I apologise for asking a question which I know has been asked often, but how long after an injection should you wait before testing mma and homocysteine?
I understand the logic in having these tests before taking any form of b12, but once you have supplemented it you can never go back to your original untreated state - so why not test at any time?
Mine have never been tested ! I've no idea of my baseline level
Same with B12
No idea what level was okay on.
Not sure if value of these tests post regular b12 treatment ?
Useful if serum b12 'normal ' but unexplained symptoms to prove functional b12 deficiency
I will watch this post and learn
homocysteine and MMA can be used at any time but they are indirect measures of B12 status and can be affected by other things - such as folate status in the case of homocysteine and kidney problems in the case of MMA so they can't really be used on their own.They can have a use in determining if enough b12 is getting into cells but there are other processes that use B12 that might be affected by problems with transfer from blood to cells that wouldn't be picked up by testing these two so it really depends on what you are trying to achieve by testing and what resources you have.
Do I understand you correctly that mma and homocysteine wouldn’t show up a functional deficiency of b12? I thought both were markers of faulty b12/ folate metabolism at whatever point they occurred.
they will certainly show if you don't have enough B12 to recycle homocysteine and MMA back into building blocks, which would be one consequence of functional B12 deficiency. However, these are products from just 2 of the processes that go on and there are many other processes that might be affected. We are all different and processes run with different efficiencies in people. It is possible that in some people the processes that recycle MMA and homocysteine are 'prioritised' over other processes and we don't have any way of knowing what is happening with the other processes.Basically, there are some who aren't entirely convinced that MMA and homocysteine will always pick up functional deficiency.
There are several studies that confirms that you can have b12 defiency with normal MMA and homocystein. Both MMA/homocystein normalices in two weeks with proper b12 treatment (b12 injections) and its not meaningsful to do any b12 related test again. It takes at least 6 month (up to 12 month) of not adding b12 before tests shows real results, and a patient with b12 defiency can never again be without b12 treatment that long. You probably need b12 injections for the rest of the life, making tests of b12 serum, MMA and homocystein not useful. The only test that could be interesting is HoloTC which shows active b12 - the b12 that is available at cell level to ensure that enough active b12 is in the blood. This test is very quick to show if the active b12 is enough, so the test should be taken just before taking a new injection - then showing the lowest value. If you dont have enough b12 this test will decrease every day after injection. The other tests takes many month to normalize and show real test results.
The b12 serum test (kobalamin) is NOT relevant at all for perniciös anemi (PA) patients. There are at least three studies/reports that confirms that the b12 serum test uses intrinsic factor to determine the value, and PA dont have intrinsic factor. That makes the test results from the b12 serum test TOTALLY irrelevant - too high!
active B12 shows the amount of B12 that is bound to transcobolamin - the protein that allows B12 to move into cells. High levels of holo-T or Active B12 don't prove that B12 is actually getting into cells.
You have a point, but I cant find any studies/reports of cases where there this potential problem in the final stage for the b12 is documented - have you? But there are plenty of studies/reports of problems in the earlier steps for b12. If you get b12 treatments I think HoloTC is the only test that might be useful, if its taken just before the next injection. A low test value should indicate that the patient is not getting the b12 injections often enough. Middle or high value could indicate either problem at cell level or a good injection intervall making the healing process possible.
people who are on injections can and do also report high levels of active B12 but still not feel ok. Both serum and active B12 only tell you what is going on in the blood, not what is happening with serum B12 in cells. Active B12 is more accurate than serum b12 - particularly in the sense that it won't show as much variation when performed on the same sample several times.
just read this. Hadn't read MorningMist! Have you any Pubmed etc references for this?
References doctor will have to take seriously!
Hi Gambit62
".... there are other processes that use B12 that might be affected by problems with transfer from blood to cells that wouldn't be picked up by testing these two ...."
Are you able to explain further? My MMA and Hmcy are higher end of normal after SI twice a week and 8-weekly NHS injection. Despite SI I still know when my NHS injection is due and start feeling tired. I now have 6-weekly NHS injections after bone marrow biopsy showed B12 problem with red blood cell formation. Full blood count always in range except MCH - always just above range. I would like all injections official - worry if emergency admission into hospital.
