Hello All,
I was wondering if on the days we do not inject is our bodies still healing with the b12 injection. I do EOD of methyl b12 and take multi b vitamins thought out the day every day and a liquid sublingual b12 every day. I'm begining my third month and the day of no injection my symtoms are the different than on the day of injection.
The half life of a B12 injection averages about 6 days from the studies I've seen so the answer is yes.
I wonder how our bodies decide what is excess and what is not? If the half life is 6 days, why do I get symptoms outside the 48hr mark? Or is it to do with the sheer amount of work B12 has to do in the body? 🤔 very interesting
Once your liver stores have been repleted, cells have adequate B12 and the transport mechanisms have been saturated, there is nowhere else for the B12 to go but into urine.
Whether someone with PA can utilize liver stores is something I'm not sure about - some textbooks indicate that the mobilization mechanism of B12 from the liver is not well understood. If a significant part of this mechanism relies on re-absorption from bile that would be an issue due to lack of intrinsic factor breaking the "enterohepatic recirculation".
Interestingly, at supra-physiologic levels of B12 (to be expected with frequent injections), intracellular levels of B12 may be reduced as I mentioned here : healthunlocked.com/pasoc/po...
So injecting beyond a certain point may cause your cells to fight off the excess B12 so hard that it might reduce the amount of active cellular B12 - probably not to dangerous levels, but possibly sufficient to trigger some symptoms.
Interesting! Thanks! It would be nice if we could come to a greater understanding of how B12 really really works. And how replacement therapy helps/doesn’t help. And then, of course, we need to get all the doctors to actually absorb THAT information. So, you know, mission impossible.
well thank you, well yes so one the second day or any days within the six days then our b12 is still working on our bodies, I feel it working still the next day but I wansn't sure if it was symptoms felt because i'm out already or it is just healing symptoms the day after an injection. and yes I have PA and it's been 2 months of injections EOD.
Surley this is the misunderstanding of many medics that liver stores can be restored then utilised ?Brilliant if this was actually the case.
Simple .
Also the wrong reason b12 Injections are refused or only prescribed 2-3 monthly
If dietary b12 deficiency of course once B12 replete your body can use it.
My personal experience of being told by some doctors I'm now sorted as B12 replete so no longer b12 deficient is incorrect .
If we could access any liver stores of B12 wd would be well .
Theory is overtaken by our bodies reactions/ symptoms.
My understanding ( not a scientist or doctor)
Is liver stores run down slowly ovef years for many many reasons.
Usually caught earlier if a matter of not eating enough B12 and if damage has not already occurred can be rectified swiftly .
If theres an actual absorbtiin problem then I thought the same problem is present utilising any b12 in your liver .
Everything I've read can make sense in theory .
My body tells me different.
Untill this is researched and understood fully we literally are going round in circles.
I've also read about once the process is overridden by saturation of B12 there's no going back to the natural process that was failing anyway.
A pancreas will stop doing any work at all when injected insulin is needed .
Initially a type 1 diabetics treatment csn give erratic symptoms as the pancreas kicks in occasionally giving hypos to the person.
Once the process is 'overidden' the person is more stable.
Super physiologic levels of B12 I'd personally risk versus not enough as so much not understood.
I do think a drip of B12 straight into a vein continuously woukd benefit and eliminate alot of the rollercoaster of symptoms 😐
Any treatment can give side effects/ symptoms.
The textbook information on how a healthy body utilizes B12 from the liver is not applicable at best and not proven even for a healthy body.
Seems it may apply to a body that has a restrictive diet by choice.
Indeed.
I also read that damage to/poor liver function is often not factored in for the "older" patient. But lickily, there are also several other B12 storage places in the body that could contribute.
When I read medical information about the body aging, I often wonder if it's not a case of the condition gets so severe that even the medical field can detect it.
I am not going bonkers, and i did in fact, find some studies which do indicate/confirm that we store B12 other than in the Liver - See my response below.
These seem to be for local use, perhaps more shorter term storage days/months? Please see full response below.
I feel, after all my high anxiety and proven nerve damage - I am hyperaware of my body and my symptoms. Going to the GP just kept my anxiety up.
