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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By sysbodyodor

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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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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2nd licensed Gene Therapy drug approved

The 2nd GENE THERAPY drug to be approved by the EU authorities has hit the market in Europe.
The first gene therapy drug, Glybera, was approved by the EU in 2014.
The new drug, Strimvelis, is for 'bubble boy disorder'.
Gene Therapy will likely be a cure for genetic systemic malodor disorders.

Gene Therapy is of interest to those with metabolic genetic malodor disorders because gene therapies will likely be 'cures' for genetic disorders. So if someone has a sub-par FMO3 enzyme that causes systemic body odor and/or halitosis, gene therapy could be considered the 'holy grail' cure.

Gene therapy has been suggested for about 30 years but a main obstacle was that it often involves viruses and these could cause a severe/fatal immune reaction. Also there may be some resistance from big pharmas as a one-treatment cure may mean loss of revenue. And investment costs and cost of treatment were seen as too costly (Glybera cost around $1.2 million per treatment.

But finally the obstacles seem to be clearing, and the technology has caught up.

FMO3 protein
Oxidizes/reduces many sulfides and  amine (and phosphates)
Gene produces a 532 amino acid code (and a stop at 533)

How would gene therapy be relevant to metabolic/systemic body odor/halitosis ?
My view is that most causes of systemic B.O/halitosis are probably to do with a sub-par FMO3 enzyme issue. In these cases gene therapy should make the FMO3 enzyme work normally. Gene therapy has taken 30 years to get to this stage but over the next 10 years could quickly become cures for genetic disorders.

How do Gene Therapies work ?
My impression is that they are usually manufactured viruses that are put in the target gene to make the gene work correctly. It will probably be to do with what type of fault you have in the gene. For FMO3, Most people have 'missense' faults, where an incorrect amino acid has been put in the 532 amino acid sequence. So this would probably require a 'missense' drug. Another severe type is a 'nonsense' fault, where the 532 long FMO3 code is told incorrectly to stop early on (a false stop). One drug, Ataluren, is being targeted to ignore this 'false stop' so in the case of FMO3 the 532 code will ignore the false stop. But 'nonsense' mutations are much rarer than missense and I presume a nonsense targetting drug would not help with a missense mutation.

Links to story on Strimvelis drug approval :
BBC news site
News18.com

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By sysbodyodor

fecal body odor, gene therapy, genetics, metabolic malodor, research

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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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Trimethylamine in humans : communicatory role ?

New paper on TMA in humans.
Seems to be a speculative paper looking at past papers to hypothesize that trimethylamine may have some sort of role in humans, possibly a communicatory role. Probably a negative role

Mitchell and Smith :
The paper is of special interest as the 2 authors have a long history in TMAU research, and could be called TMAU pioneers. Mitchell wrote a lot of early TMAU papers from the 1980's onwards, and Smith is a Professor (retired) who did research in the 90's. Neither of them has been involved in TMAU papers for maybe a decade.

Link : Trimethylamine-The Extracorporeal Envoy (jan 2016)

My interp of the paper :
There seems to be no new research done. They have looked at past papers and seem to imply there may be a communicatory role for TMA humans, probably a negative role I guess (i.e. implies ill health).

They make a point of saying how TMA is detectable to the human nose at very low levels (at least, as recorded in 1 or 2 anecdotal papers). Probably one of the volatiles with a lowest detectable odor.

Overall it is a mildly interesting hypothesis but seems speculative and I don't feel it added anything new that might help TMAU people at the moment.

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By sysbodyodor

research, TMAU research

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study : FMO's promote longevity and health span

New paper on the FMO group of enzymes by Uni of Washington researchers. They look at FMO's in nematodes, and the conclusion in this paper is that "FMOs are conserved in eukaryotes and induced by multiple life span-extending interventions in mice, which suggests that these enzymes may play a critical role in promoting health and longevity across phyla." 

Link to abstract (pubmed)

My own view on the abstract :
I only have access to the abstract. To me it seems to say that the FMO group of enzymes (FMO3 the most abundant in humans) may play some sort of positive health and longevity role in all animals. I presume this must be taken as a 1st paper on the connection and not a mainstream consensus.

Connection with Fecal Body Odor /  TMAU  / systemic body odor :
It's my own view that FMO3 may be the main suspect in human 'metabolic malodor' syndrome. So any resaearch on FMO enzymes and FMO3 in particular I think may be of use to those with metabolic malodor. FMO's tend to oxidize many common small sulfides and amines, so I suspect people with 'FMO3 metabolic malodor' will smell of these sulfides and amines.