I've seen scepticism that MMA and Homocysteine tell the whole story in articles or at least one article by a haematologist but I don't think it is available anymore - it was a general article about treating patients that was enlightened enough to recommend leaving people who reported needing more frequent injections as they are even if serum B12 comes back high.
I'll keep searching - thanks for your help
Was it "the limited value of methylmalonic acid, homocysteine and holotranscobalamin in the diagnosis of early B12 deficiency" ? (you barely need to read it now !)
It was an article about research by Andrew Goringe et al in haematologica/ the haematology journal 2006- from the Department of Haematology, University Hospital of Wales, Cardiff. In conclusion, they find that they are in agreement with Solomon that MMA and tHCY cannot be regarded as gold standard for B12 deficiency assessment.
6 weekly is not often enough. If you have b12 defiency symptoms international b12 experts (Mayo clinic and B12 clinic in Netherland) recommends twice a week until the symptoms are gone - at least for 3 or 6 months up to three years. If you dont have b12 defiency symptoms the recommended intervall by international b12 experts for PA is every 4 weeks - for example by ass professor dr Jörn Schneede Umeå hospital - one of the leading international b12 experts.
Citat in Norwegian (use Google translate):
Et enkelt regnestykke viser hvorfor noen pasienter kan ha
behov for kortere doseringsintervaller enn 3 måneder. Om vi tenker oss en
pasient med perniciøs anemi som ikke lenger produserer IF i det hele tatt.
Denne pasienten har ingen IF-mediert enteral resorpsjon lenger og mister ca.
10-15 µg per dag. I tillegg kommer behovet for "ny" B12 på 2-3 µg. La oss si
at denne pasienten har et døgnbehov på ca. 15 µg. Vi gir 1 B12-injeksjon a´
1 mg og ca. 500 µg av dette retineres i kroppen. Det betyr at denne
pasienten etter ca. 30 dager vil ha behov for en ny injeksjon. Denne
pasienten er selvsagt et ekstremtilfelle, men kan brukes for å definere
yterpunktene for doseringsbehov.
Source: meforum.info (cant paste URL link)
That's rocket science for the NHS!
Depends on your GP. After B12 deficiency was discovered, I was later found to have functional B12 deficiency, diagnosed by my GP after having my MMA tested - because I was continuing to deteriorate.
Because MMA was found to be raised, despite a then very high B12 result (as expected), the lab confirmed my diagnosis -as my GP had had the foresight to also have renal tests done-which were fine and ruled out this as a cause.
Later SIBO was also ruled out as a cause.
Which left only functional B12 deficiency.
Which is why she ensured, from diagnosis, that I was given 2 injection a week.
MMA was tested in all six times and remained raised for three years - and then fell into mid-range.
I believe frequent B12 injections were, and still are, the answer for me.
Was homocysteine also raised, or MMA alone, if you don't mind me asking? My neuro implied that homocysteine alone would not cause neuropathy, although he may have meant small fibre neuropathy specifically, leaving me somewhat confused. Did you say that you'd seen a metabolic specialist, as that is where I am headed next apparently. Thanks
Well my homocysteine level was "normal" - dont remember the result - when tested by haematologist. I saw Adult Inherited Metabolic Diseases consultants -who looked at DNA. They could not find any problem relating to MMA - and couldn't have been more apologetic for being unable to help me ! I really liked them, and was pleased to have had the Pernicious Anaemia Society suggested for support. They were also aware of PAS's involvement in research trial.
I hope these are the same people you will be seeing. Wishing you luck.
Thank you. I thought it was you who had mentioned seeing them, and am not quite sure what to expect. The second of those two links I put on has a diagram showing possible genetic problem locations, but you'd think they would have found them if they checked DNA, although maybe they don't look at epigenetic changes/SNPs. CblA, CblB and CblD-2 would seem to tie in with MMA difficulties alone. My issue seems to be CblG, but we shall see. Best wishes
I had twenty-three gene tests - of these, only two heterozygous variants (in MTHFR and in MTRR genes) were detected, of uncertain significance. Disorders (listed seperately for each of the tests) included cblA, cblB, cblC, cblD, cblF, cblG. The reason for referral heading was written up as "Diagnostic Test for Methylmalonic acidemia (MMA) ."
