On a 'sort out ' of random notes in numerous notepads in the quest of getting well I came across this:
whilst B 12is not toxic raising b12 levels with injections csn affect the way its transported from the blood to cells.
1/3 of population needing b12 Injections need to keep their levels high and csn never do well on -2-3 monthly regimes
The medics seem ignorant of this fact as woukd surely not stop or reduce b12 Injections if thus was understood or taught ??
As in my non scientific head.
If you medically needed them I.e an absorption problem of any sort when b12 is not reaching the cells.
or a diagnosis of PA.
Once this process has to be overridden as no longer works.
The treatment has to continue as the treatment needed also makes any function that was there even less efficient
At best over supplementing a waste of time with B12
At worst make tge process less efficient.
Blood to cell transported transcobalmin .stripped of cyno/hydro / aden
( notes then jump) probably as got too technical for me.)
my summary
if an absorption problem/ PA
B12 shoukd be supplemented for life by b12 injections
Testing...not recommended
Base frequency on symptom response
If tablets/ sublingual trialled abd symptoms return or wirsen.
assume non dietary cause
Treat with b12 injections for life.
I have put on the bottom BCSH.
Can anyone help with this.??
PAS coukd use the scientific paper for future guidelines fir treatment.
I now feel this is vital to put to GPS who are always Tring to reduce or stop b12 injections.
In other words once on injections when medically needed you stay on them.
If dietary from a fad diet .
I.e like my friend . A living example
a course of b12 injections.
A change in diet
going by symptoms
then a b12 test .
No need for further injections as dietary and the actual process was working with the correct intake.
These notes I'vemade over yesrs trying to understand.
G'ps have to take responsibility that if b12 injections deemed medically needed to prescribe they are medically needed to continue.as a proportion coukd never go back to a even poor/ broken system as its been overridden
To help my understanding.
Insulin treatment replies the job of the pancreas. When my husband first went onto insulin injections his diabetes was brittleness.ie kept collapsing with hypos
The reason given was the pancreas would occasionally decide to kick in .randomly dropping his blood sugar .
His diet kept exactly the same. Ect.
As time went on the insulin regime overrode the pancreas so it gave up on the job completely.
surely similar
Any scientists
Any papers
Been bugging me as seems so vital and makes sense of what's happening
Written by
Nackapan
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This is super interesting and exactly the question I have been trying to understand myself. I don't think anyone really knows. Why do I need 2x daily after 6 years? Why do my relatives need 1x daily after 1 year and perhaps 2 on days when they exercise? There are still others that need EOD or weekly years on as well. What makes those people different from the people that get along on 4 shots per year?! Some thoughts:
It might have something to do with transcobalamin (TC), as you write above. TC II is the well-known one, that transports the B12 from the intestine into the cells in the body.
I've been meaning to do more research on this. One paper I found from the 70s found that after an injection, the level of TC II antibodies increased. I do need to see if there's more recent research on this. But assuming this could be the case, it can be one explanation - fewer transporters requires constant higher levels of B12 to ensure they are all properly saturated?
In the US you can also get unsaturated B12 binding capacity of transcobalamin measured (UBBC) - I'm not exactly sure of the details, but it measures how much B12 the TC can bind (not the amount of TC itself). We know that starting injections naturally reduces UBBC, so perhaps in some people UBBC drops too much, and again we need much more B12 to take advantage of the remaining transport capacity?? Again that's my own hypothesis, I haven't read enough of the literature so say anything for certain.
One direction to look at is people with genetic transcobolamin deficiency - they will have low levels of both TC II and UBBC. In the literature, it has been determined quite clearly they need at least once weekly injections - no way could they last 3 months. So the increased need for injections with PA, to me, could point in the direction of some sort of transcobalamin issue.
Edited to add: almost all of those people with genetic TC II issues need hydroxocobalamin. So there is something more to this story that I don't yet understand.
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So there are also TC I and III, the Haptocorrins. TC I is produced in the salivary glands and protects the b12 from stomach acid. I'm guessing that won't play much role in what we're discussing here.
