Wevers & New Halitosis disorder : DMS and CH3SH

A new paper by Drs Wevers, Winkelman, Tanger et al, puts forward the theory that there is a newly discovered disorder that can cause metabolic/systemic halitosis.

The volatiles that cause the smells : DIMETHYLSULFIDE and METHANETHIOL .
Enzyme at fault : SELENBP1 .

title : Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis
Pubmed Abstract :  link
Full paper : Link

First impressions of this new paper/discovery :

1. IMHO it could be classed as the MOST IMPORTANT METABOLIC BODY ODOR DISCOVERY SINCE THE 'DISCOVERY' OF TMAU IN 1970.
The reason being that the concept of 'metabolic/systemic body odor' has relied on 1 compound (Trimethylamine) to prove the concept and be the 'sole' disorder, so more compounds to the list are welcome.
In a perfect world society would say 'let's now find all the metbo compounds' ... but society is not interested.

2. They feel that the gene to blame is SELENBP1 for this new disorder.
I still suspect FMO3 is to blame, so I will keep an open mind for now.

3. DMS and CH3SH are the compounds to blame for this disorder.
People with 'fecal body odor' (as it's known) complain of smelling of many nasty smells. To me, DMS and CH3SH are far better suspects for causing FBO rather than TMA, and they are probably in my top 5 list of potential FBO smell suspects, so to see them identified is very welcome.
I suspect there may be a few more (probably mostly Volatile Sulfur Compounds, thiols') suspects to add to the list, but I regard these 2 as potentially 'main players'.

My example list of FBO suspects (guesses):
Probably VSCs or Thiols ... e.g.

DMS
Methanethiol
Dimethyldisulfide
H2S
Cysteamine (?)
Way down the list .... TMA

When someone has metabolic BO, the 2 questions are :
1. What compounds are causing the smell ?
2. What enzyme(s) are supposed to neutralize those compounds.

So in this case I think they have identified bigger 'players' of the group of compounds that cause FBO, but wrong enzyme (could be wrong).



The 'urine' test for the new 'metbo disorder' : High Dimethylsulfoxide.
For the urine test they go for DMSO level.
Perhaps DMS and CH3SH are too volatile to rely on in a urine test, and may already have dissipated or altered. They seem to go for the OXIDE of DMS, which is perhaps the natural end product, and judge it on higher levels.
I would suggest this is definitely a test we should take.

About Wevers, Tangerman, Winkel et al :
The paper included the 3 above Drs, as well as many others. They have known to have a long interest in the causes of Halitosis, including metabolic causes.
That said, this paper may have taken 10 years (or more) to publish, so my 2 thoughts on their research are :
1. Whilst I welcome it, I am not relying on any breakthrough in society and Drs knowledge of met BO/hali in the near future.
2. I'm hoping perhaps they have 'stored' research and will announce treatments, test options, as a quickfire bundle of announcements this year, but I'm doubtful.

So in conclusion, my current view is :
Potentially 'top of the list' compounds identified to cause metbo body odor.
For now, I'm still a 'FMO3ist' rather than thinking it is SELENBP1.

Them :
compounds : DMS and CH3SH.
enzyme : SELENBP1

Me :
compounds : DMS and CH3SH (and a few more VSCs, thiols etc).
enzyme : FMO3   

Other potential metbo disorders :
I write mostly about my opinion as to the cause of FBO, which seems the main complaint.
I am sure there will be other metbo disorders, but these will be limited to perhaps 1 compound (or a small family), and to other genes.
FBO seems a wide spectrum of smells, so IMHO is most likely a 'broad spectrum' gene, whereas other metbo genes will have a  one distinctive smell (probably), such as isovaleric acid.   

What compounds make feces smell ?
Everyone knows the smell of poo can vary, so for the most part it seems that the compounds that make the smells are varying too. A guess would be they are mostly VSCs / Thiols, and a few other compound families thrown in. But for the most part they would seem to be sulfur compounds.
It may be a surprise to know the World Scientists do not yet have a definitive list of the compounds that make poo smell. Occasionally a researcher (such as Levitt et al) will do a few papers, but many might disagree with them.   

