Vitamin B12 plays an important role in the body and if you are feeling tired or weak it could be a sign you are deficient.
There are two types of vitamin B12 in the body, these are active B12 and inactive B12, both make up Total B12. The simple difference between the two forms is that active B12 is the form used by the body.
WHAT IS ACTIVE B12?
Active B12 is when B12 binds to transcobalamin protein (known as Holotranscobalamin or HoloCT) and is made available to cells for use in the body, hence being called active B12.
The most widely used B12 test on the NHS checks total levels of B12. Active B12 typically makes up 10% - 30% of the total B12 in the body, so being in the “normal,” range of the total B12 might hide a B12 deficiency. It’s the levels of active B12 you really need to be concerned with if you are worried about thyroid issues, fatigue or any other symptoms associated with a vitamin B12 deficiency.
WHY TEST YOUR B12 LEVELS?
The two main reasons to check your Vitamin B12 levels are:
- You’re concerned about a thyroid disorder
- You are experiencing unexplained fatigue
WHAT ARE THE SYMPTOMS OF VITAMIN B12 DEFICIENCY?
Some of the symptoms of vitamin B12 deficiency include:
- Neurological features
- Sore tongue
- Bone marrow suppression
Low vitamin B12 levels
B12 as a key co-factor in metabolic methylation is involved in several vital biological processes. Therefore, the increase of food sources high in vitamin B12 (see picture) and supplementation - ideally with a methylated form of B12 - are important for rapid restoration of the B12 status, which is indicated by low serum levels.
High vitamin B12 serum concentrations without supplementation: the pitfalls of interpretation
High active B12 concentrations may be due to excessive levels of the vitamin, increased levels of its transport proteins  or related to autoimmune or haematological disorders .
High or supraphysiological serum B12 levels without supplementation have been associated with many health problems kidney failure, blood disorders, cancer, and liver or autoimmune diseases. [2,3] All conditions may show elevated concentrations of B12 transport proteins.
Elevated serum B12 levels may also be associated with a functional deficiency of the vitamin. Functional deficiency is caused by a failure of uptake into processing within the cells, Uptake can be reduced due to abnormal increases of B12-binding proteins or the formation of immunoglobulin-B12-complexes.It is unknown, whether B12 should be supplemented in these conditions.
Recent findings in diseases associated with oxidative stress have revealed that intracellular oxidative stress results in local functional B12 deficiency . Treatment with glutathione and/or vitamin C, a key regenerator of intracellular glutathione, may provide therapeutic benefit.
As supraphysiological levels may serve as a new important diagnostic marker in serious conditions unrelated to the individual patient’s B12 status, further investigations to rule out an underlying health condition need to be initiated, if supplementing with glutathione and vitamin C fails to improve levels.
 Jeffery J, Millar H, Mackenzie P, Fahie-Wilson M, Hamilton M, Ayling RM. An IgG complexed form of vitamin B12 is a common cause of elevated serum concentrations. Clin Biochem 2010; 43:82–8.
 Remacha AF, Zapico E, Sarda MP, Rojas E, Simo M, Remacha J, et al. Immune complexes and persistent high levels of serum vitamin B12. Int J Lab Hematol 2014; 36:92–7.
 Andres E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM 2013; 106:505–15.
 Solomon LR. Functional cobalamin (vitamin B12) deficiency: role of advanced age and disorders associated with increased oxidative stress. Eur J Clin Nutr 2015; 69:687–92..