But now I am doing all I can - i.e. B12 SI and supportings Vits etc. So,with that in place, i have stopped fencing with my GP, and i am trying to get on with my everyday. Having just done a four mile+ hilly walk, after years of fatigue, i have all the evidence i need.
Good on you for your hilly 4 mile walk.
I do not advise and understand the drive to find someone who can and will treat successfully. I have observed here that many 'stop fencing' with their GP and it seems to be the best course of action.
I am in a way lucky as the best I could hope for in the USA was loading once a month and oral B12 and folic acid. I would likely have experienced neurological damage with that treatment. The GP I was paying did not believe in injections at all. I made the choice to go with what I could learn by reading books. No way I could have known that EOD was not even close to healing. What I call my less worse phase.
I did not know that B12 could be found elsewhere in the body. It is a moot point for me as I do not methylate B12 well without self testing for that reality.
A talk someone posted recently by a doctor mentions that he treats patients with methylfolate and not folic acid. It sounds like some people do not methylate folic acid very well.
Methylation is important to almost every process in the human body.
Where are these b12 storage places? Any literature I've seen only mentions the liver. My b12 depletes rapidly without injections so I'm very doubtful that my body is storing it elsewhere.
I read it in a Techoid link, I think.... I will go dig it out.
I saw a really interesting talk recently posted on this forum. The pathway for recycling the B12 is very effective in someone without PA. But it uses the same approach in the gut to get it back into the body that is broken in people with PA. So normal people don't really "store" it but most is not lost. But this does not work when people have PA.
Hockey_player yes this is the entereohepatic recirculation, which is broken in PA due to lack of intrinsic factor. But only a maximum of 5mcg of B12 enters the bile every day (according to "Advanced Haematology" 7th edition textbook, page 60), so it seems that only an additional 5mcg would be lost daily if none was recovered.
5mcg might not seem like a lot. But the recommended daily amount of vitamin B-12 for adults is only 2.4 micrograms (mcg). I don't see how you are getting that only 5mcg is lost daily: if you have injected say 1000 mcg of B12, most of it is peed out within a few days. There is numerous studies tracking the amount lost. One for example says: Cynocobalamine is primarily excreted through the kidney. Approximately 50% to 98% of the injected cyanocobalamin is in the urine. A significant portion is excreted within the first 8 hours. So we can excrete HUGE amounts of B12 in a short time if it is extraneous to the amount we currently need.
I think I was WRONG there...it is just the liver... I thought I read it was stored temporilary in larger muscles. Apols Showgem.
Hi Showgem,
Regarding B12 storage:
The majority (>50%) of B12 is stored in the liver (1–3% methylcobalamin; 60–80% adenosylcobalamin) with total stores reaching up to 5 mg (ref1). 30% is stored in muscle (ref2).
ref1 :E. Laird, A.M. Molloy, in Reference Module in Biomedical Sciences, 2014 available online at sciencedirect.com/topics/bi...
ref2 : Messina M, Messina V. The Dietitian’s Guide to Vegetarian Diets. Gaithersburg, MD: Aspen Publishers, Inc., 1996
Found it.. !
Its primarily in the Liver, Yes - but there are much smaller stores elsewhere for " local" processing...these are not part of the digestive process. - I spend so long trawling through papers/links - that i eventually forget where i have read things Showgem.
======
Vitamin B12, aside from being stored in the liver, is also stored in other tissues in the human body. Here are the storage sites along with sources of information: ( = ChatGPT Search)
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Muscle Tissue: Muscles store a portion of the body's vitamin B12, though to a lesser extent than the liver. This storage helps ensure the availability of B12 for metabolic processes.
Source: Stabler, S. P. (2013). Vitamin B12 Deficiency. New England Journal of Medicine, 368(2), 149-160.
Kidneys: The kidneys contain significant amounts of vitamin B12. They are involved in the vitamin's reabsorption and metabolism.
Source: Carmel, R. (2008). Current concepts in cobalamin deficiency. Annual Review of Medicine, 59, 195-206.
