I seem to remember Sally Pacholok saying physical symptoms came first and later they are followed by neurological. I hope I got that the right way round. She seemed very certain.
However, I later came across another article which seemed to say the opposite. Can anyone kindly clarify the current understanding on which set of symptoms usually comes first.
Thank you.
Cetus
You can’t have specific methylcobalamin deficiency. You can only have B12 deficiency. Once they enter the cell all forms of B12 are transormed into cob(II)alamin - they are all identical.
I believe that a B12 deficiency will start to effect all of the processes which require B12 at roughly he same time. But the rate at which those processes show effects will vary. So impairment of red cell formation will show effects very quickly because the turnover of red cells is very high (the average red cell has a lifetime of a few months). But nerve impairment, although it starts at the same time, will take much longer to show effects as the turnover of the myelin sheath is much, much slower than that of red cells.
fbirder Thank you for your reply. So as a rule of thumb it is physical symptoms before neurological.
As an aside .....
I wanted to consider only those symptoms caused by a shortage of methyl-B12.
I get different improvements depending if I take one active form of B12 rather than the other. My initial problems were with fixed after I took enough adeno-B12 but I was left with a heck of a lot of remaining trouble on the other pathway. Sigh!
I switched to taking each active form separately and eventually discovered I was sensitive to excess methyl-B12 but not adeno-B12.
I can't at all understand why I am so sensitive to methyl-B12 because almost everyone says they don't get this problem and theory says the excess B12 is excreted. However after a few days of increasing my dose I get breathless all day long.
Regards,
Cetus.
If you look at this post healthunlocked.com/pasoc/po... done a diagram and explanation of the workings of Methionine Synthase (the enzyme that MTR codes for). You can see that it is cob(I)alamin that is bound to the enzyme and is then released. The enzyme doesn’t bind to, or release methylcobalamin.
The action of Methylmalonyl-CoA mutase is a lot more complicated and I can’t say I’ve looked at it in any detail.
But I can say that adenosylcobalamin is, according to people who understand it much better than I do, no better than any other form of B12 - because the adenosyl group is removed as soon as it gets into the cell. The same happens with hydroxocobalamin which may be better than either of the coenzyme forms ncbi.nlm.nih.gov/pubmed/258...
Many people find they are sensitive to methylcobalamin (including me). There is some thought that it has something to do with catechol O-methyl transferase and how that is involved in the biochemistry of neurotransmitters. I stopped injecting methylcobalamin and went back to hydroxocobalamin. And all is good.
fbirder Thank you kindly for the link. I had assumed from this diagram imgur.com/a/WzQL668 that the MS (MTR) reaction worked in two stages. First the methyl is attached to cob(I)alamin making methylcob(III)alamin and then secondly that methyl group is given up to homocysteine to make methionine.
I don't want to get bogged down in the potentially wacky world of dodgy B12 genes but I'm trying to understand the very different benefits I get from the two active types of B12. As it happens, tests show my B12 pathways have more than a few pathological quirks (especially on the adeno-B12 path but also MMACHC) which probably mean I don't absorb B12 conventionally and therefore need think outside the norm.
Thanks for your reply.
That diagram, like most, makes it look as if a methyl group is transferred to cobalamin to form methylcobalamin, which then binds to the MeSe enzyme. If this were so then you could see how methylcobalamin in the cell might be useful.
But that’s not how it works in reality. The cobalamin and MTHF both bind to the enzyme, along with a molecule of hCys. A methyl group is then transferred from the mthf to the hCys, via the cobalamin. So methylcobalamin is formed, but only fleetingly.
I do understand your warning about misinterpreting genetic results. Genetic results are useful mainly to interpret what is causing observed symptoms, rather than the other way around.
Things are simpler for me as I have no MTHFR problem and glide past the many detailed ponderings on the web about it.
On the other hand, I have some very severe B12 symptoms and the genetic results give some clues about what is underpinning them.
By the way, I think you and the textbook agree. Their diagram has left out the MS label for the formation of methyl-B12 but it is mentioned in the footnote.
Thanks once again.
I presume that the tests that show these quirks are genetic tests.
These tests are massively overblown on clickbait websites.
Just look at all the nonsense about MTHFR mutations. What they don’t tell you is that just about everybody has mutations in the MTHFR gene. Less than 1% will have no mutations at all.
It’s the same with all the other genes. There are very few mutations that have been shown to actually have any deleterious effects. And those that do tend to be severe enough to show up in infancy.
I like to take a straightforward approach in my own treatment of PA.
At the start I received my (inadequate) injections from my gp with no advice given to me regarding co factors. After reading up on it and also having a blood test showing slightly below range potassium I then looked at my injection frequency and intake of co factors.
I now si weekly, am careful to have a good daily intake of potassium and folate rich foods, take a folate/folic acid supplement and a multi vitamin (being careful not to take one with excessive amounts of B6).
The above regime seems to have sorted my energy levels and tingling in my hands. I’m left with digestive issues and these are much reduced by using betaine HCL and pepsin, digestive enzymes and every now and then using a good quality probiotic as well as eating plenty of prebiotic foods (ie lots of veg).
As you had a good response to your initial treatment with hydroxo I would be inclined to look at your co factor intake.
Thanks for your post. I am doing every other day SI and still have neurological symptoms. I haven’t had a PA diagnosis, but have iron deficiency anemia. I suspect this all stems from my stomach; I have had three stomach surgeries; the last was a bowel resectioning.
I was interested in your statement about taking HCL and Pepsin. How do you know how much to take? What amounts did you begin with?
Many thanks!
Sita
PS. My hematologist felt that I could not have PA due to a 470 level of B12, but I had been supplementing for years.
I started with 1 tablet a meal, increased to 2 with main meals and now I take 3. I don’t feel any discomfort from taking them so I’m guessing I’m not taking too much.
Hi Jan
Thanks for your response. Can you tell me what your symptoms were prior to starting your regime and what has improved? Many thanks!
My symptoms were tiredness, extreme tiredness and exhaustion! Also, feeling twice my age, alcohol intolerance, tingling fingers and tinnitus (which is the only thing that hadn’t improved so maybe that’s not B12 related). Then there were the gastro symptoms of over fullness (the lightest meal felt like I’d just eaten Xmas dinner with all the trimmings), sometimes painful stomach, bloating and constipation (it felt like my bowels had forgotten to work).
Hi,
We're all individuals with different genetic make-up so my view is that in some physical symptoms present first, in some psychiatric symptoms, in some neurological symptoms and in some, a mixture of all type of symptom.
Link about B12 and neuro-psychiatric symptoms
stichtingb12tekort.nl/weten...
Misconceptions about a B12 deficiency
stichtingb12tekort.nl/weten...
PA and B12 Deficiency Symptoms
pernicious-anaemia-society....
b12deficiency.info/signs-an...
I am not medically trained.
I do remember reading an article which stated that... it depends on the person. I think one thing is that B12 deficiency tends to result in lots of different symptoms. At first people write them off as age or tiredness related. So it may depend on when you realise and discover the cause of "all" your problems.
Unilateral neurological symptoms 
List of Neurological Symptoms
Neurological Symptoms of B12
Neurological symptoms 
