Active B12 test: what the result means (HoloTC)

Vitamin B12 in blood is shared between two carrier proteins: haptocorrin, bound to which B12 simply circulates, and transcobalamin, bound to which B12 can get into cells and take part in DNA synthesis and in the working of the nervous system. This second part, the one attached to transcobalamin, is called active B12 or holotranscobalamin (HoloTC), and it makes up only the smaller share of all the B12 present in blood.

Because active B12 reflects exactly the amount the body can really use, some studies and guidelines consider it a more sensitive marker of early B12 deficiency than the ordinary (total) B12 test. That is especially relevant when total B12 is still normal but symptoms are already there. Active B12 is often assessed together with homocysteine and methylmalonic acid, which rise when cells are genuinely short of B12.

• When there is tiredness, weakness, shortness of breath or dizziness that could be linked to megaloblastic anaemia
• When signs involving the nervous system appear — numbness, tingling, problems with strength or balance, confusion, worsening memory
• When the ordinary B12 test is borderline or unclear and symptoms persist — active B12 can help assess B12 status more precisely
• When a problem with B12 absorption is suspected — coeliac disease, Crohn's disease, pernicious anaemia, a state after stomach or bowel surgery
• When following a strict plant-based (vegan) diet, or when there are other risk factors for B12 deficiency

A high active B12 is less common than a low one and most often does not mean there is too much B12 in the body, because an excess is usually passed out in the urine. A rise can be linked to liver disease or to disorders of the blood-forming system. The result has to be assessed together with other markers and with a doctor's assessment.

Causes listed for a high result:

• Liver diseases (for example cirrhosis or hepatitis)
• Myeloproliferative disorders of the blood-forming system (polycythaemia vera, chronic myeloid leukaemia)

What is usually looked at after a high result:

• Liver markers and a complete blood count — they help tell the possible cause apart
• Whether the result repeats in other tests and whether there are related symptoms
• Discussing with a doctor whether further tests are needed

A low active B12 shows that cells are short of available, usable B12, even if the total B12 test still looks normal. The most common causes are not enough B12 in food, absorption problems, or a lack of intrinsic factor. A deficiency that lasts a long time can cause anaemia and damage to the nervous system.

Causes listed for a low result:

• Not enough B12 in food — most often on a strict plant-based diet
• Absorption problems — coeliac disease, Crohn's disease
• A lack of intrinsic factor (pernicious anaemia)
• Long-term use of medicines that reduce stomach acid, interfering with B12 absorption

Symptoms that can go with a low result:

• Tiredness and weakness
• Numbness, tingling in the hands or feet
• Problems with balance or walking
• Confusion, worsening memory
• Pale skin

What is usually looked at after a low result:

• Homocysteine and methylmalonic acid tests — they help confirm a real B12 deficiency at the level of the cells
• A complete blood count because of possible anaemia
• An assessment of absorption problems (coeliac disease, pernicious anaemia) with a doctor
• An assessment of diet, especially on a plant-based diet