Good science on the superiority or at least the equality of supplements over injections, and yet injections seem overwhelminly prevalent. This is a source of confusion to me, as a set off down the road to raise my B12 from 109 pmol/L, with aim to bring my hematology out of its pernicious anaemic purgatory (RBC, palettes, hemoglobin all out of range).
Here's a link to one good study: ncbi.nlm.nih.gov/pmc/articl...
Any direct clinical experience or view on this appreciated.
Injections are superior for many reasons:
- Oral b12 comes in two primary forms - liquid and pills. Sublingual liquid has a (potentially) different absorption process in that it attempts to get into the bloodstream sooner through salivary ducts. Potentially also more is absorbed. However, PA sufferers usually have problems with B12 absorption from the stomach, therefore pill administration is pointless and sublingual is possible only in some PA sufferers. It is not understood why this is.
- The body will only absorb up to around 30% of sublingual doses, but usually around 10%. So, a 1,000mcg dose per day will equate to around 100mcg absorption.
- Injections flood the body with 100% going into the bloodstream. Hydroxocobalamin is a DEPOT injection which means it stays in the system for longer. Sublinguals last 1 day.
- Oral is very expensive. Injections cost a few bucks per go.
- Oral depends on patients taking oral doses EVERY DAY. If you miss a day, levels will go down and the patient is exposed to possible further damage.
"Patients that come to our practice sometimes show initial recovery as a result of oral supplementation, but quite soon relapse and may not even recover in the end. When that happens, patients must be injected. So, the assumption that ‘the patient doesn’t have B12 deficiency, because oral supplementation doesn’t cure the patient’ is incorrect. "
b12-institute.nl/en/diagnos...
You state “ injections are poorer” . I totally disagree . They are the only way that the significant numbers of P.A, patients can cope with their B12 deficiency .
Hi Pickle - passive absorption - the mechanism which is under review only results in an average of 1% being absorbed - bit different from 30%.
Is there any data to back this up?
pretty sure we have had this conversation before but plenty of articles out there like this one
hi Pickle. You quote ‘injections that go straight into bloodstream’. Is that true of subcutaneous injections?
I raised my levels on sub-lingual supplementation, I guess it’s dependant on each individuals health situation. But interested to note you say levels can go down if you miss a supplemental dose. But I’d read that B12 serem levels reduced down quite slowly?
My observations is that what's often missing from the dialogue in the forum is the difference between people's reactions when they've received loading injections and when they haven't.
Many people state 'sublinguals did nothing for me' but what are they comparing this to? The injections? If so, then it seems likely that sublingual could never match the power of an injection. So of course someone would not feel the same impact.
But what if they have a severe deficiency and attempt to treat it with daily sublingual doses, without injections? In this case, they cannot compare it to injections because they've never had them.
So how many will they need and for how long? Some Dr's and reports say 3 months minimum at 2,000 per day but that this is CONDITIONAL on someone taking it every day. And they cannot miss a day.
If they do miss a day they risk a 'relapse' of symptoms and as per the B12 Institute report, they 'may not fully recover' on sublinguals and injections are needed.
This 'may' is too grey an area to risk not taking injections. My personal experience is that sublinguals will not resolve the symptoms sufficiently, but possibly could if someone took a sublingual dose every day for 3 months without fail. That is a strict discipline to follow and the patient risks damage that can't be recovered if they miss one day. And then have to start injections.
So why wouldn't someone just start with injections to avoid such a situation? Perhaps they dont' want needles in their arms. But they will need to be compos mentis and routine and have alot of faith in their own process. Whereas 6 Hydro injections over 10 days gives them the best start to resolve. And they may not even notice sublinguals after that since much of the repair has already started to happen, even though levels are continuing to increase via their sublingual self-administration.
