MMA Question

[Sleepybunny]

If you supplement with B12 will MMA (Methylmalonic Acid) levels drop?

I'd be grateful  for any links to research that show this.

Thanks in advance for any replies.

[Gambit62 Administrator]

MMA builds up if you don't have enough B12 to use it to help generate energy for cells.

Supplementation may or may not reduce levels of MMA depending on whether or not it is sufficient to raise B12 levels to a point where the body can reprocess it.  So, it would depend on doses, method of delivery and how the individual responded to that particular form of delivery.

Some people respond to high levels of B12 in their blood by producing a protein that binds to the B12 and stops it actually passing out of the blood and into cells where it can be used.  So, if this is happening then supplementation isn't going to result in MMA being reduced.

Low doses taken orally are also unlikely to have any affect if there is an absorption problem going on.

Which is a very long way of saying it depends ... not just on the supplementation but also on the individual.

One reason why elevated MMA can be an indicator of a continuing deficiency at the cellular level even when levels of B12 in serum are good.

MMA can, apparently be raised by other conditions - which is why it is used as a specific marker for B12

Sorry no links to research

[deniseinmilden in reply to Gambit62]

Thank you Gambit - you have so much knowledge with in-depth understanding and are able to put things so clearly!   

[Sleepybunny]

Thanks Gambit,

I've been trying to find out under what circumstances it is possible to have B12 deficiency with normal range MMA.

I found that the possibility is mentioned in "Could It Be B12" by Sally pacholoka nd JJ. Stuart in Chapter 1.

[fbirder]

I've had two MMA tests and both were 'normal' yet I feel terrible if I go 10 days without a jab. So I'm sure there's some other thing that B12 does that may not be one of the two commonly researched topics.

It's quite clear that I'm not alone - but nobody knows what causes it.

[Polaris]

Hi SB - I dont't know if this helps. I believe the MMA urine test is supposed to be more accurate.

Bottom of page 3 and several references to research at the end:

cmim.org/pdf2014/funcion.ph...

Methylmalonic acid

"The conversion of methylmalonic acid to succinyl-CoA requires B12 as a cofactor and hence accumulation occurs if B12 is not available. An increase in methylmalonic acid level is an indicator of vitamin B12 deficiency in tissue and this persists for several days even after replacement is started.2 Measurement of methylmalonic acid may be the most representative marker of metabolic vitamin B12 insufficiency. The interpretation in older patients (>65 years) and those with impaired renal function is, however, potentially challenging because levels can be falsely increased. High levels of plasma methylmalonic acid, however, usually indicate cobalamin deficiency. Methylmalonic acid is measured using gas chromatography mass spectrometry, a high cost test. "

[fbirder in reply to Polaris]

Unfortunately, I'm pretty sure the urinary MMA test isn't available on the NHS.

[Gambit62 Administrator in reply to fbirder]

This is a link explaining why MMA in urine is better than MMA in serum - down to the fact that serum levels can be high in a number of other conditions but this doesn't seem to be the case with urine ... though sounds like its about measuring MMA/creatine in Urine that may be the key

onlinelibrary.wiley.com/doi...

[Sleepybunny]

Someone I know with many symptoms of B12 deficiency, had a normal range MMA but was supplementing with B12 at the time hence my original question.

I wanted to help them by finding out if it is possible to be b12 deficient with normal MMA levels.

My instinct is that it is possible and that no tests not even the urinary MMA are foolproof.

[fbirder in reply to Sleepybunny]

If you're supplementing with B12 and it's getting levels up to a sufficiently high amount so that it's doing that particular job then MMA levels should be normal.

However, I'm becoming more and more certain that there's something else that B12 does. Something that doesn't produce abnormal levels of MMA and homocysteine, yet still produces symptoms in people unless they supplement with very high amounts.

With a bit of luck the research that Martyn mentioned in a recent blog post -  martynhooper.com/2016/05/07... - will be looking at just this sort of thing.

My guess is that they'll be doing a metabolomics study. This uses techniques like mass spectrometry and/or nuclear magnetic resonance spectrometry (NMR) to examine just about every compound in a sample. The idea is that certain disease states will produce abnormal levels of some compounds (like MMA) and comparing people with that disease against controls (without it) may allow you to pinpoint the compound(s). Once you've found them you can use the same techniques to identify them. That should make it easier to postulate a biochemical mechanism that could be responsible for that disease state.

I know a bit about the subject as I used to share an office and some equipment with some metabolomics people.