News & Views on Systemic Body Odor and Halitosis such as trimethylaminuria TMAU. If you have fecal odors or bowel odors it may be metabolic/systemic

24 February 2012

TMAU different lab : different diagnosis

Chlorophyll is suggested for TMAU
There is confusion in the malodor community about differences in outcomes of TMAU urine tests in the (few) labs that test for TMAU

In fact, probably all the labs testing are of a good enough standard of accuracy (they will probably be using the same type of technology (eg GC/MS, or ESI, or NMR) so the numbers will be accurate  wherever you test.

However, there is 3 big differences at each lab

1. The protocol and shipping instructions etc
2. Whether they test both trimethylamine and trimethylamine-n-oxide
3. INTERPRETATION OF THE RESULT DUE TO CHOSEN REFERENCE RANGES

It is probably the 3rd of these that causes most confusion to sufferers. Many are probably not aware that there is no agreed consensus on reference ranges and each lab sets their own. This means setting the range where someone's figures are deemed to be 'abnormal' etc. For instance, the Denver lab seems to set their oxidizing capacity % at around 85%. This means anyone under 85% is deemed 'subnormal'. However a top expert on the subject has the % set at under 90%. There are also papers where 'subnormal' is regarded as below 95% or even below 97%.

To add to the confusion, some labs only go interpret results using their chosen % (like Denver). However, other labs also take into consideration the level of TMA present in the urine, and have set a limit they think should not be exceeded by a normal person (eg Sheffield). I would say, taking the 2 factors into consideration is correct. So you will be told whether your TMA is over a certain limit, and also your oxidizing ratio/%

To further add confusion, some labs only test TMA and do not test TMAO. They believe there is no need to test TMAO and that if someone is over a set TMA limit then they are a 'TMAU case'. Arkansas do this. However, without the TMAO figure, you cannot know how much of the TMA you oxidized, so you cannot tell if you are TMAU1 or TMAU2.

When it comes to secondary TMAU, this is where someone has a normal oxidizing %/ratio, but a level of TMA over a set limit. It seems that Denver do not take this into consideration, whereas Sheffield does.

Then it comes to where the labs have set their levels. The easiest place to get a 'positive' TMAU result would seem to be Arkansas. They have a TMA limit set at around 6.6 (?). Unfortunately they do not test TMAO. Sheffield has a TMA limit at around 10.8. Denver does not seem to have a TMA limit, so it looks like you will not get a TMAU2 diagnosis there.

One thing to keep in mind though, is that if the lab tests both TMA and TMAO, you should be able to compare the figures with reference ranges from other labs, and decide which lab you want as your 'diagnosis'. This would likely only be of use to you personally.

Protocol and shipping is another problematic issue. There are various versions of what to do. My own advice to this would be do not rely on 1 sample. You want to get an idea of your long-term pattern rather than just one urine test. In my opinion, going by the lab with the 'meanest' TMAO % capacity limit (set at around 80%), I would say you are only TMAU1 for sure if you are under 80% for every sample (or almost every sample) in the urine test, no matter what the DNA test says (I will mention that another day). In fact I would put the % higher but for now I go with the conservative figure so that everyone can agree on that.

The question with the 'cut-off' point for the oxidizing ratio/% is where it should be set. Sheffield have it at around 80%, Denver 85%, an expert says 90%. I would go with 90%, and perhaps even higher. I would go with whoever has expertise in the area who has set it highest, with a view it may be even higher in the future.

As for a TMA limit, as mentioned some do not have a limit. I would again go with the 'most liberal' view, in this case Arkansas at around 6.6. And if an expert says even lower I would go with them too. I think the TMAO oxidizing ratio was originally suggested at around 50%, and then 80%. Over the years it has went up. TMA was mentioned as being 'over the limit' at around 18 a decade ago, whereas Arkansas now have it at around 6.6.

There is also the question of when testing, how to provoke the odor, if at all. As I mentioned above, I would test a number of times until I was reasonably sure about what range my 'oxidizing ratio' seemed to be around. I would aslo do one test using a 'TMA capsule' (probably around 600mg). This is known as the (phnotype) 'carrier test'. This would be so that I could see for sure how my FMO3 enzyme handled a known dose of TMA rather than relying on bacteria to convert choline to TMA.

I have mentioned before that I do not believe in most cases that TMA is the only culprit for odor, and that many other FMO3 substrates may be more likely candidates. I see TMA as a 'FMO3 signature metabolite' or even a trojan horse, but it at least should give you a good idea of your FMO3 capacity. However, I suspect that some people may have 'twitchy' FMO3 enzymes that only collapse at certain times (say when emotional), that may not fail even the 'urine carrier test', although I think it less likely than using choline.

These are just some thoughts for now. Longterm I think the goal for testing malodors would be a broad-range  urine VOC test using Nuclear Magnetic Resonance which is thought to spot everything.  

So in summary

If the lab tests TMA and TMAO levels accurately and you have the numbers, you can compare the results with other labs reference ranges

Denver does not seem to have a TMA limit and does not seem to take TMAU2 into consideration. It has it's oxidizing capacity set around 85% (and perhaps a grey area to 90%)

Arkansas does not test TMAO level, so you cannot tell what your oxidizing capacity is and cannot tell if it is TMAU1 or TMAU2. However, it's TMA limit is set the lowest and is therefore the easiest place to get a 'positive'

Sheffield has a TMA limit of 10.8 and a an oxidizing capacity of around 80%. So it's hardest to get an official 'TMAU1' diagnosis here.  

My own ref range would be (pure guesswork subject to change)
TMAO capacity should be over 95% (probably higher)
90-95% = grey area
under 90% too low

TMA limit, I will go with whoever is lowest. For now it's AK at around 6.6

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