MMA and Homocysteine - why?

I've had a couple of PMs and read a few posts about these two tests - especially MMA. So I thought I'd write my thought down in a separate post.

What are MMA and homocysteine.

B12 does lots of things in the body. Two of the more important (and ones we can actually test for) are:

Methylmalonic acid, combined with something called CoA is converted to succinyl CoA by an enzyme that requires adenosylcobalamin to work. Succinyl CoA is an important chemical in the biochemical process that 'burns' glucose to produce energy (You may recall from school studying Krebs cycle - or the citric acid / tricarboxylic acid / TCA cycle). A lack of B12 means that this reaction doesn't proceed as fast as is ideal, resulting in a lack of energy and a buildup of methylmalonic acid.

The other important process is the methylation of homocysteine to form the amino acid methionine in a process that requires methylcobalamin and methylfolate. If B12 is low then homocysteine builds up - with possible bad consequences.

The two tests are both involved and expensive, so GPs may be loath to give them. The homocysteine test needs to be run within 2 hours of the sample being taken.

Why test for MMA and/or homocysteine?

We all know that the blood tests for B12 aren't too useful. Many people have high serum levels of B12, yet still have symptoms of B12 deficiency. There are many possible reasons why this may be so. One reason is that the B12 isn't actually getting to the places in the cell where it's needed. If this is the case then levels of MMA and/or homocysteine will be raised. So a raised level of either of these might persuade the GP that you have functional B12 deficiency and that you do need more frequent injections.

When should you test?

Testing for these two markers should, ideally be done before B12 supplementation - to show that B12 deficiency is actually the problem. I believe it should also be done during supplementation - to show that the B12 deficiency has been fixed.

If you're trying to show that your symptoms are due to a functional deficiency then you really need to demonstrate that you have high levels of one or both of these markers while on supplements. Ideally you want to leave a sufficient gap since your last jab for you to start suffering the symptoms again. So if you normally inject weekly, because you start feeling bad after 8 to 10 days, then testing the markers after 12 to 14 days should show raised levels if you are functionally deficient.

What if I test normal?

I need to inject weekly. If I forget then, by day 9, I get very fatigued. When I was going for an MMA test I waited 16 days between jabs - and I was wrecked. The test was normal. So I'm not functionally deficient. So why do I need weekly jabs? Two reasons - the haematologist reckons it's a placebo effect, and he's entitled to his opinion. Personally, I think it's a cop-out and there's something more complicated going on.

Because I've not had a homocysteine test I'm not sure if there's anything amiss there. I keep asking and they keep saying they'll do one - but no results forthcoming.

Remember I said that these are two of the processes that B12 is involved in. Well, it's my opinion that B12 does a lot more than 2 things. We know about some (it's involved with monoamine neurotransmitters) but I'd be surprised if there weren't others. There's some research talked about on the PAS site that I think is looking for further markers to investigate the possibility of other problems in people with high levels of B12 but low levels of life quality.

Last edited by

12 Replies

  • Brilliant fbirder. Thank you. I'm going to cut and paste you into my file. Shouldn't be too painful, so long as you're full of B12.

    Perfectly answers my previous post. Thanks again.

  • Another 1 to file. Thanks f.



  • Just to add - MMA is best done as a urine test - this is because MMA can also be raised by kidney problems so it is important to be able to look at the relationship between MMA and creatinine is looked at as this is a better guide to what is going on with B12.

  • The only problem is that the NHS obviously disagrees, so the urinary test is only available done privately.

  • not every one using this site is based in the UK and even amongst those that are some do choose to go private.

    Perhaps if the urinary test had been done and ratios had been looked at your MMA would have shown an abnormality.

  • As you say, MMA can be raised by kidney problems. My MMA wasn't raised, so it matters not how they tested.Indeed, the only time the urinary test would be preferable would be if the serum levels were raised and kidney problems were suspected.

  • I meant to reply to this thread the other day but forgot.

    Functional deficiency can result in short-term fluctuations in HCy and MMA. Catch this at the wrong time and your test results will be normal.

  • Interesting! Do you have a source for this? Both of the processes that produce high levels of these markers are things that happen continuously, so I can't see any great reason for diurnal variation. And they're obviously not eliminated rapidly otherwise high levels couldn't build up.

    But if there is a large variation in MMA then that would be an argument in favour of the urinary test.

  • I’ve read it in a few places and definitely would have saved them. I’ve been looking through my favourites, which is about two miles deep and no joy so far. My dyslexic side does not lend to being organised.

    One place I can definitely remember this being mentioned (as my interest was piqued by night sweats and autonomic dysfunction) is, The clinical review of b12 d – Hunt et al, in the BMJ. There are comments at the end of the review and one to look for is by a Canadian Internist.

  • Hi

    That's helpful thanks, I wonder if you can give me some advice. Back in 2012 after a year of monitoring my B12 (hovering around 147 -158), I convinced my GP to do MMA and homocysteine blood tests with the following results. MMA 0.37 (0.1-0.42); homocysteine 17.5 (0-11.3) At this time I was 28 years old. The haematologist (who I never saw) wrote a letter to my GP saying I may be heterozygous for something (as was much of the population) and that I may/ may not need B12, but it wouldnt do any harm. Following this I had 1st 6 shots (loading dose) and then bloods monitored for a just over year until dropped back to 164. I was then allowed new loading doses and 12 weekly injections. I have had the homocysteine retested since (as I was concerned about it and the implications of it being high). This has never gone well. 1st time - got lost. 2nd time, didnt get to hospital in time, 3rd time I had to drive my blood to the hospital from the docs (took about 50 mins at least and not on ice). Results back as 10 (0-20) but I dont trust them as the procedures were not followed... should I push for another test? Is there a value in having this info?

    Also I have always been a fairly stressed person but my anxiety has been notably worse since the b12 has been low and this is still a problem - is it likely B12? or just anxiety due to other causes? (I have a family member who developed an acute mental illness around a year before my b12 1st got tested and it has been quite stressful). Thoughts welcome, particularly with scientific support that I can use with the GP.

  • You say you are getting jabs every 12 weeks. This is the standard treatment for people without neurological symptoms. Apart from the anxiety, do you have any other symptoms of B12 deficiency that get worse between jabs?

    Have you been tested to see if it is PA, or is there another possibility (veganism, gut surgery, pills for stomach acid)?

    Experts make two recommendations that your doctor should know about (well, a lot more than two, but two urgent ones).

    Once treatment starts any further testing is pointless.

    It is important to determine the cause of the deficiency.

    I've written this summary - - that includes links to some scientific documents and has extracts of the top points.

  • Well done, fbirder! You have a knack for explaining complex information in a way that makes perfect sense.

    Thanks :-)

You may also like...