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

23 June 2018

someday : 'fecal body odor' debate in Parliament ?

Someday politicians could be having a debate about 'fecal body odor' 'metabolic body odor' 'systemic body odor' 'TMAU' in their parliament / senate / congress etc.

Recently a 'M.E.' debate was held in the UK Parliament.

Here is the UK 'request for debate' stage (to show the interest of the MPs of all parties)

Someday they could be talking about (choose your label) :

It shows that politicians are very aware of M.E. and realise it is ignored.
Perhaps the same politicians who have sympathy with ME would be sympathetic to FBO.

What can be done ?
One could write their local politician about FBO etc.
e.g. MP, Senator, Rep, UK, USA, Canada, anywhere.

Also could look for politicians sympathetic to M.E. etc and write them.

Health systems and researchers are not interested in FBO/TMAU etc.
They need to be forced by politicians to act.

MPs make All Party Parliamentary Groups.
M.E. seems to have a group (2016) ME APPG

Full video :
Recent UK Parliament M.E. debate (in backroom, not main chamber)

Other awareness ideas :
Bus ad
Write to high profile 'TV Dr's/naturopaths'

Get new posts by email

12 June 2018

FMO3 survey to understand patterns in community

I would suggest its better to do the FMO3 DNA test first rather than the Urine test.
It's important we see a pattern of FMO3 variants to use as proof and to understand.

The FMO3 coding part is a 532 amino acid sequence (3 x 532 nucleotides)

Ways to FMO3 DNA test :
Full sequencing (hard to access)
23andme (23 of the 532 codons)
Geneology dna tests (raw data ... about 25 codons ?)

Ethnicities often have 'haplotypes', certain groups of variants.

Below is an 'ad-hoc' quick FMO3 survey.
The results will be made public.
Intention is to look for patterns.

Link for the survey (e.g. to share)

Problems with DNA testing :
If via a Health system lab, they don't give the 532 data, but rather mention variants they think important. They are likely very conservative.
If via 23andme : You need to look in the raw data. Not too hard. E.g. search FMO3. 

Why FMO3 ?
FMO3 oxidizes 1,000s of substrates, that are sulfides. amines, or phosphate containing.
It is my current opinion that FMO3 weakness is the cause of most cases of 'fecal body odor'.
Most enzymes have only maybe 1 to 10 substrates to alter.
But the oxidizer group, which includes FMO3, have 1,000s of substrates to alter. 

Get new posts by email

23 April 2018

Paper : TMAO converts back to TMA by bacteria

New paper :
Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota.
Reading Uni UK.

About :
How some gut bacteria can break down TMAO back to TMA.

Full paper : Link

Significance to TMAU :
Probably not that significant as most gut TMAO in humans would likely be from eating fish. Fresh fish contain a lot of TMAO.
Not unless the TMAO comes back from the blood into the bowel.
This would be known as TMAO reduction (to TMA).
Probably not the same as cleaving TMA from choline etc.

Main reason for posting the paper is bits and pieces of mild interest.
Not read the paper proper so the points below may be inaccurate.

Possible interesting points re TMAU

It says :
Enterobacteriaceae are the main TMAO reducers ?
Most of the TMA creation was around the lower small intestine and cecum, not the colon ?
Most of the TMA is absorbed, very little in feces ?

Not really much connection with TMAU but good to know research is going on about the gut flora and TMA metabolism.

Get new posts by email

1 April 2018

Comment on the NEW UK TMAU Test (Sheffield)


In early March the 'Sheffield TMAU Test Team' kindly gave a lecture at the UCL Adult Metabolic Unit in London to a group of TMAU patients.

Below is an abridged version of the lecture
Sheffield NEW TMAU Test lecture slides (hosted on SCH site)

The main 'changes' seems to be :
Almost no TMAU2 cases (this used to be a very large group).
A large amount that had no detectable TMA (this is a new category).
A big drop in TMAU1 cases (?)