I don’t consider this to be a good study at all , after reading all of it . Very few participants for a very short time , and only 7 were P.A. patients . It is not mentioned how these 7 were tested for P.A. ( Positive Intrinsic Factor antibodies test is not mentioned ! ) So i really cannot understand why you can call it “ Good Science “ . I totally disagree .I am a proven Pernicious Anaemia patient ( Positive Intrinsic Factor antibodies test) who took huge doses of oral and sub-lingual B12 tablets and also nose and mouth spray for at least 6 months , and my symptoms just got worse . Only injections help me . We hear time and again on this forum , that members only get help with injections. And most of us have to resort to self-injecting to keep any resemblance of health , because neither 3 monthly or 2 monthly injections are sufficient .
hi Wedgewood, so your blood levels didn’t improve while taking oral supplementation?
I have no idea because i was not tested . I started taking oral , sublingual tablets , mouth and nose sprays and also used patches when I was sure I had B12 deficiency . , because of my many B12 deficiency symptoms , including totally num feet . My GP had tested ne and said that my B12 was normal, and I was sent on my way . ( I found out later that my B12 was well below range ) …. That’s when I started to take all those different B12 supplements in huge doses . This was certainly for several months , and was costly . But I was truly desperate. I was then driven to consult a private GP , who arranged an Intrinsic Factor Antibodies test —Hey presto — positive . There is more to tell , but it will take ages. Suffice to say that I eventually discovered this forum , a life-saver !
Agree, I’be not been been diagnosed with PA, just B12 deficiency and yet oral did nothing for my well being despite blood levels rising, maybe it’s an age thing. I only know that it’s only injections that help me and I’d much rather tablets helped 😉, much easier than sticking a needle in myself.
This is just my personal experience- I was regularly getting the sense that for me personally, my twice weekly self injections were not having a proper impact. I did a fair bit of reading online, about how much b12 is excreted via urine, and the limited amount that can be absorbed from a dose. It would seem for, me that a daily dose is required, and affordability prohibits this via injections. I have also been watching the situation unfold, where people are finding it more difficult to obtain b12 ampoules from Germany, and indeed my last order was far from smooth sailing. Because I can see major stress from this looming on the horizon, (it appears to be becoming more and more pot luck to buy them online) I have decided to stop my twice weekly injections, whilst I still have some left, and have instead gone to a daily dose of sublingual drops, made by Nature Provides. They have no nasty additives, which can be an issue in supplements. I am 6 weeks in so far, and whilst it is very early days, I certainly feel very well, upbeat and hopeful. I cope badly with stress (which is why I never have my 8 weekly jab at the surgery, even though it was reinstated), and stress most definitely contributes to my physical health, like so many of us here. It would make my heart sing if it turns out I don't have the stress and anxiety of trying to obtain ampoules, plus the sheer expense of all that comes with this method. And for what it's worth, I am very impressed with Nature Provides as a company ( if I am allowed to praise them on here ).I did try the Jarrows sublingual lozenges my husband uses..and they were not bad daily, but they contain xylitol and that can have a laxative effect, especially with daily consumption, and I want to absorb every bit of my healthy food.
I want to emphasise, that I am totally aware this will not work for many people on here, they absolutely need the injections to for good health and recovery. And who knows, maybe longterm I will too? B12 deficiency is most definitely not a one size fits all. I also want to emphasise that I was diagnosed over 8 years ago, when my b12 was found to be just 89. So I have had a long long time of injections for recovery- in other words, this is not something I would recommend for someone who has just been diagnosed and needs a serious set of loading doses etc.
But I wanted to try this, and so far, so good. So if it helps just one other person on here, then the post is absolutely worth it. 
Have a good day friends x
🤗
ty Monkharris,I’ve just ordered these online too I’m sick to death of the stress that self injecting causes me,I use every excuse under the sun to delay doing it.
I’ve decided on a different approach now and will make a serious attempt at sublingual drops,I used to have a lot of success with the better you oral sprays so I’ll also go back to them for my b multis and D3/K2.
I’ll update after I’ve tried it for a few weeks,I’m very symptomatic when I delay the shots so I think I’ll see any results quickly,it’s worth a try.
Thats good news isn’t it - can I ask how much B12 a day you take of the Nature Provides supplement please? And what your current Actuve B12 serem level is? I’ve used Biocare sub-lingual B12, good but does work out pricey. And I found taking B12 was quite stimulating.
