I often wondered about the average dietary B12 intake for those not taking supplements (or injections). Although perhaps of only academic interest to most forum members I found a mention of this in a paper:
"The Neuropsychiatry of Vitamin B12 Deficiency in Elderly Patients" (2012)
"In the United States, the average daily adult dietary intake of vitamin B12 is about 5 mcg–30 mcg, of which only 1 mcg–5 mcg are effectively absorbed, given its complex absorption process. "
So on average, at the higher end, intakes would be around 10mcg per meal (assuming 3 meals a day).
The approach I have been considering from this research is to shake out a 10mcg B12 tablet with the natural forms of B12 onto my food at each meal. I'm guessing that Haptocorrin binding to B12 (necessary for absorption) may be assisted by having longer exposure time in the mouth before being swallowed, like a tablet would be. There are some studies showing enhanced absorption with sublingual so this is a somewhat educated guess.
I still currently take a 100mcg or 250mcg in the morning ( along with lower doses lunch/dinner). Even though the research tells me the 10mcg 3xday should work, the dosage still make me hella nervous 😅
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I can imagine your trepidation! I have no other useful comments to make except you can't overdose on it 🤣
Oh and don't forget, as we age, supposedly our absorption gets worse - low stomach acid or gut motility, not sure - and plenty of papers showing low B12 even in 50 & 60 y.o.'s (i have no idea how old you are) but good to add an extra margin for that
Interesting information. For non-PA individuals, this is fine. Also, there is re-absorption from the gut. If you have PA, this does not work. Also, there is more loss from the gut. Hence, the maintenance dose for PA patients is 1000mcg/day which gives about 12-13mcg/day into the blood on average....
If we could all absorb 13 mcg a day (this is 3 x the daily RDA for B12) from 1000 mcg tablets , this forum wouldn't exist and none of us would be ill. Hence why treating with tablets is not the gold standard treatment - injections are.
I think all studies show that even PA patients can absorb this much B12 on average (range is about 5-20mcg from a 1000 mcg oral dose). This is by passive absorption. The problem with orals is: In the beginning, when one is very low on B12, it will take a while for the levels to build up to have any significant noticeable effect. My wife absolutely refuses injections and it takes her about 10-15 days to show effect with 1000 mcg orals. And she is only mildly B12 deficient with very mild symptoms of fatigue etc. and keeps on stopping the orals when she starts to feel good. With an injection, one is giving almost 1000mcg directly into the blood with a single injection with Hydroxo and about 150-300mcg with cyanocobalamin injection, which has immediate effect. Also, the absorption is variable with orals, and when I was on orals, a bout of diarrhoea led to B12 deficiency symptoms coming up, obviously due to a rapid transition of the B12 through the intestine and hence, less absorption. Hence, I also do not recommend or use orals myself and even for maintenance, a monthly injection (in case of cyanocobalamin) should be used.
Those studies may be misleading. Here is the response from the Dutch B12 institute's Caution note about the use of oral B12 supplements page b12-institute.nl/caution-no...Although some scientists accepts that oral supplementation has been proven as equal to injections in the treatment of B12 deficiency, we think their efficacy on symptoms has not been scientifically established yet. Almost all research is not, or hardly, linked to symptoms, but only to B12 blood serum values.
Also in the famous paper The Many Face of Vit B12 deficiency ncbi.nlm.nih.gov/pmc/articl... under the section How Should Treatment Be Given? there is an extensive review of the pitfalls of the various studies that supposedly "proved" oral B12 is just as effective. They should all be taken with a grain of salt.
I agree with the statement of the paper that efficacy of treatment is different from absorption studies. However, direct studies of absorption and a rise in blood serum values, along with effect on metabolites such as homocysteine and MMA IN THE LONG RUN, does mean that the oral B12 is being absorbed. I have already mentioned earlier that absorption does not necessarily mean an equal therapeutic effect, especially since the absorption is very low and the therapeutic effect may only start after several weeks, with a full effect only after one or two months, during which time the neurological symptoms can continue to deteriorate. Also, even for maintenance, the variable absorption is a problem.
Hence, I fully agree that the regimen of treatment as finalized originally by the US doctors who did the first tests and clinical trials on B12, and that the maintenance injection of once-a-month cyanocobalamin should be used. I am not convinced of hydroxocoblamin loading doses followed suddenly by 3-monthly injections though, as I found that one has to gradually reduce the frequency, as is also the recommended schedule by the US doctors(using cyanocobalamin). This is my personal experience as well.
am111 please read the blog by Professor Wolffenbuttel, an expert in the treatment of B12 deficiency.
Some relevant excerpts:
"There is no good evidence that oral/sublingual supplementation can safely and effectively replace it. So, unfortunately, it doesn't work 'as well'….. The 2018 Cochrane analysis (recommended reading for all) is crystal clear…. the authors concluded that the available studies provide only very low quality evidence that oral B12 is as effective as im B12 IN RESTORING NORMAL B12 LEVELS IN THE BLOOD. However,we treat a person with complaints, normalizing the serum B12 level is in no way the aim of the treatment.
