Axis Shield | Why Use Active-B12

On theoretical grounds, the level of Active-B12 (HoloTC) should be the optimal marker of vitamin B12 status. About 70 % or more of plasma vitamin B12 is bound to haptocorrin and is therefore biologically unavailable for most cells; the rest comprises Active-B12, which is the part of plasma vitamin B12 bound to transcobalamin (TC), the protein that delivers vitamin B12 to the tissues of the body.

As Active-B12 (holoTC) has a shorter circulating half-life compared to holohaptocorrin the earliest change that occurs on entering negative vitamin B12 balance is very likely to be a decrease in plasma Active -B12 (holoTC) concentration (1).

1. Herzlich B and Herbert V, Lab Invest., 1988; 58: 332-7.

Active-B12 correlates to a reasonable extent with the total serum B12 assay as shown in the accompanying diagram.

However, the plot below shows the agreement is evident at the extremes (either very likely deficient or very likely not deficient). There is a substantial proportion of patients (between 20 and 50% depending on the population studied) with total serum B12 levels above the cut-off used to define deficiency but with low Active-B12 levels, indicating likely deficiency. These patients would therefore be undetected and untreated.

It is suggested therefore that Active-B12 is more diagnostically accurate than the total serum B12 assay. This is difficult to demonstrate because there is actually no gold-standard method for comparison, all currently available techniques have limitations that compromise diagnostic accuracy.

Available Lab Tests for B12 status	Comment
Total B12 assay	Requires pre-analytical manipulation of sample. A poor predictor of B12 status prone to false positive and negative results. Ill defined reference intervals due to variations between methods. 80% of what is measured is not Active-B12.
Homocysteine (Hcy)	Not specific for B12 deficiency as levels also depend on folate and vitamin B6 and some lifestyle factors. Levels also influenced by age and renal function.
Methylmalonic Acid (MMA)	Not an easily accessible test requires expensive instrumentation. Specificity is debatable as levels also depend on age and renal function as well as vitamin B12 status.
Active-B12 (holotranscobalamin)	Expected to have high sensitivity and good specificity. No pre-analytical sample treatment required.

The clinical use of Active-B12 could be as a resolving test for indeterminate B12 results, as in the algorithm below. It may also replace the total B12 assay altogether and the expected improvement in diagnostic accuracy could remove most of the need for supplementary tests used with the total B12 assay.

News

Coming Soon ! The full video recording of the Euromedlab 2007 Active B12 workshop will be available in the next few weeks, register for your copy.

Live CME Web Conference on vitamin B12 deficiency, Prof. Ralph Green, Dec 13th 2007, register now.

Meetings

8-11 December, 2007
American Society of Hematology, Atlanta, booth 544
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