Systemic Body Odor Blog

TMAO Research, tmau

3 September 2017

September 03, 2017

Mice on high choline diet deficient in choline : Paper

This could be a very important paper for the following malodor problems :
TMAU (if you believe that TMA is the sole source of your malodor).
Possibly 'FMO3 malodors' (if you think many FMO3 substrates cause your smells).
Possibly (in theory), if low blood choline caused smells (this is an unknown).

2017 Paper :
Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption
Romano KA et al
Unis of Wisconsin and Harvard

link to paper : low blood choline in mice (2017)

in the news : link

Summary
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.

link to paper : low blood choline in mice (2017)

in the news : link

My interp
It seems they wanted to see how mice differed between groups that had 1:abundant bacteria that turn choline into TMA ... and 2: mice that had a cloned enzyme that blocked microbes changing choline into TMA.

The results were
The TMA-microbe rich mice had low choline blood levels even on a normal choline rich diet.
This is because the gut microbes COMPETE with the host for choline (and microbes get first go).
This caused significantly lower METHYL DONOR metabolite levels in blood and liver, as choline is one of our main methyl donors.
The low blood methyl/choline levels in blood seemed to cause behavioral problems (e.g. anxiety).

Choline
Seems to be one of our main METHYL DONORS (in the blood).
Is an important fat decongestant for the liver.
As we can make some, it was regarded a non-essential nutrient, but now it is accepted that we cannot make anywhere near the amount we need, so is in effect an essential nutrient.

Behavior problems
It's interesting they report the 'low choline blood' mice as having behavior issues such as anxiety, as many with TMAU report of anxiety.

My thoughts
I have thought this before, that low choline blood may be an issue for anyone with 'TMAU' who eats a high choline diet, or even worse for someone following a low choline diet.
As said, choline is important for the liver and as a methyl donor.

NAFLD
I do wonder if perhaps those with TMAU are prone to non-alcoholic fatty liver disease. Perhaps in general or in a particular way. Very speculative.
Many Drs feel that most westerners will have some fatty liver say over 40+, due to diet and lifestyle. But perhaps low choline could be an issue.

Appropriate tests :
1. I guess a liver ultrasound to see how the liver is. (mainstream test)
2. Choline blood test. This is not mainstream and seems very hard to find. It should be mainstream but it's not.

What can a TMAU person do to raise choline blood levels ?
It would seem impossible as the choline will be altered to TMA before it is absorbed.
One choline expert suggested phosphatidylcholine was less easy for microbes to alter, and may be worth a try (unlikely ??).
My own view is that testing for choline blood level would be the best option, so we could see if there was a 'syndrome' common to us.

TMAU low choline predicament (my theory)
2 scenarios
1. High choline diet (normal west diet) > TMA microbes eat the choline before they are absorbed > person has low blood choline.
2. Person goes on low choline diet > even lower in blood choline level.

They cloned an enzyme in the microbes that did not produce TMA
I note they mention they had an enzyme cloned and put into microbes that stopped production of TMA.
My guess is this approach would be an obvious therapy for TMAU.
Something we should certainly investigate.
My opinion : PROBIOTIC THERAPY with CLONED MICROBES that don't carry CHOLINE-TMA enzyme is one of our best hopes.

Could low choline blood levels cause the smells ?
I guess it's possible that LOW CHOLINE BLOOD levels could cause the smells for metabolic/systemic malodors to do with related enzymes (e.g. FMO3) , but for now it must be deemed an outside chance but definitely one worth following up.

My advice for now
Try and find a test supplier to do the choline blood test (possibly very difficult).
And perhaps a liver ultrasound to see if you have some fatty liver.

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Body Odor, fecal body odor, fmo3, FMO3 research, important, metabolic malodor, possible future therapy, systemic body odor, systemic malodor syndrome, TMAO Research, TMAU research, trimethylaminuria

20 April 2017

April 20, 2017

Finnish study : TMAO and gut flora

A new study to do with the TMAO - Heart Disease theory put forward by Hazen et al from Cleveland Clinic in 2011.
By A Finnish group, probably with help by the Cleveland Clinic team.

