Summary: I require very high dose/frequency B12 injections just to avoid neurological deterioration; some thoughts about what might be wrong with me
Two years ago (May 2021), I was found to have undetectable levels of Vitamin B12 after about a year of worsening neurological symptoms. At the time of diagnosis, I had extreme fatigue (could only talk for short periods at a time, couldn’t read at all), brain fog/memory decline, neuropathy and weight loss. I was given six B12 injections over two weeks and began improving almost immediately. However my symptoms began deteriorating again a week after the sixth injection. I was sure I needed more injections to recover and managed to persuade my doctor to give me one injection per month. For the next six months I saw some very slow and minor improvement in my symptoms.
In November 2021 I had an acute nasal infection which was treated with antibiotics (I’m not sure if it has completely gone away). I received a monthly B12 injections around this time. About a week later my neurological symptoms started began worsening quite suddenly. At this point I discovered that the recommended treatment in the UK for a B12 deficiency with neurological symptoms was injections every 2 days and began self-injecting at this frequency, however my symptoms didn’t return to the baseline of a week earlier until I increased the frequency to daily. Since this point I have not been able to reduce the frequency without symptoms increasing and have seen very limited further improvement in symptoms. I currently inject 5mg B12 subcutaneously daily (I previously injected intramuscularly).
I believe I am meeting all co-factor requirements and have experimented with methylfolate up to 15mg daily. I consume plenty of potassium and am taking more niche minerals such as molybdenum/iodine/selenium/lithium. I have tried injecting all four forms of cobalamin. It is quite clear to me that something occurred in November 2021 that has left me unable to utilise injected B12 properly.
My primary hypothesis is that I have developed antibodies to transcobalamin ii. There is very limited info on this online but I have found a paper (@sciencedirect.com/science/a..., which describes a patient who had antibodies to transcobalamin ii that interfered with cellular uptake of B12 from serum. Interestingly it postulates that an infection may have “stimulated the general production of antibodies, or possibly antibody to the invading organism crossreacted with TC II.” I find this particularly interesting because my need for very high frequency B12 began shortly after an acute infection.
Another paper (@pubmed.ncbi.nlm.nih.gov/163... describes a patient who had very severe neurological symptoms arising from a Vitamin B12 deficiency that only responded to injections after treatment with steroids. The authors suggest that “It may be that the intrinsic factor antibodies in our patient were of particularly high affinity and cross-reacted with TCII (both these proteins share significant amino acid sequence homology (13)), preventing transport of circulating B12 into cells” and that the administration of steroids had the effect of blocking the antibodies, eventually leading to a complete recovery.
I would be very grateful for anyone’s thoughts on the above wall of text and would encourage any discussion/criticism of my theory, including suggestions about anything I might have missed. I would also be interested if anyone has any thoughts on how I might take this forward with a view to actually being treated. Unfortunately I have had some bad experiences with doctors (particularly neurologists who seem to know nothing about B12 at all) so my level of trust is very low. I am thinking a hematologist may be the best place to start?
Many thanks
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jeremycat_
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I need to go to bed but wanted to answer briefly because i've been looking into this too & you describe me perfectly! (4mg/day after a bout 4 months into 1mg daily SI. That was over 6 years ago).
Is this the Carmel paper from 1970-something? If not can you please post the name/author/date?
I too have been hypothesizing about TC II ABs.
There are recent papers on " Macro B12 " eg 2022 paper by Wolffenbuttel. And others.
Put the two together, if TC II abs are creating macro b12 complexes then it would explain a lot.
i've tested negative for IFABs and GPCABs a hundred times over the 7 years. I exaggerate. 4 times i think. Genetic tests were all negative too.
I emailed Dr Wolffenbuttel last year but never got an answer. Automated reply that he retired.
I also have a story about how steroids helped counteract b12d symptoms, prior to injections, but too long to type out now. It was also not a sustainable solution as i developed cushing's syndrome... root cause was still some sort of b12d that only injections addressed.