Media links to the story
Gizmodo
Medical Xpress
Science Daily
Genengnews
UCLA press release

Dr Wevers webpage

 

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By sysbodyodor

Body Odor, fecal body odor, fmo3, metabolic malodor, metabolic/systemic malodor, metabolic/systemic malodor research, systemic body odor

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New paper : TMAU might not just be FMO3 disorder

New TMAU paper by Monell et al.
Conclusion (?) : TMAU might not just be because of FMO3 enzyme.
Paper funded by NORD grant crowdfunded by TMAU community in 2011.

Around 2009-2011 a TMAU community group spearheaded a crowdfunding campaign to get the NORD TMAU grant past it's $25K trigger point so that researchers could put forward proposals for the grant. The grant was awarded in 2011 to a Monell Chemical Senses proposal. This month the paper has been published in a peer journal.

NORD grant TMAU paper : Genetic analysis of impaired trimethylamine metabolism using whole exome sequencing

Conclusions
Thus, variants in genes other than FMO3 may cause TMAU and the genetic variants identified here serve as a starting point for future studies of impaired TMA metabolism.

My interp of the paper 

My interp is they are saying genetic TMAU may not just be just to FMO3 enzyme flaws. In particualr they mention PYROXD2 enzyme, which has been mentioned in TMAU circles before (can't recall why).  

My own view on the paper (bad analogy ... suspects and safehouses)
If you think of 'volatiles' as the suspects, and FMO3 as the safe-house, they are saying the suspect (TMA) stays at various safehouses, TMA is to blame for all the smells, and only TMA should be followed about even when it leaves FMO3 'house' to other safehouses.

My own current view is the only safehouse to watch is FMO3, and note all the 'volatiles' that stay there. In fact I reckon TMA is a 'small player' and other FMO3 'safehouse' suspects are more likley to blame for smells. Probably the likes of dimethylsulfide.

So this new paper has went in a direction that doesn't fit with my current thinking, but it is 'new' in that they are suggesting TMA might be metabolized by enzymes other than FMO3 (?).

Paper view
Current Safehouse : FMO3
Suspect : TMA is only suspect.
Paper : TMA might have other safehouses.

My View
Safehouse : FMO3
Suspect : many. TMA a small player
My view : No need to follow TMA. FMO3 is only safehouse that matters, Keep an eye on the all suspects at FMO3 house.

Overall, I think so little research has gone into FMO3 and TMA that we may be at 'chapter 1' of understanding them. As this was a small one-off study, I don't expect much more 'TMAU' research on it. But since TMA has been suggested as having a connection with cardiovascular disease, perhaps TMAU people will be able to read on such research from this aspect in future.

Other comments on the paper :

None of the 10 people seem to report fishy smell. Most report 'sulfury'/fecal smells
My impression is that Monell feel TMA causes a fishy smell, but through influence have broadened this to saying TMA might cause smells more broader than that. Personally I think the smells are not due to TMA, but to other volatiles (e.g. sulfides), and in a way TMA is probably a 'small player' but a good biomarker of FMO3 function (? not even sure about that).    

Only one has FMO3 mutations that would be regarded by clinicians as TMAU1 
In academia and the clinical world, the teaching is that genetic TMAU is caused by serious FMO3 mutations. But in this paper only one has taught 'serious' mutations (at codon 148). Or at least, I think faults at 148 are bad. I note that they are not the worst TMAU result in the paper (at about 56%).

All the other FMO3 faults listed are carriers of common 'benign' FMO3 faults

Common FMO3 variants carried by whites by %  :
codon 158 : 20-50% ?
codon 308 -  up to 20% ?
codon 257 -  up to 15% ?

