Will I ever be able to store B12 in my liver and muscle?

[xyz011]

I have been getting B12 shots weekly (cyanocobalam) for over a year. I used to be exhausted before the week ended, now it is just sometimes. I am wondering when and IF I will ever have enough B12 shots that some gets stored. I am thinking by now most or all of my nerve repair is being done??

[GGourmet]

I think someone else with more knowledge should answer this. My understanding is that hydroxycobalamin can be stored in the liver but not methylcobalamin or cyanocobalamin. These are used for short lived serum top ups.

[Gambit62 Administrator]

Although B12 will be stored in your liver the mechanism that allows it to be efficiently released into your blood is broken so you won't have a useful store. B12 is released from the liver in bile into the ileum for reabsorption but if you can't absorb B12 from you diet in the ileum you also won't be able to use the B12 that is being released from your liver - it's like having a reservoir but there's a huge hole in the pipe.

[fbirder in reply to Gambit62]

is B12 only released from the liver into the bile? Is there no direct secretion into the blood supply?

[Gambit62 Administrator in reply to fbirder]

not found any references to other release mechanisms but if you want to look into it I'd love to know the results.

[fbirder in reply to Gambit62]

I have looked and found nothing. I would be surprised if there wasn't some equilibrium between liver and blood.

[Gambit62 Administrator in reply to fbirder]

been thinking about it a bit. My understanding is that the B12 stored in liver is bound to haptacorin so unless there is some process to remove that and allow it to bind to TC - then some equilibrium between liver and blood isn't actually going to allow you to use the B12 that is passing between the two anyway.

However, long way from being an expert.

[Foggyme Administrator in reply to Gambit62]

Gambit62 / fbirder ...also been thinking about this 🤔🤔.

Here's some thoughts/information and a research paper I've found:

The majority of B12 (70-80%) is bound in the blood to haptocorrin - so called inactive B12.

A minor proportion (20-30%) enters the blood bound to transcobalamin (also called holotranscobalamin or active B12).

B12 is transported to the liver via the portal system and stored in the liver on transcobalamin 111.

Transcobalamin 111 also circulates in the blood - and so carries B12 to the cells...so B12 stored in the liver on transcobalamin 111 is able to re-circulate in the blood via the portal system.

Here's a couple of links that speak to B12 transportation, albeit in a very simplified way (the second one has a basic diagram that shows transportation mechanisms)

active-b12.com/vitamin-b12-...

veganhealth.org/b12/dig

And here's a research paper that speaks to the transport of B12 from food to cells and also includes information about transmembrane transport of vitamin B12 in its free (non-protein bound) form (very dense...I'll probably only ever get the basics of this...there's much that's way over my head 😖😱)

researchgate.net/publicatio...

Also left a reply for xyz011 below.

Sorry if I've over-simplified a very complex topic...but my goodness, you've raised some interesting questions...so more research for me, I think 😀

Still have places to search for papers specific to portal system circulation of B12...may have time to look tomorrow and if I find anything, I'll pop in another reply.

👍

[Gambit62 Administrator in reply to Foggyme]

thanks foggyme - so had gotten the form that is stored in the liver wrong ... but still means that the TC111 needs to be converted to TC11 so it can be absorbed by cells - which presumably means using the processes that happen in the ileum.

will have to try and find some time to look up the genetics

[Foggyme Administrator in reply to Gambit62]

Yes...see what you mean. This is going to bug me...so will join you and keep looking...

👍

[xyz011 in reply to Foggyme]

you administrators ROCK! Thank You!

[Foggyme Administrator in reply to xyz011]

LOL...rocking as I type. Thank you xyz011 😊

[mcenerny in reply to fbirder]

Cyanocobalamine has to go through a long process to become available - if you try adenocobalamine or methylcobalamine it gets to the cellular level more directly. The liver has to remove the cyanide from cyanocobalamine first - it is used in injections because it is cheap, not good. Your genetics have a lot to do with which form is best for you. Sublingual lozenges bypass the digestive system as well. It also helps to take R-Lipoic Acid for the neuropathy.

[fbirder in reply to mcenerny]

All forms of cobalamin, cyano, hydroxo, methyl and adenosyl are treated the same in the cell (the cell where it is used) and in the blood.

Transcobalamin does not distinguish between the different cobalamin types. It binds with them all and transports them all into the cell.

Once in the cell the top ligand (cyano, hydroxo, methyl or adenosyl) is removed. The resulting molecule is transported to the area of the cell where it is needed, where it is converted to the required co-enzyme type (methyl or adenosyl)

ncbi.nlm.nih.gov/pubmed/258...

