I went to my appointment with the inherited metabolic diseases consultant, after waiting over a year for DNA tests, and having appointment altered because he was on sabbatical. Quite apprehensive because he'd told me "there's always a story" and because this is the last port of call for me in my search for answers.
How disappointing to find that he is still on sabbatical, and that the appointment was a colleague telling me they don't have my results back.
Also dieticians - again, and blood tested for liver function- again.
I was offered a telephone appointment once they had my results - but my partner told them this would not be possible for me, because of my memory and cognitive problems. So luckily, new consultant will see me again in a couple of months.
Incidentally, I did mention the Pernicious Anaemia Society's recent research trial outcome, and she read the newsletter about the results regarding evidence that some people need more frequent B12 injections. Her response: "..but you haven't got a Pernicious Anaemia diagnosis".
This is all very frustrating.
I was discovered to have B12 deficiency in February 2016, also low folate and ferritin and osteoporosis of the spine I was given injections: loading dose and then 1 injection every 3 months. Before very long, I was rapidly deteriorating. I was found to have raised consistently MMA (350-400 nmol/L - range of 0-280 nmol/L) even though my B12 was now reading >2000 ng/L. I was then diagnosed as having functional B12 deficiency, confirmed by laboratory. I was put back on loading dose of 2 injections per week for a long time, then deteriorated again.
Many tests and consultants later, I self-inject every other day and have done since September 2017 . It doesn't make me completely better, but it stops me getting worse. I am at the stage where I am seeing gradual improvements, but still have no entirely symptom-free days and still have blips for which I can find no reason.
I am a vegetarian with a B12- ,folate- and ferritin- rich diet, not that it makes any difference since I self-inject frequently and take a good multivitamin and mineral tablet daily plus D3 on prescription. IF (and I don't believe this to be true) this was ever a diet-related condition, that could not now be the case.
My main fear now is that my raised MMA will be written off as "my normal", I will be left undiagnosed, and so if anything eventually becomes available due to this new research finding, it won't be available to me. As far as I'm aware, there is no research or recommended treatment for functional B12 deficiency, beyond Talbot and Turner's "frequent injection" advice. I once showed this to a haematologist, to which she replied "..but look at the date." I think it was published in 2009.
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Cherylclaire
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Well if you'd like to take my body with you to show them you're not alone, it's always available: it's not much use to me!! 😁 😁
If you find any answers I will be very grateful to hear them.
I've been daily SI for 4 years and while the improvement is huge and ongoing, particularly with regards to my cognitive function, balance, etc, I am still way too far from OK and it takes almost nothing to set me back big-time. I'm not vegetarian and now have to eat more meat than I'd like to for haem iron.
I have often thought that we perhaps share some common condition - and have self-treated it in a similar way.
I will let you know if anything comes of this, but I'm now doubtful. The good thing is that I know this would have completely floored me not long ago, and now it is more of a weary >sigh< situation.
Giving up ? No not at all. Just being realistic.
Wouldn't it be great if we could go to these consultations in pairs ? In groups even !
I "follow" you because of the similarities in our cases!
OMG - I've never thought of that!! What a superb idea it could be a chorus of "no it's not like that - you listen to us"!
I've avoided Drs for several years because of the disbelief and enviable mental slur! I hate it when I've said "but there are lots of us like it, with the same sort of issues and part-solutions" and they look at me as if to say "yes, and you've brought your invented family in with you, along with your invented complaint!! 😁 🙃
If I can get and keep well enough to do it, I'm going to ask to be referred to a particular gastroenterologist I've found who might be able to give me some information to help with the digestion/malabsorption problems I get.
I listen to quite a few science programmes and it seems that a lot more knowledge is available, it just doesn't get disseminated. As a result I tried emailing some Universities but didn't get any replies and it's hard to find time to follow it up when I have to work full time.
I couldn't do anything about it before because I didn't have enough memory to work with but if I can get my life back together (I'm currently fighting an UTI with antibiotics that shouldn't be taken with B deficiencies or anaemia - oh joy - because the safe ones didn't work!) I will try again to see if something can be done to help us.
Don't panic - if you're taking them and you're OK then it's fine.
Some antibiotics lock up vitamins and minerals in your body while others strip them out of your system but others work in other ways and are OK.
You can have a problem with the type of antibiotics that deplete your resources if you have any tendencies towards deficiencies because your body has a problem that has caused the deficiency in the first place and so it isn't going to readily restore the balance back after the bacterial infection has cleared and you have finished your course.