Here's some thoughts on the old/new test.  The views may be inaccurate.
Maybe over time things will become clearer.

Interference :
A main reason given for the 'changes' is that the old test was prone to interference.
In effect saying there were many false 'positives'.
This may be true or not, but for some reason IMHO the old test was better at spotting the METBO smell disorder most people have.
Perhaps the incorrectly detected volatiles were a better measure of the disorder the person has.
Who knows ?


Liberal (and fair) new ref range :
The new test has what could be termed a 'very liberal reference range' (TMAU1 = <94%).
The old test was very conservative. (TMAU1 = < 79%).
With the new test ref-range, old test results would maybe have been 70% positives ... which I think is likely in a group who identify with systemic body odor.
Instead, the new test gives 16% positives.

TMA and TMAO levels
New TMA levels are way lower than the old test levels :
TMAO seems slightly lower but not much,
but TMA levels in general seem way lower on average.

You'd think there would be many more TMAU1's but it's not the case.
Old test 'positive' rate : around 33%
New test : around 16%

I accept that the new test may be more 'precise' at detecting TMA, but have long guessed most metBO cases are not based around TMA anyway.
TMA should still be an excellent biomarker of FMO3 function, but I have doubts too.

For some reason I think the new test now misses the vast majority of FMO3 smellies, the 'mild genetic transients'.

New Sheffield ref ranges.

TMA:  < 7.7 µmol/mmol creatinine
TMANO: < 119µmol/mmol creatinine
% N-oxidation: > 90-94%

Old Sheffield ref ranges.

TMA:  2.5 - 10 µmol/mmol creatinine
TMANO: 17 - 147 µmol/mmol creatinine
% N-oxidation: > 79%

A new explanation for the lack of TMAU2's is that in fact most might be 'mild genetic TMAU1's'.
I tend to agree with this theory.
I don't think 'normals' ever fall into the 'zone'.

New big group of 'non-detectable TMA' cases
Of 722 tests, 147 had no detectable TMA level.
The old test thought that a normal human would have at least >2.5umol TMA.
I tend to agree with the old test. Humans probably have some TMA in them.

Old and New test can't be compared
It's been said the old and new test can't be compared.
Both use Gas Chromatography/Mass Spectrometry and have the same scale for ref range.
So to me they are directly comparable.

What can be done to change the UK system ?

TMAU / metBO people are poorly served by their societies.
It will be by miles the biggest 'rare disorder' (i.e. not rare).
Any Health Service test labs that offer the TMAU test regard it as very charitable and to question is an insult.
Their set-ups suit the department workers.

Any change to an acceptable minimum standard will have to come from politicians.
Examples :
People can write to their MPs
Let people test direct and self-pay for the TMAU test.
If only one lab tests, it is the national lab, and has a  responsibility to do more ... e.g. have a website and contact point.

Perhaps if anyone lives in the Sheffield area they can contact their politician to insist of minimum levels of help.
Ultimately the test should be done at all NHS 'rare disorder' test labs.     

TMAU / MetBO people worldwide should always remember our current help is below a minimum standard.   

That said, thank you to Sheffield CH for the slides and lecture.

Get new posts by email

31 March 2018

North Carolina Uni tests for TMAU

Update :
This lab will let a Dr order the test as long as :
1.the patient is DE-IDENTIFIED for the sample.
2. the patient name is not disclosed.
i.e. they do not find out the patient details.
This would be a special arrangement by your Dr.
Insurance will almost definitely not apply.
It seems the ZEISEL LAB in Uni of North Carolina has a TMAU urine test, but it's set up strictly for researchers.

Test (urine) :
Trimethylamine and its oxide TMAO,
(tbc ... not clear of choline is just the blood test)

Where :
ZEISEL LAB at CHAPELLHILL site, Uni of North Carolina

Cost : 
currently $208

Access to test :
It's set up strictly for reserarch purposes, requiring e.g. ...
A researcher with an IRB and Uni proof etc.
Unidentified samples.
Not a CLIA test.