My context for the study :
Currently of limited interest to me.
Posted moreso that others can read it thorough if they wish.
I am skeptical about the microbes listed as being associated with TMA production.

The Study (in terms of TMAU interest) :
531 Finnish men had their gut flora DNA tested to 16S standard.
Presumably they had a connection with CVD.
Since TMAO will probably require therapies to lower TMA levels, it will very likely mean therapies for TMAU.

Since the theory is TMA-oxide is associated with CVD, they looked at microbes that may be associated with high TMAO levels.

The microbes they associate with TMA-oxide
Peptococcaceae
Prevotella
unknown Clostridales

Looking at my Ubiome results, which are 16s standard testing :
I had :
Peptococcacae : none.
Prevotella : about 0.18%.

Understanding of gut flora :
I view the knowledge of the gut flora as at the very early stages. A bit like before America discovered.

Final thoughts on the study :
I believe TMA is only a biomarker of FMO3 function, and a small player in the range of FMO3 volatiles someone with a FMO3 isssue may smell of.
So I am sceptical that a therapy that may only reduce TMA in humans will solve what I regard the most common type of systemic/metabolic body odor (FMO3 substrates body odor). BUT HOPEFULLY I AM WRONG.
But it may be that reducing TMA levels reduces the load greatly on FMO3 to levels where the enzyme can handle all smelly substrates.

Back to this study, it's great so much research is going into understanding TMA metabolism in humans, and for sure it will result in 'TMA therapies' as they are associating it with heart disease. So we can expect many more studies like this, and much greater understanding of TMA metabolism in humans.
Compare this to pre-2011, where we were lucky to get a TMA paper every 5 years.

Paper :
Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort : Link

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

5 September 2016

September 05, 2016

TMAO reduced by vit D + B vits

New TMAO paper.
In this they check the TMAO plasma levels of 27 people over a year giving Vit D to 1 group, and vit D + some B vits to another (?).
The conclusion seems to be that Vit D + B vits lowered plasma.
Personally I don't take much from the study.

Paper : Plasma TMAO and B vits + Vit D
research by German and Danish group

Why was this paper done :
Because of the Cleveland Clinic 2011 theory that TMAO may be a big causal factor in CVD. Since then, I guess atherosclerosis researchers worldwide have been testing if there's any connection between known proposed 'help' to avoid heart disease and TMAO levels. In this case they checked Vit D and some B vits. I have not heard of the labs before. It seems pretty random to me (small group etc) though they did test them for a year it seems.

Quote from paper :

"CONCLUSION:
B-vitamins plus vitamin D lowered plasma fasting TMAO compared with vitamin D. Vitamin D caused alterations in choline metabolism which may reflect the metabolic flexibility of C1-metabolism. The molecular mechanisms and health implications of these changes are currently unknown."

What's this to do with systemic body odor ?
TMAU is the only fairly well documented 'systemic body odor' disorder. So any research to do with TMA metabolism will be of interest.

My own view :
This won't change anything for me. I tend to find B vits a struggle. Don't know why. I think they are often methyls. Personally I think we need to look at testing rather than guessing with supplements. I will be taking the P&G TMA-blocker pill when it comes out. So I won't be taking vit B, D for 'TMAO plasma levels'.

My view on systemic body odor :
My own view is that perhaps most have an issue with FMO3 enzyme function, rather than just the volatile TMA alone. FMO3 enzyme alters many sulfide,amine and phospine containing volatiles. I think FMO's were intended to deal with poisons in plants.
So I am not much excited about 'TMA therapies' alone, but will still be trying them when they are avialable.

Acronyms :

CVD : cardiovascular disease

TMA : trimethylamine

TMAO : trimethylamine oxide

TMAU : trimethylaminuria

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TMAO Research, TMAO-CVD

3 September 2016

September 03, 2016

TMAO and Alzheimers ? (new paper)

New paper. Since 2011, Trimethylamine-n-oxide has been postulated by a Cleveland Clinic paper as having a connection with atherosclerosis (and so Heart Disease). Before this 2011 paper trimethylamine metabolism in humans was ignored. Since then it has been suggested as possibly having a role in many of the worst health problems in humans.

