Apologies, still not clear. Not PA but referring to 'functional B12 deficiency' only.

[Gillybean1]

If a person is supplementing with B complex and B12 sublingually for a long time (and no renal problems) and undertakes an MMA test at this time, will the MMA be high, low, or normal, if there is 'functional B12 deficiency' ?

Kind regards, G

[fbirder]

A functional deficiency is when there is plenty of B12 in the blood, but it's not getting into the right places in the cells.

For an MMA test, low is normal.

In the situation you describe, if MMA is high then there is either an absorption problem causing a B12 deficiency, or a functional deficiency, or something else. If B12 blood levels are very high then there is possibly a functional deficiency.

Having normal/low MMA doesn't rule out a functional deficiency, but it does make it very unlikely.

[Gillybean1 in reply to fbirder]

Hello fbirder.Thank you for your reply and taking the time .

What is the UK range for MMA then.. i have only seen <32 ug/l Would 15 ug/l be normal or optimum, is there a too low figure, or a heading too high figure ?

Kind regards G

[fbirder in reply to Gillybean1]

Less than 32 mcg/L is normal.

[Gillybean1 in reply to fbirder]

Thank you fbirder for your reply. Back to the drawing board......

Every best wish, G

[Sleepybunny]

Hi,

An article about MMA from Dutch B12 website.

Units and ref ranges may vary from those in UK.

stichtingb12tekort.nl/engli...

[wedgewood in reply to Sleepybunny]

Good article -Thanks !

[wedgewood in reply to wedgewood]

How is it that a small country like the Netherlands has such a great institution like Stichting B12tekort ( B12Deficiency Foundation ) and also the only B12 Deficiency Clinic that I know of ? Amazing small country ! ( 17,000,000 inhabitants)

[Cherylclaire Forum Support in reply to wedgewood]

Good question. Perhaps they say the same about the Pernicious Anaemia Society, and perhaps the answer is the same. It starts with one person....

[Gillybean1 in reply to Sleepybunny]

Many thanks for taking the time to respond Sleepybunny,

Kind regards, G

[Cherylclaire Forum Support]

In 2016 my GP had my MMA tested after having started me on B12 injections, because I did not respond to the loading dose and got very much worse when on one injection every 3 months. My B12 was also tested, and renal tests done to rule out renal problems. She suspected functional B12 deficiency. This was confirmed by the hospital laboratory.

My serum B12 was by then over 2000ng/L and my MMA was around 350 nmol/L (range: 0-280 nmol/L). This is considered "raised" not "high".

It stayed at between 350-400 nmol/L for three years, despite frequent B12 injections. The 6th time it was tested, by DNA consultants, it had dropped to comfortably within range finally in 2019 : 205 nmol/L.

Although MMA tests are difficult for a GP to request, my GP was persistent despite being refused three times. She knew about functional B12 deficiency and methylmalonic acid (MMA) because she had had one previous patient with this condition- 10 years before me. She considers raised MMA (and functional B12 deficiency) to be rare because we were the only 2 cases she had treated in her 20-odd years in primary care.

Methylmalonic acid is very rarely tested before B12 treatment starts- and MMA will rapidly return to normal levels once B12 is replete: the loading dose would do that. So any MMA test done after this point should show that the B12 introduced to the bloodstream by injection has successfully linked up with the logjam of MMA that has built up during the wait. Except if you have functional B12 deficiency.

It is my opinion that my MMA level was eventually corrected only by the frequent B12 injections that I was by that stage self administering. The one other patient apparently has managed her condition well on the NHS frequency of just 4 injections a year, but could, as I told the GP, have been self injecting as well. Perhaps not. We are all different and there is no way of knowing. Worth asking the GP "How would you know ?" though.

While my GP's own experience is that raised MMA is rare, the DNA consultants have seen cases many times higher than my own.

MMA can be raised/high because of renal problems, because of small intestine bacterial overgrowth (SIBO) -or because of functional B12 deficiency. Renal problems can be eliminated as the cause by a blood test, SIBO needs a fasting series of breath tests which are taken over 4 hours.

At one time, there was a Stichting B12 Tekort report on MMA that concluded that "mildly raised MMA nearly always indicates functional B12 deficiency". If I can find this again, I will let you know.