Brain and Central Nervous System: Vitamin B12 is stored in small amounts in the brain and central nervous system, reflecting its importance in maintaining neurological health.
Source: O'Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. Nutrients, 2(3), 299-316.
Bone Marrow: This is another site where vitamin B12 is stored, playing a crucial role in hematopoiesis (the formation of blood cells).
Source: Allen, L. H. (2009). How common is vitamin B-12 deficiency? The American Journal of Clinical Nutrition, 89(2), 693S-696S.
These sources provide a comprehensive understanding of the distribution and storage of vitamin B12 in the human body beyond the liver.
========
I am NOT staying this trawl changes much ShowGem. The liver is the key storage element and recycling mechanism. But B12 is involved in complex body wide set of interactions.
I read further information on the studies you listed on kidney storage as this seems to be where b12 is mostly found other than the liver.
I haven’t had time to read it all completely but the conclusion was that they don’t really know much about it.
The studies were done on rodents, the b12 isn’t available in the kidneys for very long, weeks, not months it seems.and whether humans with b12 deficiency because of a broken system can access this b12 we won’t know without further research.
Personally I’m not waiting, I was near death because of my b12 deficiency and I don’t intend to go back there again while I wait for answers.
I would suggest that you need to read all of the studies before you reach a conclusion. I have read them all.
I see these good peoples work as good news myself.
I would not wait either.
I was not advising you should. On the contary, go your own B12 way, as we all need to do.
All the information i have posted on B12 stores was at your request.
Thank you for taking the time to look up these articles. I didn’t mean to sound rude and I apologise.
It’s probably me not being that computer savvy but I found it difficult to access and read these articles. I am short of time as so much going on this week but I will try again at another tim.
No worries. We are all in it together Snowgem. Take care. 
Is storage the right word for those other places? Lots of processes in the body need B12 to operate effectively. To me a "storage place" is somewhere to keep extra B12 in case it is needed later.
Nackapan:
"If theres an actual absorbtiin problem then I thought the same problem is present utilising any b12 in your liver ."
Thats what I'm not sure about. The loss of enterohepatic recirculation would definitely cause an additional loss of 5mcg of B12 that is not recovered from bile. But I'm not sure whether it will affect mobilization of liver stores of B12. I had stated that it would in my B12 primer so this may be where I've caused some confusion. I'm looking for better research on the process of mobilization of B12 from liver stores - in some textbooks it has been described as "not well understood" so it seems to me this is an open question.
It's not so much that medics have a misunderstanding about B12 being available from liver stores in PA, so much as that, as far as I'm aware, the process of B12 mobilization from the liver is just not well understood. If someone has encountered something more concrete on this process, I'm happy to update my knowledge.
So when a medic says that someone with PA "can use the stored B12 in their liver", as far as I know, we simply don't know whether this is true or not. We know that B12 recovery from bile would be a problem but this only contributes 5mcg to the picture, so I think its an open question.
Until our bodies say different!
Nackapan,
If I understand correctly, you're saying that because a return of symptoms is experienced in a fairly short span of time without injections, this proves that someone with PA cannot utilize their stores of B12.
I don't agree that's the case. It possible that current B12 deficiency treatment protocols for those with PA are poorly designed and that injections should be much more frequent but of a lower dosage (for example) to more effectively control symptoms.
If the treatment is inadequate due to poor understanding of B12 metabolism, and symptoms return as a result, that's due to poor research/lack of adequate knowledge on how to treat B12 deficiency properly in PA. It doesn't necessarily imply that stores of B12 cannot be, or are not utilized in PA. As I said, I think that's an open question, but open to hearing about any research which would shed light on that.
I agree with @Nackapan. We know that we are unable to utilise stores of b12, our experiences prove this to be true. Our plasma b12 becomes depleted without having frequent injections and we become symptomatic very quickly.
Our plasma b12 becomes depleted without having frequent injections and we become symptomatic very quickly.
Regarding plasma B12 - this is not the case, serum B12 often remains highly elevated (well over the normal range) even while symptoms return - this is why testing B12 once treatment begins is not recommended.