What will happen because of this paper ?
I can see 3 possible outcomes :
1. nothing will happen
2. They may keep researching and do a few more papers that don't have much impact.
3. The research world is bowled over by the paper and they all throw money and research into it (to various degrees). Very unlikely I think.  

Things to remember about the paper
Done in nematodes, but they say could apply in humans
Might be a one-off paper with little impact (hopefully not)
Researchers have no history of an interest in TMAU etc.

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By sysbodyodor

FMO3 research, research

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First TMA-oxide therapy product soon

A TMA-oxide 'over the counter' therapy product will be available soon. Intended for the CVD market, there is a chance it may help 'IN THEORY' with TMAU too. We will need to wait and see.

In 2011 TMA-oxide was put forward by Hazen et al at the Cleveland Clinic as a possible main biomarker and cause of atherosclerosis. TMA-oxide in humans is the odorless final product of TMA metabolism in humans.

TMA > oxidized to TMAO

A main source of TMA in humans is from the breakdown of choline/lecithin
Choline/lecithin > TMA > TMAO

Cleveland HeartLab press release : link

Cincinatti newspaper link

Cleveland Clinic article : TMAO and gut

A press release was issued on 20 Aug by Cleveland Heartlab. They plan to start a TMAO test for the CVD market by December.

TMA-oxide therapy product (over-the-counter)
Of interest to the TMAU community is that they also have an agreement with Proctor & Gamble to release an over-the-counter product that will "help people manage their TMAO levels".

What is it ?
At this point they do not say. It could be anything from a choline > TMA enzyme blocker, to a branded chlorophyll product ? Since it's OTC, I would keep my expectations it will help with TMAU on the low side. P&G have many retail product brands such as Vicks, Metamucil, Pepto-bismal, which I consider not likely to have much affect, I think we should keep TMAU hopes on the low side. But who knows. It might even be something the TMAU community already are advised to use as a TMAU protocol, like chlorophyll.

But I am guessing work might be happening on a Choline > TMA enzyme blocker which would be good

My thoughts :
As I often say, I think most people with systemic BO have 'FMO3 BO', meaning they can smell of many sulfides and amines. I suspect TMA may be a 'small player' of a range of sulfides and amines, so even if this product reduced TMA, I am not sure it may help many of us. I hope I am wrong. It's great there is now so much interest around TMA/TMAO and FMO3 due to a proposed CVD connection (which I am not sure is correct yet). Hopefully more therapies to come, especially from Cleveland HeartLab.

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By sysbodyodor

Hazen TMAO research, research, TMAO Research, TMAO-CVD

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New TMA research to document TMA producing bacteria

New research attempting to list some/all trimethylamine producing bacteria in a mammal (mouse) for first time.

Research inspired by Dr Hazen's theory that TMAO may be a risk factor in cardiovascular disease.

Research paper abstract : 
Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide : link

Romano KA, Vivas EI, Amador-Noguez D, Rey FE

University of Wisconsin-Madison, Madison, Wisconsin, USA

I have mentioned before that the hypothesis by Dr Hazen et al at the Cleveland Clinic first proposed in 2011 would lead to a lot of research into trimethylamine metabolism, which in turn would be beneficial research for people with trimethylaminuria (TMAU). Up until the CVD hypothesis (still being debated), there was little to no interest in TMA metabolism or FMO3 enzyme. 

I have read only the abstract of the paper. It seems they are microbiologists who are aware of the TMAO-CVD hypothesis and aware that almost nothing (perhaps nothing at all) is known as to which bacteria in the gut break down choline to trimethylamine. 

The abstract does not say which bacteria break down choline to trimethylamine in the gut. It seems they tested 79 common gut types in a mouse. 

Interesting observation about choline in the paper :

The paper says " Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host.". This is a surprising observation. I would have thought the less tma-producing bacteria in the gut you have, the less choline that is available to the host.  I guess we will need to wait for more evidence on this observation   

My final comment :

It's great that the CVD-TMAO hypothesis of 2011 is leading to interest in TMA metabolism in humans. It's a coincidental bit of good fortune for people who feel they have TMAU only as it has lead to more research around the world into TMA metabolism and FMO3 enzyme (or even for those who feel FMO3 may be more to blame for their range of malodors, as I suspect). Really no research was ongoing into TMA metabolism or FMO3 before this hypothesis.