TC III on the other hand, according to many sources, is a storage molecule. It binds and holds onto B12 for later use. So perhaps TC III is defective to some extent in those that need very frequent injections. One chemistry book I found talks about the half-life of the TCII-B12 complex - it's about 5 minutes! The TCI-B12 complex has a half life of 9-10 days however. They do not talk about the half-life of TIII! So defective TC III of some kind could be another factor. (The book is behind a paywall, link.springer.com/chapter/1...
From ncbi.nlm.nih.gov/pmc/articl... : "No specific function has been assigned to this protein other than binding a large fraction of Cbl in circulation. This may prevent loss of free Cbl and its lack of specificity for Cbl may aid in clearing corrin–like compounds from entering the cell via the TC-receptor pathway." -- by protein they mean both haptocorrins. [From Quadros EV. Advances in the understanding of cobalamin assimilation and metabolism. Br J Haematol. 2010 Jan;148(2):195-204. ]
There was a flurry of research in the 70s and 80s on transcobalamin, but not much recently, though there is more and more genetic research into the various genetic cobalamin deficiencies mentioned in the Quadros paper, as well as enzymes and other things involved in B12 metabolism. Any one of those mechanisms could be responsible.
I don't know at exactly which point the various cobalamins get converted but there could be an effect there as well.
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One thing all researchers agree on is that B12 has a very complex metabolism. Probably much we still don't know.
So I haven't answered your question, but I do admit it is a great question.
TCI (the haptocorrin in saliva) is the first of all the processes for extrinsic factor (food that contains B12) to go through. If there is little or no protection at this early stage, there will be little chance of B12 making it through to cell/tissue level, especially where other problems involved later in the process.
Plenty of people have problems making sufficient saliva to coat food in order to protect it. Saliva is easily accessed, so perhaps a test could be devised to measure saliva for haptocorrin. Insufficient haptocorrin would be the first point at which the whole B12 process could go wrong.
Inappropriate leaching of haptocorrin could be another. How many here have inexplicable "burning tongue syndrome ?" I am just guessing here, since I have found no documentation on this. I am beginning to hate the word "syndrome" as it seems in many cases to have become an excuse to stop investigations.
In 2012, I first suddenly got a problem with salivary ducts and glands. The ducts had strictures and were misshapen, the saliva could not travel along them from the glands- resulting in pressure, numbness and swelling. Not permanently - suddenly, when hungry.
I was found to have B12 deficiency in 2016 and B12 injections started. Later, when unresponsive on one injection every 3 months, my MMA was found to be raised and I was diagnosed with functional B12 deficiency. Treatment upped to two injections a week for six months. When I got worse again, this was reduced to one a month and I was sent to haematologists. I eventually started self injecting at an EOD frequency in order to reduce symptoms as much as I was able.
A senior ENT consultant, in 2017, told me that I should continue at this frequency, to be persistant as it would take a long time to get better and not to get disheartened and give up. He also said that I was right about lack of/ reduced salivary haptocorrin being a factor.
Interesting! Yes many people do seem to have saliva issues separate from any other autoimmune disease.
I do agree TC I could be an issue for those taking supplements, but what about those on injections? I would assume TC I wouldn't play a role there but I could be wrong!
It would be another reason for being unable to access B12 from food or tablets - one that perhaps is often overlooked -and remains undocumented or researched.So worth mentioning as important, although perhaps not relevant to the question raised.
TCI and TCIII often completely dismissed in research - beyond saying that their function is not understood.
Nackapan - you are right. There is absolutely no point in us fighting so hard for injections for self and others, then fighting for a more appropriate frequency, only to have them stopped suddenly when declared unnecessary later on. Or cured/ able to survive on tablets from H&B/ addicted/ hypochondriac/having an abnormally high B12 level.
Usually by a "new" GP. One who does not know how you were at first, has never seen you, and has not looked at your medical file beyond the last page with the latest blood results on it. And now that none of us get to see a GP, never mind get to see them twice, this will be an ever increasing problem. Wondering, since this is "only" a vitamin, when nurses will get the final word on this ?
So it is vital that, once on B12 injections at a frequency that works, these are not able to be stopped on a whim.
Which, of the 10 top questions chosen for research by the Priority Setting Partnership, will encompass ringfencing of successful treatment to be given - for life ?
From the latest update on this, the third research team will be developing a Functional Outcome Score for GPs to be able to evaluate treatment response as part of a care plan. This is to determine whether a patient might need more or less injections.
