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

 

Get new posts by email

Read More

By sysbodyodor

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

4 comments

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.

 Get new posts by email

Read More

By sysbodyodor

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

No comments

Young Mom TMAU Youtuber

This young American mom has started a youtube channel about TMAU.
Looks like she plans to update the channel quite regular.

Note : This video is an embed from source.

If video is deleted it will auto delete here too.

As TMAU is so taboo, quite often people delete videos in hindsight.

Visit her channel here : click link 

Get new posts by email

Read More

By sysbodyodor

Body Odor, community, media, personal stories, personal treatment, systemic body odor, systemic malodor syndrome, tmau, TMAU personal stories videos, video, videos, youtube

3 comments

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.

---

Get new posts by email

---

Read More

By sysbodyodor

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

No comments

2nd batch ubiome results : fecal body odor

This is my 2nd batch of my Ubiome microbiome dna results.
I don't see anything that may be a biomarker for 'fecal body odor'.
But I don't know how to interpret the results.
And also the technology and understanding of the microbiome is at an early stage.
I still think microbiome testing is worthwhile (as it's so cheap)

2nd batch of Ubiome results :
I tested before in 2014. This new batch of 3 was part of their Xmas offer '3 for price of 1'. I have only briefly looked at the results.

Note :
These are just 4 examples of the data given in Ubiome results.

Fecal Body Odor / FMO3 malodor
I reckon FBO is caused by FMO3 substrates, so I tend to look out for anything to do with FMO3 substrates in the results.

FBO and dysbiosis :
I think gut dysbiosis goes naturally with 'Fecal Body Odor' (a syndrome). My question is  :
Do people with FBO have a particular gut dysbiosis ? or
Do those with FBO have general gut dysbiosis ?
This is where I think microbiome testing will be very useful, but perhaps the understanding is at too early a stage.

My interp of my results :
I can't make much of it.

Of initial interest is :
Secondary metabolite biosynthesis.
Flavone and flavonol biosynthesis 0.7X
Flavonoid biosynthesis

I mention these 2 as they were low and the word 'flavone' is maybe associated with Vitamin B2 and/or flavin enzymes ? Maybe not.

Closing remarks :

Next time I might try using 'American Gut' purely as they are a different lab.

I suggest doing these tests even though they currently may not give us any relevant info, mainly as they are the right way to go and they are cheap.

Sometimes Ubiome do special offers 3 for 1 etc.

What do I think causes 'Fecal Body Odor' :
I think the smells are probably mostly sulfides, and some amines, of a certain structure (soft nucloephilic) that are probably naturally oxidized mainly by FMO3 enzyme.
My theory is :
The person will have a weakness of some % of the FMO3 enzyme
They will tend to a certain or common gut dysbiosis, exacerbating the problem due to overload.

---

Get new posts by email

---

Read More

By sysbodyodor

Body Odor, fecal body odor, fmo3, gut dysbiosis, metabolic malodor, my results, stool dna

No comments

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

---

Get new posts by email

---

Read More

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

No comments

TMAU Youtubers

Recently there has been an increase in 'TMAU Youtubers', which all sufferers are grateful for as it raises awareness and brings comfort. Metabolic Malodor is a very 'taboo' subject, which is why it is so unknown. TMAU is the only test on offer for the concept of  'metabolic malodor', so many who feel they have a metabolic malodor disorder identify with TMAU. My own belief is that most cases may be more to do with all 'FMO3 substrates' (many sulfides and amines) rather than just trimethylamine, but TMAU is the only test on offer currently.

This is a new TMAU Youtuber. This is an embed of their video. If they delete their videos it will auto-delete here too. You can subscribe to her channel for updates.

---

Get new posts by email

---

Read More

By sysbodyodor

Body Odor, media, metabolic malodor, personal stories, raising awareness, systemic body odor, systemic malodor syndrome, TMAU personal stories videos, video, youtube

No comments

New FMO3 paper by Shimizu et al (2015)

New paper by FMO3/TMAU researcher Prof. Shimizu in Japan, and others with a similar research background.

102 people who presumably contacted the lab about a malodor concern were DNA tested for FMO3 faults.
Using their own subjective reference ranges (no consensus on a ref range currently exists), 79 were decreed to have TMAU

The paper seems to be a simple testing of 102 people with a self-reported malodor concern in Japan. Such papers are useful as statistics, and sadly pretty rare. I would say no collection of data on the subject is a tragedy for the community in that the lack of data keeps it regarded as a 'rare' condition.

Of those tested, 79 were 'positive' for TMAU, which hiostorically is quite a high number in such studies. Using my own guess at a reference range, I would expect it to be even higher if not all 102.

Full paper (2015) : TMAU in a Japanese population

The paper wishes to point out the following as important for context :

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Trimethylaminuria results from reduced capacity to convert trimethylamine to trimethylamine N-oxide, a reaction catalyzed by FMO3.
Mutations of FMO3 are known to cause trimethylaminuria, but an understanding of the phenotypic consequences of different FMO3 genotypes (haplotypes) is lacking.

