B12 clearance from bloodstream.

[MorningMist]

I hope I am not misunderstanding something here but can anyone explain what causes b12 to build up in the blood when it is water soluble and excess is supposed to be excreted by the kidneys? Claims that you get rid of what you don’t need are obviously incorrect but this is never mentioned.

[dot-dash]

That sent me down a rabbit hole.

There are a few papers from the early 60's that measure the half-life of B12 in the blood to be 5-6 days - so that's roughly the rate the kidneys chomp through it.

Separately, or overlapping, the "many faces of cobalamin deficiency" paper points to this from 1984 which covers 'why does hydroxo- hang about longer?" (sciencedirect.com/science/a...

And although this 1966 paper is about B12 in liver, the intro talks about hydroxo vs cyano in plasma (sciencedirect.com/science/a..., and from this 1961 paper (doi.org/10.1038/189138b0):

"Why hydroxocobalamin is absorbed slowly from the site of injection, why it is retained for a longer period in the body and builds up consistently high B 12-levels in the blood, may be explained by its greater reactivity and the formation of stronger bonds with substances in the body which bind B 12. This might have been suggested by the results of previous investigations into the binding of hydroxocobalamin to serum proteins."

So roughly - it binds to other stuff in your blood and elsewhere

Oh, and about that 'revert to one injection every 2 months" guidance for PA treatment - at least partially informed by this clinical trial, dating from 1965 "Comparison of hydroxocobalamin and cyanocobalamin in the treatment of pernicious anaemia" doi.org/10.1016/s0140-6736(.... All based on that 200 ug/ml target vs any symptoms. Sample size of 8!

"The effect of a single intramuscular injection of 1000 µg hydroxocobalamin or cyanocobalamin was studied in 16 patients with pernicious anaemia in relapse, the end point being the time at which serum vitamin B12 fell below 200 µg per ml. In the 8 patients given hydroxocobalamin that time ranged from 4 to 10 weeks, mean 7.2, and in the 8 given cyanocobalamin from 1 to 6 weeks, mean 3.2. No significant difference was found in rise of Hb and packed cell volume.

A crossover trial was then made with monthly injections of the 2 cobalamins, each for 3 months, the dose being reduced to 500 µg after 6 months and to 250 µg after 6 months more and finally raised to 1000 µg every 2 months; 12 patients completed the course. Analysis of variance revealed highly significant differences between patients, doses and types of cobalamin. The last was the greatest, hydroxocobalamin giving higher values for serum vitamin B12 than cyanocobalamin.

In another trial 5 patients were given a single injection of 4000 µg hydroxocobalamin and 5 were given cyanocobalamin. The time before serum vitamin B12 fell to below 200 µg per ml was from 4 to 12 weeks, mean 8, in those given cyanocobalamin. One of those given hydroxocobalamin had a value of 680 µg per ml 19 months after injection; the time of fall in the 4 others was from 12 to over 82 weeks, mean 21.

The superiority of hydroxocobalamin over cyanocobalamin in maintaining normal serum vitamin B12 values leads to the conclusion that the former should be the standard preparation for treatment of pernicious anaemia; 4 initial injections of 1000 µg on alternate days, followed by maintenance injections of 1000 µg every 2 months, are suggested"

(posted an non-accessible abstract link, so here's the long version)

[Nackapan in reply to dot-dash]

So Gps are thus still concentrating on numbers rather than symptoms. Wish it was so simple

All i know was my first ever b12 serum level was 106pg/ml( 200-900) only done as I collapsed!!!

Would've loved to have known what my level was when well .

'My norm'

I still think once on injections 💉 it bypasses any normal function of processing from food so much much higher serum levels needed .

Perhaos a different scale used when on injections ?

If a dietary cause as in my sisters case .

Injections never had .

High dose b12 tablets did work before vile symptoms set in.

[WiscGuy in reply to Nackapan]

Good point on blood chemistry plus hypothesis vs observation of actual symptoms, especially as relates to repair of neurological damage. This seems to be a long-standing problem in determining appropriate (ie, effective) treatment of B12 deficiency with neurological symptoms.

[Nackapan]

Ive often 😕 wondered this too.Will have a read . Thanks

[Gambit62 Administrator]

The kidneys only have a finite capacity to remove B12 so if you put B12 in faster than this it will build up - like running water into a bath faster than it can drain out of the plughole.

One reason why B12 levels may stay high in some people is that it can get bound to another protein which stops the kidneys filtering it out but also means that your body can't use it. There was an article on this a few years ago but I don't have the reference to hand at the moment.

[Cornwaller in reply to Gambit62]

The analogy with a bath assumes that the kidneys remove b12 in a manner which is not concentration dependent. I'm not sure if this is a reasonable assumption?

[Gambit62 Administrator in reply to Cornwaller]

it is an analogy not a perfect model - even if the functioning of the kidneys does increase with concentration there will still be a limit where the kidneys can't remove the B12 fast enough and the concentration starts to build up.

[Cornwaller in reply to Gambit62]

Your right, there will be a limit. So the question is where is the limit and is it limiting in this case?

[Asselchen]

It's because some of the b12 in the blood binds to the transport protein haptocorrin to form holo-haptocorrin. And the half life of that is relatively long.

[MorningMist in reply to Asselchen]

Yes and holohaptocorrin is the form taken up by liver cells, so for longer term storage, and that obviously varies greatly in individuals. Will continue reading.

[lindajanes]

Could this be related to the inaccuracy of the blood serum test? It gives a false high reading in a surprisingly large percentage of cases as I understand it. I have read that a consistent result of 2000 is standard for patients who self inject cyanocobalamin in the U.S. That is always my reading, and my neurologists and primary care doctors have considered it normal for me. However, I never had a low blood serum B12 level and was only diagnosed with PA when hematology discovered antibodies during a battery of tests related to another concern. I had all the symptoms and irreversible nerve damage by the time this discovery was made. That happened despite the fact my mother and one of her sisters had PA because of lack of understanding about the margin of error in the blood test.

[Iheartb12]

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