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The problem with testing total vitamin B12 levels

A vitamin B12 deficiency is a common health condition that is notoriously difficult to spot and diagnose. Find out more about why an active vitamin B12 test is a more accurate way of diagnosing a vitamin B12 deficiency compared to a total B12 test.

What is vitamin B12 and what does it do in the body?

Vitamin B12 is a nutrient that is used in many of the body's processes including tissue and cell repair, red blood cell production and the functioning of nerves and DNA. A lack of vitamin B12 can cause red blood cells to be large and misshapen which affects their oxygen-carrying capacity, causing anaemia and associated symptoms. It is found mostly in animal proteins such as meat, fish, milk and eggs, as well as some fortified cereals and yeast extracts such as marmite. The body has a store of vitamin B12 in the liver so can often manage for a few years with these reserves if not provided with B12 from food, however eventually these reserves will run out too.

What causes a B12 deficiency?

There are several reasons why people can become deficient in vitamin B12. The most common cause of vitamin B12 deficiency is an autoimmune disease called pernicious anaemia. In the stomach B12 combines with a protein called intrinsic factor in order to be absorbed by the gut. In pernicious anaemia, the body’s own defence system attacks the parietal cells in the stomach wall that make intrinsic factor meaning that it is impossible to absorb vitamin B12 from food we eat. The cause of pernicious anaemia is unknown, however is more prevalent in women aged 60 and over, people with a family history of the disease and those with other autoimmune conditions.

Another cause of vitamin B12 deficiency is a limited diet - particularly vegetarian and vegan diets as they lack animal products (the main source of B12). Even a healthy, varied vegetarian or vegan diet can result in B12 deficiency and all vegans are advised to supplement with vitamin B12. There is also a link between vitamin B12 deficiency and thyroid disorders. Hypothyroidism (an underactive thyroid) can lead to low B12 as it can cause digestive issues that hinder the body's absorption of the nutrient.

Symptoms of a vitamin B12 deficiency

As vitamin B12 is necessary for so many functions in the body, symptoms of deficiency can be equally varied and also affect different people in different ways. Symptoms typically include fatigue, breathlessness, loss of appetite and other stomach issues, weight loss, mouth and tongue ulcers, nerve damage including loss of sensation in fingers and toes, muscle weakness, sight and memory problems, mood changes and heart palpitations.

What is the difference between total vitamin B12 and active vitamin B12?
Not all vitamin B12 in the blood is available to be used, there are 2 forms of vitamin B12 in the body. Vitamin B12 in the blood is bound to proteins known as transcobalamins. The majority of vitamin B12, approximately 80%, is transported on the inactive transcobalamin I (often referred to as haptocorrin). When B12 is bound to transcobalamin I it is considered to be inactive, as B12 attached to transcobalamin cannot be used by the vast majority of the cells in the body. The active transport protein for vitamin B12 is transcobalamin II (holotranscobalamin), which carries about 20% of B12 in the blood [1]. Only B12 bound to transcobalamin ii (Active-B12), is taken up from the blood into the cells of the body.

Total vitamin B12

The problem with testing total vitamin B12 levels

Only active vitamin B12 is taken up from the blood into the cells of the body. This means that measuring the total level of B12 in the blood could give a misleading result and although the result may show as being within the normal range, levels of useful active-B12 maybe low. Active B12 typically makes up 10% - 30% of all the B12 in the body, so someone sitting in the “normal,” range with the widely used serum tests might actually be B12 deficient. Testing only the total B12 level could fail to diagnose a deficiency accurately.

How do I know if I am deficient in vitamin B12? 

If you follow a restrictive diet such as veganism, suffer from a thyroid or other autoimmune disorder, or experience symptoms of B12 deficiency, we would recommend that you get tested. A deficiency is diagnosed through a vitamin B12 test that measures the levels of B12 in the blood. Our Vitamin B12 (Active) test is a home blood test which makes checking the amount of active B12 in your body easy and quick. Treatment for B12 deficiency will be either daily supplements, tablets or injections which your doctor can prescribe. If you have low levels of vitamin B12 it is important to find out whether it is caused by an autoimmune condition; pernicious anaemia is diagnosed through an intrinsic factor antibodies test and/or a gastric parietal autoantibodies test. If diagnosed it is treated with regular B12 injections from your doctor. If you think you might be at risk of a vitamin B12 deficiency, it’s never been easier to get the vitamin B12 tests you need. 


1. O’Leary, F. and Samman, S. (2010). Vitamin B12 in Health and Disease. Nutrients, 2(3), pp.299-316.