FMO3 survey to understand patterns in community

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

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

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

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

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

Link for the survey (e.g. to share) https://tinyurl.com/y7kyxzpc



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

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

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By sysbodyodor

fecal body odor, fmo3, systemic body odor, systemic malodor syndrome

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the 'big 3' FMO3 variants : a cheap way to test

There are 3 common variants for FMO3, that perhaps most 'FMO3 smell people' carry. The easiest and cheapest way to find out is to do the 23andme.com test, or an ancestry test that lets you download the raw data.

FMO3 is a 532 amino acid sequence, and 23andme only test about 50 of the 532, but it does test the 3 main variants at codons 158, 257, 308.
It would be interesting to see if most of carry 2 or more of these.

Estimates of carriers of the 3 main variants :
E158K : 40% people ?
E308G : 20% ?
V257M : 10% ?

DIY STUDY
We should be aiming to flood PUBMED with papers about TMAU, SysBO/Hali etc.
PUBMED is where researchers look to see whats going on.

But for now, as beggars, we can try a DIY STUDY.

Question 
Do you carry E158K, V257M and/or E308G ?

Feel free to put your result in the COMMENT SECTION.
Anon if you want ?
e.g.
E158K : AG
V257M : AA
E308G : AG

HOW CAN I TEST FOR THIS ?
A cheap and easy way to test for the 3 most common FMO3 variants is :

1. Find and buy an ancestry test that lets you download the RAW DATA ...
or buy 23andme.com test.

2. Look for these 3 variants :

rs2266782

variant known as E158K

normal : GG

variant : A

rs1736557

variant known as V257M

normal : GG

variant : A

rs2266780

variant known as E308G

normal : AA

variant : G

FMO3 PROTEIN is a 532 amino acid sequence, but there are 3 most common variants. E158K V257M E308G . Many people carry these faults (Whites carry maximum for the 3 : 45%, 25% 10% ...  estimate from memory). No-one is bothered much to find out if they are 'pathogenic' or not, but it would be interesting to see if those who identify with metabolic malodor tend to carry them in a mix.

My own current view :
I suspect most cases of 'metabolic/systemic body odor' are due to weakness in the FMO3 enzyme, but there may be other enzyme disorders too.

COMMENT SECTION
Feel free to put your result in the comment section. Anon if you want.

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By sysbodyodor

fecal body odor, fmo3, genetics, important, systemic body odor, TMAU research

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Wevers & New Halitosis disorder : DMS and CH3SH

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

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

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

First impressions of this new paper/discovery :

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

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

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

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

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

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

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



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

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

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

Them :
compounds : DMS and CH3SH.
enzyme : SELENBP1

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

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

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

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

Dr Wevers webpage

 

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By sysbodyodor

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

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Could low Choline cause the smells ?

Spec thought :
Could LOW PLASMA CHOLINE cause the smells associated with FMO3 enzyme ?

For now it's a spurious idea, but I wonder if the smells associated with FMO3 enzyme weakness/overload might be caused by a LOW PLASMA CHOLINE level.
Probably not, but something to think about.

How could the person have low plasma choline ?
The gut bacteria break down the choline in the gut before it can be absorbed into the bloodstream.

Some things choline plays a role in :
Seems to play a role in brain function.
Deficiency seems to be associated with Fatty Liver.
It seems it is a main part of the mucus in the colon that protects the gut.   

Is any test lab bothered about Choline ?
It seems not.
So far, no lab testing choline plasma level can be found.
The health-system ignores choline testing.

So for now, this is a very speculative idea.
But a guess would be that even if not connected to smelling, 'TMAU' cases may be naturally prone to a choline plasma deficiency.

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By sysbodyodor

metabolic/systemic malodor, systemic body odor, systemic malodor syndrome

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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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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

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TMAU : Choline status should be tested

Campaign.
TMAU test protocol.
Add CHOLINE status as part of a 'TMAU profile screen'. 
Who to campaign to : National Health Systems.
My hope of success : currently about 5% ?

Currently those who think they have TMAU (trimethylaminuria) do the TMAU clinical test (the urine test). This tests levels of trimethylamine and it's oxide (TMAO).

It is known that choline is closely associated with TMAU. The theory is choline gets changed to TMA in the gut. This makes me wonder if TMAU people may often have a natural blood choline deficiency despite taking choline.

Choline currently seems to have a quasi status as an essential nutrient, Probably in time it will be regarded essential. It seems to be a good emulsifier of fats in the liver. This makes me wonder if TMAU people may be naturally prone to non-alcoholic fatty liver.

Many 'normal' people have NAFL, but it would be interesting to see what the % was in TMAU people. Maybe it will turn out low choline plasma is a cause.