List of diseases postulated as having a possible connection with TMAO (so far, all since 2011) :
Diabetes.
Chronic kidney disease.
Atherosclerosis (e.g. heart disease, stroke)

And now, a paper postulates that TMAO may be associated with Alzheimers (Alz) :
Paper : TMAO and Alzheimer's
Xu R, Wang Q
Dpt of Epidemiology and Biostatistics, Institute of Computational Biology, School of Medicine, Case Western Reserve University, Cleveland
ThinTek LLC, Palo Alto

Context of the paper (my view) :

Seems to be a 'computational' look at microbiome stats to look for a connection between gut microbiome compounds (only) and Alz. The conclusion seems to be TMAO could be of interest as a biomarker.

I have not heard of the authors or labs.

It should be kept in mind that it seems pretty speculative (for now) and many of these types of papers are put out, often contradicting.

I'm not thinking it's correct or false or significant (yet).

Quote :
We identified common genetic pathways underlying AD biomarkers and its top one ranked metabolite trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. These coregulated pathways between TMAO-AD may provide insights into the mechanisms of how dietary meat and fat contribute to AD.

What's this to do with systemic body odor ?

Currently the only volatile tested for SBO is trimethylamine (TMA), and the only documented SBO is trimethylaminuria (TMAU). Until 2011 there was no interest in TMA metabolism in humans. Now since the CVD-TMAO theory (and other diseases), TMA metabolism is of great interest. This co-incidence is very good news for those who feel they have TMAU only (i.e. only smell of TMA), as it means great interest in TMA metabolism and will likely lead to 'therapies'. P&G already have a deal with Cleveland Heartlab to produce an over-the-counter 'TMAO-management supplement' (at a guess, a 'TMA-blocker pill'. It is not known when.

My own view :

Currently I suspect that FMO3 enzyme is the right enzyme highlighted as being the main 'SBO enzyme', but that the smells are not limited to TMA. So I am a bit cautious about hoping 'TMA cures' will mean 'SBO cures', but will be buying any TMA therapy by the crate.

I currently have no opinion the 'TMAO connection theory' to diseases, but grateful for all the attention/research to TMA metabolism.

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fecal body odor, metabolic malodor, metabolic/systemic malodor, TMAO Research

8 August 2016

August 08, 2016

1 Year since P&G TMA-blocker announcement

A year has passed since Procter and Gamble announced a deal with Cleveland Clinic to market an over-the-counter trimethylamine inhibitor drug.

Who is the tma-inhibitor for ?
The 'drug' is intended for the 'atherosclerosis' market, which is one of the main causes of diseases (e.g. heart disease). This is why we can be sure it will be created. In 2011 Hazen et al at Cleveland Clinic put forward a theory that trimethylamine-n-oxide may be a main factor in causing atherosclerosis. It's not known how currently accepted this theory is among atherosclerosis experts.

What's this to do with systemic body odor ?
Currently trimethylamine (TMA) is the only fairly well documented volatile identified as causing 'systemic/metabolic body odor'. This new pill will inhibit TMA formation in the gut from it's precursors (e.g. choline). If you think TMA is the only source of your SBO then this would be an ideal therapy. But I suspect those with FMO3 weakness may be vulnerable to all FMO3 substrates (mainly certain many sulfides and amines), so I am a bit concerned it may not be ideal, but we will see. It's a lucky break for TMAU people that TMAO has been suggested as a CVD cause, and the best way to block it is at the pre TMA stage. They mention they could have targeted the TMA - TMAO stage but this would have made CVD patients smell of fish. Lucky for us.

When will it be available ?
Studies can often take maybe 5 years. 1 year has gone. They have only done mice-work so far. No word of human trials. But since it is likely a natural product it may not have to go through rigorous safety trials. So it could be anytime really, but it could be 4+ years.