Hi Que6tI am currently taking 3000mcg per day, which is a 1 ml dose, or 13 drops. I hold it under my tongue for as long as possible. I honestly don't know where my B12 level is, because where I live, GPs will not test b12 at all once a patient has been prescribed b12 ., because phlebotomy always flag it up! But I do have a number of little symptoms I keep an eye out for, and when they appear, I know its time to up my game so to speak.
Hoping that at some point next year we may be able to afford a private blood test, but with the current cost of living crisis here in Old Blighty ...
For info, the ingredients list for these drops are
Reverse Osmosis water
Methylcobalamin
Adenosylcobalamin.
And that's it, nothing else. I recommend you read the reviews of it on their website, and on Amazon. Both positive and negative reviews- might find it useful ?
Like I say, its early days, so I am keeping an open mind and taking it as it comes, and it wont work for everyoneby any means - but I want to give it a fair chance, because if this can work for me, with just a top up jab now and again if needed, then I alleviate myself of this total stress of trying to obtain 100 ampoules at a time.
Best wishes:)😀
Strictly speaking it is a literarature review rather than a study - ie bringing together the results of several studies.
Oral is certainly less invasive from a medical perspective and it can be quite effective for some people - it seems to work for me.
Problem is, as others say, that it doesn't work for everyone but unfortunately the trend in medicine is to go for the average and apply that to people rather than listening to patients and using clinical judgement on an individual basis. You definitely can't blame studies or literature reviews for that.
Thank you for sharing.
If you feel that some of the responses you receive are going a bit far please report them rather than trying to respond to them. This is an area where people can get very emotional and react on that basis.
Thanks for pointing out that this is a literature review, rather than a standalone study.
I'd like to acknowledge that everyone has their own personal experience to share, and that what works for one might not seem to work for another.
Studies show (ashpublications.org/blood/a... that about 1% of a macrodose, taken orally, makes it into the bloodstream. This means that a 1000 mcg supplement leads to 10 mcg of absorbed B12, well above the 1.5 mcg daily recommendation. This is regardless of the state of an immuno-compromised terminal ileum.
From the study, 'Excellent hematologic responses were also documented in 91 of 91 patients with pernicious anemia who had received 300 to 2,000 μg or more of oral cyanocobalamin daily'
re absorption of 1% - think the usual term is on average 1% but there may be quite a bit of variation between individuals. I find oral works for me but I'm taking around 9mg per day.
This article on comparing responses to oral B12 may be of interest
smw.ch/article/doi/smw.2017...
it showed considerable variation between patients and also showed that although anaemias might be corrected patients were still presenting with high markers for secondary measures of B12 status, ie MMA and homocysteine, indicating that they were still B12 deficient on an oral regime.
But this is only covering regular daily needs. It does not address a deficiency
One major issue I see with the studies reviewed is that no two B12 deficiencies and patients are alike. Based on their selection criteria I and several others here would never even have made the cut for the studies based on our B12 serum readings not being low enough, although I had two years of untreated neurological symptoms.
Just because someone responds to oral treatment does not mean they might not react better and have better quality of life and better symptom improvement if they were on injections. Since the patients were not moved between treatments how is it possible to exclude that for patients that saw improvement on oral, a better response might have happened from injections?
Someone who had an untreated B12 deficiency for 30 years is going to have a very different response to treatment than a younger person with a mild deficiency that has not yet progressed to neurological symptoms or whose neurological symptoms are only a few weeks old. Measurement of serum B12 alone cannot account for this. Likewise the overall health of the patient, lifestyle, diet is a major factor in their recovery and treatment reponse, how were such factors controlled for, if they even could be?
In terms of the amount of B12 delivered into the system, injections and oral doses are not comparable - based on 1% passive absorption, to get the same B12 as someone on daily injections you would need to take about 70,000mcg daily oral doses. I only remember one forum member from the US posting that something like this had worked for them and in theory its possible but seems like it would get quite expensive and very likely not covered by health insurance.