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By sysbodyodor

research, TMAO-CVD, TMAU research

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IGEM 2014 TMAU project : French Team neutralise trimethylamine with GM microbe.

Click to visit link

A group of French graduates based at Paris Descartes University genetically engineered a skin bacteria to make it rich in an enzyme (trimethylamine mono-oxygenase) that oxidizes (neutralizes) trimethylamine to TMA-oxide. The experiment was for an annual international genetic engineering contest for undergraduate teams (IGEM 2014) and was proven to work in a lab (i.e. the concept of proven 'in a test tube').

Link : Something Fishy (IGEM 2014)

The undergraduate team are based at
Centre for Research and Interdisciplinarity (CRI)

Faculty of Medicine Cochin Port-Royal,

South wing, 2nd floor
Paris Descartes University

The team seem to be called 'Paris Bettencourt' for the annual IGEM competition. Perhaps most of their funding is by the Bettencourt Foundation (Bettencourt being the founding family of L'oreal).

The experiment :

The experiment was to take an enzyme that oxidizes trimethylamine to TMA-O from a microbe and put the enzyme in a 'human-friendly' micro-organism. It was one of 4 projects they did in relation to body odor and how genetic engineering may help. In this project, they took a TMA oxidizing enzyme (trimethylamine mono-oxygenase) from a non-human bacteria (Ruegeria pomeroyi) and put it in  E.coli and Corynebacterium striatum, a skin-native bacterium.

Results :

It seems that they were able to put the TMA oxidizing enzyme into E Coli and the Corynebacterium striatum which is a skin-native bacterium 

They put the genetically modified TMM rich E Coli in a TMA liquid and it did oxidize much of the TMA to TMAO.

Possible applications :

They mention the possibility of a TMM-rich bacteria added to a spray or cream to put on the skin and eliminate TMA on the skin.

Presumably another possibility is to make a GM  skin-native bacteria rich in TMM enzyme that could be nurtured to live on humans (?)

Possibly an internal therapy answer could be formulated , such as a TMM rich probiotic.

Final comment :

The big question is whether these types of answers are only possible now or could have been found earlier but have not due to no interest in TMAU/FMO3 by the research community overall. It is also not known if the above project is being followed up on. 

The project says TMM is not just TMA specific, so perhaps it will work on other/all smelly substrates which may be the same as FMO3 substrates.

Desulfovibrio desulfuricans :

The project also seems to 'blame'  Desulfovibrio desulfuricans bacteria as the cause of degradation of choline to TMA. This is the first time I have heard of this connection. It is interesting because it has been a bacteria of suspicion and is mostly known for producing hydrogen sulfide (H2S) from sulfates. Many people with metabolic malodor and TMAU report of smelling of 'rotten egg' which H2S is one known possible source of this smell.           

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By sysbodyodor

experiment, FMO3 research, possible future therapy, research, TMAU research

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Rich investors needed for Trimethylaminuria research project

MEBO Research is in touch with a biotech start-up that is researching a therapy for genetic trimethyaminuria (TMAU) and 'overload' TMAU (secondary TMAU).

It is normal in the medical research sector and invention sector for companies to be very secretive about their projects (due to patent concerns etc), so very little can be said about the project at this stage. The only info that can be given is that the research is now at a stage where it needs £/$ millions, so realistically any investors would need to be very rich. As is normal with this type of arrangement, any rich investor could find our more about the project by signing a confidentiality agreement.

A press release was written by Karen of MEBO Research which can be seen on the MEBO blog. Below is an abridged version of the release :

Are there any affluent philanthropists or serious investors out there willing to back a promising therapy for Trimethylaminuria?

Wealthy individuals are sought for investment discussions with a trusted, UK-based, biotech company looking to raise capital for continued research into a very promising TMAU therapeutic. This treatment could potentially handle both primary and secondary versions of TMAU. It is also a great opportunity for investors to have a stake in a company actively looking at therapeutics for other disorders and diseases.

Confidentiality would be assured, and any interested parties would be invited to sign a confidentiality agreement before being shown data about the project.