[xyz011 in reply to Gambit62]

WOW, thanks!

[Foggyme Administrator]

Hi xyz011. Once the body has to rely on injections for B12, the usual mechanisms whereby B12 is stored on a continuous and going cycle in the liver no longer work in the 'usual' way ( Gambit62 's hole in the pipe).

Here's something I wrote in a reply several months ago when asked a similar question - the question in that case was about falling levels of serum B12 following injections, and why so much B12 is excreted in urine (a simplified answer 'cause it's all quite complicated...so excuse me for that 😉):

People become deficient in B12 when B12 stored in the liver runs out (can take many years) and the usual absorption mechanisms fail (for a variety of reasons). So B12 has to be obtained via injections (that's the easy bit 😀). (B12 via injection circulates around the body via the blood, with small amounts stopping off in the liver and being collected by the blood as it re-circulates (haemo-hepatic circulation - aka fbirder 's reply).

When B12 is injected, B12 attaches to transcobalamin 2 and transcobalamin 3 (TC2 and TC3) and is transported to all body tissues through the blood and cerebrospinal fluid, where it is then released in the form of Hydroxocobalamin - which is in turn turned into methylcobalamin and adenosylcobalamin so that it can be utilised properly by the cells (but please don't ask me to explain the mechanism for that 😖).

(It's actually more complicated than this and I'm purposely avoiding talk about haptocorin, TC1...etc... which are also involved in the process - but if anyone wants to have a go...👍

At the same time, TC2 and TC3 transport B12 to the liver (via the blood): a small amount is stored in the liver and the rest of the B12 continues its journey around the body in the blood...to the cells...and so on, with the blood collecting more B12 from the liver as it passes through. However, the amount of B12 stored in the liver is very small compared to the storage capacity of someone without the absorption problems caused by B12 deficiency. So...this is why blood levels are high immediately after injections, but gradually drop as the small amount of B12 stored in the liver is constantly re-circulated by the blood, as it passes through, until the B12 eventually runs low...and would eventually run out if not replaced by more B12 injections. A good reason why GP's should never stop B12 injections simply because they think serum B12 levels are too high.

In terms of the excess B12 being excreted in the urine - if circulating B12 exceeds the binding capacity of the blood (i.e there is more circulating B12 than can be bound to TC2 and TC3, then this excess B12 is simply excreted in the urine.

(50% of injected B12 is excreted within 24 hours of an injection).

So...that's why blood levels are high immediately after injecting B12 but gradually fall away if not replaced with injections 😀.

End of previous post 😀😀

So, what this means is that if B12 is absorbed in the usual way, through ingestion and absorption, the liver has a continuous daily supply of B12 which is absorbed by the ileum and gets stored in the liver...and is then taken up by the blood (and cerebrospinal fluid) for distribution to all the cells that need it. In this mechanism of absorption, the liver has a never ending supply of B12 that arrives continuously from diet...so liver stores remain 'topped-up' and there is always sufficient for all the body's requirements.

The difference when having B12 delivered by injections is that the B12 supply is intermittent rather than continuous (it only arrives when you have an injection) and the amount that can be delivered to the liver for storage is limited by the binding capacity of the blood (so lots of B12 is simply excreted in urine and never makes it to the liver for storage).

In this sense, it's never possible to get enough shots to have enough B12 stores in the liver to be able to stop having injections...if that's what you're asking. (You need the shots to keep topping up the very small store in the liver....which runs out quite quickly if shots aren't maintained).

If your symtpoms are under control and you feel fit and well, then yes, repair has taken place and B12 is 'doing the trick'.

But the vital thing is that the shots are still needed because without them you would become B12 deficient again quite quickly, your symptoms would return or get worse, and damage would start to re-occur 😖.

It's all really complicated and not sure if I've 'said it' very well (it's quite late so the my brain is flagging 😉😀)...but hope it helps to answer some of your questions (shout up if I haven't been able to be very clear I'll try again) 🙄.

And if anybody out there can add anything...😉😀

[Ajane in reply to Foggyme]

Thanks for the question xyz011.

And thank you foggyme for this very helpful explanation.

So are sprays, sublinguals & patches absorbed & used in the same way as injections? I'm guessing the body has to work harder to absorb these??

[Foggyme Administrator in reply to Ajane]

Hi Ajane. Yes, sprays, sublinguals and patches work in a similar way.

However, the uptake of B12 from injections is 100% but the uptake from the others is only 1-3%.

It's thought that with sprays and sublinguals, some is absorbed through the membranes and into the blood supply and some is absorbed through passive absorption from the gut (the portion that is inevitably swallowed and potentially floods the gut with high doses of B12).