As can be seen, many people carry common FMO3 variants. Currently they are taught as being 'benign'. But in the paper, of the 10 tested, many of them only carry one of these FMO3 faults (mainly 158). Obviously 50% of whites don't have metabolic smells, so it's still an unknown full picture to understand.

The worst TMAU urine result seemed to only carry a PYROXD2 DNA fault.
In this paper, the worst result was #52 who only carried a fault in PYROXD2 enzyme.

Worst result in paper : #52 ... TMAO% output 13% ... FMO3 faults : none ... PYROXD2 faults : carries one

The worst TMAU result had no FMO3 faults and only carried 1 PYROXD2 fault. This throws up more questions than answers. 5 carried PYROXD2 faults (3 were homozygous, 2 heterozygous).

PYROXD2 faults listed : Not in coding part of PYROXD2
To make a PYROXD2 protein, you need an amino acid code. These are the codons on the exons.
Genes also have introns, which are generally regarded as 'junk' or unknown.
In this paper, the PYROXD2 faults listed are in the intronic region (not the exons). So they are not even in the coding part of the enzyme gene.

example of how gene makes a protein.
FMO3 has 532 amino acid code to make the FMO3 protein
this means 532 codons.
Genes also have intron part.
Introns not needed to form the protein, but faults there seem to be able to disable the protein.

PYROXD2 
This enzyme has been listed before in one TMAU paper. I can't recall at the moment.

Final thoughts 
The paper is certainly interesting in that it raises questions about current TMAU  teaching. How much impact it will have ... possibly not much due to lack on interest in TMAU.

I will be looking around at PYROXD2 again in a mild way. My mind is currently too set on FMO3 and all it's sulfide/amine volatiles, rather than TMA.

I have no expertise and my interp and thoughts could be wildly wrong.
My impression is Monell can be sensitive about opinions.

My own current theory on systemic body odor/halitosis
Most people identify with 'fecal body odor'. I think this is due to sulfides, maybe some amines. I think it is due to problems with the FMO3 enzyme. Probably often a combo of FMO3 slight weakness and 'FMO3 substrate gut dysbiosis'.

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By sysbodyodor

fecal body odor, fmo3, FMO3 research, fund raising, metabolic malodor, metabolic/systemic malodor, metabolic/systemic malodor research, TMAU research, trimethylaminuria

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REACT TMAU Fund : spare a $5 ?

RE(ACT) rare disease site.
Meant for research crowdfunding.
Part of the BLACKSWAN charity.
Based in Switzerland.
Founded by pediatrician Dr Olivier Menzel.

Idea behind RE(ACT)
Rare disease groups can use it as a crowdfund site for research into their disease.
Researchers are supposed to put forward research proposals.
REACT has a expert committee who accept/reject proposals.
If no proposal is ongoing, the money goes in to a fund awaiting proposals.

RE(ACT) TMAU Fund
Throw them $5 ? (or EU/£ )

Problems with REACT
Staff seem to be not around.
Seems to be no users around.
Seems to be only one research fund ever raised of all the disorders.
Generally it seems neglected.
Yet they seem to do annual conferences.

REACT TMAU FUND : throw a $5 their way ?
Maybe if you have a spare 5 $/£/EU you could donate it to the TMAU Fund as a wake-up call.
Consider it money wasted.

Good things about REACT TMAU FUND
You can see the amount raised on their site.
Money does seem to at least stay in the fund (possibly forever).
Does not seem to get transferred into a general fund if deemed redundant.

SYSTEMIC MALODOR/TMAU community should have their research fund(s)
examples, Research Fund(s), campaigns such as awareness campaigns (e.g. Bus ad, conference) ).
Main ideas :
Needs to be transparent.
Needs to have broad support.  
Needs to be trusted etc.

Crowdfund campaigns etc
Examples : Individuals or small groups could start TMAU/Malodor crowdfunds.

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community, crowdfunding, fecal body odor, FMO3 research, fund raising, metabolic/systemic malodor, metabolic/systemic malodor research

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Putting FMO3 through the 'drug repurpose' checklist

FMO3 has been taught that it cannot be induced as most other redox enzymes can (e.g. the CYPs).
Perhaps this thinking is because so few have investigated FMO3.
A recent paper suggested a Korean herbal mushroom may induce FMO3.