Yes - most do not seem to have picked up on NICE changes from, I believe, 2015. The hree month gap became a two-to-three month one. This seems an acknowledgement that we are not the same, doesn't it ? A step in the right direction (after two steps in the opposite one). Also have never understood why there is so much suspicion surrounding this : what difference could it possibly make, for example, whether this is 8 weeks/ two calendar months ?
[I'd be on my knees either way]
How often have we heard here that patients have been told off and sent away because they were a couple of days early ? This shows very little understanding of the severity of this condition, not to mention common courtesy. What can they imagine is the gain there for us ?
The frequency changes advised by NICE can be taken or left by a GP, based on observation and trial - but not because the patient has been tested for B12 level and found to be above range. That is to be expected - and does not reflect what a patient is going through day after day.
This must be the reasoning behind the Functional Outcome Score - but it is this attitude that needs changing first, otherwise the GP evaluation will just become the next means by which they can choose to stop B12 injections.
For this to make any sort of sense, it would have to be a discussion between patient and doctor. Monitoring and onservation by telephone is not a workable solution, and the process could be hampered without mutual trust, so continuity of care would be key.
My cousin is given an injection every six weeks -and is fine on that regime. I am not certain what regime my niece is now on.I was given the usual maintenance dose of one every three months, and then later, when that didn't work, one a month.
The only regime that worked for any length of time was when I was on 2 injections a week - and managed on that for six months before getting worse. It was never intended to be permanent -and was then reduced down to the one-a-month, as my lifelong maintenance dose.
Except my GP was then told by a locum haematologist in a report not to give me more than one every two months "as per guidelines". This was when I decided to start self injecting - and started with EOD injections. It was in my best interest to get back to work, even if only on a phased return that started with a day a week !
I was lucky in that my GP sought advice from consultants on trials, and was willing to use observation and discussion to decide on the next move - and prolonged the 2-a-week regime as I was still visibly improving, despite opposition from the nurses who had to administer them. I was certainly the only person at the surgery getting this frequency of treatment, so you can imagine the panic that caused .
PS: It was supposed to be three a week - which was the GP's request -but the nurses could not manage to fit in more than two a week. Which means that they are able to alter a frequency - to suit their own timetable .
My burning tongue is driving me nuts today - which in a way shows how far I have come. I wouldn't even have noticed it years ago - worse symptoms to deal with !
GP once made a comparison between me (at that time EOD self-injecting) and the other patient with functional B12 deficiency who apparently manages well on an injection every three months - I said "How can you be sure ? She might be self-injecting and afraid to tell you. "
Even I had waited to tell her until the day after my first one -in case she tried to talk me out of it.
[This also lead me to believe that we were the only two at the surgery with this diagnosis. ]
One of the nurses once said, on looking at my medical notes on screen, "Oh, so you're the patient on one injection every two months " - so also out of the ordinary for the surgery.
[Can imagine I am also likely to have ?? mental health in notes.]
When I was given the diagnosis, and immediately frequency of injections was changed to 2 a week, there was suspicion from one of the nurses:
" Did you request these from the doctor, or was this advice from a consultant ? "
Can you imagine being able to have that sort of influence ?
At that point, my partner had to accompany me to GP and specialist appointments - not only for support, but because I couldn't understand what they were telling me, short-term memory loss meant I couldn't answer their questions or remember what I wanted to ask them, even if I wrote it down. I would then also not have known what I was supposed to do next.
So, no - no persuasive powers over GP .
One of the other nurses was also suspicious:
she kept on talking about my "poor arms" with all these injections, and so I asked her why. She said "most people get lumps appearing, and it becomes painful" (!!!!) She wondered why I was different. I said, half-jokingly "Perhaps I'm soaking it up like a sponge ? "
"You're certainly enjoying it" was her response.
Enjoying it ? I felt nothing. Nothing at all. I honestly couldn't have told you whether she was really injecting me- or throwing it straight into the bin behind me.
Have felt like that myself sometimes."Surely they are all missing something. Something worse than B12 deficiency."
But that was when I thought I was slowly going down the plughole, and had been told I was deficient in a vitamin that I'd never even heard of.
I can plead ignorance though - just as I wouldn't expect them to know anything about a secret mitred dovetail set.