Because the processes of cell renewal, nerve function and energy release that use B12 also need a wide range of vitamins and minerals to work properly, if you are short of anything, it becomes a limiting factor and reduces the functioning of your body.
Some antibiotics rely on specific levels of things, particularly minerals, in your system and so can be affected by the fluctuations that occur when you take supplements if you need to because of abnormally dropping levels.
Calcium is one mineral that affects the serum levels of some antibiotics and therefore magnesium supplements, which have an effect on calcium, can upset the balance. To that end, potassium, which is also affected by magnesium/calcium can become unbalanced and so you can develop (or worsen) neuropathy if you don't have enough potassium available in your body's reserves.
To be honest they are all interlinked and it's fine if you don't have an underlying problem but can be a nightmare if you do.
However that said you always have to look at the prognosis: if you will die or be much worse without the antibiotics then you have to have them in the short term and fix the deficiency problems afterwards in the long term coz if you die the long term is irrelevant!!
Ideally you chose ones that have minimal negative effects (eg last week I tried Amoxycillin) but if the bacterium causing the infection are resistant to or unaffected by them then you must have the least-worst of the antibiotics that they ARE susceptible to and deal with the deficiency problems afterwards.
Trimethoprim badly affects folate and last year I thought "oh that's OK; I have my own supplements and can just increase those"! Never will I be so gung-ho again!! Because I have so many malabsorption problems, it cost me a fortune in methylfolate and I was desperately deficient - and therefore nothing worked well - for months. It took more than 6 or 8 months to get everything stabilised again!
I have chrons disease and now lyme ..so I have malabsorption of lots of vitamins and j do have to treat the lyme with 3 types of antibiotics..also I'm on prednisone for 10 days. It's being a nightmare. Cannot sleep, my internal tremors are so bad, restless leg,....I have 40% of my methfr compromised, I did a dna test. And my functional doctor doenst think I need B12. My homoceystein is 10 and my mcv is 96, ferritin 38...my b12 keep super high 1400 but I cannot absorb it...which tests do I need to do for my doctor to believe me? Please I'm desperate....
Which are the antibiotics that shouldn’t be taken with B12 deficiency? OMG do the issues associated with this ever stop? I never gave a thought to antibiotics!
I've never gone through the list to find out all of them, I just check the information on each one carefully before I take them.
Trimethoprim causes significant problems with low folate so would be a good one to avoid if possible.
I'm on nitrofurantoin now which has warnings for B deficiencies, anaemia and contraindications for taking magnesium but seems doable.
Amoxycillin and tetracyclines seem to be fairly OK for me but definitely aren't suitable for everyone.
Basically ALWAYS read the information leaflet VERY carefully and do not trust your Dr or pharmacist to know what your situation is. If you have any doubts discuss your problems with them and highlight any issues that you find in the information that you feel apply to you. If they take a judgement and decide to take the risk then keep them informed of how it goes.
There is a heme iron called ProFerrin made by Colorado Biolabs proferrin.com that is very good. I can take it without problems normally caused by iron.
Although it's currently not available in the UK and Colorado Biolabs don't export it at the moment, I'm sure it will be available in the future - especially with the current fashion for veganism.
Once a product has been developed its only a case of supply chain.
The idiot heamatologist to whom I was referred told me that I didn't have PA (purely because I hadn't had an IF antibody test). He was quite adamant. Until I asked him what was causing my low B12.
He flustered and conceded that it probably was PA.
I recommend asking exactly this question if anybody ever tells you that you don't have PA. Tell them you're a carnivore, that you don't abuse nitrous oxide, that you don't take PPIs or metformin, and that you don't (as far as you know) have a fish tapeworm. So what the *&#@ is causing your low B12?
Pretty much what Martyn Hooper said to me - without the *&#@ ! - at the PAS meeting I went to 2 weeks ago. But getting a doctor to say it ? It's next to impossible to get anyone in the medical profession to say the P word these days !
Thanks fbirder - any interesting developments, I will let you know. Meanwhile, another wait looms.
No, that was another test that hadn't been heard of in my health centre and therefore wasn't available. I was too ill to talk to anyone when I was bad - I couldn't remember any words or what I'd just said - so if it wasn't in my prepared-at-home written notes when I was fighting for treatment I couldn't ask or challenge what was said. Plus I was a jibbering wreck and struggled not to cry if anyone spoke to me - or even just smiled at me sometimes!! 😁
Since then I've managed to get well with my own treatment and haven't "bothered to waste my time with them since".