As I said, becoming symptomatic quickly may indicate that more frequent/lower dose B12 is a better treatment strategy, not that liver or other stores cannot be utilized.
Your experience does not prove what you think it does.
But in my case I believe it does prove it, as I said my b12 does become depleted.
A GP did test my levels again when I reported my symptoms returning before he would agree to me having more frequent injections than the usual 3 monthly. Although it had become high following my EOD loading doses, a few weeks later it had already reduced by half.
By the time I was given more regular injections following that blood test my symptoms had returned and I believe that is why I have neurological damage continuing after 6 years. If stores of b12 had been available to me surely that would not have been the case.
I hope one day we will be able to inject measured doses with a pen the same as my father would inject his insulin.
Research is absolutely needed but unfortunately many have presumptions based on how they think it works which seems to be very different for many with b12 deficiency.
"But in my case I believe it does prove it, as I said my b12 does become depleted. "
But your experience does not generalize - many people with PA experience returning symptoms although their serum B12 is normal or high. This is why all B12 treatments experts advise not to retest B12 levels after treatment has begun as they are not a reliable guide to whether treatment is being effective.
So clearly there is something else going on. Unless the argument is that those people can access their B12 stores and you cannot, but I don't think we can assume that. As with many things B12 related, we need more and better research on B12 metabolism , on the condition of PA and how to treat it most effectively.
We can't jump from personal experiences to assuming that some biological process is not working when we don't yet even have a good idea of how that process would work in a healthy person yet.
If you still have neurological damage, then it would make sense to have every other day injections?
If I understand rightly you haven't an absorption problem.So once on supplements or a richer B12 diet you can store and utilise b12 from your liver .
I hope I'm correct with that at least.
Its very hard to explain how your body tells you if you've not experienced this.
I've often posted saying it drip of B12 might be better ...who knows ??
I like to hear research too .
When you say it doesn't prove you cant utilise b12 from.stores in the liver what does it prove if symptoms return then relieved by a b12 injection then ?
Nothing I've read or the neurologist I saw read has convinced me oral b12 works as well for most people with PA or another absorbtion problem .
The reason B12 injections were invented
Of lower more frequent doses are better has been proved.
He did advise subcutaneous b12 injections .
He kindly wrote this to my G.p .
Also advising to keep them at 2 weekly at that stage.
Also stated his opinion on every available paper.
He was not convinced ( his terminology ) B12 injected even if stored coud be utilised as the process was obviously broken .
He had a keen interest as was recently needing B12 injections himself and not coping on the NHS regime.
He was trying to make sense of this .
He needed more frequent b12 injections 💉 like most do witb sn absorbtion problem.
He had an absorbtion problem.
He slso stated his body was not reacting to the theories hed read.
A breath of fresh air as didn't see him fof B12 .
My sister got b12 deficiency through lack of enough b12 in her diet .
Once replete her body obviously csn store and use the B12 if available !
An open question with no conclusive answers seemingly not on the horizon.
So meanwhile??
we have to do what we can to keep as well as possible .
I still think it indicates you cant utilise any b12 stores in the liver.
Otherwise it doesn't make sense at all needing frequent injections .
Hopefully we will get to know some day
Theory is theory.
People are people .
with no othef choice or guidance at present .
I will not stop injecting to rely on using B12 stores in my liver.
I've tried longer breaks ,
I've tried many regimes over 5+ yrsts now .
I am still on this forum to listen to what works for people.
We shard personal experiences,learn ftom each other.
So many case studies from here alone could prove certain theories incorrect.
I like answers/ reasons like the next person.
They are simply not there yet.
Also to those thst are new to this it's very important to treat as quickly as possible in loading doses to prevent as much damage as possible .
Worry about theories later for discussion.
.
I fail to understand how an experiment on mice can relate to humans with PA.
Until further investigations are done on liver stores and humans where this process is broken we can only go on our symptoms and what works for each individual to relieve these symptoms and to heal as much as possible.
If 2 or 3 monthly works that’s wonderful but we’re all different and some need to inject weekly or daily.
I do wish b12 vials were available in differing doses as maybe more often but less would work better.