So sadly for the community, the test is there but currently beyond reach.

TMAU 'Profile' test
Choline would be added to the TMAU test, as TMAUers are probably naturally deficient in choline before and then extremely deficient after testing.
So TMA, TMAO and CHOLINE would make a natural TMAU PROFILE TEST.

This test is like 3 times cheaper than the Denver TMAU CLIA test.

Hopefully someday we can find a way to access this test.

Other ideas for tests for a TMAU PROFILE :
Maybe a sonar of the liver to check for NAFLD fatty liver. This can be caused by choline deficiency.

The lab also test Folic acid status and a few other choline metabolites including methionine.

Get new posts by email

25 March 2018

Potential 2 year FMO3 Study

A Metabolic Consultant has offered to do a 2 year study on 2 ways to improve FMO3 function.

Part 2 (part 1 in the paper). would focus on NONSENSE mutations, which are rare but usually severe.
Part 1 would focus on MISSENSE mutations, which will be the vast majority of TMAU1 cases.
Speculation suggests that TMAU2 cases could also possibly be mild missense cases.

I make MISSENSE part 1 as this will be the vast majority
e.g. E158K E308G etc

What's needed for the study to happen :
Youcaring is suggested as it's free and has few clauses : Youcaring
But any crowdfund site would do.

Study cost : about $US 100,000

Why ? 
Someone will be hired fulltime for 2 years.
Plus equipment etc

Study basics :
1. Using ATALUREN to see if it helps with NONSENSE mutations.
2. DRUG REPURPOSING : going through many drugs in FMO3 cells to see if any improve FMO3 function. This would help with MISSENSE mutations.

Drug Repurposing often happens in pharma-world.
Such as viagra originally being for heart disease.
Often multi-uses are found for drugs accidentally.

The study needs funding

A best option would seem to be crowdfunding.
possible scenarios :
A trusted individual or collective to take on the crowdfund.
e.g. A group of respected older women ?
Using the REACT Fund as a trusted proxy (if they let the consultant have the money)
Any other ideas

Fuller outline of the potential study

 Time-lines for the project (at half-yearly milestones):

Study component
Year 1
Year 2
Generation of a range of FMO3 nonsense and missense mutations and the in vitro tools for their functional analysis in a cell culture system

Evaluation of the efficacy of read-through agents and other drugs in our in vitro cell culture system, including acquisition of structural and functional evidence


2.  Repurposing of existing drugs:

TMAU is caused by a functional deficiency of the FMO3 protein.  Many of the missense mutations of the FMO3 gene are hypomorphs, ie there is some residual activity of the enzyme, albeit not enough to prevent the accumulation of TMA.  Augmenting expression of the faulty gene through activation of the FMO3 promoter, could improve overall FMO3 enzyme expression, with significant amelioration of the disorder(19).  Libraries of known therapeutic agents are commercially available that can be used in high throughput screening assays to screen for possible opportunities to “repurpose” the drug, ie apply it in a therapeutic context for which it was not originally designed.

We propose to use the cell culture models developed by us in a high throughput screening approach to identify new potential therapeutic agents that could augment expression of the FMO3 gene.

If we demonstrate potential in vitro efficacy of specific well-established therapeutic agents, we will then potentially be in a position to move to clinical trials in patients with trimethylaminuria, particularly if the therapeutic agent identified has an existing therapeutic track record in other disorders.