I feel this is an unhelpful attitude on my part and I will try again, now I have achieved a good level of emotional stability and can remember sufficient vocabulary quickly enough to be able to robustly put my case.
It was only in December that I still couldn't talk fluently (I had a do a piece to camera for our local news programme and wasn't really good enough - thank goodness for some kind editing!) but I nearly can now - woohoo!! 👍
I know exactly how you felt- and I can't call it an "unhelpful attitude" on your part because of this. Just doing the best you were able to do on that day, with that person.
If how you were was not either notable or explicable by experts, or quantifiable for their feedback reports or your medical file, that is absolutely a failing on their part not your's.
All of these symptoms that are only too familiar to us (whether we personally experience them or recognise that others do), and which continue to go unrecognised by nurses, GPs, consultants and those who should by now be experts in B12 deficiency symptoms (or at the very least, as familiar with these as we have had to be) are not of our doing, not our fault, and need to be professionally acknowledged if we are to get any useful treatment at some point in the future .
I once read about research that was carried out: a B12-deficient person allowed himself to deteriorate again over a period of years in order to log main indicators of his deficiency as they occurred by regular testing - MMA being an early riser, homocysteine being a very,very late marker. The final one, I believe.
One might call this crazy, and a single person's findings might not count at all, but who here has not been tempted at some point to just stop in order to prove how bad bad can get for them, especially when some symptoms are ignored/ dismissed in favour of a plasma test result or a misdiagnosis ? Especially if recording everything gets labelled as obsessive, rather than being seen as a useful aid to poor memory and concentration issues when on a 10-minute deadline ? All way too slapdash, this.
I told a student to stop talking last week, because I couldn't focus on helping him solve a practical problem by elimination and listen to him simultaneously ! It's just how it is some days.
You always give good support and carefully considered replies on this forum. It is appreciated. You certainly helped me find a balance.
Found the write-up on that experiment I was talking about earlier:
The subject : an initially replete 54yr old male with a B12 deficiency possibly caused by defect in the intracellular cobalamin metabolism.
The object: to deplete himself by withholding treatment and eating a diet low in B12 until significant metabolic disturbances observed, monitored by weekly blood tests.
The results:
MAX: B12 606pmol/L at start - decreasing to MIN: 171pmol/L on DAY 728
MAX: HoloTc (live B12) >128pmol/L at start - MIN: 33 pmol/L on DAY 742 (the ONLY day when below lower range-limit)
Total Homocysteine: 8.4 - increasing to MAX: 14.2 on DAY 609
MMA: 0.17- upper limit of range exceeded: DAY 386 - MAX: 0.90 on DAY 658
Findings: HoloTc not significantly more sensitive than either serum B12 or TH, and much less sensitive than MMA. MMA had 4 distinct peaks, first exceeding upper range limit on day 386.
Oh wow - really interesting! Thank you for finding and posting it!
As you say, very brave in the interests of science!
It would be fascinating to see how one of us who crashes really quickly shows up under lab testing - but I'd need to be paid enough to compensate me for not being able to work during recovery before I'd be willing to try it.
Up to 18 months ago ago I was losing cognitive function and motor skills to the point of struggling to do my jab (I always keep emergency kit with me, in case I forget in the morning) once I got to 28 hours after my previous jab. A couple of months ago however (albeit on a less busy/stressful day) I got to 32 hours after my previous jab before I realised that I'd got side tracked in the morning and had forgotten one because of the "death is coming to get you, ha ha!" symptoms crept up on me.
I'd be (almost! 😁) willing to offer myself to see how levels of things changed as symptoms came back if there was a research project wanting a subject.
Sleepybunny I asked my GP for homocysteine tests but he says they are not on his list of available tests. I did hear from a consultant that the usual way around this is for the GP to get a freindlt consultant to make the request -- but there's little chance of my GP doing any more than the minumum.
I looked into private homocystene tests and found a couple of companies but came away with the impression that homocysteine is best analysed fresh and not after travelling in the post for a few days.
Have you considered seeing a private GP? Some work in partnership with private hospitals so you might be able to get a homocysteine test on same day as seeing GP.
I got given a homocysteine test on NHS by haematology consultant at a central London hospital, referred there by my GP because my MMA was found to be high after starting B12 injections.
MMA test was requested several times by GP, but apparently not available at local hospital- again, eventually had to be a central London hospital lab but still NHS.
I think all of this would depend entirely on the tenacity of your GP.
Was told by haematology that homocysteine was "normal"- (really is like blood out of a stone getting info on your own 5 tubes of blood!)- which did not tally with raised MMA.