If there is anything you want to know, please ask.
I was really expecting something to be evidently wrong - but it wasn't. It is hard to let go of what feels like the last chance to get answers. Not just for me but for my family, who have autoimmune conditions -Grave's disease, psoriasis, vitiligo etc -but also because my sisters' children are autistic.
Hi. Sorry if I am being particularly dense - do you mean they tested for genes relating to all the cbls and didn't find anything amiss, or that they related MTHFR and MTRR to all those, but weren't sure of the level of effect? I think both are relatively common, but in conjunction are likely to pose more of a concern, especially for folate deficiency. In fact all 4 (MTHFR 677 and 1298, MTRR and MTR) all raise risk, especially if you have 2 or more. I also have MTHFR but with MTR (plus COMT). If Dr Chandy is correct, insufficient B12/folate changes DNA methylation, epigenetically increasing risk of our predispositions becoming actual - like autoimmunity.
I have read that methylation is also being considered as an element in autism, which you probably already know
spectrumnews.org/news/dna-m...
and treatautism.ca/2015/03/31/a...
Thank you.
Thanks for that, bookish .
No, I think it is probably me - I have the list in front of me (tested in 2018) and although this was explained at the time, do not completely understand it now.
The results showed only 2 variants:
MTHFR gene: heterozygous c. 1073G.A detected (Arg358Gin)
MTRR gene: heterozygous c. 1102G.A detected (Val368Ile)
Uncertain significance. Not previously reported.
Both genes "associated with recessively inherited disorders."
(I'm assuming that means "not a huge problem, as heterozygous not homozygous.")
Results are shown in 5 columns headed Gene, Ref Seq, Disorder*, Detected sequence variants. Pathogenic potential.
* The disorders being checked for mostly related in this case to Methylmalonic acidemia (MMA), but homocystinuria, megaloblastic anaemia, IF deficiency and cblA/B/C/D/F/G/X included, with nothing of note found for me.
Other disorders/deficiencies are also listed here.
Let me know if there is something you are specifically hoping is included under Gene or Disorder.
Thanks for sharing that. No, I have no expectation really, just hoping that someone will think about testing us better if there is some hint of a problem be it genetic or more likely epigenetic. Now that we know of 6 generations in that undiagnosed/twilight at least until the PA developed in the earlier 3 (non-supplementing) generations. No-one will even do MMA or homocysteine and Dad has never had IF Ab tested in 40 symptomatic years. I'll let you know how it goes in September! Best wishes.
- Yet I got 6 MMA tests.
I think having a persistant experienced GP getting the first one done and giving me a diagnosis then prompted the following haematologists' 4 tests - if only in an attempt to prove her wrong !
The sixth and final test, the one that had finally dropped into range, was done by the Metabolics team - unfortunately, this was over three years and, crucially, countless B12 injections later !
I haven't even seen my GP for three years, not even for blood tests.
I now only see an Oral Medicine consultant. Next time, I am going to ask if it is possible to test my saliva for haptocorrin.
Last chance at an answer.
Please let us know how you do in September. Wishing you and your family hope.
Thank you! And good luck getting the saliva tested.
One more - chriskresser.com/methylatio... xx
If you haven't seen them, these B12 genetic SNP papers may interest you
genesandnutrition.biomedcen... and
ncbi.nlm.nih.gov/pmc/articl...
Cheers
Thanks bookish - I have seen the second but not the first paper. A quick glance looks very complicated but will persevere .
I knew b12 metabolism was complex but that article is by far the most comprehensive explanation I have read. Thanks for posting the reference.
Thank you for that explanation. I suppose that explains the twilight world many of us inhabit, aware that something fundamental is amiss but unable to find anything to prove it. That has been my situation for years and it certainly applied to my mother too.
Blood tests after loading jabs
Improvement Timeline after starting B12 deficiency treatment. 
What are your symptoms after 4 months of treatments? 
Would blood tests 3months after last b12 injection be accurate?
My Vitamin B12 test after injection 