Quote from the Cochrane analysis: “ 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 . ” In other words, we need more than the shoddy work that has been published over the past 20 years."
....
"in everyday practice, some patients can switch to oral supplementation with a very high dose of B12 (i.e. 1000-2000 mcg per day), but it is impossible to predict in whom this can be done safely, and many are at risk of exacerbation of the symptoms that can then persist permanently. "
I have read these papers and my conclusion is same as theirs and I agree with you (also read my reply to jade_s). I would not go for orals. In fact, I was mislead by one doctor who put me onto orals and I had continuing problems because of it. At the same time, please read this paper:
I was on methylcobalamin tablets and almost all of the clinical trials are for cyanocobalamin. I was put onto methylcobalamin tablets and they certainly did not work well for me. I am wondering though, if cyanocobalamin tablets work much better, as the above paper suggests and the clinical trials also say and whether the problems people have been facing while being on orals has to do with the wrong salt being used.
I may also mention here that my B12 serum tests always came out high on the methylcobalamin tablets, but I still felt the symptoms.
Veganhealth has the following section on this study:
"A cross-sectional study from Romania found that vegans supplementing with cyanocobalamin had higher levels of holotranscobalamin than those supplementing with methylcobalamin (150 pmol/l and 78.5 pmol/l, respectively; p-value=0.030; Zugrav et al, 2021). However, those taking methylcobalamin supplemented less and the amounts varied.
A holotranscobalamin level of 78.5 pmol/l is well above the minimum healthy range indicating that the methylcobalamin regimen was adequate. The average dose for those supplementing with cyanocobalamin and methylcobalamin was 582 µg and 988 µg, respectively. The frequency of methylcobalamin intake was 21% daily, 36% twice per week, and 43% once a week. Without assessing MMA levels and more precisely correlating values with intake amounts and frequency it’s not possible to determine a reliable regimen. "
A few thoughts.
It is true that there has been better testing on the efficacy of cyanocobalamin to raise or maintain B12 status. When cyanocobalamin is disparaged, as it often is by alternative health practitioners, the body of evidence backing its effectiveness and safety is something I would point to as a counterargument. The level of cyanide is also not of any great significance in comparison to other common dietary sources.
Methylcobalamin does seem to have greater light and heat sensitivity thus proper storage seems to be of even greater importance than cyanocobalamin. It is also true that all B12 forms are disassembled to the base cobalamin before being used in the body, so even if you take an "active form", it is never directly used by the body , in that state.
However, I do often see claims that 1000mcg or 1500mcg of methylcobalamin is needed where only 50mcg of cyanocobalamin would be sufficient. This is based on a misreading of a study where all participants had a B12 defiency and total gastrectomy:
Passive Absorption being the only possible absorption method meant that a dose of 1000mcg+ would be necessary for these individuals. Another group received intramuscular cyanocobalamin 1mg weekly.
The study has nothing useful to say about the amount of methylcobalamin needed to maintain adequate levels in individuals without a B12 defiency and without a total gastrectomy.
The three natural human-usable forms of B12, hydroxocobalamin, adenosylcobalamin and methylcobalamin are all found to varying degrees in food.
As long as the supplement contains the stated amount of B12 and the B12 is stable and not exposed to bright light/heat, I see no reason why getting B12 this way would be any worse or less effective than from food. In fact, in foods, the B12 is bound to a protein from which it must be removed, requiring adequate stomach acid. Free B12 from a supplement, not bound to a protein, does not have this issue.
I have no problem with people choosing cyanocobalamin as I believe there is good evidence supporting its efficacy. But I also don't agree with the idea that methylcobalamin, or the other natural forms are ineffective or required in huge doses to work. How could this be, since those are the forms of B12 most people are consuming in food ? (who do not supplement or inject), and are not having issues unless absorption problems exist.
Thanks for the reply and the link to the paper. This is the first paper I am seeing that uses Methylcobalamin tablets. I have used methylcobalamin and it does not work fully for me while the equivalent amount of methylcobalamin injection (/100) works much better. What could be the reason? I don't think it is absorption since I do feel a "kick" after taking it. It could be something to do with absorption over some 8-10 hours vs. 15min-1hr. for IM/SC injection. A one-time intervention is perhaps better handled by the body than a slow one.
The problem I felt with methylcobalamin is that if I missed even one dose or was late by 6 hours or so (this was on 750mcg/day), I would feel down. I felt the same on methylcobalamin injections and if I was late, I would feel the effect. Cyanocobalamin is much more diffuse, as it takes time for the body to convert, so I don't feel an immediate up or down, but only gradually over time. Perhaps this could be the reason for possibly better results with cyanocobalamin orals, if at all (not sure, only as per one article). The downside with cyanocobalamin though, is that one starts feeling better with even a single tablet of methylcobalamin while cyanocobalamin tablets take a week or so to start having an effect which builds up over time.