Might be worth having homocysteine checked again privately, as long as I don't need to stop injections prior to test !
Interesting, though, and wondering if MTHFR gene mutation likely to have been one of the DNA tests for which I'm currently awaiting results ? I'm thinking "yes".
Low hCys strongly suggests there is no problem with methylfolate and that any MTHFR mutations you may have (and almost everybody has at least one) it's not affecting the working of the methionine synthase enzyme.
Any problem with methylfolate wouldn't cause MMA to be raised. So that's two things that go against a MTHFR problem.
I would guess the genetic tests would be looking at other enzymes that may play a part in the functioning of the enzyme methylmalonyl-CoA mutase (coded by the MUT gene). As well as MUT mutations in other genes - MMAA and MMAB which are involved in the conversion of cob(II)alamin into adenosylcobalamin - can also cause raised levels of MMA.
My own main problems seem related to my MTR gene (methionine synthase) and perhaps also the MTRR gene for recycling methylB12. In addition to symptoms of low folate, I also get symptoms of methylamlonic acidemia but, although they can be severe, they can come and go.
It's just a wild guess, I'm starting to wonder if the folate processing side of B12 is getting so depleted that it also depletes the B12 on the methylmalonic side as they are said to form a shared pool of B12 which later gets converted to the two special forms.
Mutations to the MTR and MTRR genes are so common that almost everybody has at least one. I have at least two mutations in MTR and four in MTRR.
Mutations in MTR are very unlikely to increase the requirements for B12. Mutations in MTRR may increase the need, but very slightly.
The conversion of homocysteine to methionine requires a molecule of cob(I)alamin (Co1 - which comes from B12), a molecule of tetrahydromethylfolate (THMF), and a molecule of homocysteine (hCys) to bind to the methionine synthase (MS) enzyme (which is coded for by the MTR gene). The methyl group from THMF is transferred to the Co1 which then passes it directly to the hCys, forming methionine, which is released from the MS, along with a molecule of CoII and a molecule of tetrahydrofolate (THF).
If a MTR mutation hinders the function of the MS enzyme then it should require less Co1 and, hence, less B12.
You can see that Co1 enters the reaction and is also produced in the reaction. So the Co1 just goes around and around. If the recycling were perfectly efficient then we would never need to add B12 into the cycle. But it isn't perfect.
One imperfection is that about one in every thousand times around the cycle the Co1 is oxidised to cob(II)alamin - Co2. The enzyme MTRR reduces the Co2 to Co1, allowing it to go back into the cycle. Mutations to the MTRR gene can hinder the efficiency of this reduction.
No reputable, repeatable studies have ever shown a negative effect from any of those mutations.
@fbirder. Thank you very much for taking the trouble to go into the details. I appreciate it. I'm acutely aware that it is folly to start by looking at genes and infer the existence of disease. I'm pleased to say I had my genetics analysed only after I had discovered B12 symptoms and started to treat them.
I'm not sure I understand your comment, "If a MTR mutation hinders the function of the MS enzyme then it should require less Co1 and, hence, less B12."
Isn't B12 a required co-factor in order for methionine synthase to work at a fast enough rate required for the body to function normally?
I also recall you once wrote here that methionine synthase is strictly two reactions, although I am not sure if that is relevant here.
I was given to understand that if B12 is low then Methionine Synthase won't work well enough to take up the methyl groups formed in the folate cycle and this can give rise to the hypothetical "folate trap" where folate levels are high but they are not accessible.
I'm not sure I understand your comment, "If a MTR mutation hinders the function of the MS enzyme then it should require less Co1 and, hence, less B12."
Isn't B12 a required co-factor in order for methionine synthase to work at a fast enough rate required for the body to function normally?
Yes, B12 is involved in the function of the MS enzyme. So if the enzyme isn't working at full capacity it should require less B12. When a car factory ramps down production due to Brexit fears then it requires fewer steering wheels.
I also recall you once wrote here that methionine synthase is strictly two reactions, although I am not sure if that is relevant here.
Yes, a methyl group passes from MTHF to Co1 (reaction 1) and then immediately on to hCys (reaction 2). It's really one reaction in two stages, with the Co1 acting as a catalyst.
I was given to understand that if B12 is low then Methionine Synthase won't work well enough to take up the methyl groups formed in the folate cycle and this can give rise to the hypothetical "folate trap" where folate levels are high but they are not accessible.
That is totally correct.
