As a follow on from my first post here: healthunlocked.com/pasoc/po... , I visited Dr K at Nuffield on Friday at Cambridge and he strongly suspects I have non-autoimmune functional B12 deficiency and based on history and symptoms, he has prescribed a 3 month trial of B12 injections every other day. He suggests after the 3 months is up that I visit a functional doctor to investigate GI issues, which he feels are the cause of the B12 deficiency. Having only learned of PA after googling my blood tests a week or so ago, I have a lot of catching up top do and thanks to this and the PA socienty resources, I'm feeling more aware but clearly have a long way to go.
Dr K said he tried to keep up to date on rsearch and B12/PA clinic findings around the World and recently attended 2 day B12 conference locally. His diagnosis and recommendations/treatment plans reflect this I feel and I wondered what members thought about a few interesting things discussed in the appointment. These are not recorded word for word but are approximately what was said or discussed:
1. oral B12 isnt available in a converted form so with functional B12 where it isnt converted properly from diet or supplements, a converted form (eg hydroxocobalamin) is required to readdress a B12 deficiency. EDITED 26-9-22 - I meant to say active as opposed to converted - brain fog, sorry!
2. There is not point in ever testing your B12 levels as they will be high and you have no pre-supplementation test result available. The latest B12 deficiency info is to "treat for symptoms" and determine the treatment based on relief of symptoms.
3. Come off all your supplements except magnesium and folate (400-500mg on injection days, currently every other day) and if B12 trial supports ypur healing path, will have a clearer idea of whats going on re digestion and root cause for further investigation. Previously I was taking digestive enzymes, Solo brand multi B vits, liquid adenosylcobalamin and methylcobalamin, mangesium, probiotics, reduced glutathionine, zinc, vitamin C, D3 and K2, and lots of natural anti virals/bacterials (as I suspect chronic epstein Barr virus and resulting dysbiosis and development of 'IBS' since childhood following 2 nasty virus episodes is root cause - funniy enough, When I mentioned this to Dr K, he agreed I could be right, much to my surprise!).
4. Long term oral supplementation of unconverted B12 can reduce sensitivity of uptake at cellular level and make the situation worse in functional B12 deficiency
Many thanks!
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Beccy_123
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Sounds like he is a keeper and interesting to hear that he went to a B12 conference locally.
He does make very valid points, was open to functional medicine and it is difficult trying to put your own personal jigsaw together with regards to gut health, dysbiosis and the microbiome.
"1. oral B12 isnt available in a converted form so with functional B12 where it isnt converted properly from diet or supplements, a converted form (eg hydroxocobalamin) is required to readdress a B12 deficiency"
All forms of B12 are broken down to the base cobalamin molecule in the body before being rebuilt into whatever forms are needed in the body (hydroxo/adenosyl/methyl). Some people do react badly to some forms or get on better or with less side effects with one particular form over another, but there is no functional difference. I believe there are rare genetic defects that cause some people not to be able to metabolize one form to another but this kind of problem already becomes an issue in infancy afaik. Research paper on genetic defects in B12 metabolism : ncbi.nlm.nih.gov/pmc/articl...
Hydroxocobalamin is broken down just like all the other forms. It has other advantages though such as light/temperature stability in comparison to methyl or adenosyl that make it very suitable for injection (along with cyano).
Point 2 : Agree unreservedly. This is best practice.
Point 3 : The number of supplements does confuse the issue, but I wouldnt completely stop Vitamin D tbh. Glutathione is either useless (it breaks down in the gut and is not absorbed) or dangerous (in liposomal form), as body cannot control its levels in cells. The rest, yeah, stop for a while to clarify where symptoms are coming from.
"4. Long term oral supplementation of unconverted B12 can reduce sensitivity of uptake at cellular level and make the situation worse in functional B12 deficiency "
Well there is no such thing as "unconverted" B12, as explained above, all forms are broken down and rebuilt by the body.
I'm quite dubious about whether there is any evidence for long-term supplementation of any form of B12 causing or exacerbating this problem of cellular level uptake. However the documentation and research on functional B12 deficiency is very thin on the ground. I only know of that one study which found antibodies to transcobalamin in those receiving frequent B12 injections, but IIRC they did not confirm significant problems with B12 utilization in the cells or functional deficiency. Hopefully more research will happen on this.
I dont hear many stories about people developing B12 deficiency after years of taking 500mcg or 1000mcg tablets though, so I think if it does happen at all, its very rare. None of them seem to have found this forum at least and it seems quite a locus of B12 information online.
Methylcobalamin and Adenosylcobalamin are the active forms of B12. Hydroxocobalamin is a storage form of B12 found in the cells, it can be converted to either of the active forms. All three are natural forms of B12 that the human body can use, found in various amounts in animal foods. They are all broken down and rebuilt the same way. So no, nothing to change in my response.
Thanks! What I don't understand yet is, after 5-6 years of oral supplementation, if still B12 deficient, but still having high B12 serum levels in 2016 and 2022 (which must be from supplements in 'active' form as plant based for 5-6 years), how do some folk become B12 deficient? Is it not getting into the cells from the blood stream, or is something not working within the cell? Or do I just need 1,000's x more than normal healthy human? I'm picking up bits of info from reading and scrolling the posts here but I am assuming not all is known about B12? Brain fog DOESNT help lol!
Supplements that are in inactive forms (such as hydroxocobalamin or cyanocobalamin) should work just as well as the active forms, maybe better depending on how you react to the particular form. Many folks dont get on well with methylcobalamin, for example As I said, theres no functional difference in terms of how the body ultimately uses them.