WHAT THIS STUDY ADDS
Severe trimethylaminuria is caused by mutations that severely impair FMO3 activity.
Most affected individuals present with moderate or mild forms of the disorder, due to factors other than FMO3 genotype.
Although for the majority of sufferers sequencing of FMO3 would not be informative, reduction of trimethylamine burden should prove beneficial.

***************

Personally I would strongly disagree with the last point in particular very strongly. Anyone who thinks they may have a metabolic malodor problem should do the FMO3 DNA test. FMO3 and TMAU are not 'intensly researched' subjects where everything is understood about them. To me very little is known about TMAU and FMO3, so as much data is needed as possible, especially test results. Also I believe the reference ranges are set too conservative, looking at it the opposite way from someone who thinks they have a malodor problem. If someone feels they have a metabolic malodor problem and have say a few SNP's that are currently regarded as 'harmless', then personally I think the person is right.  

So I am grateful for such papers, and in this one the number deemed positive for TMAU was relatively high, but I personally feel the reference ranges are still too conservative and so many will get 'false negatives'.
       

---

Get new posts by email

---

Read More

By sysbodyodor

Body Odor, fmo3, FMO3 reference, FMO3 research, tmau

No comments

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.

Read More

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

No comments

Systemic Body Odor article

This is a 2011 article I have written about 'systemic body odor', in particular the type commonly known as 'fecal body odor', which I believe to most likely be caused by FMO3 deficiency/overload, and/or another another oxidizing enzyme.

In this age of modern medicine, most individuals would assume that all ‘obvious’ health problems have been characterized and diagnosis and treatment regimens developed. However, it may be a surprise to some pediatricians that perhaps at least one ‘obvious’ health problem remains right under their noses and underappreciated: systemic body odor, including a form wherein individuals can smell of a broad spectrum of bowel-related odors, including fecal- and gas-like smells. Before the internet, most sufferers thought they were the only ones with such strange body odor, but with the maturing of the internet and development of online communities, it is clear that systemic body odor could be a far more common problem than first thought. The typical pattern is despite good hygiene the odor persists because it is being produced internally. Typical cases seem to start at a young age, especially around puberty and the mid teens. Most cases are probably ‘transient’; making presentation of the symptoms to a doctor difficult. Many cases also are almost undetectable to the person and to their family, perhaps due to desensitization, which makes monitoring the condition extremely difficult. A wide range of ‘bowel’ smells have been described (generally based on social accusations), including fecal, gas, rotten eggs, sewage, garbage, rotten fish, or burning rubber.

The first obvious cause would be genetic. However there seems to be a size-able number of individuals who develop the problem in their 20’s, 30’s, or even older; suggesting there may be an environmental factor involved. Individuals also may exhibit adverse reactions to certain medications and herbs, perhaps indicating an issue with one or more of the drug-metabolizing enzymes.

Although it may seem a trivial disorder when compared to other metabolic disorders, the psychological impact cannot be underestimated. Individuals suffering from this problem end up are ostracized from society, exacerbated by the fact they cannot detect the problem themselves and so cannot monitor their condition. Suicide rates likely are very high due to depression and anxieity. Some have expressed an opinion that the problem arises in the form of halitosis rather than body odor. However, because most sufferers cannot detect the odor themselves, it may be hard for them to know what their own odor problem actually is.

Currently, the only generally accepted form of ‘systemic body odor’ is trimethylaminuria, which was first diagnosed around 1970, although the condition was actually described in the Indian epic,

, and in Shakespeare’s

. The genetic form of TMAU is due to deficiencies in flavin-containing monooxygenase 3 (FMO3), an enzyme which can oxidize a wide range of substrates, including nitrogen, sulfur containing compounds. Trimethylamine in humans is thought to come mainly from bacterial degradation of dietary choline and the breakdown of trimethylamine N-oxide from seafoods (not freshwater fish). Despite being known for over 40 years, a minimal amount of research has been devoted to the disease, and it is not covered by the disability act, leading to individuals being caught between humiliation at work or destitution.

One major question is whether TMAU completely explains the majority of cases of ‘benign’ systemic body odor, given that very few complain of being told they smell of fish. Most are told they smell of feces, gas, bowel smells etc. Although many sufferers are proven to have TMAU based on a positive phenotype test result, there does seem to be anomalies, with quite a few such individuals subsequently being ‘negative’ for the genotype test. One theory is that it may in fact be mostly ‘body odor due to FMO3 deficiency’, with gut dysbiosis also playing a role in pushing the person over their saturation point. However, previously undescribed FMO3 mutations also may contribute. Perhaps ‘fish odor’ is a baseline marker. Another question unanswered is how common is TMAU? Carriers have been estimated to be present in the British population at 1% frequency, but in areas of Australia, Ecuador, and New Guinea, carrier frequencies as high as 3 to 11% have been reported. Another question is why parents cannot usually smell their child who suffers from this disorder? One theory is that perhaps ‘carriers’ are desensitized to the smell. (If you think of anyone with any type of body odor or halitosis, the question is, why doesn’t a loved one tell them?) Also, most TMAU positive cases are ‘mild’.Given that the gut flora may slowly change with age, there also may be the chance of such changes increasing risk for the disorder. To complicate matters further, FMO3 is not easily inhibited or increased, unlike many other drug metabolizing enzymes. However, indoles have been shown to inhibit the enzyme.Some females also exhibit TMAU symptoms at the onset of menstruation. Finally, sufferers often report that ‘strong emotions’ can instantly induce their odor problem, perhaps due to increased sweating.

