Hi
I'm getting a little confused and trying to understand what is actually measured with blood tests...
Does a serum Total B12 reflect what is or isn't stored in the liver at the time of the test or just what is circulating ?
Does an Active B12 test measure the store differently, is the store in the liver 'Active' ?
At what point does the body start to deplete what is stored ?
Many thanks for any explanations or links to help understand!
Total and Active B12 are to do with the B12 in the bloodstream.
There are two types of vitamin B12 in the body, these are active B12 and inactive B12, both make up Total B12. The simple difference between the two forms is that active B12 is the form used by the body.
What Is Total B12?
Total B12 is a measure of both active and inactive forms of the vitamin B12.
Vitamin B12 is bound to two proteins, one is haptocorrin the other is transcobalamin. When vitamin B12 is bound to haptocorrin it is not taken up by cells for the body to use and is therefore an inactive form of B12 stored by the body.
What Is Active B12?
Active B12 is when B12 binds to transcobalamin protein (known as Holotranscobalamin or HoloCT) and is made available to cells for use in the body, hence being called active B12.
forthwithlife.co.uk/blog/wh...
The liver continually releases B12 into the bloodstream.
Much of that B12 gets recirculated via the digestive system. Then re-absorbed and stored in the liver.
What we need each day is the difference between the amount we use in our bodies and the amount that is successfully recirculated.
In the best cases, that is as little as three micrograms a day - possibly even less.
But if you do not absorb B12 adequately, you will need more than three micrograms - possibly much more.
Worse, if you do not absorb B12 well, and that is causing the failure of enter-hepatic recirculation, you also will have problems absorbing any extra B12 you take as a supplement.
See here:
b12info.com/wp-content/uplo...
Just realised I meant to post this in the B12 group - no wonder I couldn't find my post - it was here .....Brain fog ! So thank you so much for taking the time to answer so thoroughly, off down another rabbit hole now 🙂
Yours is just one of many we have had recently which seem more appropriate to the Pernicious Anaemia Society!
I've given up pointing that out. 
Hi Helvella
I would say it’s a fairly comprehensive answer.😊 I learnt something today! There’s just so much to learn - lifelong learning is just that!
Good question Spritze 🤗
helvella
This is something I too get really confused about so I’ll ask one question at a time
First
Is active B12 in the blood cells?
Seems obvious but I want to clarify this for others who might also be reading this
No.
It is floating around in the serum attached to the protein transcobalamin.
I do NOT know what happens to B12 within cells.
In general, we do not have the technology to measure anything within cells.
And that explains why testing serum B12 is pointless after injections have started - it gives total B12 amounts, which will be high, while giving no information about the efficacy of B12 treatment.
Thank you helvella. No need to respond tonight. Just posting to get it done and out there
Second question then. Well it’s not so much a question, more repeating what you’ve said in the way my brain has interpreted it
Transcobalamin then, is responsible for transporting it to cells for uptake?
Maybe just a brief read of the summary/abstract would help?
Certainly knows more than I do!!!
Yes - it is concerned with the genetic basis but it starts with a simple explanation.
Transcobalamin receptor gene polymorphisms and mutation in an elderly population
Andrew McCaddon
Daniel F. Carr
Hudson Peter
Stuart J. Moat
Edward V. Quadros
Open AccessPublished:May 02, 2023DOI:doi.org/10.1016/j.clnesp.20...
Summary
Background & aims
Cellular uptake of the essential nutrient vitamin B12 (cobalamin) occurs via the transcobalamin receptor (TCblR/CD320), a ubiquitous membrane receptor. Polymorphisms in the receptor exist, though the effect of such variants across patient populations is unknown.
Methods
We determined CD320 genotype in 377 randomly selected elderly individuals.
Results
Three polymorphisms and a codon deletion were identified in the exon 2 region. Haplotype variants had significantly higher holotranscobalamin (holo-TC) values and a higher holo-TC/total cobalamin ratio. TCblR haplotype explained 46% of the variability in holo-TC values.