Surely by now they have had sufficient feedback from all of us about symptoms to know that their own version of what B12 deficiency entails falls way short of the truth ? Either they're not looking, not listening or they simply don't believe us.
In which case, we are wasting our breath - and our hard-won energy.
How they can be so cruel and condescending, I just don't understand. Just bananas. 😪 It's stories like this that keep me coming back to the forums to reply on people's posts. So much injustice and suffering. I recently got a hold of my old endo's note and boy were there some gems in there. 😤 I nearly had a panic attack when my GP recently suggested she would stop prescribing meds and I should go back to him. Um NO thank you.
On the Enjoying it ... I actually DO enjoy injections, call me crazy, because I feel them working instantly 😂 But it took several years before I could really feel any sting. And it's just these past few months that I started noticing that injections really sting. 😆 Amazing how nerves could still be healing so many years later. I bet you were soaking it up like a sponge and still are!!
Really hope so.But still not enjoying it, even though B12 injections started in early 2016. Over six years now. But yes, I still think that I'm getting better, and more to be had.
Do not feel an instant anything, just recognise when I'm depleted. Sometimes, an injection seems like a dud one and I get nothing at all. Perhaps when I've already overdone it - and so counter-effects diminished.
Still think that nothing will change until the teaching changes - which might mean teachers having to be taught. Are they going to like it ? Not sure that's important !
I'm glad you're still improving. After some years, the timescales seem to get longer. I can't do more than I did last month, but there's a difference with one year ago. I too think there's more to be had 😄
Interesting about the 'dud', i too sometimes feel absolutely zero and it's usually when i've overdone done it.
I agree about the teaching! What's ironic is that medicine has supposedly moved towards 'evidence based medicine' and more recently 'personalized medicine' but i don't actually see that happenening. As you say as long as doctors aren't trained to change their approach, nothing will change. C'est la vie i guess 🙄
Sometimes like to look back at old diaries - to remind myself of how far I've come.[One day, Nackapan , if you aren't keeping a diary, we will all be able to remind you !]
I've been looking at research on TCI and TCII (haven't got anything on TCIII). Thinking of how to break it down into English !
Yes I too love reading my very early diaries. Just amazing. Sometimes I reminisce with hubby & remember the odd symptom which never made it into my journal and which he never even realized I had... like not being able to remember the link between some numeral & what number of things it actually represents. Crazy stuff.
Me too.Good that Nackapan started us all thinking about why ring-fencing B12 injections needs addressing. No use getting slowly better over years if a new GP can put a stop to that and send you right back into Square One.
If this is our greatest fear, and hasn't stopped post-pandemic, then what can we do to ensure this never happens to any of us ?
Not afterwards, trying to get injections reinstated over the phone as a deteriorating individual.
It's definitely an uphill battle... even when the guidelines say "EOD until no further improvement" they don't even follow that. I guess it's due to the obsession with labwork. Perhaps if there was a better test that could reflect low transporter levels or whatever, they would believe it. It's a shame the Schilling test doesn't exist anymore. I can imagine a new & improved version that could show cellular uptake / saturation. What I mean is there is definitely some cellular/metabolic/genetic defect, we're just unable to measure it with existing knowledge/technology... or no one has gone down that route yet.
I've been criticized for being "obsessed" with this both here and offline, but I am 100% determined to figure this out in my lifetime. I doubt I can, since I don't have a lab or training or funding etc, but no one can stop me from reading papers and emailing researchers 😂
Yes our diaries, tell our story. My handwriting was awful as I could barely hold a pen, let alone write but I did 💪🏽.
Interesting about the numbers but also must have been difficult for you. 😢
Are you aware of Oliver Sacks (neurologist) ? He did a huge amount of work about Brain impairments and such as the inability to distinguish between colours, recognition of physical items (a spoon for example). What the use of that item was (to eat with) and other things like if I waved at you, you’d have no idea that I was saying hello or goodbye.
Plus, he used himself as a case study as he recognised he had some cognitive deficits himself. Worth a google of his name, if you fancy, have energy.
Yes I keep a diary.The less written on a page the better day.
A blank page coukd be too ill or too busy doing things !!
So it is completed retrospectively.
For everyone a good reference even if it can be upsetting to look back at times its also good to know a bad day is not the same ax a bad day 3 years ago .