What else we know so far
It won't be 3,3 dimethyl butanol (DMB). In an interview Dr Hazen said this is too weak for a pill. But they likely have stronger alternatives, so that's not a bad thing.
It will be a natural product probably.
Probably still has to go through human trials but not as long as normal for a non-natural drug.
You won't need a prescription and can buy over the counter.

Look out for :
Any research papers or interviews by Hazen and/or Wang, or Cleveland Heartlab.

I am pretty sure once the pill is available the SBO community will quickly know. I'm hopeful it will be on the sooner side but we need to wait I guess. These sort of research products, you hear nothing until they make a press release or publish a paper, or perhaps elaborate in an interview.

Hopefulness rating (for TMAU) : 9/10

Links :
P&G press release : Aug 2015
Cleveland Clinic TMAO paper 2011

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DMB pill, Hazen TMAO research, TMAO Research, TMAO-CVD, TMAU research

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30 July 2016

July 30, 2016

Paper : firmicutes produce more TMA than bacteroides

New paper :
The aim seems to be to see how trimethylamine precursors (choline in foods etc) affect TMA-oxide levels in a group of healthy young men. The conclusion seems to be that those with a higher ratio of Firmicutes / Bacteroide gut bacteria generate more trimethylamine from precursors.

The paper was done with the 2011 Hazen et al TMA-oxide - Heart Disease theory in mind, which links TMA-oxide with blood vessel damage.

Research paper :
Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: a randomized controlled trial

Cornell University

Link

What's this to do with systemic body odor ?

My own current opinion is that most cases of systemic/metabolic body odor are probably to do with FMO3 enzyme and it's substrates. Most cases are probably an FMO3 weakness that means overload of FMO3 substrates at any time. The volatiles produced by gut bacteria are probably often FMO3 substrates. Currently the only volatile accepted as causing systemic/metabolic body odor is trimethylamine. With the interest in TMA-oxide since 2011, it's likely a TMA blocker will be a therapy.

My opinion :
My 2 main points are :

1. This seems to be a one-off research paper. From a lab with no previous history on TMA-oxide. Cornell is greatly respected but I don't know how significant or accepted the result will be.

2. I feel there is too little known about the gut flora overall. Both in knowledge and in testing. So for me I can take or leave the info. It may someday prove to be important, but for now I don't know.

My Ubiome stool DNA results :

Previously I wrote how my Ubiome Stool DNA result was lower than average in firmicutes. For now I wouldn't take this as my norm. As I say, I think not enough is known about the gut flora for me to think anything. So I won't be making any changes due to this result. I'm waiting for the Procter & Gamble TMA-blocker to come to market.

Summary :
It's too speculative for me to make any conclusions from this at the moment. I will keep a lookout though.

Other Links :
Cornell in-house article on TMAO (4Aug16)

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stool dna, TMAO Research, TMAO-CVD

10 July 2016

July 10, 2016

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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18 June 2016

June 18, 2016

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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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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2 May 2016

May 02, 2016

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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5 April 2016

April 05, 2016

TMAO Research China : Resveratrol inhibits trimethylamine

Chinese Research April 2016.
Resveratrol inhibits TMA-producing bacteria and helps friendly bacteria.
This in theory should help with trimethylaminuria (TMAU).
But be wary.

About :
A new research paper saying that resveratrol inhibited TMA-producing bacteria growth in mice gut (?). Since Hazen et al at Cleveland in 2011 put forward a theory that TMA-oxide may be a factor in atherosclerosis, researchers will now be looking at ways to stop TMA production in the human gut. This Chinese lab seems to be about how natural nutrients may play a role in human health. In this case they checked the effect of resveratrol on TMA and TMAO production in the gut.

Their conclusion :
Glancing at the abstract and news releases this is my first impression of what they say.
Resveratrol inhibits TMA producing bacteria.
Some say it favors bacteriodes over firmicutes.
They say it favors the lactobacillus and bifidus family (good species).

Links :
Resveratrol TMAO paper in news : Eureka Alert
Medical News Today
Abstract in mBIO medical journal
medicalresearch.com interview

My comment on this paper :

Resveratrol is a polyphenolic compound naturally found in peanuts, grapes, red wine, and some berries.
Linus Pauling Inst.