[Hidden in reply to Cherylclaire]

[erased]

[Cherylclaire Forum Support in reply to Hidden]

If this is the same one as Sleepybunny's link, I can't find that particular sentence .

The other thing I've noticed on this link is that in Amsterdam, my MMA levels of 350-400 nmol/L would have still been considered within range. Stichting B12 Tekort commented about the lack of agreement about upper levels.

Found it: I was wrong- this was actually from the Mayo Clinic -mayomedicallaboratories.com... and the test ID was MMAS:

"In pediatric patients, markedly elevated methylmalonic acid values indicate a probable diagnosis of methylmalonic acidemia. Additional confirmatory testing must be performed.

In adults, moderately elevated values indicate a likely cobalamin (vitamin B12) deficiency. "

However, their reference values are <or=0.40 nmol/mL, which again are higher than general UK top range value.

[Gillybean1 in reply to Cherylclaire]

Thank you Cherylclaire for taking the time to reply.

So does that mean i dont have a 'functional B12 deficiency' if my MMA is 23.0ug/l (range <32) and serum B12 active >256.0 pmol/L (range 25.1 -165) and Homocysteine 5.22 (range 3.70-10.40 umol/L)

I do not have renal problems, I am not on B12 injections, but do/did take Bcomplex and sublingual B12 for some time up until a few days before the tests.

Kind regards, G

[Cherylclaire Forum Support]

It is difficult, isn't it ?

It all looks fine, but Stichting Tekort mentions that although MMA and homocysteine are considered to be more sensitive than serum B12, Solomon has reported patients with normal results all round who had B12 deficiency symptoms that were responsive to B12 treatment.

So it seems likely that you don't, but not definite - according to LR Solomon in 2005.

Stichting Tekort say the most widely used value for MMA is 0.27 . Professor Dr Rima Obeid agrees (in Methylmalonic Acid: a biomarker for vitamin B12 deficiency).

I think my homocysteine was 7.3 pmol/L when tested. "High" would be above 15, although a grey area exists between 10-15. Anywhere below 10 is considered normal.

Not much is known about B12 deficiency in general, even less is known about functional B12 deficiency and tests appear either unreliable or give conflicting indication. Researchers cannot agree either.

There is a short survey currently on the Pernicious Anaemia Society website which is attempting to determine what exactly researchers should be concentrating on with regards to both diagnosis and treatment of B12 deficiency from a patient's perspective.

[Gillybean1 in reply to Cherylclaire]

Thank you Cherylclaire for your reply.

Yes its a tricky area. I guess after 10 years trying to resolve my health, knowledge of both Mother and maternal Grandmother with PA (Grandmother mis diagnosed in the 1950;s with MS) i wondered if for me this was the missing link. With all other significant bloods in order and, numb tingling extremeties, yellowing skin, tinnitus,vision changes, muscle weakness, scalloped grooved tongue,memory flunking, nerve sting on face etc etc, i wondered if i had been 'missed' as i have supplemented B Complex for 20 years +

I was until a few days ago happy to self inject to see if 'anything' changed, I would rather have the support/security of it being legit on medical notes...but needs must.

There seems to be so much negative info out there on UK medical sites ,linking high doses of B12 and B6 for that matter to increase chance of lung cancers and some others, particularly if you are male.

With that kind of negative info out there, i havnt a chance in getting any NHS approval of what i would like to try, just to see if B12 makes that last piece of the puzzle fit.

I wish you well and thank you for your time, kind regards, G

[Cherylclaire Forum Support in reply to Gillybean1]

My GP didn't bat an eyelid when I told her I was going to self inject - she just asked when I was planning to start, and I told her "yesterday" !

I think she had realised by then that the consultants weren't willing/ able to help me. Disappointing when she'd tried so hard. She was glad to see me much improved at the next visit, and knew exactly what I'd been through. Why continuity pays -if you've got a good GP to start with. I'd had six months of NHS injections at a frequency of 2 a week previously on her instructions, so she was well aware it wouldn't kill me.

I also can find no other answer for all the strange symptoms, neither could any of the consultants. Now and then I either decide that it doesn't work, must be something else, or I get a good few days and think I can reduce the frequency. I only appreciate what B12 does for me when I stop taking it.

Sometimes I forget how much worse it was.

[Gillybean1 in reply to Cherylclaire]

Am really glad you pushed on with it and found your way....very brave.

Take good care, and thank you for your replies. G