Which test was used for the diagnosis: serum B12 (normal/total) or Active B12 (holotranscobalamin)?

The serum B12 test is still used in most laboratories in the Netherlands as the ultimate diagnostic test for a B12 deficiency. A normal serum B12 level however, does not preclude a deficiency as is evident from scientific literature.

Serum B12

The serum B12 test can give false normal or even false high results, even while a deficiency exists. And a (moderate) low level does not automatically mean a B12 deficiency. It has been agreed that an obvious too low level means a B12 deficiency; a serum B12 level below the 148 pmol/L gives a specificity of 95-100%.
However, there is a large “grey” area where a deficiency is possible in spite of a normal B12 serum level.

41.5% of the patients from our survey had a serum B12 level below 100 pmol/L which is an obvious deficiency. Of these patients 23% were not treated immediately, with all the risks that this entails.

What was the level of serum B12?

Many patients are missed by using only the serum B12 test. Because a B12 deficiency could lead to permanent neurological damage, diagnosis should not only be based on the serum B12 level (unless obviously too low), but MMA should also be tested if a deficiency is suspected. This applies in particular if neurological and/or neuropsychiatric symptoms are present. Experts in medical literature are calling for combining serum B12 (or Active B12) and MMA tests in the event of a suspected B12 deficiency.

What was the level of Active B12?

Of the patients who have been tested and knew their results, 20% had an extremely low level of under 10 pmol/L, 26% had a level between 10 and 20 pmol/L and 35% had a level between 20 and 35 pmol/L.

The official reference value for Active B12 in the Netherlands is 21 pmol/L. In the international scientific
literature it generally is 35 pmol/L. Levels below 35 pmol/L would very probably mean a deficiency.
Between the 35 and 50 pmol/L is seen as a “grey” area, which requires further testing by means of MMA, at least.

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