Another issue is the number of labs clinically testing for TMAU and no standardized range that is clearly linked to the disease. As such, each lab sets their own range. Currently there are only 3 known clinical TMAU phenotype testers known in the USA: in Arkansas, Denver and San Diego. One lab only tests for TMA and not TMAO and it is not possible to gauge FMO3 function via TMA levels alone.  

Another published form of systemic body odor is dimethylglycinuria, from a 1999 case. However no other cases have been reported, despite occasionally being clinically tested for. Possibly there is a need for a broad range of malodorous human VOCs to be tested for in cases of systemic body odor that would provide clues to other causes. Another possibility for systemic body odors is that the person is a carrier of a very serious metabolic disorder already known to cause a smell, such as isovaleric acidemia. At the moment they are regarded as being ‘asymptomatic’, however perhaps a transient odor problem is possible. In most cases on the forums though, the main form seems to be what they call ‘fecal body odor’, which would seem to indicate the drug-metabolizing enzymes in particular, given the wide range of smells involved. The problem of systemic body odor needs urgent attention, to stop people living meaningless lives.

Some ideas for research have been the founding of a body odor and halitosis research center and clinic, which could include all forms of these conditions including apocrine body odor. There are already a few ‘taste & Smell’ clinics in the USA, but not for odor conditions. Other ideas are handheld or wrist ‘odor’ sensors to monitor the condition, special diets, future treatments for whatever enzyme is responsible, add TMAU to the newborn screening program, add TMAU testing to the pediatric unit, etc etc.

At this stage, discovering all the forms of systemic body odor is a priority, so that treatment and reseach can follow. Thank you for reading.

General Reference links on TMAU :
Gene Reviews TMAU article
Genetics Home Reference TMAU article  Gene Reviews TMAU article  
Trimethylaminuria: The Fish Malodor Syndrome
Eugène M. Trimethylaminuria; Orphanet encyclopedia, August 2002
2006 paper : Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children
Trimethylaminuria and a human FMO3 mutation database
Dr Eileen Treacy overview of TMAU for OMMBID
Sheffield Children’s Hospital TMAU phenotype testing overview and procedure (pdf document)
1991 paper : The identification of trimethylamine excess in man: quantitative analysis and biochemical origins

Interesting TMAU case studies :
2006 case study : trimethylaminuria in an adolescent
2007 paper : Human breath odors and their use in diagnosis
1970 case study : First reported case of TMAU
2003 paper : TMAU related to the choline concentration of infant formula

FMO3 Reference:
2005 paper : Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism
2006 paper : Mutation, polymorphism and perspectives for the future of human flavin-containing monooxygenase 3
2008 paper :  Flavin mono-oxygenase (FMO)--the 'other' oxidase

Links alluding to commonality of those at risk of TMAU due to FMO3 enzyme deficiency:
2008 dissertation case study : 8/12 positive for TMAU phenotype test did not show any mutants in DNA test  
2007 case study : Transient trimethylaminuria related to menstruation
1999 paper : Mild trimethylaminuria caused by common variants in FMO3 gene
1999 Dr SC Mitchell letter to lancet : Trimethylaminuria: susceptibility of heterozygotes
2001 paper : In vivo variability of TMA oxidation is partially mediated by polymorphisms of the FMO3 gene
2000 paper : Biochemical and molecular studies in mild flavin monooxygenase 3 deficiency
1996 case study : 3.8% of 421 random volunteers are <90% in TMAU urine test
1997 case study : 11 of 100 random New Guineans are <80% in TMAU urine test
2000 : A Kashyap and S. Kashyap letter to lancet

Other possible issues with FMO3 deficiency
2000 paper : Population-Specific Polymorphisms of the HumanFMO3 Gene: Significance for Detoxication
1997 case report : TMAU associated with seizures and behavioural disturbance
2007 paper : Genetic polymorphisms of human flavin-containing monooxygenase 3
2002 paper : Human flavin-containing monooxygenase (form 3): polymorphisms and variations in chemical metabolism

Possible Fecal Body Odor cases ?
1973 case report : possible FBO case. Systemic cause not regarded
1997 : neonate with a pungent odor

---

Read More

By sysbodyodor

Body Odor, fecal body odor

5 comments