Please e-mail MEBO ( maria.delatorre@meboresearch.org or karen.james@meboresearch.org ) who will put you into contact immediately with the relevant company.         

links :
Full press release on MEBO Research website
MEBO Research blog
MEBO Research website

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By sysbodyodor

announcement, FMO3 research, possible future therapy, research, TMAU research

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New Hazen paper : Fecal transplant mice get TMAO artherosclerosis

A recent theory suggests TMA-oxide may cause atherosclerosis. TMA-oxide is oxidized trimethylamine. Hence a therapy is likely to try and reduce or neutralize TMA levels produced in the gut

New paper from Dr Stan Hazen et al re TMA-oxide and CVD  :  Fecal transplants in mice

Dr Stan Hazen research has often been reported here as since around 2011 his lab has suggested a strong connection between TMA-oxide plasma levels in humans and risk of atherosclerosis (CVD). This research may have an added benefit to metabolic malodor sufferers who feel trimethylamine is the sole cause of their malodor, as any resulting therapy may mean neutralizing or blocking TMA production in the gut, thus the person will absorb no TMA into their bloodstream.

Fecal transplant in mice to give them atherosclerosis
In this paper they seemed to use 2 strains of lab mice and gave their fecal transplant microbes to a strain of mouse that was microbe free in the gut. One strain of mouse seems to have a high TMAO 'flora', whereas the other does not. It seems that the transfer of the feces from the high-TMAO producing mouse caused the donor mouse to develop CVD. So they seem to be saying risk of CVD is highly likely to be due to a TMA rich gut flora and when they transfered this flora to a mouse with no gut flora, the mouse then developed CVD.

This seems to be more evidence for the TMAO-CVD connection theory, though I guess it is still a theory to be given a consensus in the CVD research community.

The paper says at the end :
Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.

So they are suggesting that altering a TMA rich gut flora should reduce the chance of CVD, but also for the TMAU community it should mean reducing or negating or blocking TMA in the gut, possibly by altering the gut flora. This may lead to anti-TMA probiotics, for example. It is also very likely that research will be done to see which microbes generate TMA in the gut.    

     

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By sysbodyodor

fecal body odor, gut dysbiosis, Hazen TMAO research, metabolic malodor, possible future therapy, research, systemic body odor, systemic malodor syndrome, TMAO-CVD, TMAU research

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New TMAU paper : Archaea neutralise TMA in the gut

About : New paper that says that archaea microbes neutralise trimethylamine in the gut. In future perhaps 'archaeabiotic' treatment will help people with TMAU and perhaps do away with the need for diet control etc.

This is a paper about the possible role of archaea microbes in neutralising trimethylamine in the gut. Archaea are methane producing organisms common in many people guts but not all. In the microbe breath test, some people are shown to be methane producers as well as hydrogen producers, whereas some are just hydrogen producers. It seems that archaea produce this methane.

The paper says that perhaps in the future people with TMAU may be able to use an 'archaebiotic' to in effect 'neutralise' trimethylamine in the gut. This would be in practice a 'cure' for TMAU, but anyone with a FMO3 deficiency would still have that deficiency.

Full paper : Archaea and the human gut: New beginning of an old story Link to full paper

My view on this :
This is very good news. If something can neutralise TMA in the gut then there is no TMA going to the liver. It neutralises the TMA load. However the person still has an FMO3 deficiency if they are TMAU1. For those who feel they only smell of trimethylamine, it is in effect a working cure I guess. However FMO3 oxidizes many sulfides and amines in humans, and I believe that most people with an FMO3 issue smell of other sulfides and amines mostly, and it would not seem to be a cure for that. Not unless it also neutralises those volatiles too.

Overall though it is a very positive step and the 'archaeabiotic' would be a natural solution rather than taking a drug.  

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By sysbodyodor

gut dysbiosis, metabolic malodor, possible future therapy, research, TMAU research

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Female hormone estradiol shown to inhibit FMO3

Post about : Italian researchers proving that the main female sex hormone,  17β-Estradiol, does inhibit FMO3 levels 'in vitro' human DNA/RNA testing.

In 2007 a paper was published where adult females who menstruate who have a TMAU diagnosis were TMAU tested daily over 120 days to check their TMA/TMAO fluctuations. It found that some tend to have a much lower ability to oxidize TMA during menstruation.

Now a group of researchers in Italy have checked out the DNA/RNA capabilities of human FMO3 'in vivo' to see if a few steroid hormones did affect FMO3 levels. It seems they found that the main female sex hormone  17β-Estradiol did inhibit FMO3 production. Other hormones they tested did not seem to affect FMO3 production.

