Pernicious Anaemia Society
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MMA Testing; B12 Side Effects

I had a B12 test that came back 163 pg/mL.  Folate is in range.  I've decided to pay for an MNA test to see just how serious this is but I've begun to supplement with very small amounts of sublingual B12 for a few weeks.  I have difficulty with both methylcobalamin (it makes me very tired, almost groggy) and hydroxycobalamin (gives me energy and focus but a bad headache); thus the very low levels of supplementation.  My most immediate question is how much the low supplementation would affect the MMA results and how long I should wait after my last use (tiny amt of hydroxycobalamin yesterday) to get the MMA test since I don't want to waste my money -- it's an expensive test.

My second question (maybe best for another post) is whether others have had these types of reactions to B12.  For anyone familiar with genetics, I am COMT V158M and COMT V62H homozygous, heterozygous for  MTHFR 1298C and no mutation on MTHFR c677T. 

17 Replies

The B12 level is really low even if it is in normal range.

I guess you are trying to persuade your GP that B12 is the problem - and this is why you are looking at MMA

MMA will be elevated - along with homocysteine if you don't have enough B12 - but the same also applies if you don't have enough folate.  Your folate is good so a high level for MMA would be a good indicator that you have a B12 problem but, given how near the bottom of the range you are I find myself wondering if it wouldn't be more productive to have a go at trying to get through to your GP that normal range doesn't necessarily mean no problem when it comes to serum B12 - the following may help


alert on the pitfalls of interpreting B12 on test results only:

and this is a checklist of symptoms


Can't comment on the COMT variants but did find this article on MTHFR A1298C which implies that that should be a factor as you are heterozygous.

Most likely is an absorption problem, which could be an auto-immune problem, PA, could be lowering of stomach acidity, or could be a drug interaction.

The body is usually very good at storing and recycling B12 but if there is an absorption problem this affects the recycling process as it relies on storage in liver and release in bile when needed to be re-absorbed in the ileum.  It can take decades for a deficiency to develop but once it does get hold it tends to snowball - in terms of symptoms at least.

You mention headache from hydroxo - I initially go headache with methyl - but it went quite quickly.

The problems with methyl may be indicative of a methylation problem

look down until you get to the protocol relating to homozygous (two copies)

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Thank you Gambit for your reply -- appreciate it.  In the US under 200 pg/ML is considered deficient.  How long did it take for your headache to go away?  The headache from the hydroxy B12 was pretty bad and that's way I was cutting the 1000 mg pill into tiny pieces.  What do you think about the impact small amount of B12 would have on my MMA test?


I'm neither a medic nor a biochemist and given how much person variation there is with B12 I really wouldn't like to say though if you aren't feeling much if any better with the small amounts you are taking then the chances are it won't be having much impact.

I think it was probably a few weeks before the methyl headaches went - I use a nasal spray and I can occasionally get an 'ice-cream headache' from the spray - though that really only lasts a few moments. 

I suffer from hormone related migraines - found that these got worse for a while after I started supplementing with B12 but then found that supplementing with some B6 helped with those - but B6 is a vitamin you can overdose on - can cause neuro symptoms at levels over 100mg a day over 6 months or more (and they don't always go when supplementation stops) ...  In the past B6 was frequently used to treat headaches but guess the discovery of the link to neuro problems was probably a nail in the coffin for that.


As I said in another reply I went ahead and had the MMA test yesterday.  I think/hope my small supplementation won't have too much affect on the test, as I would like it to be an accurate reflection of my B12 status and a good use of my $$. 

Maybe I should hang in there a little longer with the hydroxyl B12 and see if the headaches will go away.  Thanks for the reminder about B6.  I had read that you need to be careful about not taking too much.  I took a small amount one day to see if the B6 would do anything for me and I got a headache anyway. 


I was treated by my GP at a level of 176. Your level is low, I can't comment on the genetic effects on absorption though. Injections may be better absorbed than sublingual supplements?


Did you have symptoms at 176?   I read some research that says the sublingual supplements are as good as injection. 


I had a lot of symptoms, numbness, pins and needles, loss of balance, mental confusion to name a few. I was also very susceptible to getting infections and on regular antibiotics.

Before I got more frequent injections I used a sublingual spray as a top up, between weeks eight and twelve. It worked quite well. I also took it with me on holiday, as I was doing more activity and had less chance to rest. Thankfully my GP has allowed me six weekly injections since last September. They've made a huge difference.

