Vitamin B₁₂ deficiency

What is it?

Vitamin B₁₂ is needed to produce an adequate amount of healthy red blood cells in the bone marrow. Vitamin B₁₂ is available only in animal foods (meat and dairy products) or yeast extracts (such as brewer's yeast). Vitamin B₁₂ deficiency is defined by low levels of stored B₁₂ in the body that can result in anemia, a lower-than-normal number of red blood cells.

Vitamin B₁₂ deficiency can develop for the following reasons:

• Absence of intrinsic factor, also called pernicious anemia — Intrinsic factor is a protein secreted by cells of the stomach lining. Intrinsic factor attaches to vitamin B₁₂ and takes it to the intestines to be absorbed. An absence of intrinsic factor is the most common cause of pernicious anemia. Absent intrinsic factor is often associated with a condition called atrophic gastritis, a thinning of the lining of the stomach.  Atrophic gastritis is more common in elderly people of African-American or Northern-European descent. In these people, pernicious anemia develops at about age 60.

In children, decreased levels of intrinsic factor can be an inherited (genetic) condition. When this happens, low levels of intrinsic factor produce symptoms of juvenile pernicious anemia in patients younger than age 10.

Pernicious anemia occurs more commonly in people who already have diseases that are linked to immune-system abnormalities, such as Graves' disease, hypothyroidism (under-functioning thyroid gland), thyroiditis (inflammation of the thyroid), vitiligo and Addison's disease (adrenocortical insufficiency).

• Removal or destruction of the stomach — Vitamin B₁₂ deficiency can develop in people who have had surgery to remove part or all of the stomach.
• Overgrowth of bacteria — Some people develop vitamin B₁₂ deficiency as a result of conditions that slow the movement of food through the intestines (diabetes, scleroderma, strictures, diverticula), allowing intestinal bacteria to multiply and overgrow in the upper part of the small intestine. These bacteria steal B₁₂ for their own use, rather than allowing it to be absorbed by the body.
• Dietary deficiency — Vegans (strict vegetarians who do not eat any meat, fish, egg or dairy products) can develop vitamin B₁₂ deficiency because they lack vitamin B₁₂ in their diets. In patients with bulimia or anorexia nervosa, vitamin B₁₂ deficiency also can be related to diet. However, your liver can store vitamin B₁₂ for up to five years, so it's rare for diet to cause this anemia.

Symptoms

Symptoms tend to develop slowly and may not be recognized immediately. As the condition worsens, common symptoms include:

• weakness and fatigue
• light-headedness and dizziness
• palpitations and rapid heartbeat
• shortness of breath
• a sore tongue that has a red, beefy appearance
• nausea or poor appetite
• weight loss
• diarrhea
• yellowish tinge to the skin and eyes.

If low levels of B₁₂ remain for a long time, the condition also can lead to irreversible damage to nerve cells, which can cause the following symptoms:

• numbness and tingling in the hands and feet
• difficulty walking
• muscle weakness
• irritability
• memory loss
• dementia
• depression
• psychosis.

Diagnosis

Your doctor will ask you about your diet and about any family history of anemia. Your doctor also will review your medical history for medical illnesses (diabetes, immune disorders) or surgeries, such as stomach removal, that can lead to B₁₂ deficiency.

Your doctor may suspect that you have vitamin B₁₂ deficiency based on your medical history and symptoms. To confirm the diagnosis, he or she will examine you and order laboratory tests. During the physical examination, your doctor will look for a red, beefy tongue, pale or yellowish skin, a rapid pulse and heart murmurs resulting from an anemia-related increase in blood flow demands on the heart. Laboratory tests will include:

• Standard blood tests to measure the level of red blood cells and check their appearance — In vitamin B₁₂ deficiency, red blood cells are unusually large and appear abnormal.
• Blood tests to measure B₁₂ levels — Levels of iron and folate also may be measured to check for deficiencies in these nutrients.
• Blood test to measure methylmalonic acid level — The blood level of methylmalonic acid increases when a person has B₁₂ deficiency.
• Blood tests for intrinsic factor antibody — Your doctor may order special tests for antibody levels to determine if you have pernicious anemia. Most people who lack intrinsic factor in their stomach have these antibodies in their blood.
• Bone marrow biopsy — Occasionally, a bone marrow biopsy is done to help confirm the diagnosis. In this procedure, a small sample of bone marrow is taken by inserting a needle into the pelvic bone just below the waist on either side of the spine. The bone marrow sample is examined in a laboratory to look for other causes of anemia and red blood cell abnormalities.

Expected duration

With proper treatment, symptoms of vitamin B₁₂ deficiency begin to improve within a few days. In vegans and other people whose B₁₂ deficiency is diet-related, oral B₁₂ supplements and a diet designed to increase consumption of vitamin B₁₂ should cure the condition. People with pernicious anemia or people who cannot absorb vitamin B₁₂ from their intestines will need injections of vitamin B12 every one to three months indefinitely.

Prevention

To prevent vitamin B₁₂ deficiency, vegans should take adequate amounts of vitamin B₁₂ supplements to make up for the shortage in their diet.

For people who cannot absorb B₁₂, the condition cannot be prevented. However, once it is diagnosed, regular injections of vitamin B₁₂ will prevent symptoms from returning.

Treatment

Treatment for this condition involves replacing the missing vitamin B₁₂. People who cannot absorb B₁₂ need regular injections. When injections first are administered, a patient with severe symptoms may receive five to seven during the first week to restore the body's reserves of this nutrient. A response usually is seen within 48 to 72 hours, with brisk production of new red blood cells. Once B₁₂ reserves reach normal levels, injections of vitamin B₁₂ will be needed every one to three months to prevent symptoms from returning. People who cannot absorb vitamin B₁₂ should continue to eat a well-balanced diet that provides other nutrients (folic acid, iron and vitamin C) necessary to produce healthy blood cells. Sometimes people can take high doses of oral B₁₂ to provide replacement instead of undergoing injections, but a physician should closely supervise this.

In people whose vitamin B₁₂ deficiency is related to overgrowth of intestinal bacteria, treatment with oral antibiotics, such as tetracycline (sold under several brand names), may stop bacterial overgrowth and allow the absorption of vitamin B₁₂ to return to normal.

Vitamin B₁₂ deficiency resulting from inadequate dietary intake is the easiest to treat. The condition can be reversed by taking oral vitamin B₁₂ supplements and adding foods containing B₁₂.

When the anemia is severe and the red blood cell count is extremely low, blood transfusions may be necessary for the first couple of days until the vitamin B₁₂ injections begin working.

When to call a professional

Contact your doctor for a physical examination if you experience unexplained fatigue, palpitations, shortness of breath, sore tongue or any other symptoms of vitamin B₁₂ deficiency. This is especially true if you are a vegan, are older than age 50 and of African-American or Northern-European descent, have an autoimmune disorder or have had your stomach removed.

Prognosis

The outlook is excellent because this form of anemia responds well to treatment. However, it is possible that nerve cell damage will be permanent. Some residual damage to the nervous system may remain in people who sought treatment late in the illness.

Additional info

National Heart, Lung, and Blood Institute (NHLBI)
https://www.nhlbi.nih.gov/