It's not clear how much is absorbed via the blood and how much through passive absorption.

It's also not really understood why sprays, sublinguals and patches work for some people, but not for others.

👍

[Ajane in reply to Foggyme]

Thank you. I had started to use sublinguals & spray to see if they worked for me, but as of yesterday, after sending a letter in desperation, my GP has agreed to me having another 6 loading doses to try & alleviate my exhaustion.

So relieved to have finally been listened to 😊

All the best Xyz011 - it can be a long road to getting the right treatment 😕

[Foggyme Administrator in reply to Ajane]

That's good news Ajane 😀...hope it makes a difference.

Also hope that your GP is aware that if you have neurological symptoms, you should remain on every other day injections until no further improvement - for some, this can take many months. Once you've reached this stage, injections should be every eight weeks (not many GPs know this - details contained in the BNF - GP will have a copy - second item down so will. have to look further than they usually do).

Neurological symptoms aside, if your symptoms (including exhaustion) have a pattern of returning before the next injection is due, then getting better once you've had another jab, then this is a sure sign that you need more frequent injections.

Some GPs will agree this, many won't - but it's worth trying to negotiate.

Good luck and I hope you begin to feel much better very soon.

👍

[Ajane in reply to Foggyme]

Thank you. Yes, I have been trying to get that point across, but this is at least an improvement in treatment, so I'll take it from there.

I guess cases like mine which need protracted every other day injections are rare enough for the average dr not to see them often enough to set a precedent. Let's hope I'm blazing a trail for the next poor person through the door with a B12 deficiency! 😊

[Foggyme Administrator in reply to Ajane]

Hi Ajane. Unfortunately, I think the issue is that GP's are woefully unaware that B12 deficency can cause neurological symptoms, and frequently does. Patients are often dismissed and symptoms ignored - or attributed to anxiety, depression...or a whole host of other things. Sadly.

And blazing a trai...you certainly lay are. Hopefully anybody who follows will fare better than you...thanks to the way you're re-educating your GP. So hurrah for that 😀.

Hope things continue going in the right direction 👍

[Ajane in reply to Foggyme]

I'd say my GP is better than most, but 'injections every other day until no further improvement' doesn't seem to compute! I'll keep plugging,but may well end up self injecting.See what transpires when I speak to the neurologist again. Thanks for all your help & encouragement 😊

[Foggyme Administrator in reply to Ajane]

Yes...anybody would think we're asking for a controlled drug...

Keeping everything crossed for you 👍

[xyz011 in reply to Foggyme]

WOW, that response was wonderful! I am going to print this response and keep it as a resference (still foggy at times)! This explains my total exhaustion that hits me at times I believe! Thank YOU, THANK YOU!

[Foggyme Administrator in reply to xyz011]

Just pleased you're pleased xyz011 😀😀.

Just thinking about your total exhaustion and wondering if you also have other symtpoms that return as well?

If your symptoms return sometime prior to your next injection being due, and remain untill you have that injection, it's worth having a discussion with your GP to see if you can have your injections more frequently. Might be worth keeping a symptom log to see if you can find a pattern - then share this with your GP, as evidence.

Many people find that three monthly injections are not sufficient to keep them symptoms free and well. Some negotiate more frequent injections with their GP's (not always easy unless you have a knowledgable GP who understands B12 deficency and realises that more is not dangerous and that one size treatment does not fit all). Some top-up between injections with high dose sublinguals, nasal drops, patches etc (though these do,not work for all). And some decide to self-inject B12 between surgery jabs as the only way to remain symptom free (usually as a last resort when negotiation for increased frequency via GP fails).

It's also worth noting that if you had neurological symptoms when diagnosed with B12 deficiency, you should have had a more intensive regime of injections (after the six loading doses - every other day until no further improvement). The maintenece dose for those with neurological symptoms (after the intensive regime) is an injection every eight weeks (information about this in the BNF - your GP will have a copy - it's the second item down so further than GPs usually read).

So...if you ever had neurological symtpoms, might be worth asking your GP for eight weekly injections (as per all the guidelines - BCSH, NICE, BNF etc.).

Good luck...and I really hope that your total exhaustion soon becomes a thing of the past.

Put up a new

Put up a new post if you need any more help.

Take care xx

[xyz011 in reply to Foggyme]

Thank you so much, again. I had major neurological symptoms and was fighting like mad for more injections a year ago. I have decided to keep a journal. I live in the USA, so my GP is probably not familiar with those documents. My GP is pro keeping me on shots!

[Foggyme Administrator in reply to xyz011]

A GP who is all for,keeping you on shots...wow...a real gem.

Excellent news 👍