I have no idea where these [TCII Abs, macro b12] could be tested but if you find out please let me know!! I imagine one of the famed b12 hospital clinics like Wolffenbuttel's , but how to get our foot in the door? I feel like we sound like a bunch of crazy people hopped up on b12 😂
Thanks for replying! Sorry that you're also struggling with this, but at the same time it's good to have someone to discuss with. Yes the first paper I referenced was Carmel (1977) - forgot to add the links sorry. I tested negative for PA as well, though have only been tested once.
I'm determined to try and find a doctor somewhere who might be able to help with this. Did you find that you needed the much higher dose from the start or did that start later, as in my case? It’s interesting that the steroids seemed to help you! But they are a nasty drug by the sounds of it…
Yeah steroids at those dose definitely not recommended.
Like you my increase came after a bad period.
I started out daily. Well EOD for a few days but noticed the non injection day was much worse so quickly went to daily. I did SI from day 1.
After 3 months I switched to another brand of b12 and crashed hard, but it took me 1 month to figure out what was happening. Ended up worse than before injections.
Switched back and noticed that before the morning injection, i was swaying, neuropathy was worse, a few other signs. It would go away after a jab and come back in the evening. I read about people doing 2x day so started doing one at night, and I was much more stable. After a few weeks i started crashing again, more than the reversing out effect i'd already had in the first months. I added a 3rd , felt much better but still swaying & neuropathy pain/burning and some other issues, then a 4th and finally felt human. The swaying & burning were one of my 'signs' that things were going in the right/wrong direction because they immediately reacted to injections already in the first days of SI.
I've periodically tried to reduce, intentionally or by circumstance, and i regress within 1 day. Swaying, dropping things, neuropathy, burning, blind spot in vision... with covid or really hot days i've had to add a 5th, though that need has been less and less.
My relative had to increase from 1x day to 2x on exercise days, after about 1.5 years on SI.
I don't mind doing all those injections but it's gotten very expensive! What cost ~6 euro 7 years ago for a box of 10 is now ~10 euro 😭 But it lets me hold down a job & have a life! 😄 It took me 4 years of this regimen to be able start working part time, another 2-3 to have a more or less normal life. I just started exercising last week!
Thank you for your reply. It is helpful to know others are more successful with injecting more. Comforting to know I am not the only crazy person who is benefiting from being hopped up on B12. 😂
Good morning!I'm sorry but I don't have time for the reply I'd like to write as I must get to work but:
Lots of us have noticed that the worse you are before you get treatment, the more you need to SI daily to be well going forward.
5mg is the most I've heard of to date but I don't think any of us had got down to undetectable levels either.
Good for you for working out that what you need to be as well as possible.
I only need 1.5mg /day but have needed that much every day for 8 years. I continue to improve on that, despite other health issues, but can't be late in doing my jabs. I know several people also use the stronger ampoules and need more than 1 jab per day.
Don't be surprised if you aren't ever able to cut down, or certainly not much, unless you are almost sedentary for another reason. Most of the higher requirement people seem to need it forever.
I need lots of additional supplements too, also including methylfolate. This also seems to go with the territory. I'm almost always running some sort of deficiency symptoms, despite my best efforts.
Just wondering if you've had your gut function checked? They found I'd got chronic pancreatitis and don't produce pancreatic enzymes when I asked to be checked out. It seems I don't digest food properly, don't absorb nutrients properly and don't metabolise them properly!
Quite a bit has been asked over the years about developing antibodies to B12 and I look forward to reading your articles later.
Thank you for your post and good luck!
The good news is that all of us on higher doses have continued to improve year on year so it seems there's nothing detrimental in doing it, other than the cost and hassle factor.
Thanks for your response! The strange thing about my case is that I think I was a ‘normal case’ for the first six months in that I didn’t deteriorate on monthly jabs and actually had some very slow improvement. Then very suddenly started deteriorating and have needed ever higher doses since then. It’s not really an acceptable situation for me as even on 5mg a day I feel I am just ‘treading water’ and not really finding any improvement. I’m unable to work and have a fairly low quality of life.
Thanks for the heads up about checking my gut function! Hope you find the papers interesting – I think the second one is particularly of interest.