Thats without speaking of the fact that many PA sufferers dont seem to have any response to oral treatment at any dosage. I highly doubt that so many are moving to self-injection outside the medical system frivolously when oral doses would be just as effective for them. I know many here report trying to move onto tablets/sublinguals, and though for some this works, for others it does not.
In a severe deficiency where stores of B12 in the body are very depleted, its important to make as much B12 available as possible quickly to begin correcting the damage and getting stores back up. Injections are the most efficient and safest way to so.
I appreciate that Cochrane reviews are very well regarded but I don't regard the research as being particularly convincing for all the above reasons.
This is an article not a study. The article discusses some studies. There is a big note saying the article has been updated and gives a link to the updated article.
Thanks for pointing that out. In the updated article they mention that:
"No trial reported on clinical signs and symptoms of vitamin B12 deficiency, health‐related quality of life, or acceptability of the treatment scheme."
and in part of the conclusions:
"Further trials should conduct better randomisation and blinding procedures, recruit more participants, and provide adequate reporting. Future trials should also measure important outcomes such as the clinical signs and symptoms of vitamin B12 deficiency, health related‐quality of life, socioeconomic effects, and report adverse events adequately, preferably in a primary care setting."
Seems like a lot more work needed to draw conclusions either way.
Thanks for this.
It seems to me that that this all comes down to regular bloodwork to verify hematology; if your RBC, palettes, hemoglobin recover to normal range then who are we (as the patient), to question whether one treatment is working over another.
AFAIK, the body can only absorb so much B12 per day, and thus a macrodose in excess of absorption limits will simply pass through, regardless of how deficient we might be in that moment.
whilst the normal mechanism for absorbing B12 through the terminal ileum does indeed seem to have an upper limit I don't think that applies to passive absorption, which is what is being talked about with high dose oral being used in patients who have absorption problems.
Just looking at RBC, haemoglobin etc is not going to be enough to tell if someone is B12 deficient or not. 20% of patients who are B12 deficient do not present with any form of anaemia. The name Pernicious Anaemia is extremely misleading. B12 is used by several cellular processes and symptoms may be down to any one of these processes no longer functioning properly. There are at least 2 ways that lack of B12 can affect nerve function without involving any form of anaemia.
An oral dose is limited by the 2 mechanisms of oral B12 absorption, intrinsic factor which saturates approx every 3 hours with a very small dose of B12 (believed to < 2mcg) and passive absorption which absorbs ~ 1% of any dose. Intrinsic factor is very limited but I'm not aware of any limit to B12 absorption by passive absorption except that massive doses (in comparison to the RDA) would be needed if you were trying to reach a dose equivalent to an injection.
The limit on usability of B12 from an injection is unaffected by oral absorption limits, the limiting factor being the binding capacity of the Transcobalamin II in the blood. This is usually fully saturated and even exceeded by an injection.
I don't know whether its possible to saturate the binding capacity of the blood with oral doses in extremely high doses but it seems like it might be possible at least in theory.
Correction of haematological parameters is an important data point but patient symptomology should take precedent - if B12 deficiency symptoms are returning or worsening while on oral treatment regimes or insufficiently frequent injections, this is more important than if haematological markers are normal.
This is similar to the way in which there is no haematological gold standard test for B12 deficiency itself. It is not understood why more B12 would be needed than seems apparent from blood tests but hundreds (thousands?) of B12 deficient patients including retired physicians and a neurologist (i gather from Nackapan) see that symptoms return if injections are not frequent enough, without any indication of issues from haemotology. A lot more research is needed to find out exactly why this is the case.
I may come across as blunt but it is to help you.You come across in tone as someone who seems to have decided that they will use oral administration to resolve their deficiency, and are attempting some confirmation bias to use oral supplements to treat your deficiency.
Ive been there.
Do not assume you can save yourself with oral. You WILL need injections. Take it from me - oral will not cure you. You must get levels up with injections to recover
Pickle500,
In a scientific context confirmation bias is ignoring evidence contrary to the theory you are trying to prove. I don't believe that this applies to the poster. Reality is that some people manage well on high dose oral - from the 1920s to the 1960s the only treatment there was was high dose oral, in the form of liver concentrate.
