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

2 January 2021

my (current) opinion on FMO3 MALODOR (imho Fecal Body Odor)

My CURRENT opinion (self-styled expert) on the cause of 'FECAL BODY ODOR' (it's actually worse than that, as it can be fart smells, rotten egg, burnt rubber .... it's sulfide smells from the colon) 

It's all to do with FMO3 ENZYME (weakness, overload etc)

(my view hasn't changed much, but my opinion is more fixed and precise)

Type 1 genetic : SEVERE RARE (the fish smellers)

The FISH SMELL is the SEVERE TYPE.
Only severe's will tend to have a fish smell.
This is because most have enough FMO3 to keep the fish smell down, but severe's (and perhaps some overloaders) don't.
Fish Smellers may smell to a Dr as they are severe (and so smell more often)

This is RARE.
Its a tiny part of the community.
It will be people with RARE SEVERE VARIANTS (e.g. 153)
It ties in with previous estimates by any expert/health professional who has taken a look at TMAU. 

TYPE 2 genetic : the (quite) common FECAL BODY ODOR type

This group is quite large.
Estimates could be like 1%-4% or more ???  AT RISK
Its based on haplotypes / compound mixes of the common FMO3 SNP's 
(e.g. 158 (40% Whites ?) 308 (20% Whites ?) 257 (9% Whites ?)

There are 7 variants where at least 1 ethnicity has +1% carriers.
Mixes of these 7 probably make up the bulk of the community.
The common 7 variants OFTEN vary by ethnicity, though 158 seems common among all (esp White and Black). 
308 is not so common in Blacks (3% compared to Whites 20%).

Variants, it depends how bad they are predicted/proven to be ?
Maybe 40% carry 158, but how bad is it ?
Geneticist will say harmless ? But is it ?
Maybe it will turn out an issue in CFS often ?
FMO3 is an ignored enzyme.

Variants, silents and introns :
Variants change an amino (158 308)
Silents are wrong nucleotide, but amino ends up correct (eg 147, 285)

Perhaps SILENTS can play a (bad) role when part of a mix ?? (i.e. with 158,308 etc)
Its all about little flaws adding up.

Introns :
this is non-coding part of a gene.
Perhaps if you have enough flaws they add up is 0.5 points etc ??
Introns play no part in code, but is seems variants there can have negative affect. 

TYPE 2 will also be prone to FMO3 GUT DYSBIOSIS

I suspect FMO3 plays a role in the colon (cells) as an on-site oxidizer.
Current thinking is FMO3 needs an oxygen environment and so cannot survive in colon, but who knows ?  
It will also mean it keeps the microbiome in a good state.
With lower FMO3 you will be prone to sulfide dysbiosis, and so bigger load for FMO3 to oxidize.

So type 2s have bigger gut sulfide load + lower FMO3 to oxidize it (lose lose)

So Type 2s are PRONE to this dysbiosis by default

TYPE 2 (genetic) Smells 
not fish (it seems). Seem to have enough FMO3 to deal with that
But perhaps TMA is the main load, causing the overload of sulfides etc (???)

Type 2 (genetic) smells are 
Fecal
Fart
Rotten egg
Burnt Rubber
endless list of horrible sulfides (maybe a few amines thrown in)

POINT 3
It might be LOW CHOLINE MALODOR ??

person eats lots of choline ... its turned into TMA in the gut = Low blood choline 
health professional puts them on low-choline diet = low blood choline

Choline status could be easily checked in a trial, but no-one interested.
Currently Health Systems don't seem to check choline (nor do known private labs).
Maybe ask your Dr/Metabolic clinician to annoy them.


POINT 4
Best current test for FMO3 Malodor ... FMO3 GENE TEST.
Result will say you carry a few common SNPs
Result will say this is NORMAL.
If done by a Health System, result will not include silents, some common SNPs, introns.

Health system : you do not have FMO3 problem
Probable Truth : if you carry 2 or more of the SNPs (haplotypes etc, 158 308 257 etc) ... FMO3 is probably the root cause, but you are not a SEVERE. (unless you maybe have 153 etc)  
 
SUMMARY ...
Main (new) point is imho the FISH SMELL is probably severe type (type 1), the person will have a rare severe variant (at least 1, plus also maybe some of the common 7)     
Type 1 genetic will be rare, and maybe 1-5% of the community ?
Type 2 genetic will be many, and like 95% of cases

Type 2 genetic will probably pass any current TMAU URINE TEST
They will maybe have 2 or more of the common SNPs, plus maybe a silent.
Many introns are very common (e.g. 75%, 50%) but perhaps they tend to carry more of them too.

Perhaps there are no 'overload' TMAU cases that are not genetic.
Perhaps any who are the current TMAU2 have small flaws ?

CURES/THERAPIES :
Probably loads (for most) for decades but no-one interested 
1. Drug repurposing trial ?
2. Eat (protected) FMO3 ? (the load is in the gut)
3. Eat FMO3 rich probiotics ? 
4. Check choline status ? (it might be 'low choline malodor syndrome')  
5. TMA-blockers (P&G are creating one for consumer market)
6. Other things (like health companies wanting to stop poop smell for consumer market)
7. Need an ESENSOR (as most can't smell it ... imho the brain ignores blood smells)
   
TMAO is now associated with artery damage (Cleveland hypothesis 2011)

How Best to Help Yourself
1. Contact your Politician. Health System does not care.
2. Tell health professionals you smell of poop, not fish. This won't help really, but at least they will see a trend.
3. Tell health professional you identify with TMAU, you think its FMO3, but its probably sulfides.
4. Ask someone to conduct a choline status study (e.g. metabolic clinician).
5. Pressure Metabolic Clinicians especially.  

Do not think of health professionals having your best interest. Need to badger them.
But political pressure is best.

Bit of a ramble but meant for anyone seriously interested.
It is just an opinion (a hypothesis) to documenting the cause of what is known as 'FECAL BODY ODOR' (though its actually more smells than that !)
   

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FMO3 DNA testing
Update Aug 17 :
Genos is back with it's EXOME test
link

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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