DRUG REPURPOSING :
A (new ?) method of (relatively) 'inexpensive' enzyme research is to check how drugs past their patent period to see if they may be of any use in other health conditions.

Drug Repurposing for enzyme disorders (e.g. FMO3)
For enzyme disorders this probably involves checking the reaction of  the enzyme to a list of unpatented drugs in a lab (e..g FMO3). In this case a priority would probably to be to see if it can INDUCE FMO3 (i.e. make it work harder) so you maybe get another 10-20% output.

Main benefits of Drug Repurposing (?) :
It's RELATIVELY inexpensive.
It should be reasonably quick and easy to do (? a year ?)
A lot will be known of the drugs already.  
May learn more about enzyme (e.g. a group of compounds induce/inhibit)

RESEARCHER INTERESTED IN FMO3 DRUG REPURPOSING
A researcher has shown an interest in putting FMO3 through the 'drug repurposing' check.
As usual funding would be the issue.
A opening estimate is that it may cost around $US 74,000 (probably mostly to hire someone to run the checks.)
An opening estimate is that it would take around a year.
They are looking at possible ways of getting funding but it's difficult.

It's something the community can think about.

Links about Drug Repurposing :
NIH USA website
wikipedia
101 website
findacure UK 

FMO3 and Systemic Malodor
My own interest in FMO3 is because I currently suspect it is my main suspect enzyme for most cases of 'systemic/metabolic malodor' (i.e. caused by an enzyme deficiency or overload, not hygiene etc).
FMO3 oxidizes many sulfides and amines in humans. But other enzymes cannot be ruled out.

Current possible therapies for TMAU or FMO3 'smells' :
TMA inhibition/reduction in the gut (e.g. Cleveleand Clinic working on a reducer to be marketed as a supplement by P&G. Not known when it will be available).
TMA metabolization in the gut (e.g. 'probiotic' that metabolizes TMA. Probably a 'methanogen' which will take it the methane route.)
'Gene Therapy' (probably ideal option)

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announcement, crowdfunding, fecal body odor, fmo3, FMO3 research, metabolic/systemic malodor research, possible future therapy, research, systemic body odor, systemic malodor syndrome, TMAU research

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Can FMO3 be induced by Korean mushroom ?

FMO3 experts teach that (in general ?) FMO3 cannot be induced or inhibited.
This is despite 'redox' enzymes often being induced/inhibited by foods/drugs/compounds.
A good example is a grapefruit compound greatly inhibiting enzyme CYP3A4 (discovered by accident).
FMO3 is known to be inhibited by certain indoles mainly in cruciferous veg (Cashman et al).
Also menstruation hormones have been shown to inhibit FMO3 (Cashman et al).
But still, the teaching seems to be that FMO3 cannot be induced/inhibited.

One view could be that so little is known of FMO3 (and perhaps other redox enzymes, but perhaps FMO3 is less important) that perhaps FMO3 can be induced/inhibited by compounds in food/drink/drugs. We don't know.

Paper : Korean herbal mushroom induces FMO3 
In a research paper last week, the authors seem to think they have shown that FMO3 can be induced by a Asian mushroom commonly used by Korean Herbalists.

Korean paper (University of Seoul, Seoul, Korea):
Korean herbal mushroom induces FMO3 in mice in research paper.
mushroom : Phellinus baumii

Quote :
"PBE was responsible for the induction of Fmo2, Fmo3, and Fmo4 expression. PBE also accelerated the metabolic clearance of carbendazim in vivo and so could be applied to the detoxification of xenobiotics such as drugs, pesticides, and nicotine."

pubmed link to abstract

My own view of this :
It's a one-off paper, perhaps biased to Korean herbal compounds.
I won't be looking to buy the mushroom.
The more I try herbal compounds, the worse I feel.
I think FMO3 was thought to develop in the animal/plant warfare fight, as plants developed poisons, FMO3 was developed to metabolize these (could be wrong),

But, it raises the question again about FMO3 INDUCTION as a possible therapy.

