As previously mentioned, my B12 and folate levels were very low when tested 2 weeks ago, as they had been 2 years ago. Hence why I saw Dr K and am currently self-injecting EOD.
However, at the same time as I ordered my well man blood test which showed those results, I thought I might as well try a urine MMA test from Neovos 'just to be sure'.
I got the results of that a couple of days ago, which showed my MMA as being 'optimal'. At the point I did that test I had taken no supplements at all. How can that be?
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mma is a secondary indicator of B12 status. It is a product of a cellular process. An individual has different sets of genetic variants that affect the efficiency of a process so deficiencies may impact the process at different severities. This is onereason why individuals have different symptoms when first presenting.
It is also a reason why the normal range for b12 is so large as this is based on where most people are okay - and there will be some individuals who are okay below the normal range which is why symptoms are so important in evaluatimg the likelihood of deficiency
Thanks. So, if I understand it correctly, does that mean that even though my active B12 was low (33pmol) and folate was also very low (2.6), the 'normal' MMA means that my body had somehow learned how to function with the low B12 in the last two years (low B12 in early 2023 which I didn't treat, stupidly) but my symptoms only became really bad 2 months ago) as it impacted the process in a different way? Excuse my ignorance!
a) if symptoms came on very suddenly that would imply that the issue is actually folate rather than B12 as B12 deficiencies tend to develop slowly and the symptoms also tend to develop slowly over years - to the point where they aren't really noticeable unless you reflect back over a long period of time. This is because there are specific mechanisms that store and regulate B12 levels in the blood so it can take a long time for levels to fall. The processes regulating folate (B9) levels in the blood don't tap into stores in the same way and are much more related to dietary intake.
Please note that that I have deliberately moderated the above by saying 'tend'. People are very different and for some people the symptoms of a B12 deficiency do seem to come on pretty quickly.
b) Of the two tests that look at what is going on with processes that use B12, MMA isn't affected by folate deficiency, but homocysteine is. Again, not seeing issues with MMA would suggest that the issue is folate rather than B12.
c) B12 has a very wide range which means people vary a lot in what level is right for them - for some it may naturally be a level below the normal range because the normal range reflect where 90% are okay. That also means that being in the normal range means that you are okay because people tend to maintain B12 levels at a point that is right for them. This means that serum B12 tests aren't really that good at identifying deficiency on their own - they need a context - which would include symptoms on a single point test, but would also include what is happening with levels over time. Falling levels indicate an absorption problem, meaning that your body is no longer able to maintain B12 levels at the correct point for you and that is likely to mean that you are deficient.
d) Serum B12 is only accurate to 20% (meaning that is the variation that you would get if you looked at the same sample a lot of times). Active B12 has less variation but a single point test is still only a single point test and doesn't provide the full context. Trends on tests provide context, but variations need to be significant compared to the accuracy of the test. Symptoms also provide context, but can be difficult to interpret because of overlap with other conditions, eg folate deficiency.
e) Please note that if a folate deficiency is due to absorption problems rather than diet then that dramatically increases the possibility of B12 absorption problems - this is because both are absorbed in the ileum (though mechanisms are slightly different).
Genetics is off-topic for the forum. Its complex and there are all sorts of 'if's 'but's and 'maybe's associated with it because it is an area where we don't fully understand what is going on - and are only really starting to scratch the surface. Mapping genes and identifying variants is only really the starting point on understanding how variant's relate to each other.
Different genes code for different proteins and how they work in different processes. There are a huge number of proteins involved in controlling the various processes that go on in your body, let alone understanding the impact of different variants on those individual processes, let alone the impact on multiple processes. Predicting what is actually going on is like trying to predict how current weather conditions are going to develop and what weather we are going to have in a few days time.
Thanks for the really detailed reply. I fully understand what you're saying.
I guess it's possible that the problem is just folate, although my active B12 has been low for a while - 43pmol in March '23, 44pmol in July '23, and 33pmol in August '23. I have also had subtle symptoms of B12d for at least a couple of years (i recognise them now), before the obvious neuropsychiatric symptoms alerted me that all was not good (thankfully). My folate was just in normal range in March '23 (5) and obviously very low (2.6) last month.
Presumably if folate deficiency was the issue I should still be carrying on with the SI of B12, as taking folate on its own would be bad.
There is a very small risk of neurological issues if high dose folate is used in the presence of a B12 deficiency. Taking folate of itself doesn't necessitate the use of B12, though the recommendation is to treat a B12 deficiency before starting treatment for a folate deficiency - but that would mean an injection before starting on treating the folate deficiency
Hi there—I was having all kinds of symptoms, some neurological, when I asked to have my B12 level tested. It was barely in the “normal” range. My folate was off the charts. I was given 2 injections 10 days apart and told I would now be on a monthly injection schedule, even though I still felt awful. I asked to have my MMA and homocysteine levels tested at that point, and both came back in the normal range. Not sure if the 2 injections I had prior to testing would have affected these results.
I changed doctors and asked to be referred to a hematologist and now have an injection every other week after having loading doses weekly for a couple of months. So I’m not so sure if the MMA test is the best indicator of PA or B12 deficiency. I just know that after over a year and half of injections, I am finally starting to feel better and am lucky that my hematologist actually listened to me instead of just looking at my test results.
I'm glad that you are making progress with the more frequesnt injections. My serum was top end as I'd been taking very high oral doses (and folate was originally actually high and reduced to mid range when I started methylfolate). My MMA and homocysteine were normal when eventually tested, after 4 years of intensive oral self-treatment. But I am still benefitting now that I am getting weekly injections. So much still that isn't understood and no test that can be definitive that B12 injections will not help.
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