I actually found that I personally improved using a nasal spray and went from being unable to balance walking to being okay at the top of a ladder pruning an enthusiastic grapevine. I was on 2 monthly injections at that point and had been for over a year. They didn't last more than 24-48 hours but I did see a huge improvement in a few weeks of using a nasal spray ... and a few months later years of depression and suicidal ideation started to ease so for me supplementation by methods other than injection definitely works.
I so not assume that because high dose oral worked for me it is going to work for everyone because the evidence is that it doesn't - even if you are looking at studies based purely on raising serum B12 levels.
ncbi.nlm.nih.gov/pmc/articl...
table 2 quite clearly shows that the levels of oral supplement used in the studies were not effective in raising serum B12 levels in all patients.
Neither would I assume that if something doesn't work for me it won't work for everyone else.
Im confused by your post.
On one hand you say that oral absorption is only at 1%. Yet you recommend oral to recover from a deficiency?
The evidence suggests that oral would not be sufficient to recover from a deficiency. Ive provided the document that also suggests those who take oral or sublingual 'may not fully recover'.
And I offer personal experience of not getting a diagnosis and self treatment and the pitfalls.
So I am totally lost here.
I agree that patients given oral MA|Y not recover. This is very different from WILL not recover.
I also believe that patients should be able to make choices about their treatment. If they want to try oral they should be allowed to try oral.
I don't think patients should be forced into one treatment over another, whether that is oral or injections.
Using an oral route to raise B12 levels is going to be a slow process so injections would be preferable as the initial treatment in the case of a severe deficiency where there is risk of permanent damage if the deficiency continues. That is true whatever the cause of the deficiency.
For maintenance people should be given the choice either way. Yes they should be monitored and listened to as well if they change their mind.
I believe it is naive at best and medically negligent at worst to not highlight the dangers of attempting to treat a clear deficiency using oral administration.
Regardless of the flimsy data we mine off the internet, the body can only absorb sublingual or oral at miniscule amounts.
To recover from B12, I understood from this forum that someone would ideally need injections to get B12 levels as high as possible, as quickly as possible and keep them there.
Your experiences don't suggest that your 'initial treatment' was via oral. Majority of people get loading doses of injections and THEN use oral to maintain levels.
So, recovery from B12 deficiency--especially if there are neurological features of which haven't been divulged or explored with the poster--WILL be impeded if someone attempts to use oral to recover without an awareness of the risks involved.
Without highlighting the dangers, the poster risks further damage and long term issues.
B12 levels are meaningless. One person can have a myriad of symptoms at 200 and another fine at 100. The point is that deficiency is apparent and therefore injections at regular doses are suggested to get levels up quickly.
Oral will not only risk further damage vut will take considerably longer to take effect and thus risk the poster missing a day here or there or assuming they're fixed when in reality there's not enough B12 swimming in the blood.
Im not a scientist and neither is anyone here, apart from FlipperTD.
Please tell me if Im wrong
My own treatment experience was initially oral doses of around 5k to 10k a day. This did not work well for me and I sought out injections after a couple of weeks and was very glad I did as had a much stronger response. After 5-6 months I was able to drop to oral treatment as I felt the injections were not really affecting my symptoms any more one way or another. I've got by on ~ 1k daily since then and monthly injections. However, to my knowledge I do not have PA or any absorption problems, just a severe deficiency. Gut and digestion issues also cleared up completely by the 5 month marker. I don't have a good explanation as to why high dose oral would work for someone rather than regular injections, especially in early treatment but I guess there's a lot about this condition we dont understand....
Thank you. So even though you have a known dietary deficiency, unequivocally, the oral did not work for you during 'initial treatment'. But it did post-injections since its more convenient and less invasive to the body.
This is basically what Im trying to highlight to the poster.