My main thought on this paper :
The notion that FMO3 INDUCTION may be worth exploring as a possible FMO3/TMAU therapy. This would be to say boost function by say 10-20%.
FMO3 induction would probably only be any use to those with FMO3 weakness/deficiency.

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By sysbodyodor

fmo3, FMO3 research, metabolic malodor, metabolic/systemic malodor, metabolic/systemic malodor research, possible future therapy, systemic body odor, systemic malodor syndrome, tmau, TMAU research

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Metabolomic Profiling for Systemic Body Odor

This post is meant to be thought provoking.

Need to discover all volatiles/metabolites that cause systemic body odor.
Once discovered, these volatiles will be known as the biomarkers for the diagnostic test,

Trimethylaminuria (TMAU) was 'discovered' in 1970 by Denver Dr's. A patient's mother had said sometimes their child smelt of fish (they had another serious disorder) and the Drs decided to test the TMA level since they knew this volatile smells of fish.

So the only volatile currently tested for systemic/metabolic body odor came about in an anecdotal case and no-one has looked any further than this since (that's if they even look for TMA). It goes to show how much 'sufferers' need to further the understanding of systemic body odor themselves, as no-one is looking.

Personally I think maybe 1% population could be 'prone' to  transient systemic body odor, probably 'fecal body odor'. Maybe even more. I would guess it may well be the biggest 'undiscovered' metabolic disorder left.

Metabolome Testing
It's only about 18 years since the FMO3 enzyme DNA code was fully documented. So genetics is still at a fairly new stage. Along with genetics, the other science that compliments it is human metabolomics, the study of the metabolites in humans. Again this is a fairly new science, both in knowledge and the technology needed. It does seem to be maturing now.

Metabolomics for understanding systemic body odor
When a disorder is fully understood it will have a 'phenotype' test where they look for the known biomarkers in human fluid to see if the person has the disorder. Since the concept of systemic body odor has not been documented, it will currently need a test like an exploratory metabolome test to look for higher levels of metabolites (probably volatiles). Once they document the biomarkers for systemic body odor, you can then use these biomarkers as the 'disorder test'.

How to do a Metabolome test
First you need to make sure it will look for the 'suspect' metabolites. In the case of SBO, these will probably be sulfide volatiles, but I wouldn't rule anything out for now. I would guess most labs would do a very broad spectrum exploratory test.

examples of 'suspect' volatiles I would look for in systemic body odor :
dimethylsulfide
dimethyldisulfide
methanethiol

Personally I would be looking at FMO3 substrates, as I reckon this enzyme may be to blame for the biggest group of SBO sufferers.

Ease of testing
Since it's a new science, I am unsure of how many labs do metabolomic testing. It's probably not a regular in the mainstream medical health industry (e.g hospitals). Probably more a test done at University labs where trends for testing probably start off.

Also, as usual most labs will probably insist only a Dr can order the test. The usual obstacle to testing used in the medical health industry. Hopefully someday the law will change to allow people to self-pay any test.

Testing Centers :    
Looking around I am not aware of too many potential test centers. A quick google search came up with these possible leads :
Uni of Alberta
Baylor Clinic
Human Metabolome Technologies (Boston)  

The system :
I would say at the moment, expect the system to be against you.

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By sysbodyodor

Body Odor, fecal body odor, metabolic/systemic malodor, metabolic/systemic malodor research, systemic body odor, systemic malodor syndrome

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P&G TMA-blocker will be stronger than DMB

In a magazine article in April about the gut flora, this statement was made

"Hazen says DMB, the olive-oil molecule from his study, is too weak to put into a pill. He’s working on creating stronger inhibitors."