"Until further investigations are done on liver stores and humans where this process is broken we can only go on our symptoms and what works for each individual to relieve these symptoms and to heal as much as possible. "
I definitely agree that we need to wait for human research that might confirm these findings in future. But I do find it interesting to consider preliminary findings like this and how they might relate to effectiveness of various types of treatment.
Showgem,
"I do wish b12 vials were available in differing doses as maybe more often but less would work better. "
Yes, that's exactly my suspicion - that more frequent, lower doses could end up being more effective than the large doses that are standard at the moment. But I've never seen B12 ampoules available in the kind of smaller doses that would be needed to try this.
And as you said, what is effective versus symptoms is most important at the end of the day.
The B12 I get come in 10,000 mcg vials. I inject 1,000 each time so that is 10 doses. But if I wanted to, I could use smaller doses. I would just need to get more needles when I buy the B12.
ah, interesting one. Does it have an expiry date for usage once opened?
Yes- it says one month. I should probably buy more after one month. It is only about $6 for the 10 doses. But the pharmacist said that the reason is that it could get contaminated. We are very careful to use rubbing alcohol and keep things sterile and he said off the record that this is OK.
I have found smaller doses (500mcg/injection) more frequently is right for me. To avoid throwing away half an ampoule my husband takes the rest. (yes, different syringe) He tested very low B12 before supplementing (though barely in range) and is having some cognitive decline, so this works for us. No wasting half the ampoule and we are both getting the B12 we need, although he has shown so much cognitive improvement that I am thinking maybe be should up his dose/frequency.
That all indicates to me that if you reach a B12 intake level that gives you coloured wee...you just scale back a bit...?
Anyone who understands that their body utilizes B12 injections at a rate of more than EOD has disproved those studies. Definitively.
No need to suffer following old textbooks.
Wow, I don't know where I got my information but way back when I started injecting I read that the half-life is 7 hours...which explains why some have to dose so often. I often feel it wearing off about the end of day two...makes sense.
I think the half life is much faster than that. The plot is from: sciencedirect.com/science/a...
Ooh this is interesting! 3000mcg of oral is more than current oral tablets hold isn’t it? And 40mcg is much less than our current 1mg
I can’t quite tell which one is total and which one is combined but that’s cool.
You know what would be equally interesting? A scatter plot showing how often PA patients need injections. It’s set my math brain going (my year 10 math class is doing data and graphs so it’s on the brain!)
Interesting that they were trying to find this out back then in the 1950’s. It’s a very limited study and I don’t know how accurate it was, I assume that the b12 wasn’t the little vials that we use today hence the smaller amounts injected in the study.
If there is a scatter plot, I think that another variable that should be considered is the type of B12 injected. I think that the UK uses hydroxocobalamin because it is not excreted as quickly as cyanocobalamin. I use cyanocobalamin because I can get it over the counter with no prescription in Canada.
A quartered scatter plot? One quarter for oral and then the others for each type?
Hmmm interesting.
You could also maybe have a bar chart for each type of B12? Along the x axis, choose different time periods, the bar height represents the number of people doing it that often.
I use hydroxocobalamin because I can buy it over the counter in Australia which I’m very thankful for.
That's for 40mcg of injected B12. But I have come across similar reports describing something similar to a 48 hour half-life.
But it seems most common to see B12 half-life in plasma reported as 6 days, for example in the cyanocobalamin pharmaceutical insert : s3-us-west-2.amazonaws.com/...
Perhaps there is a distinction I'm missing between time to clearance of the injected B12 and the half-life of B12 when in plasma.
This is a commonly referenced study from 1963 claiming a half-life of 5-6 days:
Although I would not cite it as an authority, the six-day half-life has also made it onto the B12 page in Wikipedia, seemingly unchallenged.
This is the point at which I realize I have no pharmaceutical training I guess 😅
There are a few people on this forum who need injections more often than every other day. You could try every day for a week and see if that improves the situation?
yes that is true, and I think also if it is early in our treatment of injections that matters too. I'm hoping.
Cofactors - B complex?
The Railway Worker 
Wheres my delivery
Gluten and B12 deficiency 