Papers come out all the time saying one thing then another contradicts is. So I wouldn't give this paper much weight at the moment. But it puts the spotlight on resveratrol as a possible use for TMAU therapy. They are probably looking at compounds high in the Mediterranean diet that might explain their supposed healthy heart role.

What has this to do with systemic body odor ?

Acronynms :
TMA - trimethylamine
TMAO - trimethylamine oxide
TMAU - trimethylaminuria
CVD - cardiovascular disease
SBO - systemic body odor

My own view is that FMO3 substrates may make up about 95% of cases of 'systemic/metabolic body odor'. However, at the moment only the substrate TMA is documented as being a 'systemic body odor' cause. So for SBO, everything currently revolves around TMA. Since 2011, a theory was put forward that TMA-oxide may cause CVD, which ironically was good news for those with TMAU as it will likely mean a therapy to reduce/inhibit TMA.

My final comment :
It's an interesting read but like I say it should be taken as 1 paper from a lab that focuses on natural nurtients for a living. I don't know if the TMAU community have been trying resveratrol already. I don't follow diet/supplement discussions closely. But I suppose resveratrol is another to talk about.

The best news is that there is probably 'TMA-inhibition' research going on around the world that we don't know of.

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TMAO Research, TMAO-CVD

19 March 2016

March 19, 2016

Hazen paper : TMAO CVD role found ?

Papers by Dr Hazen et al are of great interest to the Trimethylaminuria TMAU community as in 2011 the Hazen lab put forward the theory that TMA-oxide plays a role in CVD.

Since they are likely to look for way to reduce/block trimethylamine formation in the gut, this would have the dual purpose of also being a potential therapy for those with TMAU.

In this paper, they observed 4000 volunteers, so was a very big study.

Links :
Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk

Hazen et al, Cleveland Clinic (March 2016)

Pubmed abstract

Science Daily article

My impression of the paper
It seems to me the conclusion is that TMA-oxide damages the blood vessels and then cholestorol etc set in at the damaged point, causing a build-up. Something like that (?).

Effect of paper on Trimethylaminuria future
It's good news for those who feel TMA is the only volatile they smell of, as this means the infinite funding for this research will continue as it is for heart disease. Already they plan on some sort of 'TMAO management' supplement to be sold by Protcor & Gamble in the future (date unknown).

more Hazen papers this year
As the TMAO-CVD theory is about a serious illness, we can expect perhaps 2 or more papers by the Hazen lab this year.

My view on systemic/metabolic body odor
My own current view is that most with systemic body odor probably smell of the whole range of FMO3 substrates, which will be many sulfides and amines. Not just TMA. So while I am excited about the Hazen research, I am also wary that a 'therapy' for TMAU may not have the desired outcome for someone with 'FMO3 body door'. TMAU was 'documented' when researchers tested a patient solely for TMA in 1970. No other volatile has been tested for since.

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28 February 2016

February 28, 2016

New Hazen TMAO paper : LA - Cleveland

Another paper by Hazen et al re TMAO.
Seems to suggest TMAO shown to cause vascular inflammation.
All this CVD - TMAO research will likely help with therapies for TMAU

Yet another paper from the Hazen lab at Cleveland Heartlab re the proposed TMAO - CVD theory. This one was a joint paper with a LA Uni lab. They seem to suggest TMAO plays in role in inflammation of the vascular tissue. I think inflammation damage here is thought to be the main cause for CVD problems. Maybe this is the 1st paper to show the exact role TMAO plays in CVD, though I haven't been paying close attention to the CVD role.

Relevance to TMAU :
If someone thinks their sole source of malodor is TMA, then this research will be of great interest, because they will likely look for ways to stop TMA formation in the gut. Already there is talk of a DMB pill which interferes with TMA formation, but this could take months/years to come to the market.