Targeted TMAU profiles tests :
So my first 3 tests for a TMAU profile test would be :
TMAU urine test (I would do DNA test as well).
Choline plasma test.
Liver ultrascan (to look for NA- fatty liver)

---

Other speculative tests I can think of  (quickly written) :

Very speculative other tests for a TMAU profile :
Leaky gut test.
Ethanol test (to detect candida). Now no longer available (from Biolab UK).
Microbiome stool DNA test.
Biotin test (as I was once deficient in biotin).

I would add many others, but perhaps the first 3 are a realistic aim to convince conservative metabolic consultant for a TMAU profile.

Re ethanol test.
This was a test done by Biolab UK where you had to attend the lab. Ethanol is proposed as being generated only by yeast in humans.
I see now they have discontinued it, and refer people to do microbe organic test by Great Plains, which I don't think is as accurate (or at least, not a decade ago).  

Ultimate biochemical test for Systemic Body Odor :
A broad screen of volatiles known to cause systemic body odor. Currently they don't know the list of volatiles, so at this time this would be EXPLORATORY.
Once it was known what volatiles cause systemic body odor, they could then create a profile test with these volatiles.
Likely suspect volatiles (my guess) : dimethylsulfide, dimethyldisulfide, trimethylamine (small player).

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By sysbodyodor

campaign, gut dysbiosis, metabolic malodor, metabolic/systemic malodor, systemic body odor, systemic malodor syndrome, tmau test, trimethylaminuria

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Youtube : Young lady talks TMAU & Fecal Body Odor

Saying it like it is.
Note about the video :
This is an embed of the original, not a copy.
If this original is deleted or 'sharing' is disabled, it will auto-delete here too.

Comment
Most people report of metabolic fecal/fart smells.
Currently trimethylamine is the only metabolite tested, so the only metabolite test on offer.
People with systemic malodors identify with the TMAU concept, but not the 'smell'.
There still seems a lot to discover about the 'systemic/metabolic malodor' syndrome.
Personally I think for most cases they have identified the correct enzyme but have limited it to one metabolite that may be a 'small player'.  

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By sysbodyodor

fecal body odor, metabolic/systemic malodor, systemic body odor, systemic malodor syndrome, TMAU personal stories videos, video, videos, youtube

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Putting FMO3 through the 'drug repurpose' checklist

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

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

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

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

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

It's something the community can think about.

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

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

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

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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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Can FMO3 be induced by Korean mushroom ?

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

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

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

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

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

pubmed link to abstract

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

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

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

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By sysbodyodor

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

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FMO3 gene results with GENOS

I got my Exome test results back from Genos (DNA test).
Cost was $399 (time limited special offer).
Exome is coding part of the Genome (essential part).
For FMO3 the test listed my 2 'wrong amino acid' variants, but not the 'silent' one.
I can't be sure it is FULL SEQUENCING, but rather a 'list of suspects'.
Overall I think it was worth it.
Best overall DNA tester I know (being both for consumer and none of the obstacles of clinical labs).

I got my exome DNA results back from GENOS.
I am very happy with the service, the process, support, and the info given.
My only gripe is I am not sure if it is FULL SEQUENCING (i.e. every codon of a gene).
It possibly is, I don't know yet.

Ways DNA labs test and give results :

1. Test for list of suspect variants/codons only (usually cheapest way).
This is no use really. Still too much unknown of the other bits. This is where they test suspect codons only. This means they choose the list of known suspects, but many more variants may yet to be discovered as fault-causing. You want to know every variant you have, not just suspects.

2. FULL SEQUENCING, but only give SELECTED variants/codons info to the person.
This means they tested every codon but they may only give what they think is relevant info on certain variants. So you still can't be sure you are getting the whole picture.  

3. FULL SEQUENCING and give ALL VARIANTS whether they be thought relevant or not.
This would be as good as FULL SEQUENCING in theory I guess.

4. FULL SEQUENCING (i.e. every codon of the gene)
This is best/good, though I guess in theory you only need to know the variants, so #3 may be more practical. #3 is the same as #4 but without the 'perfect' parts (which presumably won't affect function).

I am hoping Genos is #3, but I have not found out yet. It may be #2 which would not be so good.

EXOME, GENOME :
Exome  = coding for all the proteins in humans
Genome = everything (Exome + Junk + promoter regions etc)

It's thought maybe 80% of faults are in the exome part.
The main reason for EXOME testing rather than GENOME is cost (at the moment).
Exome is obviously the part you can't do without. The essential part.
But people can have faults in the junk part of a gene and it can cause deficiency even though it's junk.
   
MY GENOS DNA RESULT
I have fully sequenced the FMO3 gene before so knew my FMO3 coding part result.
It spotted my 2 carrier copies of the common variants at codon 158 and 308.
These are reasonably common (in caucasians anyway).
There is debate if they affect function (obviously I would say they do).
Some say only if they were from same parent, or if person is homozygous (carry 2 copies).

