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Old 04-11-2008, 01:03 AM
Paul Golding
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Paul Golding
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Hello Deb,

I agree with the response from Glenn. I suggest that you read my posts on the following threads:
You have raised two issues in your message:
  • Why test first?
  • The meaning of a high B12 level
My previous attempts to explain these, on this thread and on others, have apparently failed to get the message across clearly. So, here I shall try to do a better job of it.

Serum vitamin B12 is a very poor indicator of vitamin B12 deficiency; it is neither sufficiently sensitive not sufficiently specific. This means that it often gives false negative results, thereby failing to detect the presence of an actual deficiency. There are also reports of it giving false positive results.

If you are interested in reading about the problems with using serum B12 for diagnosis of B12 deficiency, you are welcome to visit my web site (URL at end of this message). I suggest that you read all of the pages in the section Information and Advice for Patients. You will find that Sally's book is listed there as recommended reading, along with other references. I especially recommend that you also read reference BG1, on my References page.

These are the problems with using serum B12 for diagnosis of vitamin B12 deficiency:
  • There is significant variation in results between labs, and sometimes within a lab - use of automated immunoassay kits encourages cost-cutting and sloppiness in calibration
  • Serum B12 only represents body stores of vitamin B12 if it is in equilibrium with the body stores - it is affected by any recent supplements or injections
  • Body stores do not indicate how much B12 is actually available to the cells - the proportion of B12 on transport proteins, active B12 (holotranscobalamin), falls as deficiency develops
  • The amount of active B12 (holotranscobalamin) does not indicate the ability of the cells to utilize the B12
You can think of the above list as a series of opportunities for errors, so the serum B12 result says very little about cellular deficiency. For this reason, many experts advocate the use of the two metabolic markers, methylmalonic acid and homocysteine, for diagnosis of vitamin B12 deficiency.

Now, I shall consider the two issues that you raised.

1. Why Test First

You asked:

Quote:
They also say that once you start taking B12, when being tested for B12 levels, it will never be a true test again.

Do you feel there is any truth to their theory?
What Sally has said is entirely correct. I have explained this in a warning on my web site, on the General Advice page in the section Information and Advice for Patients. I have also copied the warning to the end of my messages in several threads, including post #14 on this one. In my reply to Eugene, in his thread "Burning skin pain undiagnosed", I said:

Quote:
The best available tests for B12 deficiency are methylmalonic acid and total homocysteine. It is essential that, for diagnosis of B12 deficiency, you do not take any form of B12 supplements or injections before having these tests. I have explained the reasons for this in detail, on my web site, and have copied the warning to the end of this message.
I must admit to feeling anger and frustration when I so often read here about patients who are driven, by the arrogance or apathy of their doctor, to taking treatment before having a proper diagnosis. By failing to test first, the doctor condemns the patient to the dilemma that I put in my warning:

Quote:
1. No blood tests, no treatment, with B12 deficiency:

* Increasing disability
* Eventual irreversible damage or death likely

2. No blood tests, taking supplements or having injections, no B12 deficiency:

* Unnecessarily taking supplements, or having injections, for life
* Risk of masking folate deficiency
Perhaps it might help if I explain the reasons in more detail.

Unlike many other nutrients, vitamin B12 is normally stored for a very long time in your body, the majority of it in your liver.

In a healthy person, your body supply of B12 is almost entirely recycled. The stored B12 is excreted in the bile, into your intestine, where it is re-absorbed; this is called enetro-hepatic recycling. According to some experts, your body store is sufficient to last for 20 years. You can read about this in detail in the article by Victor Herbert, my reference BH1. So, if a healthy person suddenly stops taking any B12 in their diet, by becoming a vegan, it can take decades for the B12 deficiency to develop.

If anything interferes with the recycling of your body store of B12, the store will eventually deplete and you will develop a cellular B12 deficiency.

If you develop a B12 deficiency for any reason, the time it takes to deplete your body stores will depend on the severity of the problem. For example, some experts quote a figure of 1 to 3 years before your stores become depleted, if you develop pernicious anaemia, where there is no recycling.

