B12 storage in the liver

[Pickle500]

Hi all

I had a quick question on liver stores of B12.

If someone has PA, do they no longer absorb B12 to their liver?

I heard that PA compromises liver storage, hence the constant need for injections? Is that correct?

Just curious

Thanks

[Nackapan]

I think its there but you cant utiluse it .

[Tiggywoos in reply to Nackapan]

does that mean it continues to build up in liver ?

[Polaris in reply to Tiggywoos]

My understanding is that excess B12 is disposed of in the urine, after being absorbed by receptors in the ileum, which is why you cannot overdose.

One of the tests for PA/B12def. is homocysteine. If this is high, it ends up in the liver, where it’s broken down by B12, B6 and folic acid. Deficiency in any one of these vitamins means homocysteine builds up.

However, it’s not the best test, as homocysteine can be high if you have thyroid disease.

[Tiggywoos]

Great post but I don’t have clue so will be interesting to see replies 🙂…

[helvella]

The common claim that the liver can store enough B12 for years is, fundamentally, a misapprehension.

If someone with "normal" management of B12 were to switch to a diet with zero B12, they could last a long time before suffering B12 deficiency.

But this is not due to having a vast amount stored. It is due to recirculation.

B12 is released from the liver, goes round the body, most of it ends up in the gut, from where it is largely re-absorbed.

Cut off that recirculation, and instead of the store of B12 dropping a tiny amount every day, it drops by a far, far greater amount.

A car radiator might lose a tiny amount each day meaning that once a year you need to top it up. But if one of the hoses is leaking, even a small amount, you lose far more and might need to top up every day.

In health, you only need to replace the tiny loss of B12. With impaired absorption from the gut, you need to make up the entire amount that is released each day.

[Pickle500 in reply to helvella]

Fascinating

Do we know how B12 gets into the liver? Does the instrinsic factor pick it up from the stomach, then take it to the ileum, and then it goes into the liver?

[helvella in reply to Pickle500]

I am no expert. Maybe a look here:

The Enterohepatic Circulation of Vitamin B 12

b12deficiency.info/wp-conte...

Twelve years old but still relevant and straightforward.

[Technoid in reply to helvella]

great paper! Some additional details on that process can be found here : veganhealth.org/vitamin-b12...

[Hidden in reply to helvella]

wow thanks for such a clear, comprehensive answer. Really helpful

[Polaris]

This is what DrJoseph Chandy writes in his book, “Vitamin B12 Deficiency in Clinicsl Practice” - generously available on line chapter by chapter :

……………………..

”The absorption route is complex, has several steps and damage to any one can disrupt the process.

Vitamin B12 is bound to protein. This bond is broken by gastric acid and enzymes in the stomach which free the vitamin.

The free vitamin B12 then binds to a protein called haptocorrrin, again freeing the vitamin B12 …………..which is made in human saliva and parietal cells in the stomach and which protects vitamin B12 from stomach acid.

As this complex passes through the more alkaline duodenum, pancreatic enzymes destroy the haptocorrin, again freeing vitamin B12, which now binds to a molecule produced by the parietal cells called Intrinsic Factor.

In the ileum, vitamin B12 -IF complex is recognised by special receptors and absorbed into the blood.

In the blood, it is bound to two carrier-proteins. Some is stored in the liver and the remainder available for immediate use.”

[Pickle500 in reply to Polaris]

Thank you for digging this out. I wonder if the two carrier-proteins in the blood are needed to get it into the liver, then?

And so injectable supplements, not attaching to carrier-proteins, would not make it in the blood to the liver?

Seems like more to explore potentially!

[Polaris in reply to Pickle500]

It was only after I sent Dr Chandy’s book to my surgery, that I was offered IF testing. To be fair, I suspect it is the complexity of B12 deficiency that makes busy doctors unable to give time to PA/B12 deficiency ?

Found more info on B12 pathway on my ipad Pickle500 if it helps in any way. I read a lot of books on B12 over the last ten years or so but, as an old lady now am finding it too complex to absorb😀

This is part of BMJ research document summary (full document behind a paywall) :

bmj.com/content/349/bmj.g5226

………………….

Page 1 under: What is the pathophysiology of vitamin B12 deficiency?"

“In serum, vitamin B12 is bound to haptocorrin as holohaptocorrin (formerly transcobalamin III) and to transcobalamin as holotranscobalamin.

Holohaptocorrin accounts for 80-94% of endogenous plasma vitamin B12. Holotranscobalamin on the other hand accounts for 6-20% of bound vitamin B12. It is synthesised in enterocytes and, through receptor mediated endocytosis, is responsible for uptake of vitamin B12 from the ileum into the blood as well as into other cells.

Only vitamin B12 bound as holotranscobalamin is presented for cellular uptake.

The malabsorption of this holotranscobalamin protein-bound vitamin B12 results in vitamin B12 deficiency in several cases.

