Vitamin B₁₂ (cobalamins), with folate, is necessary for the formation and maturation of red blood cells and the synthesis of DNA (deoxyribonucleic acid), which is the genetic material of cells. Vitamin B₁₂ is also necessary for normal nerve function. Unlike most other vitamins, B₁₂ is stored in substantial amounts, mainly in the liver, until it is needed by the body. If a person stops consuming the vitamin, the body's stores of this vitamin usually take about 3 to 5 years to exhaust.

People should not take high doses of vitamin B₁₂ as a cure-all, but otherwise the vitamin does not appear to be toxic.

Vitamin B₁₂ Deficiency

• Anemia develops, causing paleness, weakness, fatigue, and, if severe, shortness of breath and dizziness.
• A severe deficiency may damage nerves, causing tingling or loss of sensation in the hands and feet, muscle weakness, loss of reflexes, difficulty walking, confusion, and dementia.
• The diagnosis is based on blood tests.
• When high doses of vitamin B₁₂ supplements are taken, symptoms due to anemia tend to resolve.
• Symptoms due to nerve damage, such as dementia in older people, may persist.

Vitamin B₁₂ occurs in foods that come from animals. Normally, vitamin B₁₂ is readily absorbed in the last part of the small intestine (ileum), which leads to the large intestine. However, to be absorbed, the vitamin must combine with intrinsic factor, a protein produced in the stomach. Without intrinsic factor, vitamin B₁₂ moves through the intestine and is excreted in stool.

Because vitamin B₁₂ is necessary for the formation of mature blood cells, deficiency of this vitamin can result in anemia. The anemia is characterized by abnormally large red blood cells (macrocytes) and white blood cells with abnormal nuclei. Anemia may not develop until 3 to 5 years after the deficiency begins because a large amount of vitamin B₁₂ is stored in the liver.

Vitamin B₁₂ deficiency can cause nerve damage (neuropathy) even when no anemia develops, particularly in people older than 60.

Causes

Vitamin B₁₂ deficiency can result when people do not consume enough vitamin B₁₂ or when the body does not absorb or store enough of the vitamin.

Inadequate consumption: Vitamin B₁₂ deficiency develops in people who do not consume any animal products (vegans) unless they take supplements. If a vegan mother breastfeeds her infant, the infant is at risk of vitamin B₁₂ deficiency.

Inadequate absorption: The most common cause of vitamin B₁₂ deficiency is inadequate absorption. The following conditions can cause absorption to be inadequate:

• Overgrowth of bacteria in part of the small intestine
• Malabsorption disorders (such as inflammatory bowel disease, celiac disease, or certain pancreatic disorders)
• Inflammatory bowel disease
• Fish tapeworm infection
• AIDS
• Surgery that removes the part of the small intestine where vitamin B₁₂ is absorbed
• Drugs such as antacids and metforminSome Trade Names
  GLUCOPHAGE
  (used to treat diabetes)
• Lack of intrinsic factor
• Decreased stomach acidity (common among older people)

Intrinsic factor may be lacking because abnormal antibodies, produced by an overactive immune system, attack and destroy the stomach cells that produce intrinsic factor—an autoimmune reaction called autoimmune metaplastic atrophic gastritis. Intrinsic factor may be lacking because the part of the stomach where intrinsic factor is produced was surgically removed. Vitamin B₁₂ deficiency due to lack of intrinsic factor causes a type of anemia called pernicious anemia.

Among older people, absorption may be inadequate because stomach acidity is decreased. Decreased stomach acidity reduces the body's ability to remove vitamin B₁₂ from the protein in meat. However, the vitamin B₁₂ found in vitamin supplements can continue to be well absorbed even in people with decreased stomach acid.

Inadequate storage: Liver disorders may interfere with the storage of vitamin B₁₂.

Symptoms

Anemia due to vitamin B₁₂ deficiency develops gradually, allowing the body to adapt somewhat. Consequently, symptoms may be mild even when anemia is severe. Symptoms of anemia are paleness, weakness, and fatigue. If severe, anemia causes shortness of breath, dizziness, and a rapid heart rate. Occasionally, the spleen and liver enlarge. Younger adults who have pernicious anemia (due to lack of intrinsic factor) are more likely to develop stomach and other gastrointestinal cancers.

In people with nerve damage, the legs are affected earlier and more often than the arms. Tingling is felt in the feet and hands, or sensation in the legs, feet, and hands is lost. People become less able to tell where their arms and legs are (position sense) and to feel vibrations. Mild to moderate muscle weakness develops, and reflexes may be lost. Walking becomes difficult. Some people become confused, irritable, and mildly depressed. Advanced vitamin B₁₂ deficiency may lead to delirium, paranoia, and impaired mental function, including dementia.

Diagnosis

Usually, vitamin B₁₂ deficiency is suspected when routine blood tests detect large red blood cells. Doctors sometimes suspect it when people have typical symptoms of nerve damage, such as tingling or loss of sensation. If the deficiency is suspected, the level of vitamin B₁₂ in the blood is measured. Usually, doctors also measure the blood level of folate to rule out folate deficiency, which can also result in large red blood cells.

If vitamin B₁₂ deficiency is confirmed in an older person, no other tests are done because the cause, such as low stomach acidity, is usually not serious. In a younger person, other tests, including other blood tests, may be done to determine the cause. These tests (including the Schilling test) usually focus on intrinsic factor. For the Schilling test, people are given two doses of vitamin B₁₂. The first is labeled with a small amount of a radioactive substance and is taken by mouth. The second is an injection of a larger amount of vitamin B₁₂ that is not radioactively labeled. After the injection is given, the amount of labeled vitamin B₁₂ in urine is measured to determine whether the body absorbs a normal amount of the vitamin. If it does not, the deficiency is confirmed, and the test is repeated to check for the cause. This time, people are given intrinsic factor with the vitamin B₁₂ taken by mouth. If intrinsic factor enables the body to absorb more of the vitamin, the deficiency is caused by lack of intrinsic factor.

Endoscopy (use of a flexible viewing tube to directly examine internal structures) may be done to check for destruction of stomach cells that produce intrinsic factor.

Prevention and Treatment

For infants of vegan mothers, starting vitamin B₁₂, supplements immediately after birth helps prevent the deficiency.

Older people with vitamin B₁₂ deficiency benefit from taking vitamin B₁₂ supplements because the deficiency usually results from difficulty absorbing the vitamin from meat. They can absorb the vitamin more easily from supplements than from meat.

Treatment of vitamin B₁₂ deficiency or pernicious anemia consists of high doses of vitamin B₁₂ supplements. If people have the deficiency but no symptoms, the vitamin may be taken by mouth. Blood tests are done periodically to make sure the vitamin B₁₂ level returns to and remains normal. People who have symptoms due to nerve damage are usually given vitamin B₁₂ by injection into a muscle. Injections, which may be self-administered, are given daily or weekly for several weeks until the vitamin B₁₂ level returns to normal. Then injections are given once a month indefinitely, unless the disorder causing the deficiency can be corrected.

Anemia usually resolves in about 6 weeks. But severe symptoms due to nerve damage—for example, dementia in older people—may not resolve.

Last full review/revision February 2013 by Larry E. Johnson, MD, PhD