So it looks like something stronger than DMB will be used by the Cleveland Clinic for their 'TMA-blocking supplement' which will be marketed as an over-the-counter product sometime in the future by Proctor & Gamble.

Full article : Statnews April 2016

DMB : 3,3 di-methyl-1-butanol (wikipedia)
DMB is of interest to the TMAU community as it's been shown to block the formation of trimethylamine in the gut (of mice) by gut flora. It's naturally present in olive oil, balsamic vinegar etc.

TMA-oxide and atherosclerosis theory (wikipedia)
In 2011 Dr Hazen et al at the Cleveland Clinic put forward a theory that tma-oxide may be a factor (perhaps main factor) in the development of atherosclerosis. Since then the lab has been researching this and putting many papers forward to enforce this. In 2015 they said that DMB was an inhibitor of TMA in the gut of mice.

Analogs
Quite often an approach in humans to damage is to find an 'inhibitor' which stops a damaging checmical reaction. in the 'TMA precursor (choline etc) -- TMA -- TMA-oxide' cycle of reactions, the aim is to block TMA formation. 'Inhibitors' or often refered to as Analogs, and in this case they found that DMB is an inhibitor of TMA formation (from choline etc).

Better inhibitor than DMB
So it seems they are looking at stronger inhibitors than DMB to put in the P&G 'supplement'. The final product will not be a 'DMB pill'. This is even better news I guess. A heart-disease expert recently reviewed the evidence on the 'TMAO- atherosclerosis' theory and estimated that perhaps 10-20g of DMB (in divided doses) would be needed to block TMA in the gut. But something better than DMB is even better.

Possible 'resistance' like antibiotics ?
One potential 'danger' pointed out is that the article seems to say that the DMB probably alters the gut flora composition, which might mean 'immune' bacteria then become dominant. Very much like antibiotic drug resistance. DMB is not lethal to gut flora like antibiotics, but nevertheless the same resistance may occur due to flora composition change.

Good news for Trimethylamiuria people
Obviously blocking TMA formation in the gut is great news for those with TMAU. First documented in 1970, up until this interest in 'TMAO-atherosclerosis' there has been almost no interest in TMA metabolism in humans. Now suddenly TMA metabolism in humans is of main interest in human health research.

My view (in terms of systemic body odor) :
A 'TMA-blocker' pill sold over-the-counter by Proctor & Gamble will definitely happen. Anyone who thinks trimethylamine is the sole cause of their systemic malodor should regard this as possible a very good therapy for 'TMAU'. But personally I feel TMA may not be the only volatile that causes what I call 'FMO3 smells', so I am a bit worried. But maybe TMA is a main factor (indirectly) and blocking TMA may relieve the pressure on FMO3 (for example). Anyhow, I will definitely be trying it and could be regarded a 'banker' hopeful therapy that will happen while we worry about other hopes.
 

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DMB pill, gut dysbiosis, metabolic malodor, metabolic/systemic malodor research, possible future therapy, systemic body odor, TMAO Research

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How much DMB for TMAU ?

What daily dosage of DMB should a TMAU patient take to block TMA formation in the gut each day ?

Answer (estimate, in theory) : about 10-20g DMB a day (divided into doses) 

About this answer :
This is an estimate by a very respected CVD expert in a recent overview paper of the TMA-oxide - atherosclerosis connection proposed by Hazen et al in 2011.

Answer is based on Mouse studies for atherosclerosis :
The answer is not based on humans taking DMB as trials have not reached that stage. It is an estimate based on extrapolating the dosage given in mice studies. So you could say it is a 'expert estimate based on mouse studies' given the current info.

The estimate is generally from this overview paper : link

Acronyms

DMB :  3, 3 dimethyl-1-butanol
TMAO : trimethylamine-n-oxide
TMA : trimethylamine
CVD : cardiovascular disease
FMO3 : flavin mono-oxygenase enzyme (isoform 3)

About DMB :
DMB in this case refers to 3, 3 dimethyl-1-butanol.

