I finally got my transcobalamin II lab test results and, no surprise, I'm extremely low. Since I lack the proper b12 transport proteins, I'm re-thinking my supplementation program and wondering if my lack of improvement back to "normal" on cyanocobalamin is because very little is actually transported to my liver to be converted to methylcobalamin. I'd like to skip this step (and the cyanide, which I'm sure isn't great for my body when taken daily) and just use methylcobalamin injections.
After scouring the internet, I found that Oxford Biosciences sells a stable, powder form of methylcobalamin that some individuals are using to make an injectable form by mixing with sterile saline (it even looks to be potentially marked this way). BUT, I have not found whether the powder itself is sterile. Has anyone tried this approach or have any information regarding whether this product is safe to use as an injection when properly re-constituted?
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It’s really not recommended to use any injectable material that is made up into a large amount, especially in a domestic situation where is has plenty of opportunities to become contaminated , as the B12 will take some time to be used up . Single use ampoules are always the ideal choice . I have trued the Oxford Biosciences Methylcobalamin powder . One difficulty is obtaining the saline ( In the U.K. saline is a prescription item ) I did not find that Methylcobalamin had any advantage over Hydroxocobalamin which is the B12 that is used in U.K. The amount of cyanide in Cynocobalamin is of no consequence at all .
The only thing that I can suggest to you is for you to look at the site.
vitaminquick.com They sell Methylcobalamin in single use ampoules . Best wishes .
Thank you for the site - I will definitely keep that in mind, although the price is a bit of a sticky point for me. I'm currently paying around $30 for a month's supply of cyanocobalamin from Canada (I'm in the US), whereas the single use ampules of methylcobalamin from vitaminquick would cost me around $129/month - yikes! I need to inject daily due to what is apparently a rare genetic mutation that renders me extremely low in transcobalamin II, which is necessary for B12 transport throughout the body and storage in the liver. This is also why I'm switching from cyanocobalamin: without enough transcobalamin II, it's unlikely that enough of my cyanocobalamin is ever reaching my liver to be metabolized into the active methylated form.
The sterile saline is generally less of a problem in the US, so my plan was to draw up the sterile saline into a 10 ml syringe, inject into the methylcobalamin powder, then draw back into the syringe and transfer the whole solution back to the sterile saline vial (with the rubber stopper). I would use a sanitized still air box for the process (a fume hood would obviously be better, but I no longer work in a lab). I wouldn't trust the screw top vial supplied by Oxford Biosciences to keep anything sterile for long (technically, it isn't sterile as soon as it's opened). But if the powder itself isn't sterile, then my whole plan in useless, and Oxford Biosciences says nothing regarding the sterility of the powder itself. I'm assuming this is to stay under the radar, but it's also problematic for the end user. I could possibly just autoclave the entire thing after mixing to ensure sterility, but I'll have to look into whether this would damage the methylcobalamin itself.
Now I'm just rambling. Thank you for the link - it's always good to have a plan B, and I'd rather spend the money than suffer from chronic migraine and fatigue.
I’m afraid that you will always find that Methylcobalamin is a lot more expensive than Cynocobalamin. Also is much more volatile . Has to be refrigerated, and does not stay effective for as long .
Hi, I am in the US as well and am waiting to see a geneticist this spring to be tested for trans2 deficiency as well. My b12 level originally was over 1500 when I wasnt supplementing at all. So it s obvious there is a transportation issue. I need to inject a lot to feel well. I gave used oxford bioscience for years. Its great, I wouldnt worry about the quality of their vials. Many professional labs around town order from them. I have been very happy with their supplement. And it makes injecting often affordable for us in the US.
unfortunately using methylcobalamin doesn't actually get round the problems with transcobalamin as the B12 needs to be bound to TCII to get into your cells whatever form of B12 is being used.The powder will be sterile but the need to mix it with saline is the most likely point for things to become unsterile because you won't be doing that in a sterile lab.
I believe you are based in the US - it may be worth looking through other posts - know that some do manage to get pharmacists to provide methylcobalamin, though as stated at the start, that isn't going to resolve your problem with TCII
Thank you for your advice. I do understand that transcobalamin II is needed to move B12 into the cells, but unfortunately there is no treatment for transcobalamin II deficiency except to flood the body with huge excesses of B12, preferably in the methyl form, and hope for the best. It seems the methyl form is preferred because that would allow nearly 100% of the injected B12 to bind to any available transcobalamin II, even if levels are low, and be transported into the cells. With the cyanocobalamin, I'm probably losing 80% of it due to lack of transport and metabolism in the liver before it can even get to the point of entering peripheral cells. (Note: these numbers are just for illustration - I'm not a research subject and don't have actual data for myself).
