Active vitamin B12 (holotranscobalamin-holotock)

The deficiency of vitamin B12 is a global problem nowadays.

About 5% of adults are diagnosed with vitamin B12 deficiency, of which 5% are 65 – 74 years old and 10% older than 75 years.


The main function of vitamin B12 (cobalamin) in the human body is normal haematopoesis. Its deficit is the cause of megaloblastic anemia and neurological disorders. Vitamin B12 is not synthesized in the body, it is uptaken with food (animal food products).

The clinical signs and symptoms of vitamin B12 deficiency are general and, therefore, the deficit can easily be overlooked:

  • weakness, tiredness, dizziness,
  • numbness in the extremities.


Vitamin B12 (cobalamin) in the serum is associated with two proteins: transcobalamin and haptocorin. The transcobalamin and vitamin B12 complex is called holotranscobalamin (holo TC). Holo TC contains bioavailable (active) cobolamine, since only holoTC by acting through specific receptors promotes cobalamin intake in all cells. Whereas approximately 80% of the circulating cobalamin (vitamin B12) transferred in the serum by haptocorin (holoHC), is considered to be metabolically inactive because haptocorin does not have specific cell receptors other than receptors in the liver.

Genetically determined haptocorin deficiency is rare and it is not considered a serious condition. On the contrary, genetically determined transcobalamin absence or defect manifests itself in the form of typical hematological, neurological and metabolic cobalamin deficiency characteristic pathologies requiring therapy even if serum analyses show normal cobalamin concentration, HoloTC has a shorter half-life than haptocorin (holoHC), so holoTC concentration reduction is one the earliest indicators of cobalamin (vitamin B12) deficiency.

In the normal state the level of vitamin B12 in the serum should correspond to its level in the tissues, but the lack of transport protein (transcobalamin) may indicate a low serum B12 level at a normal level in the tissues or a low level of B12 in the tissues at a normal serum level.

It is often observed that vitamin B12 content is at a reference value (190 – 300 pg/mL – gray area), of which more than 20% of patients are over the age of 60 years. The ability to absorb B12 decreases with age, which is associated with atrophic changes in the gastric mucosa, therefore, the prevalence increases as the age of the world population increases. This explains situations when determining the total amount of vitamin B12 it can be within the normal range (gray area), but when determining the active vitamin B12, its content is lowered and suggests a diagnosis of vitamin B12 deficiency.


There are some restrictions in determining total serum cobalamin (total B12), most notably the fact that most of the cobalamin that is detected is bound to haptocorin. Therefore, in order to get a true picture of the vitamin B12 content in the body, it is important to identify biologically active B12 (holotranscobalamin). When diagnosing, several published studies show that holo TC is a better indicator of B12 vitamin content than total serum cobalamin.

The holo TC level is expected to be low in patients with biochemical symptoms of vitamin B12 deficiency. Particularly low values are observed for vegetarians, vegans and patients with inadequate dietary intake of vitamin B12. Moreover, a low holoTC (but not total vitamin B12) level has been observed in patients with Alzheimer’s disease.


Launching additional intake (therapy) of vitamin B12 an increase in active B12 (holoTC) can be already observed on the first day of therapy. HoloTC increase is the indicator of the proper dose of B12 vitamin.


Advantages of vitaminB12 determination:

  • holo TC only shows the amount of biologically active B12 vitamins in the serum,
  • the holo TC level reflects vitamin B12 supply in the body regardless of the amount of vitamin B12 recently absorbed,
  • holo TC is a much more sensitive and specific indicator than total B12 ,
  • holo TC does not interfere with IF antibodies (IF – Internal Factor) which is a problem in the overall case of B12,
  • changes in the amount of holoTC in the serum appear faster than total B12.


Material to be tested: blood without anticoagulant (red or yellow tube).

Blood storage time: the sample should be centrifuged no later than 2 hours after blood collection. It can be stored in the refrigerator for up to 72 hours. For prolonged storage it is frozen.


Test price is 12,95  EUR