Intrinsic factor is a protein, produced by the parietal cells of the cardiac and fundic mucosa of the stomach. It binds vitamin B12 to allow its absorption through the gastrointestinal tract, by way of a receptor on the intrinsic factor that is specific to cells at the terminal ileum. If there is resection or disease of the gastric mucosa or terminal ileum, this leads to vitamin B12 deficiency as a result of malabsorption.

Pernicious anaemia is an autoimmune disease with atrophy of the gastric mucosa of the body and fundus of the stomach. This reduces the number of parietal cells that produce the intrinsic factor necessary for absorption of vitamin B12.

Secretion of intrinsic factor parallels gastric acid; thus there will be reduced secretion in an alkaline environment created by the long term use of high dose proton pump inhibitors and similar drugs. “

…………..

Figure 1 goes on to illustrate the normal mechanism of vitamin B12 absorption.

PS There is more on Tracey Witty’s old website under ‘films’ - where a scientist in the video explains the B12 pathway.

[Pickle500 in reply to Polaris]

Thank you!

Yes I agree. Even the best scientific minds would struggle to unpick all of this. And they probably do.

Glad the book had such an impact for you

[jaybirdxNHM in reply to Polaris]

I empathise,getting old is a bind. I understand when reading, but if I then have to verbally transmit--+ no chance !!!!

[Lurcher-lady in reply to jaybirdxNHM]

And that is when you are deemed not to know what you are talking about lol. I have the same problem it’s so frustrating 😡

[Yahaci]

I felt I was going down a rabbit hole over the last few weeks. I realised that when things get over complex, its best to go back to basics.

So I don't know if I have PA, but I know B12 is essential and I felt better after injecting. So I listen to my body and supplement where necessary. The body is very complex yet resilient, I see many elderly people who are healthy though ignorant.

On the flip side I've seen OTT people who want to micromanage every nutrient. Not realising it doesn't work that way. Or go from one regime to another, and appear deranged. It's a bit like cosmetic surgery, it looks good for a while, but as they age, people look bizarre. Whilst those who didn't, look really quite good. So having an overall balanced life and approach is the best protection.

[Parlay]

I believe the circulatory system of b12 is called the enterohepatic system involving the gall bladder bile duct small intestine back up to the liver and circulates continually with our nerve cells taking what’s necessary. Some one with better knowledge than me will come along and embellish on this!!!

[Pickle500 in reply to Parlay]

Very helpful thanks

[jaybirdxNHM]

I recieved large order from Versando yesterday 12th. 11.2023 ,but I had by same delivery1 pkt of 10 in separate parcel( another £9 post). Invoice dated day before large order!!! Must be my fault, as try to order that day also, half way through said " all gone". I forgive them anything ATM . The date on this pkt is 05. 2026 The box same design and colour ,but different card and slightly different colour.Hope this bodes well for future supplies.🤞🤞🤞

[Dilly_blue]

Such an interesting thread, thank you! I’m really intrigued by it all too… and think that for me, problems with re-circulation of B12 are also contributing, as the effect of a B12 injection falls away by day 5. I have some problems with liver, and gallbladder, which seem to play a part in recirculation - I wonder how much? If only it could be proved / widely recognised that these types of additional factors perturb efficient re circulation then it would be a strong case for twice-weekly injections. I imagine this would hold true for all with PA, or those with a constellation of other autoimmune-type things going on.

I have been reading recently about haptocorrin, and how if there is a deficiency of haptocorrin then the B12 becomes denatured as it encounters gastric acid (and loses enzymatic properties), as the haptocorrin binds to B12 and protects it from damage from the acid.

Apparently antibodies to salivary glands are quite common with Aire gene mutations… I wonder if disrupted / reduced salivary flow could result in lower levels of haptocorrin, which means that although the B12 continues on it’s journey, and gets absorbed, a large proportion of it has been ‘denatured’, and therefore can’t do all of the things that B12 is supposed to. I suppose this could mean that there could be high total B12 levels, and also correspondingly high ‘active’ b12 levels (as the ‘active’ b12 (HoloTC) is that which hasn’t been re-bound to haptocorrin in the recirculation process. So if there is less haptocorrin, then it will look like you have higher ‘active’ levels, even though they are probably denatured, and possibly useless..

I will try and do some more digging on this..

Sorry can’t add references, am not at my lap top!

[Pickle500 in reply to Dilly_blue]

Thanks for your super interesting reply. Im going to cogitate on it a while!

[LFKent in reply to Dilly_blue]

A really insightful post Dilly_blue. Thank you for sharing.

[Cherylclaire Forum Support in reply to Dilly_blue]

Very very interesting to me, Dilly_blue - as I have salivary gland problems due to saliva duct strictures... and have an appointment with Oral Medicine consultant next week concerning burning tongue "syndrome" !

[Hidden in reply to Cherylclaire]

a good website is the Human Digestive System __-

wikipedia

[Dilly_blue in reply to Cherylclaire]

Ooh - please ask the Oral Medicine Consultant some questions about it, and do report back to us!