Luckily, I'm not completely lacking in transcobalamin II, otherwise I would have died long ago, I just have severely depleted levels. In fact, I functioned quite normally and never suspected a single issue until my late 20s. I do wonder if transcobalamin II deficiency can arise due to the formation of autoantibodies (just like those that cause loss of intrinsic factor), but I have yet to find any studies on this - it's just my conjecture given my atypical presentation and some anecodotal evidence from another person with the same presentation. I have a family history of autoimmune disease and only became symptomatic after a major black mold exposure, so the idea that immune stimulation started the whole thing isn't inconceivable to me.
I am hoping my current neurologist will prescribe me methylcobalamin to experiment with, but I've never had the luxury of staying in one place long or keeping the same insurance/doctors for any length of time (welcome to America, where your life is turned upside down every time you change jobs or move even a short distance), so I'd like to find a more permanent, reliable solution.
whilst methylcobalamin is one of the two forms used in process that go on in cells - adenosylcobalamin is the other - the process that gets B12 into cells combines cobalamin with the whole B12 molecule. Once in the cell it removes both the TC and the cyano/hydroxo/methyl/adenosyl part and then will recombine it with methyl or adenosyl parts depending on what process it needs the B12 for.This means that the form of the B12 that is in your blood is pretty irrelevant.
There is literature around saying that methyl is a natural form but most of this dates back to before the research that discovered just how TCII works.
Not sure what research you have that says TCII combines 100% with methyl - not aware of any such research.
The ratio of 20% of cobalamin in blood being combined with TCII applies to all forms of bioavailable B12 in the blood. If it isn't 20% then that would imply a genetic problem with TCII. Some of this will be bound to TCI which is the protein that enables it to be stored in the liver - some will be free. The limiting factor is the amount of TCII that your body can make.
I think there has been a miscommunication. I have no research saying that 100% of methylcobalamin binds to TCII (obviously all proteins have a max binding affinity for their ligand). What I meant is that if I'm injecting cyanocobalamin specifically, none can be transported into the non-hepatic cells until it gets converted to the other forms (methyl, adenosyl) by the liver. It is my understanding that this conversion does not occur in non-hepatic cells, but please feel free to correct me if I'm wrong. All the literature I've read mentions, specifically, that hepatic conversion is needed to cleave the cyanide molecule from the cobalamin and attach a methyl or adenosyl group.
My reasoning is such: if I inject methylcobalamin, nearly all the injected B12 is already in the proper form to be transported inside non-hepatic cells, should a TCII carrier become available - no cleaving of the cyanide need take place. If I am lacking TCII, then my pitiful amount of TCII can simply transport the injected methylcobalamin into my cells rather than get caught up making the round trip to my liver to first cleave the cyanide and attach either a methyl or adenosyl group. Basically, the liver becomes a bottleneck with cyanocobalamin. If I lack TCII and inject cyanocobalamin, most is useless to my body until those few TCII proteins transport it to the liver for conversion.
Obviously, the actual sequence of events would be much more complex - it is a biological system after all - but I do wonder if the ability to skip that hepatic cyanide cleavage step might make more active B12 available to my cells at any given time. This is all speculation, but since I've stopped seeing improvements using cyanocobalamin, I see no reason not to give the other forms a try. I do know some people who find they utilize one form better than the others, and the endeavor poses little risk except some financial loss.
In the above you say if I'm injecting cyanocobalamin specifically, none can be transported into the cells until it gets converted to the other forms (methyl, adenosyl) by the liver. Please note that this conversion doesn't happen in the liver - it happens after the B12 has managed to move into your cells - the process that removes the TCII protein from the B12 also removes the cyano/hydroxo/methyl/adenosyl part of the B12 leaving it as just B12 which then gets combined with either a methyl or an adenosyl appendage to form methyl B12 or adenosyl B12 depending on what process needs to run in the cell.
All that happens in the liver is storage - facilitated by a different transcobalamin protein - heptacorrin.
The liver doesn't become a bottle neck - the fact that it stores B12 does, however, become pretty irrelevant if you have an absorption problem because the release mechanism from the store involves putting the stored B12 into bile for it to be reabsorbed in the terminal ileum ... but if you aren't absorbing it there it just leaks through the rest of the gut. There may be a minor amount of passive absorption but not enough to be able to say that you are able to use the amounts stored in the liver.
Ah, ok, I will have to research this in more depth. In my reading, I keep running into sources that mention the cleavage of cyanide from cyanocobalamin occurring only in hepatic cells (or at least this is the only region that is mentioned). If this can occur in any cell, then I completely understand what you are saying - the form doesn't matter. My understanding was that specifically cyanocobalamin required a liver "pre-processing" step because not all cells could remove the cyanide. I will need to investigate further.