Link
Hazen et al Cleveland-LA TMAO paper Feb 2016

My opinion :
It's a lucky break for systemic malodor people that this CVD-TMAO theory was proposed in 2011. Up until then no-one had interest in TMA metabolism in humans. My own view is that most cases of 'fecal body odor' are in fact caused by all FMO3 substrates and not just TMA, but
1: I might be wrong
2 : It will likely lead to more research into FMO3 anyway
3 : TMA reduction will reduce the FMO3 load

My current excitement at this research : maybe 4/10
But I will be stocking up on DMB when it is on sale.

Hazen lab seems to publish TMAO papers at a rate of maybe 10 a year now, so I expect more papers from them this year. Also other labs will likely start to increase papers too.

TMAO : Trimethylamine-n-oxide
TMA : Trimethylamine
DMB : 3,3-Dimethyl-1-butanol (wikipedia)
CVD : Cardiovascular Disease

Look out for :
Heart Disease stories in the news to do with Hazen, Cleveland, TMAO
DMB pill stories (none likely yet)
Procter & Gamble announcement about 'TMAO management' supplement (no sign yet. Could be months-years)

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27 February 2016

February 27, 2016

UK TMAO Study : Not Hazen

Another TMA-oxide study to do with Heart Failure.
It was a big study, tested many.
The authors not associated to Cleveland Clinic
Conclusion seems to be TMAO is related to HF outcome.

As trimethylamine is the only documented volatile to cause metabolic malodor, any research to do with TMA metabolism in humans is of interest to this blog. Regular readers will be aware of a TMA-oxide - Heart Disease theory first put forward by Hazen et al at Cleveland in 2011

Study : Suzuki et al : Leicester UK Feb 2016
Trimethylamine N-oxide and prognosis in acute heart failure

Link

This new study is of interest because :
It does not involve the Hazen group or the Cleveland Clinic. It is a Hospital research unit in Leicester UK.
It was quite a big study (972 samples).
It seems to suggest there may be a connection between TMAO and Heart Failure, thus sort of endorsing the Hazen et al theory.
It's the biggest study I have seen to endorse this theory, outside of the Hazen et al group

elevated levels were associated with poor prognosis at 1 year and combination of TMAO and NT-proBNP provided additional prognostic information. TMAO was a univariate predictor of death and death/HF, and remained an independent predictor until adjusted for renal confounders.

What is this to do with systemic malodor ?
TMAU is the only metabolic/systemic malodor 'disorder' documented for now. I suspect for most people with metabolic malodor they have guessed the right enzyme (FMO3) but that they can smell of FMO3 substrates, not just TMA. But any research to do with TMA metabolism or FMO3 is helpful. As it is now being associated with Heart Disease, a lot of funding will go in to researching this.

My comment :
I am still open-minded whether there is a connection with TMAO and CVD, chronic kidney disease, diabetes etc. although this is the 2nd paper I have seen suggesting there may be a link. Perhaps it's more to do with TMAO being a signature biomarker of gut dysbiosis in general. But I am glad TMA is suddenly getting all this funding and research. After years of no interest, suddenly $millions is going into research TMA metabolism.

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25 February 2016

February 25, 2016

DMB food products for TMAU : bad ?

Future 'DMB pill' is exciting development for TMAU
But I am not keen on takings foods with DMB in them
Foods rich in DMB probably are high in choline and other FMO3 sulfides/amines

It seems likely that Cleveland Heartlab and Proctor & Gamble have agreed to make and sell a 'DMB pill' as a protective heart disease supplement. It's unknown when this will be available. This is being sold as a 'TMAO management' supplement. It will likely reduce TMA levels in the human gut, which is great news for those who feel TMA is the sole source of their systemic malodor.

DMB is an alcohol naturally present in certain types of foods, such as 'extra virgin olive oil' and 'balsamic vinegar'. I have a feeling these foods will be bad for people with FMO3 issues.

Reasons :
1 : They are probably high in choline ? If you think TMA is the only source of your odor, then I presume taking high choline foods may be contra-indicative.

2 : They are probably full of FMO3 substrates (sulfides and amines) which might also cause malodor or feed malodor causing bacteria.

