So I have been on 2-3x a week B12 injections for nearly 8 months, I have positive IF antibodies, and while my neurological symptoms are quite a lot better, they still bother me more than is comfortable. I had read that most neurological damage is done by the build up of Methylmalonic Acid, and so recently asked for an MMA test to see how well I am "responding" to injections. Results came back 222 nmol/L, which was on the high-ish end of the supposed "normal" reference range up to 270. I did some researching and discovered that this number is actually above the normal range of 60-210 nmol/L determined for "vitamin B12 replete" individuals. Here is the study:
I am as B12 replete as one can get with serum B12 > 2000 for a solid eight months now. I am not elderly yet, I have normal kidney function (the other variables that can effect MMA), and my folate is plenty high. I have no idea what MMA might have been before I got injections, I shudder to think. But it seems to me that with so much B12 for so long that my MMA should be on the lower end by now, not the higher, and does that mean my body is not using the B12 very well??? I am always looking for information on why so much b12 is necessary for some people with pernicious anemia, what mechanisms might be involved, so if anyone has insight, I would be grateful. I wonder if I can discover other ways to lower MMA than just injections if I might have a better outcome on my neurological issues....
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teebeevee
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serum B12 measures what is happening in your blood - high levels due to the injections - that then fall over time - mostly because B12 is removed by the kidneys.
Lots of people seem to respond to high serum B12 in a way that makes the process that allows the B12 to get into your cells less efficient, meaning that your cells may not get enough B12 to do everything they need to do - including recycling MMA.
High serum B12 but not enough B12 in your cells is called functional B12 deficiency. An effective treatment seems to be raising B12 levels and keeping them high so enough B12 gets through despite the transfer being less efficient.
Measuring MMA on its own can be problematic as it can be raised by other problems - notably kidney problems - so really needs to be done in a context that rules that out.
If your cells don't have enough B12 then MMA is usually considerably elevated - ie multiples of the top of the range.
It might be that you have a functional B12 deficiency as Gambit62 says and you might need even more B12 than you are getting to feel well. Over the years she has included some very interesting information on the subject in her replies and it might be worth looking back through them.
There are at least hundreds of us who need daily jabs and some of those need 1.5mg, 2mg or even 3mg hydroxocobalamin per day.
Thinking about it, it seems to be the younger ones of us who are more likely to be in that position.
Um also wondering if you getting enough supporting supplements as well as your folate - potassium, magnesium and iron and possibly vitamin D? Inexpensive supermarket broad spectrum multivitamin and mineral supplements are often better than more expensive branded ones and have more of your requirements, in balance, than just a B-Complex.
A very few of us need methylfolate or even folinic acid instead of folic acid to help get the repair process on track.
See Wedgewood's replies and those from others in the same threads for information on SI.
It's only a hunch but it seems to be those that develop significant symptoms when they are under 50 to 60 seem to be those who need more frequent jabs. I think there are more people above that age that need top up B12 but they seem to cope with injections every few weeks.
But I might be completely wrong!
I don't think it is a coincidence of internet use either.
Very interested to hear more about theory, deniseinmilden .
I was initially diagnosed when 57 as being B12 deficient, then later as having "Functional B12 deficiency", renal problems already having been ruled out, by GP and confirmed by blood test lab. This was because I had had the loading doses, was deteriorating badly on 3-monthly injections although B12 level was by then >2000, and MMA was tested and found to be raised: always between 350-400 (range: 0-270, I think).
My GP said this was rare: she had only found one other patient with raised MMA, who also had Functional B12 deficiency, and that was 10 years previously.
Haematologists disagreed with this, but very wary of their opinions because they also said that B12 was highly addictive and toxic. They sent me for SIBO (small intestine bacterial overgrowth) breath test, as this can also be a reason for raised MMA: results were inconclusive- problem could be SIBO or IBS. GP treated me for SIBO as this was what I was being tested for, although she did not think either SIBO or IBS were the whole story. Apart from a poor reaction to antibiotics (vertigo) the treatment did not alter anything for me.
Incidentally, the Inherited Metabolic Diseases consultant told me that he also disagreed with the diagnosis, saying that he would expect MMA to be far far higher, several times higher in fact, in a patient presenting with B12 deficiency. Slightly wary of his opinions also, as he spoke about the "euphoria" of injecting B12 (!!)
All highly confusing, especially since Stichting B12 Tekort said that a mildly raised MMA was likely to indicate a B12 deficiency .
Gastroenterology: saw 3 - all said IBS (can a set of symptoms be called a diagnosis?) although at least the last one had the good grace to do some tests prior to "diagnosis" (gastroscopy showed "flattened mucosal pattern in duodenum")- and admitted that IBS unlikely to cause hair loss, bleeding gums, dizziness, yawns etc !
So probably my advice to you teebeevee would be to get elimination testing for renal problems, SIBO and hopefully you will get more of an answer than I did. Do your homework, take a friend, have research evidence with you and don't be too shocked at the "expert knowledge" spouted ! If you take evidence to support your beliefs, they should reciprocate by naming their research sources. Best of luck.
