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

27 December 2014

TMAU1 and TMAU2 : Who would smell more ?

common metabolic malodor questions
Question : Who would smell more between someone with genetic TMAU and someone with secondary TMAU ?

My non-expert reply :
In theory I guess someone with genetic trimethylaminuria is likely to smell more as they in theory should have problems with 'normal' trimethylamine loads, but in practice I am not sure this is always the case.

There are 2 types of TMAU : TMAU1 is genetic deficiency, and TMAU2 is TMA overload. I think quite often people will have a bit of both.

TMAU1
TMAU1 sounds straightforward, but actually it's a % game. That is, how much of a % of TMA can you oxidize to TMA-oxide. FMO3 oxidizes TMA to TMA-oxide, so the % in a urine sample is meant to give you an idea of how well your FMO3 enzyme is working by calculating what % of TMA you oxidized to TMA-oxide.

People may often think someone with a genetic disorder has almost no FMO3 function, but actually a normal person has to oxidize around over 95% of a TMA load to TMAO. Depending on which lab you test at, 'sub-normal' can be anything from under 92% to under 79%. However I believe the subnormal level should be at the upper range of around 92%. So you should oxidize 92% or more of a TMA load to TMAO.

TMAU2
TMAU2 seemingly means any type of TMA overload that is not due to a genetic FMO3 deficiency. In practice it seems to mostly mean people who are generating too much TMA by their gut flora. Very few labs seem to take TMAU2 into account.

Genetic versus Overload (TMAU1 versus TMAU2)
So TMAU1 is due to FMO3 enzyme deficiency of some %, meaning the person has problems with normal TMA loads (in theory), and TMAU2 (mostly) means the person has normal enzyme function but has enormous amounts of TMA that even a normal person cannot fully oxidize.

My view on this :
Personally I don't think most people with an FMO3 isssue have a metabolic malodor problem solely caused by trimethylamine. FMO3 oxidizes many small sulfides and amines, and I am guessing most people who have an issue with their FMO3 enzyme have many circulating unoxidized volatile sulfides and amines that should be oxidized by FMO3 and most are probablty smelly. However TMA is meant to be an excellent biomarker of FMO3 function, though I have my doubts. But anyhow this is my attempt at an explanation of TMAU1 and TMAU2

Most are a mix of TMAU1 and TMAU2
My opinion is that most probably have a few small faults in FMO3 function making them around the 80%-90% efficiency mark, and for some reason are also prone to excess TMA production. A bit of a 'syndrome' (I would call it something like 'FMO3 substrate malodor syndrome'). I don't think very many are the genetically 'severe' type where function may be around 20% etc. There are quite a few common small genetic FMO3 faults that populations carry around, and I'm guessing most of us are a combo of small faults that put us just under the 'normal' function, perhaps even only intermittently. I think they are called something like 'compound heterozygotes' (small faults compounding). 2 common faults are at codons 158 and 308 in the 532 FMO3 amino acid sequence.

TMAO research :
One 'good' thing for the community is that TMAO has recently been hypothesized as being a cause of heart disease (still being debated), and so now a lot of research and funding is likely to go into understanding TMA production in humans and how to neutralise it. For those who feel TMA is the sole volatile that causes their maldoor, this would be very good news.  



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Genos is back with it's EXOME test
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Note :
Exome/Genome testing may be better option than single gene testing.

See this post : link

Note : Genos Exome Testing.

Exome testing is almost the same price now as single gene testing. Also Genos is consumer friendly, which standard DNA labs are not.

So the blog offer to test solely for FMO3 is almost obsolete, and so no longer offered.


Does Genos fully sequence FMO3 gene ?

At the moment it is not clear, but hoped this will become clear over the next few months

Note : possible 'wild west' way of testing FMO3
Use an ancestry dna site and rummage through the raw data

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