Not necessarily - only if the cleavage of the cyanide resulted in the B12 entering the pathway whereby it is stored in the liver and secreted into the bile. There is a rich vascular network in the liver itself, and certain hepatic cells secrete products directly into the bloodstream. So if the conversion bypassed the hepatobiliary system, cyanocobalamin could still be used for those with absorption issues. I will have to dig deeper into all of this. It's an interesting and useful topic for sure.
This took me a while, but I finally found the information I've been looking for. Cyanocobalamin isn't a natural form of B12, so it requires a specific intracellular protein to cleave the cyanide molecule. According to this study, that protein is MMACHC:
If you dig around a bit, it can be seen that many (probably most) cells are capable of expressing the protein, but they vary greatly in expression levels. MMACHC is mainly expressed in hepatocytes, hence why so many resources were mentioning hepatic conversion of cyanocobalamin to its active forms.
Given this information, it is possible that due to different genetic polymorphisms, a person could utilize one form of B12 better than others; this is actually mentioned in this article: sciencedirect.com/science/a...
I still need a bit more research, but it does seem that most human cells can absorb the other three forms of B12 (hydroxy, methyl, and adenosyl) when bound to TCII. In my case, this gives me reason to at least try one of the other forms in hopes of getting more active B12 into my cells. I do know that cyanocobalamin is the most rapidly excreted through the kidneys, so there is a chance that I'm excreting a good portion of my dosage before maximal absorption occurs.
In summation, the fact that different proteins are responsible for processing different forms of B12 lends credence to the anecdotal evidence that certain individuals may get better results with specific forms of B12 supplementation. Scientifically, this would depend on the specific polymorphisms present along the B12 metabolism cascade.
MMACHC is the protein that enables the cell to combine B12 with either the adeno part of the methyl part once it is in the cell. Another protein MMACHD is also involved.
This means it is the protein that is removing the transcobalamin protein once the B12 is in the cell and would be doing exactly the same job for any form of bio-available B12 in your blood (not just cyano)
the article also implies that the protein isn't specific to hepatocytes.
Whilst I agree that the differences in responses to different types of B12 are going to be due to genetic differences, genetics is off topic for this forum.
Given the number of genes that are involved in some way in the metabolism of B12 I think we are a long way from being able to know exactly how a given individual is going to respond even if we do have all their genetic variants mapped out.
I fixed the first link - it must have been a typo.
I see your point that MMACHC also works on the adenosyl and methyl groups of the B12 molecule, thus the type wouldn't matter in that regard.
For my own sanity, I'm still going to try and experiment with the other types. I simply don't know enough about my genetic information and probably never will, but I'm willing to experiment if it has any chance of helping.
Hi Gambit with regards to TCN2.If I may throw a few things at you with the aim that you may be able to help my thought process on this subject.
I am thalassemia trait (microcytic) but with a higher volume of cells therefore a reduced oxygen carrying status in very simple terms.
I have had several genetic reports done and have the TCN2 C776G GG allele (highlighted in red) meaning that I have decreased activity there.
So from what I have read up and studied to date means that I have a reduced ability to pull B12 from the Gut to the blood/or into the cells. Therefore as I am daily SI Hydroxy does this render that pathway obsolete? I mention this as I simply can not get by on any less frequency of SI. I know it seems mad and if I try to go for a hours walk that still knocks me and symptoms get worse as in fatigue/ anxiety/ racing pulse.
I am still working on healing my gut and have to go very slowly. I used to be so healthy and very active indeed.
I am continuing with tests and trying to find the best way forward with supplementation to compensate for my reduced folate carrying gene too (RFC1 and all the rest).
genetics is really off topic for the forum but my understanding would be that TCN2 is a gene that controls some of the functioning of transcobolamin which is the protein that enables B12 to get from blood into cells rather than something related to absorbing B12 in the gut. Its basically the protein that combines with B12 to make active B12There are a few variants that known to prevent TCN2 from being produced correctly which are known to cause failure to thrive in infants - but I don't think there is much known about how other variants affect the way transcobalamin is formed. To me it would seem to make sense that some variants might explain be part of the explanation as to why some of us really need very high levels of B12 after starting on injections but I'm not aware of any specific research on this.
Thank you. It's something I must learn more about as to why I seem to need so much and why it does not last very long. Especially if I try to become more active my body seems to simply gobble it up.
HI, I'm here in the US. I've been receiving cyncobalamin for the last five years and it works great. It took a year before I felt better on a consistent basis. I have a couple of the mythfr variants but unless you happen to have a double variant on a specific gene it really doesn't effect your health. I freaked out when I first discovered this but upon researching the problem I discovered that it isn't a problem. Read this article from 23 and Me, it might help you feel less anxious. blog.23andme.com/health-tra...
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