It's quite common to feel better initially on a relatively small amount of b12 to later find symptoms returning and needing a lot more b12 to get rid of them again. I don't think that this always has to do with TC II antibodies if at all, as I think those initial small doses would oftentimes not be enough to cause them. Personally I was initially feeling better on 5.000 mcg oral b12 per day. Now I need to inject daily and don't think I can ever reduce again.
Also it's common to crash after any kind of illness. Most probably due to more b12 being used up.
I've done quite a bit of research on those antibodies. Yes, there's very little out there on them. Most importantly they don't seem to be able to inhibit uptake to the cells completely. Researchers aren't even sure whether they have an effect at all or not.
What I know is, that there isn't a test for TC II antibodies available in Germany where I live.
Thanks for your response. I agree that in some cases the research suggests that the antibodies are not significant enough to inhibit uptake to cells. However in the second paper that I linked, the patient did not respond to B12 injections until treated with steroids, and the authors suggested that TCii antibodies had been blocking uptake until counteracted with the steroids.
As far as I understand yes. I'm not sure why it's mentioned in the title of the paper because they do make it clear in the text (from what I can tell anyway) that they believe it was the TC ii antibodies causing the issue in this case.
Edit: See this quote - "The Lazarus-like improvement in our patient following the administration of steroids, in the context of her previous B12 loading, may have been due to an effect on blocking antibodies. It may be that the intrinsic factor antibodies in our patient were of particularly high affinity and cross-reacted with TCII (both these proteins share significant amino acid sequence homology (13)), preventing transport of circulating B12 into cells. The administration of steroids might have abrogated this effect, allowing correction of the intracellular metabolic defect."
Ah sorry I did not realise. Here is a link to the paper - transfernow.net/dl/20230706.... I'm trying to edit my original post to include this.
"The Lazarus-like improvement in our patient following the administration of steroids, in the context of her previous B12 loading, may have been due to an effect on blocking antibodies. It may be that the intrinsic factor antibodies in our patient were of particularly high affinity and cross-reacted with TCII (both these proteins share significant amino acid sequence homology (13)), preventing transport of circulating B12 into cells. The administration of steroids might have abrogated this effect, allowing correction of the intracellular metabolic defect."
Thank you! Well, I honestly don't know what to think of this. It's the first time I've read about IF antibodies potentially reacting with TC II antibodies.
I agree that "It's quite common to feel better initially on a relatively small amount of b12 to later find symptoms returning and needing a lot more b12 to get rid of them again." I also agree that "Also it's common to crash after any kind of illness."
It is also uncommon to start with any more than 1mg of B12 every other day.
I am about 30 days from COVID dx and treatment and my experience is not dissimilar to those who likely were infected at the same wedding. I attribute this to more B12 than is common.
I will be following this thread although I have nothing to add to your research other than my own experience. I am currently taking 4 - 5 injections/day. I started with 1 ml injections/5x a day after suddenly over the last few months seeing an increase in symptoms and becoming unfunctional. I was previously on 2 1 - ml injections/week. I have been able over the last two weeks to lesson my injections to half injections up to 5x a day. I have been having to take an antihistamine earlier than usual after I began breaking out with hives all over my body sporadically. I usually take an antihistamine daily but have had to take it earlier and earlier as this rash has begun since my increase in injections.
Interesting. Unfortunately I have no substantive research to add beyond what you've already seen. I think you will find it very difficult to find a knowledgeable or co-operative GP who would actually be willing to battle for this kind of testing for you. I don't think TC-2 antibody testing is even available privately. I do wish you luck in pursuing it, its very frustrating when things happen and no-one has a good explanation, which is unfortunately common in B12 deficiency and PA.
I lost count of the number of timesI had new symptoms or a downhill turn in my condition which no medical staff could explain other than regarding me as insane/unstable and prescribing antidepressants and sleeping pills (their typical fallback it seems when they had no clue what was going on).
Specialists in B12 such as B12 Institute Netherlands or B12 Kliniek Netherlands are knowledgeable but it may be difficult to get consultancy time, they can be very overbooked as you can imagine given the global dearth of B12 expertise and massive ignorance by most GP's/Primary Care Practictioners.
Yes I think it will be impossible to find a sympathetic GP. I have seen many over the last 2 years and all have them have been utterly useless.