The effects of a B12 deficiency that has progressed to neurological damage and remained untreated for sime time are profound and long-lasting. Correcting the deficiency in terms of getting the blood levels corrected and cellular and liver stores restocked does not immediately heal all the damage - depending on how long the deficiency was untreated some of the damage may linger, having enough B12 is not the problem ( although having enough is usually very helpful to the speed of recovery), but there is structural damage which just isnt easy for the body to fix. Damaged nerves may never recover if the axon dies and are often repaired imperfectly, with lingering issues many suffer from. Recovery from B12 deficiency takes a long time and may never recover the level of health pre-deficiency. In addition, if you have PA, your B12 tank (your liver) is not connected to the car, because you have no working intrinsic factor - so frequent injections will always be needed to heal existing damage and stave off further regression.
If you had no B12 from foods, but were always supplementing at 250mcg to 500mcg daily (or some other dosage/frequency that meets the requirement), its unlikely you'd develop a B12 deficiency except by an absorption issue such as PA/reduced stomach acid etc. Vegans and Vegetarians are of course, not immune from developing PA even if they were supplementing adequately enough for a healthy person.
The only exception I can think of would be this functional B12 deficiency which I really dont understand about the details of how it develops yet.
Part of an interesting letter from Dr Wilhelmina Reitsema in 'Rapid responses' to the BMJ research B12 Def. document - last paragraph - "Is it important which form is used ....."
“There are two active forms of the B12 enzyme in the human cell.
First, Methylcobalamin acts as a co-enzyme for the conversion of homocysteine to methionine. Methionine then acts as a methyl-donor to a great number of reactions that need a methyl group, including the synthesis of myelin, serotonin, dopamine, noradrenalin, DNA and phospholipids.
Second, Adenosylcobalamin is a co-enzyme for the conversion of L-methylmalonyl-CoA into succinyl-CoA which feeds into the citric acid cycle."Is it important which form is used in treatment? In most people, it does not matter. They can convert cyano- and hydroxo-cobalamin into the active forms needed.
However, I have recently reported a case in which it did matter. The severe vitamin B12 deficiency, including dementia and psychosis, responded to treatment with high dose oral methylcobalamin, but not to equally high dose oral hydroxocobalamin. [1]
1.Rietsema WJ. Unexpected Recovery of Moderate Cognitive Impairment on Treatment with Oral Methylcobalamin. Journal of the American Geriatrics Society 2014;62(8):1611-12 doi: 10.1111/jgs.12966[published Online First: Epub Date]|. "
personally I do take a supplement with all three natural forms, for no good scientific reason but rather as a "just in case", if I do have some efficiency or other problem processing one or another and also because I think its closest to what my body would be expecting if the B12 was in my diet.
I might have to stump up 36 euro to educate myself via this paper : pn.bmj.com/content/9/1/37.long. It does look interesting.
" We describe a case of functional vitamin B12 deficiency where the repeated measurement of a serum B12 level within the normal range led to delay in the diagnosis of subacute combined degeneration of the spinal cord, and possibly permanent neurological damage as a result. Failure of intracellular transport of B12 by transcobalamin-2 can lead to functional B12 deficiency but with apparently normal serum levels, and is suggested by raised levels of either serum methylmalonic acid or homocysteine, associated with low levels of transcobalamin-2. Such patients may respond to repeated high-dose injections of B12."
This makes sense as to why, despite testing normal or high, patient symptomology should always take precedence in terms of treatment. It does sound like MMA should show elevation but maybe supplementation would affect that, I'm not actually sure by how much though.
It does look interesting, although this to my mind is only 'stage two', with most of the other genetic deficits seemingly further downstream. I thought transcobalamin deficiencies were usually infant-onset and significant, but found this suggesting a partial deficiency is possible pubmed.ncbi.nlm.nih.gov/146... which is intriguing, although not my issue. Cheers
Just to say I don't know how rare the genetic defects/epigenetic defects are, but I suspect less rare than might be supposed. More papers appearing all the time, with more genetic pathway issues, but even from the paper you quoted, both cblC and cblG are very variable with adult as well as juvenile onset (and as you mentioned, seem to respond better to methyl or adenosyl than cyano or even hydroxo). Lots not yet understood. As far as your last para is concerned, if the tablets/sublinguals are insufficient for the B12 requirement over many years the deterioration will become more obvious physically, just harder to diagnose. Father's problem as well as my own. So depends what you mean by developing B12 deficiency. We've been trying to hold it off for 40+/20+ years! Appointment Wednesday so hoping to know more shortly. Cheers
Interesting post with some useful information, thank you. My neurologist said much the same about EBV and viruses (and gluten) contributing/causing my neuropathy, but has also referred me for investigation of B12 due to long family history. I also supplemented before testing, many years ago, when I knew less of the history and how genetic B12 metabolism is. Wish I could get my dad to your Dr K. Maybe. Best wishes
Interesting! I stopped eating gluten in my early twenties when I learned how it made me feel. If I accidently eat it I'm okay but if I repeatedly eat it I crash so I wouldn't consciously eat it any more.
Interesting ....wonder what 2-day conference on B12, who was running this, who the speaker/s and who the target audience ?
There was a research paper, published in 2009, called "Functional Vitamin B12 Deficiency" by MR Turner and K Talbot, in which it is suggested that "...such patients may respond to repeated high-dose injections of B12."
Vague but it might prove useful, just because there is not much else around regarding functional B12 deficiency treatment. An interesting case study discussed.
Dr K seems like he will give your case his all - hope he can find a way to help you get back on track. Let us know.
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No PA or B12 deficiency but I am still going to supplement with oral B12 - should i get any other tests before this to rule out for sure?
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