I record every vitamin supplement.
Every pain killer .
Tried a symptom chart
Got too complicated as too many and j never found a pattern.
I was told "bordering on the obsessive" by GP - I told her I was "bordering on the desperate". Although she's probably been proved right now, because here I am, six years later, still filling out my symptoms chart, still looking for that pattern !
I would like to put the blame squarely with any consultant who starts an appointment with rapid-fire questions that start with the following:
"When did you first.....", "What was your last......",
and perhaps the worst: "At what point did you notice your memory failing ? "
That is good news about your brain waking up and thanks jade_s for the links. Saved to read at a later date and I’m very intrigued by the author Edward V Quadros, he’s written and researched quite a bit of B12. Thank you to him. No doubt far too technical for me.
There’s a few things I know and there’s a huge amount of things I don’t know.
* Mary Hodgkin (chemist) worked for 35 years work on the structure of insulin and somewhere in the 10 year mark on the structure of vitamin B12. If anyone wants to add or be specific please feel free. So, I’m speculating here, that medics think insulin metabolism is far more complex therefore, type 1s are allowed to inject when they need to called PRN (pro re nata - as required). 🤷♀️ There are so many myths about P.A. and B12 deficiency, i.e, it’s only elderly people at risk, it’s only a vitamin, good diet should solve it because we’ve good access to food.
* There are currently no N.I.C.E. (National Institute of Clinical Excellence) guidelines for P.A./B12 deficiency because they are under review. Maybe, some very smart people have come along and realised that the identification, testing is very flawed, as is our treatment. Fingers crossed. 😉
* We are all different in height, weight, length of deficiency, how active we are, symptoms, cause of deficiency, other conditions and illness including other deficiencies (cofactors). So, yes we will require different dosagesbut we can only get 1mg/L of vitamin B12 (some inject Helvert which is double the quantity in liquid). So, we have to inject more frequently and that’s why some people can survive on 2 monthly injections, others every week whilst I’m every day.
* Also, many of us have can identify that we’ve been deficient for years so when we were supposed to be treated we weren’t. That means that ‘therapeutic window’ has long gone so maybe we are trying to play ‘catch up’. Filling a bath with a jug of water a day type of thing as a very, very simplistic analogy. We will also absorb, distribute around our bodies, metabolise (use up) and excrete (flush out) at different rates. This is pharmacokinetics. 🤷♀️
* Now, the type of hydroxycobalamin/cyanocobalamin available to us. Some of us are lucky to have good GPs and have a proper treatment plan, the majority of us may be self injecting and buy from Germany or wherever. Although, I am aware that in Egypt they give depot injections. A depot is a slow release form of medication (hormones, insulin and antipsychotics are types in the U.K.) which are more effective so you don’t have such great spikes in medication then quick excretion.
* Now what is going on at cellular level, simple answer, it’s multifaceted (an enormous amount of highly complex reactions with positive and negative charged ions doing ‘stuff’ and DNA, RNA are being made or replicated. Some have domino effects, others happen simultaneously or slightly offset incremental delays).
* I know several metabolic pathways but the whole she-bang is pretty mind blowing and do I need to know that much detail ? 🤯 No, I need my energy to cook a meal.
Hoffman (2014) Pathways, Part 1: Metabolic Pathways La Roche Ltd.
* Everything is interlinked, at cellular level and body systems not this nonsense of dividing the body into parts - neurology, gastroenterology, haematology. Looking at things in isolation, in my humble opinion is rubbish. The whole is greater than the sum of its parts (Aristotle) because health is not just physical or emotional/psychological. It includes social, environment, spiritual and sexual.
* My approach: I’m numb below the knees, today I need to go to the post office - whack it in !! Now why hasn’t the kettle boiled ? Oh I didn’t switch it on 🤣😂
Gosh no lengthy reply necessary. Look after you first then setting the priority- Mum or washing.
Yesterday I was superglued in bed until 2 pm 😵💫🥴 priorities were shower, dressed, osteopath couldn’t make a meal - so slices of beef, lettuce tomatoes. Hey ho
Mary Hodgkin (Dorothy Mary Crowfoot Hodgkin) was the one who established the molecular structure of B12, for which she won a Nobel prize. Margaret Thatcher was one of her students.
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