I’d love to hear their opinion on whether dysfunctional salivary glands can lead to lower haptocorrin levels, and if so, what the impact on B12 integrity would be??

In my recent reading, I also read that human breast milk contains haptocorrin.. so I should imagine that it confers benefit to the baby (perhaps it mitigates an immature salivary gland system?? And perhaps enables additional B12 to pass unharmed through the gastric acid, even if the baby isn’t producing enough haptocorrin of its own??). As an aside, I wonder if haptocorrin is available to buy as an oral supplement??! I think it would be worthy of a trial! I am hoping to get an opportunity to speak to an Adult Metabolic consultant later in the year, so I will definitely ask lots of questions then..

I have had a discussion (appointment) with a hospital consultant (different specialism - endocrine) this morning - apparently some antibodies (some specific endocrine ones) can come and go, so it can be difficult to test whether there are antibodies present at a specific point in time. However, they did say that usually, it is easier to identify damage that may have been caused by previous antibodies, (rather than trying to track the antibodies themselves down) - but this was all with reference to certain endocrine autoantibodies, so perhaps may not translate to other autoantibodies.

I am definitely going to try and read up on whether IF antibodies can also be intermittent, as this would suggest that the only way to categorically identify whether gastritis is autoimmune (ie PA), is by doing a biopsy of the cells, to identify the damage caused by the IF ab and GPC ab. I suspect this is not often done though…

I have lots on my do-list for reading up on!

Ps - I am in no way qualified in anything relevant (medical / health) - these are all just observations and questions that I have

[Cherylclaire Forum Support in reply to Dilly_blue]

I once met a wonderful senior ENT consultant who had received a detailed report from my very determined GP. Unlike some other consultants (eye-rollers), he was highly complimentary - told me to congratulate her on her report, found it very useful, quoted from it and spoke to me about it.

I had brought up the question of haptocorrin with my GP - and she had asked him in this report. He agreed with me that salivary duct and gland problems which restrict saliva would certainly affect the protection that B12 in food (extrinsic factor) is generally afforded by haptocorrin.

He told me that it was evident from my photos and from looking at my tongue that I still had B12 deficiency (he looked, didn't need to test).

Best of all, he said that I was doing the right thing by self injecting every other day, to carry on and not get disheartened because it would take a very long time to get better. I trusted him and over time he was proved right.

A few years later, he performed a nasendoscopy on me - and so I got to thank him personally for encouraging me when I was so ill -and so afraid that I would not get any more improvements.

I hope that the Oral Medicine consultant that I see next week can help. I hope he is the same one I saw last time. When I was passed on to him, the first thing he asked me was "Have you got a vitamin deficiency ?" - before he had even had access to my notes !

A good start ....hopeful. I'll let you know.

[Dilly_blue in reply to Cherylclaire]

that all sounds amazing - exactly what you need from a health professional! And your GP sounds great as well, it is so good to hear a ‘good news’ story, for a change.

I found a research paper that said something like (from memory) 60-70 per cent of people with APECED (two copies of the faulty AIRE gene) had antibodies to salivary glands (when tested). I wonder how many people with one faulty copy of the gene have had antibodies to salivary glands?

Wishing you so much luck next week - please report back and let us know how you get on!

[Cherylclaire Forum Support in reply to Dilly_blue]

Well - here's the bad news.

My GP has left the practice recently, as has another really good GP -and both into the same field but in different hospitals: rapid diagnosis. A huge loss to one surgery - but imagine the massive gain for NHS hospitals to have all that experience at the diagnostic stage.

Sad though, personally.

[CraftyKit]

Hi

I have just quickly read through some of the posts and will read them later when l have more time. I have just one question (sorry if it was covered already). If B12 is stored in the liver can this show up on a blood test as a problem. I know it is broken down there but l was just wondering. I have had a few blood tests for something else and every now and then l get a call to come back for a liver test to be redone as the reading was high. They then ask if l drink large quantities of alcohol - my reply is usually yes once a year on holiday and maybe the odd one at Christmas, but l can't see how this would cause my results to be abnormal.

Many thanks

[Technoid in reply to CraftyKit]

Some studies have found B12 deficiency to be a risk factor for non-alcoholic fatty liver disease. journals.lww.com/ajg/Fullte...

The questions they are asking suggest they are trying to exclude alcohol as a contributary factor to the elevated liver results. I found the following video helpful on liver tests but warning that it is VERY long! It helped me interpret my own liver test results and see what kind of number was interesting and what kind of number would be alarming. I have zero faith in most doctor's ability to interpret blood tests now so if I see a low or high number I try to figure out for myself if that is a concern or not (or ask experts who know better). This forum is full of people whose doctors told them everything was fine but if you were to look at their blood result test and do a little research you might find otherwise.

m.youtube.com/watch?v=Y4Q9f...(Not working as expected?)