The clarify: I have no obvious neurological symptoms, in spite of notably deficient B12 levels per my original post. I have obvious anemia, with all CBC measures below normal. I'm 1 week into 2000/day orally, and am already improved in my road cycling (criterion races 1 / week with training in between).
Bloodwork next week to see where I am on homocysteine, methylmalonic acid, B12, RBC, hemoglobin, etc. If not markedly improved, will seek out IM, nasal, or sublingual to correct.
Thanks to everyone for the quick response and sharing of knowledge and experience.
I would just be wary of believing the numbers are enough to go on.
But good luck to you and enjoy the cycling
Interesting. In my case I never developed anemia, only the neurological symptoms.
but what if your Active. 12 levels are improving on oral B12?
but what if your Active B12 serem levels are improving on oral B12 - typo error before
Its all about the mode of delivery, not the numbers. Lets say you had a leaky bucket that held 5,000ml and it had a pin hole/small crack in the bottom. If you filled it with 100ml of sand everyday, the levels would slowly go up, but the sand would be seeping out. If you miss a day, the sand will run out and the bucket will be empty the next day.
Instead, if you filled the bucket with 500ml of sand every other day, it fills up the bucket faster and in 10 days its full to the brim or close enough to it.
So, the 500ml sand every other day will still be seeping out slowly, but it will keep the bucket fuller for longer. And you can top it up up in 2 or 3 months with 500ml sand when it starts to get low again.
Thank you for that & yep, understand the principle. Although & I wish I could remember from where, I read that Active B12 serem levels drop quite slowly. The other thing is, from the large doses individuals are taking, that only a relatively small amount of B12 is being taken up & utilised, the access being discharged. That puzzles me too, but it must have been proven to work.
Dr Chandys book is a useful resource on this. He suggests there is a window of opportunity to get levels up as high as possible and then continue injections. So there are lots of factors, such as missing said window of opportunity or delays. Some people will recover fast but most needed levels high all the the time for B12 to get into and stay in the cells.
I think Active attempts to measure B12 at a more cellular level but its also flawed if someone is on injections. Both Active and Serum are really useful for deficiency states but after treatment they're less effective at giving a true picture of what's really going on in the body. Levels just need to be kept high until symptoms subside. And injections are the best way to do this since, like the bucket analogy, they will hang around in the body for longer than an oral dose, thus increasing the chances that the B12 continues to get into the cells.
I don't think anyone can say for sure how much is excreted each day. But I think its not a clear cut process - its an art and a science.
If only there was a test to show nutrient deficiencies that exist in the cells. That would be a medical breakthrough.
"If only there was a test to show nutrient deficiencies that exist in the cells. That would be a medical breakthrough. "
Yes. A nobel prize even! But I suspect they will still only be measurable via some kinds of secondary markers which might be unreliable themselves such as MMA/Homocysteine. It would be really something though. I think the biggest problem is the blind trust that any of these blood tests are infallible markers which many of them are not (like zinc which you mentioned, like B12, probably others).
The mere understanding that results of these test cannot be relied upon completely would just be enormous and would rightly shift focus to symptoms with for example B12 tests being useful to rule IN a deficiency but not to rule it out. Diagnosis (of B12 deficiency) would not be easy based on symptoms but since the treatment is harmless and inexpensive.....
Real interesting reply, appreciated. And I guess when someone already has nerve damage, it’s about tolerance level of B12 intake. I even found 200ug liquid B12 stimulating. I had to ease off, then restart. Yes, wouldn’t it great if there was a cellular test. Bit like the saliva test for adrenal levels. Wonder if a reliable hair analysis would be indicative.
Would be a great advance. But I don't think theres such a thing as reliable hair analysis. quackwatch.org/related/hair-2/
The research review that was linked earlier was for a 2005 review. This was updated in 2017 and is markedly better but points out that more properly designed research studies (as opposed to reviews) need to carried out.
Hi, It's always interesting to read articles and studies. I don't have an official diagnosis of PA , so it's uncertain at which part of the physiological process my body is not able to access B12.
All I do know is, that I've tried high dose oral B12 and it doesn't work for me, I definitely require B12 by injection.
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