1.  Read through of premature termination mutations: (Nonsense mutations)

Premature termination or nonsense mutations arise as a result of a single nucleotide change in a gene where the change leads to the conversion of an amino acid in the protein sequence to a premature stop codon.  Such mutations often result in the protein losing most if not all of its functional capacity.  It was recognised a number of years ago that aminoglycoside antibiotics can force the transcriptional machinery to read through the premature stop mutations, and allow the normal protein to be made, restoring activity of the protein(13).  However, aminoglycoside antibiotics have significant side effects and are not a viable therapeutic option.  More recently a new class of drugs has been developed that has the capacity to promote read through of premature termination mutations, and which appear to be totally non-toxic(14).  One in particular, PTC124, has been shown to result in the production of normal dystrophin in the mdx mouse model of Duchenne muscular dystrophy(14), and has been used in clinical trials in human subjects with cystic fibrosis, with clear benefits being found(15).  In addition, there are a number of other read-through agents currently being evaluated for potential in vitro and in vivo use. An inborn error of metabolism like TMAU would be an excellent candidate for this type of therapy, as an increase of enzyme activity to perhaps as little as 10% of normal should be enough to overcome the biochemical block.

Get new posts by email

15 March 2018

Sulfide and Methane production in humans : FBO connection ?

This is a very speculative post.
It is said that in the HUMAN MICROBIOME, that people tend to be either :
Sulfate reducers (so, sulfide producers)
Methane producers

It's not clear how much is known about the microbiome but the word seems to be the population is split 50/50 being either dominant in Methane or Sulfide producer.

It would be interesting to see if those who identify with FECAL BODY ODOR and the spectrum including fart, raw cabbage etc tend to be in the SULFATE REDUCER group.
Nothing has shown up in Ubiome results yet, or at least what I have seen.

Methane in humans would tend to be produced by Archaea microbes, which funnily have been suggested as a potential TMAU therapy (they would break down TMA).

Sulfide producers would probably be mostly due to DESULFIBRIVIO bacteria, but possibly other sources.

It seems odd that in 2018 humanity still doesn't seem to have documented what cause stool smells exactly. Good guesses can be made but there seems to be no consensus and few papers.   

Get new posts by email

8 March 2018

Sheffield TMAU survey : Old and New Test

Quick update on anecdotal SHEFFIELD TMAU Test Survey.
Aim : To show differences in trends between OLD test (Nigel's pre-2017 test)
and the NEW post-2016 test.

Measurement is umol/mmol creatinine.

Conclusions :

1. TMA is 10-80 times lower for NEW test ??

TRIMETHYLAMINE levels seems to be 10  to nearly 100 times less than the old test, even though they both use GAS CHROMATOGRAPHY as the method.
The reason given so far is that the old test had 'false positives', which means many were told they were positive wrongly.

For whatever reason, the old test was more in line with numbers I would expect to be positive. My suspicion is the new test spots only GENETICALLY SEVERE TMAU cases now, whereas the bulk of us were GENETICALLY MILD or even borderline or 'carriers'.

Paper of concept 1999 : susceptibility of heterozygotes


There's 5 NEW tests in the survey of 22 (viable answers). So apart from the TMA difference trend, it's hard to make other conclusions.
TMAO levels seem similar but slightly lower. Does not have the huge variance where the OLD test had TMAO levels in the 100's. It looks like none will be over 100 in NEW test.

The 2 above comments are to do with the MACHINE METHOD ; not the 2nd part, the reference range.

Anyone can take part in the survey if their TMAU urine test was done at SHEFFIELD CHILDRENS HOSPITAL.
This would be anyone who has tested on the NHS.

AIM : To show difference in patterns of OLD and NEW TMAU test.

Get new posts by email

TMAU Stories

Get New Posts by Email

systemic BO/halitosis important links

MEBO Research malodor study 2016


FMO3 reference

Blog Archive

TMAU/FMO3 research

Systemic Body Odor links

email :

Do you have systemic body odor ?

FMO3 Survey Form

FMO3 DNA test result survey
for those who have FMO3 DNA tested
survey still OPEN

TMA blocker pill (links)

P&G - Cleveland press release aug 2015
1st mention of 'DMB pill' dec 2015
FMO3 DNA testing
Update Aug 17 :
Genos is back with it's EXOME test

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

TMAU Webinar #5 : Preti et al