I think if doctors are going to prescribe oral B12 to people, we need much more trials with different B12 forms, rather than doctors to just assume that all the different forms are equivalent in terms of their clinical effect, which is not true.
To dose an amount of oral B12 that could reach the same amount delivered via a 1mg injection, you would need to take (assuming 100% of the 1mg is used) around 100,000 mcg of B12 tablets. Because passive absorption is only 1% or so, 100,000 mcg ÷100 = 1000mcg absorbed. Intrinsic factor is more or less irrelevant when such a high dose is needed.
Most people don't dose this kind of quantity of oral B12 - I only found a single case on this forum where someone attempted that (I think he took at least 50k+) every day. In theory, that MIGHT work, but its pretty theoretical. He said it worked for him. There's a reason injections are the gold standard of treatment for significant B12 deficiency and thats because of overwhelming evidence of its effectiveness versus the poor and spotty tests of the efficacy of oral B12.
I wouldn't expect any oral dose to equivalence with an injection unless the dose was extremely high, as described above. Also, with a sublingual at those quantities, the amount of xylitol (if present) being ingested might also cause some gut issues...
Yes, any significant B12 deficiency, especially with neurological symptoms, should be treated with injections. The question is, is maintenance with daily oral doses of around 1000mcg good. Since we only need <5mcg per day or so, it should be sufficient. Unfortunately, with methylcobalamin tablets, many people, including me did not find it to be so and the reason is unclear, while there are clinical trials that claim that cyanocobalamin 1000mcg/day is sufficient for maintenance. I do not know whether this is true. We need more tests and trials to understand what is going on.
The trials you speak of are small and have produced poor quality evidence which I would not rely on or put much stock in. I agree we need more and better trials!
I don't have PA but I had an infant ileocolonic resection so I don't absorb vitamins well (particularly Vit D). I found that I have low levels of B12 a few years ago (201 ng/L in a reference range of 197 - 711). I first supplemented with 1 low dose B12 (40mcg) per day for 6 months which appeared to make no difference. I then supplemented with 1 100mcg tablet per day and this raised by levels by 100 ng/L over 6 months. I then supplemented with 1 1000mcg per day for a year and my levels raised to over 500 ng/; my long term symptoms of balance and dizziness issues disappeared. I've scaled it back to a couple of 1000mcg tablets a week as I believe B12 is stored (in the liver?). I'll get another check to see if levels are being maintained in a few months.
I don't know much about it but reading about this operation it seems to involve removal of some tissue at the terminal ileum, the B12 absorption site. This could very likely impact oral B12 absorption and re-uptake (entererohepatic recirculation).
"Another important component of B12 absorption is enterohepatic circulation. It is estimated that between 0.5 and 5.0 µg of B12 is excreted in bile per day. This biliary B12 is readily reabsorbed across the ileal enterocyte and, thus, enterohepatic circulation represents a mechanism by which B12 is conserved by the body. "
So the liver stores (might) not be as usable as they ordinarily would be - if completely broken, you would need at least 5mcg to be absorbed on top of the RDA, so assuming only passive absorption is working, 500mcg would be the absolute minimum and 1000mcg somewhat safer.
But because you still have working intrinsic factor some B12 may still be absorbed if there are still working absorption sites in the terminal ileum (here I confess my ignorance of the details of the operation). In theory it seems tablets should work for you ( for maintenance at least) but I would definitely stay at the higher end of the range, as you're doing : 1000mcg+ so that you get enough via passive absorption.
I have severe bile acid malabsorption (BAM) so I am probably losing B12 that way as well. I discovered the low B12 following appointments with an NHS dietitian who I was seeing about problems with diarrhoea.; it was she who thought I had BAM, where bile acid seeping into the colon causing diarrhoea. Curiously now that my levels of B12 are now much higher, the diarrhoea issue is much better as well.
B12 is indeed stored in the liver for some time, but there is no need to scale it back, especially since you were feeling well on 1000mcg, which is also considered the lowest maintenance dose (some studies show even 500 mcg is sufficient for most people, but for safety, 1000mcg is used). Also, if you are scaling back, you might want to check your homocysteine and/or MMA. Sometimes, we can feel absolutely fine, but these may be high if your functional B12 is not high enough. There are cardio-vascular consequences of high homocysteine, so it should be monitored, especially for those with intestinal surgeries having problems absorbing nutrients.
My GP refused to do an MMA and homocysteine tests even when my levels were at 201 ng/L; now that they are over 500 it is even less likely that they would agree to it. I'll continue with a daily 1000mcg tablet and ask for a B12 test occasionally.
There are private MMA tests available but at a cost which most likely wouldn't be expensed by medical insurance. Where I am, it is difficult to even get doctors to run routine yearly blood tests. They are actively opposed to preventive care and they're quite explicit about it. I would call this ignorant and short-sighted but. oh I guess I did 😋
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