Conclusions
This has significant implications for the clinical utility of the ‘combined indicator’ of B12 status since it is based on a standard rate of intracellular flux via the TC-Cbl receptor. Modification of the model may be required to account for CD320 haplotype.
Keywords
Vitamin B12
Cobalamin
Transcobalamin
Transcobalamin receptor
Gene
Polymorphisms
CD320
Full open access paper here:
clinicalnutritionespen.com/...
it starts with a simple explanation
Goodness! Thank you but if that’s simple I must be even more dense than I thought 😕
What my inferior brain took from it was that yes, transcobalamin is involved in the uptake of B12 at cellular level. The technicalities of how are beyond me and at this point in my learning I’m not interested but I do wonder if all cells then utilise the “uptaken” B12
To simplify and clarify the question: are we to understand that active B12 is “floating around in the serum” not doing very much until it gets into the cells; blood cells, brain cells, liver cells, etc. Can those who have adequate levels of active B12 rest easy in the knowledge that it’s doing its job?
Thanks and again, answer at at more convenient time to you. You must get so tired of having your brain picked
No we can't.
Because while it is floating around attached to transcobalamin, and that is a necessary state, the transfer of the B12 via the transcobalamin receptor varies - depending (at least in part) on our genes. Suggesting that some of us need much higher active B12 than others.
If we knew the level we need (as individuals), then the Active B12 test might be excellent. But we simply cannot apply the same reference intervals to everyone. And that undermines its utility as a test for everyone.
And people asking questions is one of the very best ways of getting to understand things.
Pushes me to get answers, and to ask myself whether I truly understand anything.
Btw, you replied to yourself
You’re right. I find that all the time. Sometimes I think I’ve understood then someone on here comes along and asks a question so incisively that it raises even more questions, which in turn makes me question my own understanding. This is a good thing
So because we individuals are so variable in our requirements for active B12 and the transfer of it is also so variable, at best the test is what? Nothing more than an indicator that ought to be viewed with, if not scepticism then at least caution?
Have I understood that correctly? I hope not 😳
Sounds as though I’m shooting the messenger. I’m not, just expressing alarm
And thank you for all this
The test can certainly identify a level of B12 which is an obvious problem.
And although exact numbers and interpretations vary, there is often a band at the bottom where they advise further testing (methylmalonic acid and/or homocysteine).
And many suggest that both Active and serum B12 tests should be looked at as indicating supplementation being required even at fairly high levels - which would probably catch everyone. (E.g. More than 500 or so for serum B12.) Though many would not technically need it that avoids anyone being missed.
And many suggest that both Active and serum B12 tests should be looked at as indicating supplementation being required even at fairly high levels - which would probably catch everyone. (E.g. More than 500 or so for serum B12.) Though many would not technically need it that avoids anyone being missed
I like that idea
Thank you for helping me understand. I can’t say I’ll remember it in a month’s time but that’s the nature of thyroid disease
Wouldn’t this be fab
It could only be over a certain age because of cost but maybe the savings would be so phenomenal that it could be rolled out for everyone but in a
Imagine a utopian Britain in which citizens would have a comprehensive annual test where simple things like nutrient deficiencies were detected and then treated before they caused disease. Think of the mass suffering that could be avoided and the savings to society and the NHS and all the other diseases that could be detected early
A big fight with big pharma would ensue. Imagine
So it should be reasonable to assume then, if a person has a 'low but in range' Active B12 level that they DO have Intrinsic Factor available and effective (...because without it, B12 wouldn't be available to bind with transcobalamin) and therefore negative for Pernicious Anaemia ? Somehow I don't think it is that simple ?! Is availability of IF on a variable scale meaning someone could have mild or severe PA ? I hope this question makes sense !!
Serum b12 levels. 
B12
Diagnosis and treatment of B12 deficiency or PA
Advice ref. B12 please
Hyperthyroidism, low B12, raised iron and ALT.
