Hello cat265,

I will reply to each question in order. I have also replied to your PM.

For information about the holotranscobalamin test, I suggest that you read my reference BH6. Here is a direct link to the document:

Active-B12 (holotranscobalamin)

There are direct links to many more references on holotranscobalamin on the references page of my web site; there is a whole section for this test.

No, the active B12 test measures the component of total serum B12 that is available to the cells for metabolism. Only about 10 to 30% of total serum B12 is attached to the transport protein, transcobalamin to become the holotranscobalamin. The proportion of holotranscobalamin falls significantly as body stores deplete, so the active B12 test should indicate a deficiency earlier than the total serum B12. I can see one serious potential weakness of this test; it still only measures the B12 available to cells, not how well they utilize it.

The MMA test measures the amount of toxic chemical left over from an incomplete reaction, due to B12 deficiency. It therefore is an indicator of actual cellular deficiency, not just what is available to the cells.

I am currently comparing active B12 and MMA, as well as total B12 and homocysteine, as my deficiency worsens. I hope to soon be able to publish my results on my web site.

Yes, it does matter, if you are trying to use active B12 for diagnosis. Once you have started treatment, your active B12 level will reflect your current body stores, even if you stop for a few weeks. Just as for MMA, or homocysteine or serum B12, you cannot return to your pre-treatment condition just by ceasing treatment.

If you want to use active B12 to assess effectiveness of your treatment, then you can do that by ceasing treatment for one or two weeks before testing. The half-life of holotranscobalamin is a few hours (the experts give a range of minutes to hours), so one week should be sufficient.

The figure of 5-6 years is what some experts say is total body storage; others say it is 20 to 30 years. These figures are for a healthy person who has built up a full store of B12 then suddenly stops taking any, for example becoming a vegan. If there is onset of a severe disease process that interrupts recycling of B12, the stores can deplete much more quickly; typically one to three years.

You should build up your stores much faster than they can deplete, even if you have the most severe case of deficiency, by using oral supplements. This is possible because of a process called passive diffusion. You can absorb about 1% of any B12 dose by passive diffusion, so a dose of 1000 µg will yield about 10 µg effective B12, even if there is no normal absorption. It will therefore take 200 to 300 such doses to fill your body stores, which normally hold 2 to 3 mg. There are some conditions where a person cannot absorb any oral dose, even by passive diffusion, but this would show up in any serum B12 test following treatment.

This is explained well by Kuzminski, in my reference BN1. Here is a direct link to the document:

Effective treatment of Cobalamin Deficiency With Oral Cobalamin, Kaminski et al, Blood, Vol 92, No 4, 1998: pp 1191-1198

You have asked the question that has been puzzling me for some time, and that I am currently trying to answer with my testing. I do not have a very clear answer for you.

Many other patients have described, on these forums, very rapid re-appearance of symptoms between treatments, but usually when using injected B12.

I cannot compare this to my own personal experience because I am unable to easily correlate my many symptoms, which vary with time anyway, with treatment. I therefore rely entirely on biochemical tests to determine the effectiveness of my treatment.

Iff (and I mean if and only if) the experts are right, you should not have any recurrence of symptoms after stopping your treatment for a few weeks. This is because, even in the most severe case of deficiency, your body stores should last for one to three years.

This leads to a few unanswered questions:

• Is the body store really filled?
• If so, is it actually available for metabolism?
• Does the body store have to be full to overflowing before B12 is available to cells?

I hope that my current research will give us some answers.

To get some idea of just how difficult this problem is, even for the experts, I suggest that you read the report by Solomon, my reference BK9:

Disorders of cobalamin (Vitamin B12) metabolism: Emerging concepts in pathophysiology, diagnosis and treatment, L. Solomon, Blood Reviews, Volume 21, Issue 3, Pages 113-130

You have asked a very good question. I am sorry that I cannot answer your question better than this, at this time.

Paul

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