Where does the B 12 go ?

[Freezeframe]

I was wondering what happens to the injected B 12? I have Pernicious Anaemia. Does the b12 in the loading phase get stored in the liver? Or does it remain in circulation in the body ? I realize that once passed the loading phase it depletes and you are on a maintenance schedule for the rest of your life. Thanks

[fbirder]

When you inject a large dose of B12 some of it will get stored, mainly in the liver but also in other tissues. Quite a lot will get passed out in the urine. The amount stored depends on the type of B12 (hydroxocobalamin is stored more readily than cyanocobalamin - ncbi.nlm.nih.gov/pubmed/303... )

Because most of the injected dose gets eliminated in the urine you need several dioses in quick succession to build stores up. That's what the loading doses are for.

Once liver stores are topped up the maintenance doses should be replacing the B12 that the body uses up, maintaining the stored B12.

[Gambit62 Administrator in reply to fbirder]

fbirder - it may just be a temporary problem but the link you have provided doesn't seem to work

[fbirder in reply to Gambit62]

Thanks. I’d included the closing parenthesis in the URL. Fixed now.

[Gambit62 Administrator]

I'm not sure how useful stores of B12 in the liver really are if you have an absorption problem as my understanding is that releasing the B12 relies upon releasing it in bile for reabsorption in the gut - something that won't be working very efficiently, so the stores will at best, run out very quickly - hence the need for regular maintenance doses.

[fbirder in reply to Gambit62]

This book extract suggests that people with Pernicious Anaemia turn over about 0.2% of their stored B12 per day. ncbi.nlm.nih.gov/books/NBK1...

They also estimate the time taken to deplete those stores to the point where a deficiency becomes symptomatic. For people with a turnover rate of 0.2% that ranges from between 1.5 and 5.8 years (it's a big range because of the uncertainty in how much B12 is stored and what level is needed before symptoms appear).

This site says that B12 is stored in the liver as adenosylcobalamin and that removal of the adenosyl enables it to be utilised by the cells. But I can't find references to back it up. The only decent papers in the last 5 years say 'we don't know'.

[Gambit62 Administrator in reply to fbirder]

not sure that the sums actually bear up against observation

- if the assumption is that an injection will mean that your liver will fully replace depleted stores - as that would mean that injections would be needed every 3 years - think the references to people with pernicious anaemia must be to people before loading doses and post loading doses everything just goes straight out of the window.

[27Protons in reply to fbirder]

That's interesting - do you know if intrinsic factor is needed to absorb the B12 stored in the liver?

[fbirder in reply to 27Protons]

To some extent, yes, IF is needed to get B12 from the liver.

We know that some B12 is excreted in the bile into the duodenum. There it will bind to any IF that is present. If there is no IF then that B12 will be eliminated from the body.

What we don’t know is how much B12 can be passed from the liver directly into the blood. Biochemical processes tend to be two-way equilibria, so it’s very likely that B12 can pass from the liver to the blood. What is unknown is the extent to which this happens. It may be insignificant. It may be substantial. The book I quote above suggests that it is significant.

We know that there is just 2 mcg (roughly - 400 ng/L times 5 L) of B12 in the blood. If people with PA couldn’t access the stores in the liver then those 2 mcg wouldn’t last very long at all. But people with PA can survive years without any input of B12. They must be accessing stored B12.

[27Protons in reply to fbirder]

Hmm, that's concerning the lack of research into the biochemistry of how vitamin B12 works. If we don't know that how were the recommended daily intake calculated for vitamin b12? As my guess would be what is needed for blood production.

[fbirder in reply to 27Protons]

The recommended doesn't need to take into account how, or even if, B12 can go direct from liver to blood because they don't calculate these things from first principles. They measure them. It is a complicated process -

ncbi.nlm.nih.gov/books/NBK1...

There's a lot that's not known about B12. But there's a lot that's not known about hundreds of different biological processes.

[27Protons in reply to fbirder]

But wouldn’t the people setting the recommended daily intake need to know how much is used from storage to come up with there recommendations. If this is not know why we not discussing formulating staple food (especially with the increase in poorly planned fashionable veganism and dangerously incorrect government ministers - broccoli is not a source of Vitamin b12) with high level (comparable to at least naturally accruing food sources like liver but ideally 5mg ) based on the low toxicity of Vitamin b12 especially for pregnant women if we going to encourage folate supplement and fortification and we have doctors ignorant enough to stop Vitamin b12 injections to pregnant women with Pernicious Anaemia while encouraging them to take folic acid.

[fbirder in reply to 27Protons]

No, they wouldn’t need to know that.

When they work out how much water people need do they do it by theoretically tracing every possible route and it takes, and every reaction it takes part in? Or do they see how people are affected by drinking various amounts of water.

Read the link I provided. They discuss the desirability of fortification of foods with B12.

[27Protons in reply to fbirder]

I notice the report talks about the desirability of fortification of foods with B12 what I find surprising is that it finds that there appear to be essentially no risks of adverse effects to the general population of high oral dose intakes of B12 (other than Cyanocobalamin in member of the population at risk of Leber's optic atrophy) but it does not recommend (or overlooks the idea of) trialing/research into the effect high oral dose fortification could have on vitamin B12 deficiency

e.g what would happen if a slice of bread contained 5mg of vitamin B12 as most of those eating the high dose fortification will probably end up consuming 10s mg of vitamin B12 and we wouldn't need to be too concerned about what the recommended daily intake is if we can consume considerably more even at 1% absorption efficiency than any realistic estimate. Which would help reduce the effect absorption issues in the elderly have on their B12 intake.