Atherosclerosis and TMA-oxide theory :
Put forward by Hazen et al of Cleveland Clinic in 2011. My impression is that the theory is that TMA-oxide may be the main factor in the development of atherosclerosis.

Connection with TMAU :
Since TMAU is proposed as being a malodor caused by TMA, any research that may block TMA formation in the gut would be a potential therapy. This is an obvious target for the 'atherosclerosis researchers' to aim for. So TMAU patients should be incidental benefactors of this approach.

Where do you humans get TMA from ?
TMA is smelly so is not normally consumed by humans. Nor is it a metabolite from human metabolism. It's only real source in humans is gut flora altering certain compounds in the diet (e.g. choline, carnitine, lecithin, TMA-oxide in fish).

The 'TMA blocker' story so far :
Hazen et al lead research into the TMAO - CVD theory. In Nov 2015 they published a paper showing DMB blocks TMA formation in mice (gut).

How long until a 'TMA blocker' drug is available ?
Cleveland Heartlab have already signed a deal with Proctor & Gamble to market an 'over the counter' TMA-blocker drug. It is not known when this will be available. I am currently presuming it may be DMB based, but perhaps they will find an even better 'TMA-blocker'.  

How can you get DMB now ?
DMB is a natural compound in things like balsamic vinegar, olive oil, red wine etc. I do not know how much you would need to take to get 10-20g daily of DMB. My own view is that these foods are probably bad for people with FMO3 issues, as they will likely contain many other FMO3 substrates that may end up causing smells (probably indirectly after being altered by gut flora).          

My own view :
I am very optimistic about a 'TMA-blocker'. But my own belief is that people with an FMO3 issue probably smell of all FMO3 substrates and not just TMA. So that concerns me but I am still optimistic. Also FMO3/TMAU was a very neglected disorder, but now TMA metabolism in humans is on the center of radars for atherosclerosis researchers. I will certainly buy DMB when available. If I thought TMA was the only malodor problem I would be ecstatic.

It also shows how TMAU/FMO3 has been a neglected disorder, as this therapy is an obvious concept which was never looked at for TMAU. Now that it is proposed to be connected with CVD we can expect lots of research into TMA metabolism.

My feelings on this (in tags) in relation to metabolic/systemic malodor :
optimistic, excited, cautious, research leads could appear from anywhere now, TMA metabolism is on the radar bigtime.

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By sysbodyodor

DMB pill, gut dysbiosis, Hazen TMAO research, metabolic/systemic malodor research, possible future therapy, research, systemic body odor, systemic malodor syndrome, TMAO Research, TMAO-CVD, tmau

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Hazen and Wang : article on DMB blocking TMA

Article from Albany Daily Star (circa spring 2016).
Concise article explaining how DMB 'blocks' trimethylamine production.
Hazen and Wang are the names to look out for re Cleveland lab research.

This article (Daily Albany Star : spring 2016) concisely explains in layperson terms how DMB 'blocks' TMA formation by bacteria in the gut. It includes quotes from Dr Hazen (well known to us) and his collegue Dr Zeneng Wang. Dr Wang seems to be the lead author of most of the research from Cleveland Clinic lab research on ways to block TMA formation in the gut. The Hazen lab was the one who in 2011 put forward the theory that TMA-oxide may be a major factor in atherosclerosis.

Read the TMA - DMB article 

Acronyms
DMB : dimethyl butanol : wikipedia
TMA : trimethylamine
TMAU : trimethylaminuria

Connection with systemic body odor :
As TMAU is the only current 'benign' systemic malodor disorder documented (really), with the cause of the malodor said to be trimethylamine, then any research that might block TMA formation in humans will be of interest to those who feel TMA is solely responsible for their smell (or partly). So we follow the research of the Cleveland lab in particular (e.g. papers with Wang and/or Hazen) and any others researching this theory.

DMB-TMA Cleveland research : What we know so far 
In Late 2015 Wang et al issued a paper saying DMB 'blocked' TMA formation in mice gut.
In Aug 2015 the lab announced a deal with Proctor and Gamble to sell an over-the-counter product to help with 'TMA-oxide management'. It's not known when it will be on sale.