I eventually gave up and have been self-injecting for over a year now.... so living proof that B12 is not toxic or addictive, just necessary for some people to function at all ! Still trying for further improvement.
HI! So I was Dx'd b12 deficient by my GP a couple years ago, and he gave me one B12 shot and considered me "cured". Yup, astounding professional opinion. After I realized what one B12 shot did for me and read up on it a bit and realized I hadn't gotten my loading dose, I went back to GP to get that. He said No to that bc I wasn't B12 deficient anymore and the most he could give me was 1 shot a month. He did refer me to a neurologist but He NEVER tested my MMA, homocysteine, etc. My kidneys are great, nice and steady, good filtration rate.
Unfortunately, the neurologist was 6 months out and I was desperate, I could literally feel myself dying from the outside in. So I acquired methyl B12 and began self injecting. I hate self injecting. So I had a small stroke of genius and realized a naturopathic physician might be willing to inject me regularly. I was right and now receive one shot from her of hydroxocobalamin and ~5 self injected methylcobalamin shots a week.
However, my MMA has been shown to be going up rather than coming down during this time. Naturopath says I'm probably missing an enzyme to utilize the B12 properly. So I guess I have "functional B12 deficiency" as well. I am set next week to get ALL the blood work for all the B12 cofactors and other stuff from her, I am also to go back to my neurologist and get a skin biopsy for small fiber neuropathy and then she'd like to see me go to a geneticist at OHSU (right across the bridge).
In the meantime my regular GP has it in his head I have hyperaldosteronism and despite having had a couple of tests and an endocrinologist rule it out, he wants me to go ahead with the CT scan with contrast. BUT in my research on those missing enzymes, I have come across the fact that one of them will cause the pituitary gland to misfire too much norepinephrine, which would account for everything the hyperaldosteronism is being blamed for, and probably then some. His main issue is my high blood pressure. I think it's all genetic. I've had two uncles die of a mysterious degenerative nerve disease that was never figured out despite tons of tests from their specialists. My grandma and another uncle died of Alzheimer's which we all know can mascaraed as B12 deficiency. I asked my uncle and my grandma's care givers if they'd been tested for B12 and no one took me seriously, wouldn't do it. I also didn't know enough to tell them to test MMA instead of serum B12, but it might not have done any good anyway. Some things are still just a mystery to western medicine, which in reality is still in its infancy.
Really, my best ally has been my naturopathic physician. As far as B12 being addictive, I think not. There is no euphoria from the shots, it's like nothing even happened to me, I just have one more band aid somewhere on my body, lol. I'm so over it. It's a full time job just getting Dx'd correctly.
You have replied to a response from 5 years ago. So here's an update:
Nothing was ever found as an alternative to "functional B12 deficiency", despite appointments with consultants, various tests and scans.
My MMA was tested in all 6 times. Firstly by my GP, who diagnosed my condition. Then 4 times by a locum haematologist. Despite the frequent injections I was given after diagnosis, my MMA was always between 350-400. Homocysteine "normal" and active B12 "high" (unsurprisingly). Then finally, three years after the first test, I was tested a 6th time by an Adult Inherited Metabolic Diseases consultant - my MMA was in range.
This, to me, would indicate that raised MMA was not "my normal", as had been suggested by the haematologist. It just took a huge lot of B12 injections to normalise my MMA level. This is probably what you might expect to see if a patient had functional B12 deficiency.
Adult Inherited Metabolic Diseases consultants told me they could find nothing genetic in my DNA to explain my raised MMA. They were lovely and apologised for not being able to help me. They even suggested I contact the Pernicious Anaemia Society for support ! While I was disheartened, as this was the end of the line of investigation, I did not feel let down at all. We just don't know everything yet.
My family history, in which autoimmune conditions abound: psoriasis, vitiligo, Grave's disease, B12 deficiency, G6PD. Also ADHD and autism.
I have a "flattened mucosal pattern at D1 and D2" (duodenum) and "patchy gastric metaplasia", I've had ventricular ectopics , my folate and ferritin levels are still not ideal, my angular cheilitis is controlled (by nipple cream!), I have (on and off) saliva gland swelling from saliva duct strictures, my burning tongue is from "nerve damage", my osteoporosis of the spine has been reduced to osteopenia (by vitamin D, Raloxifene and walking) but I now have calcification of the coronary arteries and recently put on statins.
Incidentally, the Oral Medicine consultant (who was looking at my burning tongue, angular cheilitis and saliva duct strictures) was very worried/ distracted by my "sky-high" B12 reading due to frequent injections. I brought up the subject of haptocorrin from saliva being the initial protective binder for transporting B12. I wanted to know if there was a test that could be done to measure this, since my saliva was compromised by strictures in the ducts. On my next appointment, he had completely changed his mind about my B12 self injecting frequency. He said NOT to try to reduce my injections: my body needed them. That tablets would be of no use to me. He said he had been discussing me with experts ! The only test offered was active B12 - which would not have answered any questions for me.