Quote :
Dexamethasone, 5α-dihydrotestosterone, thyroid hormone, and progesterone had no effect on the accumulation of Fmo3 mRNA. The use of increased concentration of theophylline inhibited estrogen receptor α (ERα)-mediated transcription of Fmo3 mRNA. 17β-Estradiol inhibited Fmo3 mRNA accumulation.

So it seems now the menstruation-FMO3 inhibition link has been 'explained'. I am not sure if this explanation will now be accepted by all or if it is just one possible explanation. Possibly since it is DNA research it will likely be accepted by all.

New Paper :

Regulation of flavin-containing mono-oxygenase (Fmo3) gene expression by steroids in mice and humans. : Pubmed Abstract link

2007 paper :
Transient trimethylaminuria related to menstruation : link to Full paper

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By sysbodyodor

FMO3 reference, FMO3 research, research, TMAU research

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Norwegian study about TMAO and heart failure

New paper by a group of Norwegian researchers
Study done on humans
Reinforces suggestion of connection between TMAO and Heart Diseasae
TMAO is oxidized trimethylamine
Will likely result in much more research into TMAO and trimethylamine
Might lead to a 'TMA-blocking' drug

A new research paper by a group of Norwegian researchers has reinforced the notion that trimethylamine-n-oxide may have a strong connecrion with heart disease. The researchers checked TMAO levels in patients with heart disease and healthy volunteers and assessed the outcomes. It seems they found a connection with TMAO and heart failure. One especially interesting thing about this study is that it a new group of researchers making the connection between TMAO and CVD, thus possibly reinforcing the connection the original research group made (Hazen et al) .

What does it mean for people with TMAU ?
It probably means there will be much funding and worldwide research into TMA/TMAO and possibly FMO3, and the aim will probably be to learn as much as possible about TMA/TMAO production in humans and FMO3 metabolism, and to produce cures such as a trimethylamine-formation blocking drug For anyone who thinks they have a malodor due to trimethylamine only, I guess it would mean a cure (no TMA would mean no smell ?)

My own opinion :
Personally my own current view is that I think most people with a metabolic malodor probably have 'FMO3 malodor', which means an odor from any FMO3 substrate produced in humans (including many sulfides and amines). So I am skeptical that preventing TMA production alone may be a 'cure' for 'FMO3 substrate malodor', but I hope I am wrong. They may also look at ways to alter the gut flora etc, as well as looking at FMO3 which up until this connection was neglected by research. So overall it's a very good thing for people with 'FMO3 malodors' and to anyone who thought they only had a malodor due to trimethylamine.

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By sysbodyodor

Body Odor, fecal body odor, FMO3 research, gut dysbiosis, halitosis, metabolic malodor, possible future therapy, research, systemic body odor, systemic malodor syndrome, TMAU research

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TMA-oxide and Colorectal cancer link ?

TMAO and CRC connection ?

This paper suggests a possible link between trimethylamine-n-oxide levels in the blood and colorecatal cancer.

Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study
Bae S et al, Cornell University NY

TMAU connection :
The main connection is that TMAO has now been hypothesized as being connected with Coronary Vascular Disease (CVD) and now for the first time also colorectal cancer (CRC). These being two major diseases, it is likely there will now be much research about trimethylamine production in humans and  how to stop/negate it. Obviously this would also benefit those with trimethylaminuria.

Main benefit :
It means now there will likely be much more research into TMA production in humans and a lot of money put into the research. So rather than TMAU/FMO3 research now being only associated with a 'rare'(?) disorder and little interest in research, now it is likely to get a lot of attention and TMAU will likely benefit from this research

My own opinion :
I think this is great news. However since most of us tend to smell of bowel smells (and other malodors), I personally suspect that someone with 'TMAU' actually has 'FMO3 substrate malodor' (FMO3 oxidizes 1,000s of sulfides and amnines of a particular structure) where any FMO3 substrate in large doses can make the person smell. So I am a bit pessimistic that something that stops TMA production will totally stop the malodors in someone with an FMO3 issue, HOWEVER I MAY BE WRONG.

Overall though, the fact the 2 major diseases are being hypothesized as being associated with TMAO (hopefully they aren't) means that a lot of money will now be put into research into TMA and how to stop/negate it etc.

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By sysbodyodor

fecal body odor, research, TMAU research

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