I agree that TC II antibody testing could only be done in a research setting and I haven't seen any recent studies doing this.
Do you know if the places in the Netherlands that you mentioned have experience dealing with more unusual cases of B12 deficiency such as mine? I have seen in case of neurological symptoms they recommend twice weekly injections for a period of up to 2 years. This would be nowhere near enough for me.
My understanding is that most patients who can do so, are taught to self-inject, so I think its really in their hands if they want to continue that frequency after 2 years. I'm not sure the health insurers in the Netherlands would fund a prescription at that frequency indefinitely, though I very much suspect not, I don't think thats the case anywhere in the world. They have seen a lot of cases though I am sure of that.
From what I have read of experiences on this forum, I dont believe needing an injection frequency of twice a week beyond 2 years is extremely unusual - many other forum members need this or even more frequent.
There is an injection frequency survey on this site but of course people need to be looking for and have found this site to fill that out so that already taints the results of that somewhat and makes it hard to make a true estimate of what proportion do fine on NHS-approved 3 monthly and how many need a higher frequency.
My extremely unscientific impression is that many do seem to need more. I wish there was better data on that as it could really help to change treatment protocols I think.
People who inject more frequently than twice a week are not unusual on this forum (and other B12 forums) but in the grand scheme of things I would imagine they form a very small proportion of those who suffer from B12 malabsorption.
But what is definitely unusual is that there does not seem to be any acknowledgement at all in the medical literature or by medical institutions of people who do need very frequent injections. Even 'enlightened' doctors such as Dr Chandy and these Dutch institutes do not seem to acknowledge that some people need daily injections simply as a maintenance dose.
I honestly dont know the proportion. But I completely agree there is no recognition of a requirement for that kind of dose frequency. I think its because there just isnt any decent research that comes close to explaining why that would be necessary. Unfortunately.
Even in genetic cobalamin issues you read max 3x a week and they taper to 1x or 2x week, and yet mention that eg neuropathy has not resolved. Breaks my heart.
I am very appreciative of the work that experts have done in the past. It has been helpful to me. Thing is the recommendations made did not result in the improvement predicated and they offered no solution.
I see it as 60 years ago some experts successfully treated people for PA, problem solved for some and completely solved for physicians. . 30 +- years ago some experts started dx and treating B12 differently. Problem was solved for more people and still solved for physicians.
Problem was not solved for me until I came up with my own self treatment.
Just wanted to add that I had sepsis twice, just before this all happened.But who knows if low b12 allowed that to happen or that infection produced some changed uptake somehow.
Your Journey is eerily similar to mine except no infection.
I have accepted it is highly unlikely that any medical professional in the USA or the UK will accept that I need and deserve more than 1 mg every other day. Nor will they put any effort into looking for another cause for the symptoms I experience until such time it becomes apparent in whatever testing they deem is justified. This includes the top in the field of B12.
There is currently some move towards what is called Functional B12 Deficiency. (B12 levels in range.) This allows for transcobalamin issues. Unfortunately the treatment is the same and it is not considered that if the Functional B12 Deficiency is left untreated it may develop into PA or that PA and Functional B12 Deficiency is not an either or possibility.
My personal understanding is that I have experienced life long B12 Deficiency which progressed to extreme B12 Deficiency.
If I try and not take B6 I am experience neurological pain.
My current regiment regiment is successful and improvement is ongoing.
“Simple Spectrum ” 1/2 scoop 2.4 g in juice twice a day in lieu of B-complex. Which includes 20 mg of B6 in the form of Pyridoxal-5-Phosphate and .35mg of B12 in the form of methylcobalamin.
3 mg Adenasoyolcabalamin three times a day SL tablet.
2 mg methylcobalamin. Three times a day SL tablet.
Pyridoxal-5-Phosphate .25 mg liquid in water twice a day.
Julian Owen from CluB12 will be addressing the B12d WhatsApp/Fb group this eve 10Jul @ 7pm. (request to join B12d Zoom meeting via Hugo Minney Email: notifications@b12d.org) I will be questioning Julian about determining frequency of SI and will mention TCii antibodies & availability of current research/treatment.
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