You've obviously had a very comprehensive set of genetic testing done.
You make an interesting point about how an MTR defect would cause the methionine synthase reaction to require LESS vitamin B12.
I suppose, on account of defects in methionine synthase it could make use of less B12 but does it follow that methionine synthase can't actually benefit B12 when supplements are taken?
Wouldn't that largely depend on the nature of the actual defect in methionine synthase? Guessingly wildly here, if the defect was one which impaired the provision of B12 to other parts of the reaction then an extra amount of B12 would surely be helpful. Am I clutching at straws?
Hello, I totally get what you are saying, I have had similar struggles, 8 months of 2-3 times a week injections, and I still had what I considered relatively high MMA for the amount of B12 in my blood (MMA at 222, not as high as yours), and believed this pointed to a difficulty using B12. I read the opinion of Greg Russell Jones the B12 oil guy, who said B12 can't work without B2, so I started taking a lot of B2 and other cofactors he stresses (namely selenium and molybdenum), and lo and behold, I started feeling quite a bit better within a week. So now instead of 50 percent better I felt over the first 4 or 5 months of injections after which I plateaued, even after trying daily injections for awhile --- I'd say I am now 75 percent better. And my MMA has dropped to 176 at last check. So I like to think there is something to it, but this whole experience makes me feel like a crazy hypochrondriac, and I always doubt my own observations, so who knows --
Greg Russell-Jones runs the B12oils.com site and suggests using B12 oils as an alternative to injection. The oils are said to provide a very steady supply of B12 but this can make it hard to tell if a change of dose has worked until many days later, by which time other factors may have occurred.
I have used the B12 oils and found them effective but at the moment I am taking B12 by injection as it allows better control. Pricewise, the oils are very roughly twice the price of injections.
All so helpful to me, thank you everyone. I have just been checking all the supplements I take. I noticed that B2 is also called Riboflavin. Can I ask how much magnesium should I take daily? Thanks again
There are 4 different types of B12. Which are you using? Cynacobalamin did nothing for me. Hydroxo helped some but I didn't see real improvement until I started getting Methyl. Some people I've communicated with said they have to use 2 types. I am considering asking my Dr about doing that to see if it takes me to the next level of improvement. Are you getting enough vitamin C which most other vitamins need to be absorbed? While it may not be diet it is possibly still gut related. One report I read stated that as B12 deficiency increase the body responses as reacting to foods as allergies. I found I had to remove many foods to get to feeling and seeing healing. I did a food sensitivity test, it made all the difference in the world for me. It allowed my body to stop fighting and use that energy to heal. Also my daughter's male friend has had nut allergies all his life (anaphylactic shock status). He got sick went to ER found out he was diabetic. His doctor ran B12 test and started B12 injections. After 1 1/2 years he is now able to eat nuts.
If you have myelin sheath damage you'll need specific supplements, the nutrient oils, to repair it. The liver and pancreas plays a part in the digestion, did they check to see how well they are functioning? If not well you may have to supplement enzymes and HCL, I know I do.
I did see a Dr who did spinal decompression which helped to re-hydrate the spinal discs. The spine surgeon said he didn't think I would need surgey to remove any vertabtae or disc which several wanted to do at first. However, I may need to have a spur removed because it's compressing my nerve.
Using hydroxocobalamin, as they do at NHS health centre, where I still get 1 injection every 8 weeks, just to keep a foot in the door. They know me and my family, they are starting to recognise some visible symptoms, even if personal to me only. They all know that I self-inject every other day. I am fairly sure that I'm the only patient they have who self-injects (to their knowledge!) and that they are far more familiar with people who cope well on 1 injection every 3 months (again, to their knowledge!), even the odd one or two who have a functional B12 deficiency diagnosis.
One injection every 8 weeks is not exactly a lot. Maybe it works for you but a lot of people here find they are not offered enough. I go to the other extreme and take a jab every few days but sometimes I feell I am overdoing it because at times I can feel very ill for hours after an injection. At that point I reduce their frequency.
Cherylclaire I am in the process of getting referred to a inherited metabolic diseases consultant but have been to ill to travel to get to the last few appointments.
Which metabolic clinic or hospital have you been referred to? It would be interesting to know.
I would not be able to be specific on this forum about the hospital or the specialist.
It is a main central London hospital, and quite difficult to get appointments. Check whether the specialist you are being referred to is still available, if you think this may be the same consultant. Sorry I can't be more helpful about this, and wish you luck.
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B12 stores
GP stopping my B12 injections. Replacing with oral B12
