To diagnose a person with Vitamin B12 deficiency, testing should be carried out. 

However… “the clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there’s no ‘gold standard’ test to define deficiency.” – British Society of Haematology, 2014.

Serum B12 test

The good news is that testing is usually carried out with a simple blood test – serum B12 – and results can be delivered fairly quickly. The bad news is that unfortunately a large proportion of our healthcare providers still do not fully understand B12 deficiency, its effects on all body systems and that if the person is symptomatic but falls ‘within range’ on the test, that the clinical picture is of utmost importance. Please see the NEQAS B12 alert.               

There are documented problems – (please see point 4 of the What to do next page) with the accuracy of the serum B12 test and unfortunately many health professionals are still not aware of this. The test records all B12 in the blood, active and inactive (B12 analogues), but it does not record what is happening at cellular level. The body cannot use inactive B12 and this can represent as much as 80% of the level showing in serum. 

It is really important to try and achieve a baseline reading of your B12 level, ideally before you have taken any form of supplementation. Even if you cannot absorb B12 orally, your serum B12 test could record a ‘within range’ result for a few months after supplementation, therefore giving false results and making diagnosis difficult.

Folate (B9) and Iron levels should be checked alongside serum B12 levels as these are often low too. See Ellen’s case study for more information. 


What are the different types of tests for diagnosing B12 deficiency?

As mentioned above, the most common test for B12 deficiency is serum B12. The reference range for results can be set as low as <110 – 900 ng/l in some parts of the UK. This can pose a problem with gaining a diagnosis as the test often misses desperately B12 deficient people who just fall ‘within range’.
Adding B12 and folate testing to a full blood count (FBC) or (CBC) would help doctors to diagnose a B12 deficiency much earlier than at present as they also offer clues to B12 deficiency.

 Tests from a full blood count:

  • MCV (mean corpuscular volume) is key in determining macrocytosis – (large red blood cells). High levels indicate B12 and folate deficiency but iron deficiency brings this level down so it may appear ‘normal’. The term pernicious anaemia poses a problem for doctors who mistakenly believe their patient has to be anaemic to have a B12 deficiency, but B12 deficiency cannot be ruled out in the absence of anaemia and / or high MCV.
  • MCH (mean corpuscular haemoglobin) usually mirrors MCV – if your level is high then this is suspicious for B12 deficiency, folate deficiency, thyroid issues and problems with liver function. If this level is low it can be caused by iron deficiency so a ferritin test would be of help.
  • MCHC (Mean corpuscular haemoglobin concentration) – high levels can indicate B12 and folate deficiency. Low levels can indicate iron deficiency.
  • RDW – (Red cell distribution width) This test show the amount of variation in the size of red blood cells if the RDW is high this can indicate, B12 deficiency,  folate deficiency and iron deficiency.
  • Eosinophils – If these are above range, it can indicate either allergies or parasitic or bacterial infection. So explore more with your doctor as parasites compete for your B12 and could be the cause of your B12 deficiency.

Please be aware that the Active B12 test (also known as Holotranscobalamin or holoTC) can also miss B12 deficient patients. Please see this Clinical Review from the BMJ on B12 deficiency which states: 

“There is no ideal test to define deficiency and therefore the clinical condition of patients is of the utmost importance.”

Serum MMA – (methylmalonic acid) is a test available on the NHS. Although not routinely used, it can be a very useful indicator of B12 deficiency. It is widely available through private labs.

Urinary MMA – This test is only available privately in the UK but can be ordered directly without referral, from the US. Click here to learn more from Dr Eric Norman’s website.

Homocysteine – Homocysteine is an amino acid produced by the chemical conversion of methionine. It can rise to a toxic level if B12, B6, folate (B9), B2 and magnesium are low. In the UK, this test is not routinely used but can be carried out at your GP practice or at your local hospital if requested by your doctor. This test is widely available through private labs. 

It has been thoroughly documented  that even moderately elevated homocysteine levels are a strong risk factor for cardiovascular disease, stoke, and neuro-degenerative diseases including dementia and Alzheimer’s.

MTHFR – methylenetetrahydrofolate reductase test (gene mutation). Please see more information on methylation.

    Autoimmune Pernicious Anaemia (PA) – Testing

    Pernicious anaemia is an autoimmune condition that causes your immune system to attack the intrinsic factor cells in your stomach which prevents you from then being able to absorb vitamin B12.

    The following antibody tests are used to determine if the reason for B12 deficiency is autoimmune pernicious anaemia, however they can be unreliable due to low sensitivity. It is also important to remember that there are many causes for B12 deficiency and PA is just one.

    These tests are:

    • Gastric Intrinsic Factor Antibodies. (GIFA) – Testing positive confirms a diagnosis of PA, however 40% of people with PA do not have the antibody.
    • Gastric Parietal Cell Antibodies. (GPCA) – Not as sensitive for PA as GIFA testing as these antibodies are also found in people with diabetes and thyroid problems.
    • Serum Gastrin – PA causes a reduction in stomach acid and an elevated gastrin level likely means you have low stomach acid.

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    What to do next

    Signs &

    What is
    B12 Deficiency