before pregnancy, it will become worse during gestation and may lead to premature birth and neural tube birth defects, such as spina bifida, in the child.


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About Vitamin B12 and Folate Deficiency
  • Symptoms

    The symptoms associated with B12 and folate deficiency are often subtle and nonspecific. They are related to the resulting anaemia and nerve involvement. If there is an underlying medical cause of the deficiency, usually a bowel disorder, patients may also have symptoms of that condition. Patients with an early deficiency may be diagnosed using blood tests before they experience any obvious symptoms; others may experience a variety of mild to severe symptoms that can include:

    • Confusion, memory loss
    • Paranoia
    • Dizziness
    • Fatigue, weakness
    • Pallor
    • Rapid heart rate
    • Shortness of breath
    • Sore tongue and mouth
    • Tingling, numbness, and/or burning in the feet, hands, arms, and legs (with B12)
    • Loss of appetite
    • Diarrhoea and/or malabsorption if there is an underlying bowel disorder


  • Causes

    B12 and folate deficiency may be due to insufficient intake, inadequate absorption, increased loss, or to increased need. Folate is found in leafy green vegetables, citrus fruits, dry beans, yeast, and fortified cereals. Folic acid is the synthetic form of folate that is used in medications and supplements. B12 is found in animal proteins such as red meat, fish, poultry, milk, eggs, and in fortified cereals. Deficiency due to insufficient intake of B12 is uncommon but may be seen in vegans (who do not consume any animal products) and their breast-fed infants.

    B12 deficiency can be caused by insufficient stomach acid, which is necessary to separate B12 from dietary protein. This is the most common cause of B12 deficiency in the elderly and in people taking medication that suppresses gastric acid production. Deficiency may also be due to a lack of intrinsic factor, a substance produced by special cells in the stomach called parietal cells. Intrinsic factor binds to B12 to enable absorption by the intestines. Without it, very little B12 can be absorbed. An autoimmune condition called pernicious anaemia involves damage to the parietal cells, resulting in decreased production of intrinsic factor.

    Both B12 and folate deficiencies can also arise with diseases or conditions of the gut that cause general malabsorption. These include coeliac disease (an intolerance to gluten that causes inflammation and malabsorption), bacterial overgrowth in the stomach and intestines, or surgery that removes part of the stomach, the parietal cells, or the intestines (including some forms of surgery used for treating obesity).

    Chronic disorders such as liver or kidney disease, and alcoholism can lead to decreased levels of B12 or folate, as can medications such as phenytoin, metformin (diabetic therapy), trimethoprim (an antibiotic sometimes given long-term) or methotrexate (an arthritis treatment).

    All pregnant women need increased amounts of folate for proper development of the baby. Mothers with a low folate intake before pregnancy, or in the early weeks, are at increased risk of having a baby with a neural tube birth defect (spina bifida or anencephaly).


  • Tests

    The anaemia and large red blood cells of a vitamin B12 or folate deficiency are frequently detected during a routine FBC (Full Blood Count) test. Laboratory testing is used to detect a deficiency, determine its severity, establish the underlying cause of the deficiency, and to monitor the effectiveness of treatment.

    Laboratory Tests
    Frequently requested to diagnose and monitor B12 and folate deficiency:

    • FBC (Full Blood Count). A group of tests requested routinely to screen for blood cell abnormalities. It measures cell types, quantities, and characteristics. With both B12 and folate deficiency anaemia, the amount of haemoglobin may be low and the red blood cells (RBCs) are abnormally large (macrocytic or megaloblastic). White blood cells and platelets also may be decreased.
    • Total B12. If low, a deficiency is indicated, but it does not identify the cause. If normal, a folate deficiency may still be present. If borderline low, measurement of active B12 may be requested. Measurements of total B12 can be helpful to monitor treatment.
    • Active B12. This accounts for about a quarter of the B12 circulating in blood.  Although more difficult to perform, the test is thought to be a better indicator of the availability of B12 to body tissues. It is most useful when total B12 levels are in the borderline low range.
    • Folate. Either serum or RBC folate may be tested. Serum folate is very dependent on nutrition over the previous days and falls rapidly after fasting, even if there are adequate tissue stores. Red cell folate is less affected by short term food intake but is more difficult to measure. If both are low, a deficiency is very likely. If normal, a B12 deficiency may still be present. Measurements can be used to monitor the effectiveness of treatment. High serum folate may be a sign of bacterial overgrowth in the bowels, as bacteria can produce folate.

    Seldom but sometimes used to diagnose B12 and folate deficiency:

    • Methylmalonic Acid (MMA). A blood or urine test, sometimes used to help detect mild or early B12 deficiency, or to exclude true B12 deficiency in cases of a misleadingly low laboratory B12 result. MMA production increases if there is inadequate B12 available to the tissues.
    • Homocysteine. Occasionally requested. This is an amino acid that increases in blood if there is inadequate B12 or folate available to the tissues.

    Requested to help determine the cause of a B12 deficiency:

    • Schilling Test. Once frequently used to confirm a diagnosis of pernicious anaemia. This test is no longer available in the UK.
    • Intrinsic Factor (Blocking) Antibody. A protein that prevents B12 from binding to intrinsic factor. It is present in more than 50 percent of all patients with pernicious anaemia. A positive result confirms a diagnosis of pernicious anaemia
    • Parietal Cell Antibody. An antibody against the parietal cells that produce intrinsic factor. It is present in nearly all cases of pernicious anaemia but may also be seen in other disorders. A negative result makes the diagnosis of pernicious anaemia unlikely.


  • Treatment

    Treatment for B12 and folate deficiencies frequently involves long-term or lifetime supplementation. Patients who lack intrinsic factor or have conditions causing general malabsorption usually require B12 injections. A few patients may absorb enough B12 from high-dose tablets to avoid regular injections. Folate is given as folic acid and is an oral supplement. In the UK doctors recommend that all women contemplating having a child should take folate supplements before and during pregnancy to ensure that they have sufficient stores for normal development of the baby.

    After starting treatment - the anaemia improves after a few weeks.  However, the neuropathy can take several months to improve and may never get fully better.

    If a patient is deficient in both B12 and folate, he or she will require replenishment of both. If a patient with B12 deficiency takes only folic acid supplements, the anaemia may resolve but the underlying neuropathy (nerve damage) caused by the B12 deficiency will persist and may worsen dramatically and irreversibly.