3 : Other vague reasons such as concern about acidity.

I tend to find I have a natural aversion to these type of foods, which I suspect is due to them being full of FMO3 sulfide/amines and maybe feeding bacteria that produce sulfide/amines. I had a go with the balsamic vinegar but after a week or 2 started getting migraines.

DMB pill :
Presumably the DMB pill will not have choline or the other FMO3 sulfides/amines, so I will certainly be trying that when it arrives.

FMO3 malodor :
As I always say, I do not think those with FMO3 issues have a problem solely with TMA, so I am always sceptical about something that may help only with TMA.

Links :
P&G announce TMAO management deal Aug 2015
Buffalo news : A DMB pill ?

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7 comments

19 February 2016

February 19, 2016

Cleveland : new TMAO and gut microbiota paper

A new paper by the Cleveland Clinic to do with Heart Failure and TMAO.
Posted here as any research on TMA-oxide may have a benefit for TMAU.
Abstract implies they are researching the human gut microbiome, probably mostly to learn more about trimethylamine metabolism in humans.

link pubmed abstract

My perception of the paper from reading the abstract :
Looks like another paper by the Cleveland Clinic Heartlab. Tang is usually involved in these papers. This one looks to be perhaps an overview of what is known about the human gut microbiome and what they know of trimethylamine formation in the gut (not much, it seems to me). I'm guessing it's a sort of 'starting paper' for as they go on to research more on the microbiome. Interesting to see them use the term 'dysbiosis', which is a term I often use. This seems to be the 'DNA' exploration side of their 'TMAO - CVD' theory. In this case probably exploring the gut microbe DNA, rather than human DNA such as FMO3. Should be relevant for TMAU as well.

My view :
It's good to see this lab producing so many papers on the subject. It will likely help us understand TMA metabolism in humans, which should help with TMAU. As many will know, they already have a TMA formation interfering compound in the pipeline ... DMB.

What is this to do with systemic body odor / halitosis ?
Personally I think most who complain of 'fecal body odor' actually have 'FMO3 substrate body odor', with TMA being only one substrate. For that reason I am not overly excited about this reasearch if it only stops TMA. But at the same time it may turn out to greatly help with 'FMO3 body odor' or it is a start to understanding FMO3 and gut dysbiosis, or I might even be wrong and TMA is solely to blame for 'fecal body odor'.

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17 February 2016

February 17, 2016

new TMAO blood test at Cleveland Heartlab

Since December, Cleveland Clinic has started it's TMA-oxide blood test via the Cleveland Heartlab. As regular readers will know, since 2011 Dr Hazen et al at the Heartlab have suggested that TMA-oxide may be an important factor in causing heart disease. This is what is leading them to look for ways to reduce trimethylamine levels in the gut.

Link : Cleveland Heartlab TMAO test

What has this to do with systemic body odor ?
Trimethylaminuria (TMAU) is currently the only documented type of 'benign' systemic body odor. Since the probable therapy to reduce tma-oxide levels in the human gut will be to reduce TMA levels, then those who feel TMA is their only source of malodor are likely to benefit from any 'TMA reducing' therapy that is created for heart disease. At the moment it looks like DMB will be sold by Procter & Gamble sometime in the future as it has been shown to reduce TMA levels in mice.

My own view :
I think most people with systemic body odor smell of any FMO3 substrates that happen to be too high in their body at any time. This means many small sulfides and amines that are created in humans, particularly in the gut. So whilst I am very interested in a 'TMA reducing' therapy, I do worry that TMA may not be the only compound that causes malodor in 'FMO3 maldoor syndrome'. But the eventual release of the DMB compound for sale is something to look forward to.

DMB : 3,3-Dimethyl-1-butanol
Wikipedia

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13 February 2016

February 13, 2016

new paper : Meldonium and TMAU ?

New paper on how drug meldonium might help with CVD.
The question is does it stop trimethylamine formation ?
This new paper is probably due to all the interest in TMA-oxide and CVD

This is a new one-off paper by Latvian researchers : Feb 2016
Pharmacological effects of meldonium: Biochemical mechanisms and biomarkers of cardiometabolic activity.