Nothing else now happening. I have been transferred from Oral Medicine to Periodontology. Or rather, I have been on the waiting list for a biopsy since September 2023. I've had an abscess, apparently, for three years. (Well, let's hope so !!) Strange that a transfer between related departments starts with a telephone "appointment" (triage) initially. How useful is that for a biopsy request ?
I have always chosen to be honest to nurses, GPs and consultants about self injecting frequently and about everything else. I had six months of twice-weekly B12 injections from the NHS before I began self injecting, so I'm aware of what works for me to keep symptoms under control. I have a previous post here with a photographic record of some of my visible symptoms, to which others have added their own.
I have now been self injecting, at that frequency or above, since September 2017. For me, this is what works and less is less.
True also re the nipple cream for angular cheilitis.
Not toxic or addictive - but neither is it a cure. This may also be true re the nipple cream.
...... Still waiting for the euphoria to kick in (B12 not nipple cream !)
Keep your naturopathic physician, and your sense of humour. Have all the tests you can - there might be answers in the results. Keep going. Wishing you well.
Thank you for replying and your kind words! I am so oblivious sometimes,😅.
Nipple cream is amazing stuff--brilliant to use it for angular cheilitis! I discovered it when breast-feeding my 1st baby but never thought to get more for anything. Now-a-days for most skin problems I use "Bag Balm" made in the state of Vermont and originally developed for chapped milk-cow's teats but used by (my very rural) family for years before it was approved for human use. Grandpa used it on his hands bc ranching can be very hard on the skin. When my first baby developed a yeast diaper rash and the cream the doctor gave wasn't working very quickly, my uncle Mark told me to use Bag Balm. Worked over-night. Again, another awe-inspiring expert's opinion/treatment.😁
All I know about the angular cheilitis is that it can happen with iron deficiency anemia, (because I had it once upon a time before I had to evict my uterus for attempted murder) and since your ferritin is not what it should be, maybe get a hemoglobin/hematocrit to see where your iron status is? Just a thought, you probably already have, but just in case.
I've got a cousin with 4 kids, one has vitiligo, and one has all sorts of seizures. My cousin herself has been diagnosed and then undiagnosed with about 10 different auto-immune diseases. They can't find anything, but for sure there's something going on. She's got swollen joints, strange calcium deposits here and there, even in one of her breasts--but it's not cancer or pre-cancer. She had scoliosis as a kid and her brother had it so bad he was in a brace for a while, and most of us (my aunts, uncles and cousins) have neck and muscular shoulder issues that when irritated develop into tendonitis/bursitis. I keep thinking it's all got to be connected.
Feeling a bit better today bc I learned MMA *will be elevated after a B12 shot" and I'd had one a day every day before the test. Also you pointed out it could be just my "normal". So now, I'm going to forgo my shots for about a week and a half and get retested. Not looking forward to the state I'll be in by then, I know I'll be wondering if I've died and gone to hell because of the burning from the lower back down, and my arms will probably get into the act also at that point, but I have to know, and that's the quickest, cheapest (probably not easier or least painful) way to go.
Again, many thanks for your humor and reply. You've given me some perspective and calm. 🙂 Best wishes.
A B12 injection should bring serum MMA down, not elevate it. The loading dose of 6 injections, given in the UK as a starting point for B12 deficiency treatment, would ordinarily bring MMA into range.
Two things that need checking for if MMA still elevated: renal problems (blood test) and small intestine bacterial overgrowth (SIBO) (fasting breath test series over 3 or 4 hours). If these can be eliminated, then functional B12 deficiency is the most likely diagnosis.
How would you know what your normal level should be ? No-one tests the well.
I suppose that the only way of knowing if it really is your normal is to see if it reduces over time with B12 treatment. Mine took three years to move from a fairly static 350-400 nmol/L down to 200 nmol/L on the 6th test. Sudden not gradual. I had B12 injections twice a week during this time, so you would expect a faster result. This is probably why the haematologist began to assume that this was my normal. It wasn't, but it took three years to know that for certain.
I think it's a shame that nothing could be identified from the DNA study, for my family more than myself, but accept that not everything is yet known. One of my sisters is on autoimmune suppressants and is now getting over long Covid. I have been comparatively lucky.
Thanks for sharing some life stories with us. It may be that an answer is still somewhere on the horizon, and discovering commonalities will help get us there.
The best way to tell if it is a functional deficiency is to get your homocysteine tested. If that, too, is high then a functional deficiency is possible. If it isn't high then it's not a problem with B12.
intravascular volume depletion, changes in propionic acid–producing bacteria in the gut flora, pregnancy, and thyroid disease might also affect the P-MMA level.
My MMA was 493 and the "normal lab range" here in the US is 87-318nmol/L. My Homosysteine was just slightly elevated to 11.5 as the lab is <10.4 for females. My hematologist is rechecking my MMA on Monday. I had these both checked after my normal/low serum b-12 (along with the IF blocking antibody), because I had a ton of symptoms . Thats when I got my PA diagnosis. Curious now to see what the new MMA results will be. I do not have any kidney issues. I have done 11 shots as of April 16.
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