If your stores are depleted, and you commence taking supplements or have B12 injections, you will immediately start to fill your body stores. Even if you cannot absorb much or any B12 normally, for example because of atrophic gastritis or PA, you can still absorb some. This is possible because of a process called passive diffusion, which will allow you to absorb about 1% of any dose. About 200 to 300 doses, of 1000 µg each, will be sufficient to reach the 2 to 3 mg required. If you do not have total malabsorption, or if you take higher doses, your store will fill more quickly.

So, what happens if you suspect that you have a B12 deficiency and start treatment? If your body store of B12 was not depleted, the additional intake is excreted, so it makes no difference. If your store was depleted, you will add some B12 to it, increasing the amount of active B12 (holotranscobalamin) available to the cells. If your cells are able to utilize the additional B12, this will reduce your methylmalonic acid and homocysteine.

Once you have interfered with the body store of B12, by taking treatment, you cannot go back to the pre-treatment condition. You have no way of knowing how depleted the stores were, and no safe way to deplete them again.

It is not possible to simply monitor your serum B12 level in the hope of observing the onset of deficiency. You can develop irreversible neurological damage from B12 deficiency, even when your B12 levels do not fall to abnormally low levels.

This is not just theory. You are invited to read about my current Series 4 tests, on the Introduction page in the Continuing B12 Research section of my web site. I have not yet published the results, but they confirm my results from the first series. After ceasing supplements, the serum B12 level is not useful in detecting the developing cellular deficiency.

If you were to look at the serum B12 chart for my current test series, you would not realise that I have had a true cellular B12 deficiency since last August, and that it is now an overt deficiency, with rapidly rising methylmalonic acid levels, and worsening symptoms. As they say, "please do not try this at home".

2. The meaning of a high B12 level

Quote:
When I finally got a doctor to test my B12 level, I was taking 1200mcg daily of B12 and my level came back at 1237, so my doctor told me my B12 is just fine, not to worry about it.
In the previous answer, I said that serum B12 is not useful for diagnosis of vitamin B12 deficiency.

You can use serum B12 to assess the effectiveness of treatment, as distinct from diagnosis, to some extent. Your serum B12 level represents the body storage of B12, if they are in equilibrium. I shall explain what I mean by this.

If you are taking B12 supplements, then suddenly stop, the B12 in your serum decays exponentially. The rate of decay, called the half-life, is the time it would take for the amount of B12 to reduce to half the original. For serum vitamin B12, the half life has been found to be about 10 days. This means that, if you only had B12 in your blood, and none in body stores, it would take 10 days to fall from the initial level to half of that. Because you will have some body stores, the rate of fall is more complex than that.

An example of this is shown in Chart C10, which can be found in the Ceasing Oral B12 Treatment section on the My Story page of my web site. I have attached a copy to this message, as a PDF file.

This chart shows how my serum B12 increased from 100 pmol/L to 1232 pmol/L after taking two 1000 µg B12 for 100 days. The serum B12 level fell to 1099 pmol/L, possibly because of instability when it was no longer in equilibrium with body stores. After I ceased all treatment, my serum B12 level fell to 660 pmol/L in one week, to 601 pmol/L after two weeks, and to 323 pmol/L after a total of five weeks. My serum B12 level then gradually fell to 140 pmol/L over the next few months.

The initial serum B12 level, of 1099 pmol/L, was affected by recent absorption of the supplement, and did not truly represent body stores. It took five weeks for the serum B12 to come into equilibrium with what was in my liver.

Here is another point about the chart, also related to my first answer. At what point, on that chart, do you think that I became B12 deficient? The answer is that you cannot tell. According to my interpretation of MMA results, cellular deficiency commenced within three weeks of my B12 level falling to 323 pmol/L, at about Day #140. It is impossible to see that from the B12 chart.

So, you can use serum B12 as a guide to changes in your body stores, but not cellular deficiency, and only if you wait for several weeks after ceasing supplements.

I hope that I have made things a bit clearer for you.

Please let us know if you have any further questions. If you prefer a private discussion, you are welcome to send me an Email from the Contact page of my web site.

Paul
Attached Files
File Type: pdf Chart C10.pdf (16.2 KB, 236 views)
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Megan (04-11-2008), Silverlady (04-11-2008)