Comments on the article :
The article explains how DMB acts as a 'gobstopper' to the enzyme in the bacteria, blocking it's ability to oxidize TMA. This is because DMB is stuturally similar to choline. Enzyme blockers are often 'analogs' of the substrate that act as a decoy.

It's interesting to note they mention TMA smells. Perhaps this was an influence on Dr Hazen, though it says originally they looked for a TMA-oxide blocker. Anyhow Dr Hazen is aware of TMAU since 2011.

It's a case now of waiting for the DMB supplement to be on sale, though it could take years.

So Wang went after the microbes instead. He identified a substance called DMB that looks a little like choline, and acts as a gobstopper. It gums up the enzymes that the bacteria normally use to digest choline, which prevents them from producing TMA...

...To be clear, the researchers aren’t trying to kill the microbes. Their substance isn’t an antibiotic; it just nudges the microbes’ behavior away from certain actions that negatively affect our health. “It’s a new approach to treating not just the individual Homo sapiens but also the microbes that live with us, and collectively contribute to disease,” says Hazen...

... At first, Hazen’s team tried to prevent the second part of this chain by blocking the animal enzyme. They succeeded, lowering TMAO levels in mice and making them resistant to atherosclerosis. But there was just one problem: Disabling the enzyme leads to a build-up of TMA, which doesn’t harm the heart but does smell of rotting fish....

Read the TMA - DMB article 

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By sysbodyodor

DMB pill, Hazen TMAO research, metabolic/systemic malodor research, TMAO Research, TMAO-CVD

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FMO3 DNA test survey

Click image for survey

A survey for those who have results for the FMO3 DNA test
SURVEY STILL OPEN
An 11 question blog survey
To collect some useful data about FMO3 test results
From those who have a systemic/metabolic malodor concern
All questions are optional

Tested FMO3 gene ? You can do the survey
Link to FMO3 test result survey

link to give to others
https://goo.gl/zHUan6

FMO3 survey latest 03/16   

I created this survey as a way of collecting some FMO3 test result data.
I will make some of the data public in a collective fashion so that it is non-identifiable
Maybe it will show a pattern among us

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By sysbodyodor

Body Odor, fecal body odor, fmo3, FMO3 research, malodor survey, metabolic malodor, metabolic/systemic malodor research, raising awareness, systemic body odor, systemic malodor syndrome

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2016 malodor study : MEBO Research

MEBO Research have registered a study on the USA clinical trial website.

Purpose (quote) : "The purpose of this study is to identify metabolic signatures associated with malodor conditions. The investigators will perform state-of-the art metabolomics tests and bioinformatic data mining to explore if conditions leading to malodor can be screened by metabolomic profiling of urine samples."

Link : MEBO urine metabolite malodor study

A main aim of mine has been to get a study where urine samples are analyzed for metabolites that may cause metabolic malodor. I helped in setting up this study which has been maybe 3 years in the making.

I did not have a final say on the final plan, so I view it as someone looking at the info on the clinicaltrial.gov site. My own intention was a urine testing program for metabolites (probably volatiles) in urine that may be the cause of a person's metabolic/systemic malodor. Much the same way as the 'trimethylamine' diagnosis came about, except testing for many volatiles rather than just trimethylamine. For instance, dimethylsulfide. From reading the info it seems this will be covered. My current thought is that it may also include those with 'surface' malodors, which wasn't something I had in mind. I may be misreading.

Anyhow it is a very much needed study. I am hoping it will show that people with 'FMO3 issues' will have high levels of many sulfides and amines that may cause malodor, not just TMA. The Canadian lab is probably the finest of metabolomic lab testing.

Expected completion date of study : 10 months for part 1 ? 1 year for part 2 ?          

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By sysbodyodor

announcement, fecal body odor, metabolic malodor, metabolic/systemic malodor research, research

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