Reply level was 261 so was obviously ! Told by Dr I have plenty of B12 and no way could a b12 deficiency be responsible for any of my symptoms- diagnosed with ME 17 years ago. I went down the route of doing an Active B12 test after a whole lot of asking! which proved to be 2 marks off the bottom if the range, so was referred for an MMA test which came back very high, so the serum test is not at all reliable. You need to score between 25-70 to get the MMA test.

The active b12 test was via St Thomas, a postal test which cost £30 ( 18 if you can attend) and was referred for MMA for free. This is an NHS hospital, which helped I think. I'm not sure how long you'd need to be supplement free before taking the test. I had to wait 2 weeks after taking antibiotics as it affects the MMA, but am sure they'd soon tell you. It worked out reasonably cheap that way, although the first test got rejected, so cost £60, but that was due to a misunderstanding about labelling.

So I finished my 6 injections last week, but couldn't get a 3 rd week but at least it's a start on this journey...

The b12 range at my docs needs to be under 130 to treat and they don't seem to take consideration of symptoms!

If you need anymore help, please ask, hope you can soon move forwards and get the treatment you deserve...take care.


Wow, that's quite a discrepancy between the 261 serum test result and a very high MMA.  That's a good reminder as to what many articles on B12 say -- that the MMA is more accurate.  I went to the lab yesterday for the MMA and we'll see what it says.  I had been supplementing very small (hydroxyl) and small (methyl) amounts of  two kinds of B12, and as I said in my first post,  I hope it doesn't skew the MMA test too much.  It takes about a week to get results so we'll see.  

It amazes me that you need to be 130 or below to be treated.  Seems like there's a lot of research literature supporting deficiency at anything below 200 (or 200-300).     


Hi Jo5454 . May I ask if the test via St Thomas hospital was by Viapath Nutristasis ? Or something different within St Thomas ?

I'm looking into having an active B12 and homocysteine repeated. I have a quote from Viapath for 165 for the two tests .

Many thanks xx


Hi Kittycaite....yes the Actibe b12 test/MMA was done via Nutristatis Unit, Viapath at St Thomas hosp. It was earlier this year and the Active b12 test was £30 ( £18 if you could walk in, if not add £12 p&p) and I'm sure the homocysteine was £46 then. (I didn't have the homocysteine due to it needing to be spun first and my Dr couldn't do that. I guess a local hospital may help with this? At the time I was so unwell it was enough to get the active sorted out!

The MMA was quoted as £96, so I presumed if they found the Active b12 to be in the indeterminate range 25-70 and I needed MMA they would contact me for further payment, but it was tested free of charge.

I'm not sure how they reached that quote, unless prices have drastically risen since February? If i were you id give them a ring and check the prices...let's hope it's an error!

Please message me back if you decide to go ahead as I have a few tips in relation to the testing process...

Good luck and fingers crossed its cheaper x


Thanks for replying Jo5454 xxx

That's a lot cheaper than their website . Active B12 £89.99

Homocystein and foliate £ 49.99 and I thought £ 25 for postal .

Maybe I misread wrong due to brain fog !! :/

I'll ring them !! :)

Any advice on test would be great if you could pm me please .

Many thanks xx


I've tried to message you but it won't go through .Probably my dying phone though !

Any info would be much appreciated .

Many thanks xx


where are you getting the MMa test from as i will need to pay for one too !


If you're in the U.S., you can order one on line at 


Just to give an update, I did the MMA test and it came back within range. So, just because I was curious, I did another B12 test and it was 346 so that's why my MMA test came back in range. In looking at some Google searches it appears MMA responds pretty quickly to B12 supplementation. That was my experience with this. Thanks for everyone's input on this.

Re the sleepiness from methyl B12, I take a slightly lower dosage at night and it does help me sleep, and I'm not feeling too groggy from it during the day. I take a small amount of hydroxo B12 and haven't been getting headaches. I hope to work up to a higher dosage on the hydroxo because it I think it's helping me with energy and focus and both types are helping me to feel a little more calm.

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I was reading the other day that some people with the COMT mutation can have a resulting problem processing B12 and end up producing a lot of histamine. I'm really sorry but I can't find the link. I hope you feel better soon.


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