Link : meldonium TMAO abstract
Quote from paper : Here, we briefly reviewed the pharmacological effects and mechanisms of meldoniumin treatment of heart failure, myocardial infarction, arrhythmia, atherosclerosis and diabetes.

Note : I only have access to the abstract, not the full paper

What has this to do with TMAU ?
It looks like meldonium somehow interferes with TMA-oxide formation. I don't know if this means it also blocks trimethylamine formation. If it did, then I guess it would be similar to the hoped the Cleveland Clinic have for the natural compound DMB.

My current opinion :
I guess it's worth checking up further but I'm not overly interested. Partly because I suspect people with 'FMO3 body/breath malodor' probably have issues with many sulfides and amines, not just TMA. Plus with DMB hopefully being available sometime in the future and being OTC, I'm hoping this will do the same job.

wikipedia : meldonium

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26 January 2016

January 26, 2016

TMA blocker : ohio.com article Dec 2015

media article on TMA-oxide reduction
ohio.com, December 2015

About Dr Hazen et al announcement in Dec 2015 that DMB seems to reduce TMA-oxide in mice
Link

Quote from the article :

The most recent discovery builds on the research team’s initial 2011 revelation that a biomarker called TMAO could predict heart disease independent of cholesterol levels and other risk factors. TMAO can also ferret out the disease in those whose heart disease might otherwise go undetected.

TMAO is produced during the digestion of choline, lecithin and carnitine, nutrients that are abundant in animal products, including red meat, egg yolks and high-fat dairy products.

People with chronic high levels of TMAO have double the risk of heart attack, stroke and death.

During an interview this week, Hazen said his team started searching for an inhibitor, a substance that could prevent TMAO from forming and, thus, perhaps stop heart disease.

In the beginning, they engineered a compound in a lab that worked to reduce TMAO production by gut microbes. But the synthetic compound was essentially what chemists refer to as a “small alcohol,” and they wondered if it might exist as a natural product.

“We literally put together take-home gift bags of vials and labels for the staff,” Hazen said. “We asked them to take samples of every alcohol in their pantry … vinegars, oils, distilled products.”

Researchers screened thousands of the samples. They found what they were looking for — DMB, a chemical which looks like the nutrient choline, but interferes with the production of TMAO — in some cold-pressed extra-virgin olive and grape seed oils.

So what does this mean for consumers?

Not much, yet.

The research team has only tested the TMAO inhibitor DMB on mice, so far. But the mice treated with DMB were fed the equivalent of a diet rich in red meat and fatty dairy and developed less atherosclerosis.

Hazen hopes doctors can someday use DMB to control TMAO much like doctors uses statins now to inhibit cholesterol.

my own comments on the article :

If you think trimethylamine is the sole compound that causes your malodor, then this would seem like a therapy that in practice may be a cure. It's a question of waiting for the product being ready to buy (can't say how long that is. Could be a year - 5 years, hopefully the sooner)

Personally I think people with an FMO3 enzyme issue may have malodors from any FMO substrates in humans, which are small sulfides and amine. So I am not sure something that just deals with TMA alone will be enough. But hopefully I'm wrong.

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19 January 2016

January 19, 2016

1st mention of DMB pill to block TMA

Dr. Mike Roizen, is chief wellness officer and chairman of the Wellness Institute at the Cleveland Clinic and co-writes a regular health column for the Buffalo News. In the latest column he mentions a 'DMB pill' to block TMA formation in the gut from choline.

We know that the Cleveland Clinic Heart Lab has signed a deal with Proctor & Gamble to issue an OTC product for 'TMAO management'. Until this article we had to guess it would be a 'DMB pill', but this seems the first public mention by anyone close to the researchers that this would be the case.

They also give some guidelines as to how you can get DMB naturally in your diet.

Link : Buffalo News Article

Link : Research paper Dec 2015 : DMB hinders Choline to TMA process

Link : P&G announce 'tmao management' deal : Aug 2015

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