This picture shows changes to white blood cells in untreated perncious anaemia

B₁₂ Deficiency and Pernicious Anaemia

Historical Perspective

• The presentation of B₁₂ deficiency is dramatically different from 40 years ago.
• The reason for this is the routine availability of testing of serum B₁₂ concentration.  In the past the condition was only diagnosed when there were symptoms of tiredness, loss of concentration, irritability and numbness and tingling in the arms and legs.  Examination showed evidence of nerve damage. Blood tests showed an anaemia and there were also changes in the bone marrow. This condition did not respond to iron tablets.
• Before B₁₂ replacement treatment was available the condition became worse or could lead to death – this led to the term pernicious anaemia.

How reliable is the blood test for B₁₂?

• Blood levels of B₁₂ (serum levels) are now tested very frequently.
  • There can be problems with “routine” or frequent testing.
  • It is difficult to define the appropriate normal values in a population.
  • Sometimes a value just below the normal range is not really important and can be ignored.
• Blood tests only tell part of the story.
  • B₁₂ is stored in the liver - only a small part in the blood.
  • There is actually enough B₁₂ stored in the liver to last for at least 3 years.
  • The blood levels does not always accurately reflect the levels of stored B₁₂.
    
    

Does a low B₁₂ level in the blood really matter?

• Most people with a borderline low B₁₂ will have no changes in body function.
  • If there is anaemia or changes in the blood count then it is obvious that the low B₁₂ is significant and that replacement treatment should be given.
  • There have been several proposals for tests that can show if the B₁₂ is having a functional difference in the body’s metabolism but these tests are not routinely available and may not be that accurate.
• Most people have tiredness as the major symptom.
  • It is always going to be difficult to know if this symptom is related to the low B₁₂ result.
  • If the level is only borderline low the response to B₁₂ injections may be disappointing.
• Problems with memory or concentration or numbness in arms or legs are likely to improve but these changes only occur with more severe deficiency – in this situation there are usually also changes in the blood count and the size of the red blood cells.
  
  

How should B12 be given?

• B12 replacement is given by intramuscular injection.
  • Initially 1000ug every week for 4-6 weeks.
  • A maintenance dose of 1000ug every 3 months is recommended. This dose will give B₁₂ levels well above the daily requirements.
• Oral absorption is very poor and tablets are not recommended.
• Treatment needs to be life-long if the low B12 is due to pernicious anaemia or due to previous small bowel surgery.
• Milder reductions in B12, without any obvious cause just require a course of injections   - maybe 3 injections over 3 months then follow-up yearly to see if there is any recurrence
  

Thinning of the stomach lining - a long term result of pernicious anaemia

Normal stomach lining with thick folds

What are the causes of a low B₁₂?

• B₁₂ only comes from the diet - the body cannot make the vitamin.
  • Inadequate dietary intake only occurs in strict vegans (a diet that has no meat and no food derived from animals).
• Failure of absorption is the most likely problem.
• The digestion and absorption of B₁₂ from the diet is complex.
  • Normal absorption of B₁₂ requires normal acid production from the stomach, a healthy stomach lining that produces intrinsic factor - a protein that binds to B₁₂ to assist absorption and normal small bowel function in the area close to the join with the large bowel (terminal ileum).
  • A test called the Schilling test was developed to check on normal secretion of intrinsic factor from the stomach. Is it not used very much as it is time consuming, involves radio-isotopes, requires collection of urine. The results can be difficult to interpret.

Pernicious Anaemia

• The most common cause of a low B₁₂ is pernicious anaemia.
  • This is a condition caused by an inflammation of the stomach lining.
  • The inflammation is due to antibodies against the cells of the stomach – particularly parietal cells – the cells that make acid and intrinsic factor (a protein crucial to the normal absorption of B₁₂).
  • It is called an "auto-immune disorder" - the body is “attacking itself”. Another associated auto-immune disorder leads to thyroid disease and the need to have thyroxine replacement.
  • The condition is diagnosed by the presence of antibodies in the blood to parietal cells and intrinsic factor. A gastroscopy and biopsy of the stomach is also helpful.
  • A long term consequence of having pernicious anaemia and auto-immune gastritis will be gradual loss of gastric acid secretion.  Surprisingly this has little impact on health.  There is no effect on digestion. 
  • The long-term risk of having chronic gastritis may be a slightly increased risk of gastric cancer.  This not certain  - large studies are required and not all studies have confirmed an increased risk

Other causes of a low B₁₂

• Crohn’s disease (with previous small bowel resection). Regular and lifelong 3-monthly injections of B₁₂ will be required
  
  
• Coeliac disease - problem should resolve after starting a gluten-free diet
  
  
• Previous gastric surgery (removal of all or part of the stomach for peptic ulcer or gastric cancer). The condition is likely to cause only a mild abnormality of B₁₂ absorption and long-term injections may not be required.
  
  
• Sometimes there is no obvious reason.  Follow-up tests on a yearly basis (after initial series of injections) is all that is required if no underlying cause is found