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B12 Deficiency and Pernicious Anaemia

Vitamin B12 is a very important vitamin and can cause various symptoms similar to those of hypothyroidism, one of which is tiredness.  Vitamin B12 deficiency can be caused by pernicious anaemia, an autoimmune condition.  If you go to your GP with tiredness as a symptom, the doctor will probably run a vitamin B12 test among others. However, what a lot of people may not know is that the test done on the NHS is a total B12 test.

In a similar way to the relationship of total T4 and FT4, total B12 is bound to a glycoprotein called haptocorrin.  However, B12 bound to haptocorrin cannot be used by the vast majority of the cells of the body. Only B12 bound to transcobalamin (also known as holotransobalamin, holoTC or Active-B12), which is a transport carrier protein, is taken up from the blood into the cells of the body.

NICE guidance states that “Four diagnostic test accuracy studies, using different reference standards, reported greater diagnostic accuracy for the Active-B12 assay compared with assays measuring other markers of vitamin B12 deficiency.” ​1​

They also state that “Serum holotranscobalamin (holoTC): in serum, vitamin B12 exists in 2 bound forms. It can be bound to haptocorrin to form holohaptocorrin; or bound to transcobalamin to form holoTC. Cells can only take up vitamin B12 in the form of holoTC (Hunt et al. 2014). Therefore, measuring holoTC is more reflective of vitamin B12 status than measuring total vitamin B12 or holohaptocorrin alone. Emerging evidence suggests that a low level of holoTC may be a more reliable marker of vitamin B12 deficiency.” ​1​

The British Society for Haematology state in their “Guidelines for the diagnosis and treatment of Cobalamin and Folate disorders”, “Serum cobalamin remains the first line test currently, with additional second line plasma methylmalonic acid to help clarify uncertainties of underlying biochemical/functional deficiencies. Serum holotranscobalamin has the potential as a first line test, but an indeterminate ‘grey area’ may still exist. Plasma homocysteine may be helpful as a second line test, but is less specific than methylmalonic acid. The availability of these second-line tests is currently limited.” ​2​

However, the Active-B12 test is not available generally on the NHS although it can be obtained privately from various laboratories.

The tests that can be used to help diagnose pernicious anaemia are intrinsic factor antibodies (IFAB), methylmalonic acid (MMA) and homocysteine.

Your GP can organise for an IFAB test to be done but this does not always happen.  A positive IFAB test will confirm pernicious anaemia.  However, a negative IFAB test does not mean you don’t have pernicious anaemia as it is not a very sensitive test so do be aware of this as some GPs may not be.

The MMA and homocysteine tests are better tests for the diagnosis of pernicious anaemia but only a specialist can organise for these to be done so your GP would need to refer you to a haemotologist or obtain the instruction to order these from a haemotologist.

If you are taking any B12 supplementation when you have these tests done you should inform your GP so that they can take this into account and you may have to stop taking the supplements for a few months prior to the test (although this is not ideal).

If you can’t access these tests on the NHS, they are available from some private laboratories.

Private testing laboratories

These laboratories vary in the tests that they do for B12 deficiency and pernicious anaemia:

Viapath Nutris at St Thomas’ Hospital

New Vitamin Status Testing Service | Synnovis You need to either visit St Thomas’ Hospital to have the blood drawn or they will send you a kit to take to a qualified professional such as your clinician or a phlebotomist.

Blue Horizon

Blue Horizon offers the Active B12 test and various other panels. Thyroid UK receives donations from Blue Horizon.


Medichecks offer various panels that include Active-B12. Thyroid UK receives donations from Medichecks.

For more support check out our online community:



  1. Birmingham and Brunel Consortium. Active B12 assay for diagnosing vitamin B12 deficiency. National Institute for Health and Care Excellence (NICE). Published September 30, 2015.
  2. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. Published online June 18, 2014:496-513. doi:10.1111/bjh.12959



Date updated: 08.05.24 (V1.5)
Review date: 08.05.27

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