It didn't spot a silent variant I carry. This is what makes me wonder if they only test a 'suspect list'.
Silent variants are where one of the nucleotides is wrong but the amino acid ends up the same.

FMO3 gene
532 x 3 (1596) nucleotide sequence.
makes up 532 amino acid sequence (+ stop at 533).
makes up the FMO3 protein.
Which means 532 codons where variants can be.

Clinvar list of FMO3 variants

IS IT A GOOD WAY TO DNA TEST FOR FMO3?
Well this is where I don't know (yet).
The best way is to have your full 532 coding sequence, or at least all the variants in that 532 coding sequence (even if they are currently deemed to not matter).
But I don't seem to have the full sequence (not that I can see so far), or all the variants (as they missed a silent one).
The give a raw file but I don't know how to open it.
Answer : I think so but I don't know.

FMO3 DATABASE
In my opinion we should get a FMO3 database going.
But how to, I don't know.
Ideally this would be both the Exon and Intron parts of FMO3 (not just the exons)
Intron is the 'non-coding' part of the gene (which could be junk + promoter region etc).
This would be a pipe dream.

My philosophy on spending on 'systemic malodors'
My philosophy is we don't know what causes it yet, so better to spend money on testing rather than spending on supplements.

FINAL COMMENT
So I can't say for sure GENOS is a great option for DNA testing, but it may be.
And at current price $399 it's cheaper than most FMO3 DNA gene testing .
Plus it's meant for the public and easy to test (saliva).
The question is how much prices will drop quickly and how well competitors do.
In the end you will probably be able to do GENOME testing for maybe $100, but when ?
Also remember, you may find results of other genes you might not want to know (e.g. prone to parkinsons, carrier of cystic fibrosis) so you need to factor in whether you want to know such things.

Note :
I am no expert, so terminology, facts may be wrong.

Links :
Genos DNA TEST LAB FOR CONSUMER

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By sysbodyodor

fecal body odor, fmo3, FMO3 DNA saliva test, metabolic malodor, my results, my test results, systemic body odor, systemic malodor syndrome, tmau, TMAU research, tmau test

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marine trimethylamine : a big source of greenhouse gas methane

It seems that trimethylamine produced in marine environments is often broken down to methane.
Methane is a main gas that cause the 'greenhouse effect' (Global warming).
Perhaps this is another reason for scientists to look at ways to block TMA formation.
Which in turn could lead to a therapy for human gut TMA formation.

TMA produced in marine environments : 
I only heard of this TMA connection. Probably marine microbes produce TMA. Apparently the TMA is broken down to methane, which is a major part of the gases that cause global warming.

I have tried to look for the % stats for sources of greenhouse gases, but not been too successful.
One site said

% methane makes up greenhouse gases : 16% (2nd after CO2).
% of NATURAL methane sources are marine : 88% (78% wetlands, 10% sea).
This does not include HUMAN sources (e.g. petrol, coal, farming).

I would guess the marine TMA is a by product of microbe fermentation, which then is broken down to methane. Ironically this has been suggested as a possible therapy for TMAU, in that some microbes would break down the TMA in the gut. I guess so few are thought to have TMAU it would not add much to the total world methane output.

But ... this means it's in the world's interest to find TMA blockers, so that TMA does not produce methane. This would probably mean interfering with the enzyme that produces TMA. Antibiotics are often 'microbe enzyme inhibitors', so it's much the same thing as antibiotics.

So maybe there is research going on to prevent methane formation from TMA to save the planet.

3 main ways TMA could be inhibited or broken down (I know of) :

1. Interfering/inhibiting the microbe enzyme that produces TMA (antibiotics often work this way).
2. 'Drugging the relevant microbes'. This seems to be the Cleveland method. They are tricking the microbes into working on a compound that is like choline but much more dificult for them to breakdown.
3. Use microbes to break TMA down via the methane pathway. Some microbes have enzymes that can break TMA down.

My thoughts on TMAU and systemic body odor
Any therapy that inhibited TMA formation or broke down TMA (e.g. to methane) would be good for anyone who thought their smell(s) were solely created by TMA. I am a bit sceptical that TMA is the only source of smells for most, so a bit worried such a therapy would not have the expected benefits. But I may be wrong.

Acronynms :
TMA : trimethylamine
TMAU : trimethylaminuria

Note :
graph and stats may be incorrect.
    

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By sysbodyodor

gut dysbiosis, metabolic malodor, metabolic/systemic malodor, possible future therapy, systemic body odor, TMAU research

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Bacteroidetes don't produce trimethylamine from choline

 2012 paper suggests bacteroidetes phyla are poor at degrading choline to trimethylamine.
Firmicutes, Actinobacteria, and Proteobacteria can produce TMA.
Ubiome suggest Firmicutes make up 60% of normal flora, Bacteroidetes 30%.
My own Ubiome results average (of 4) were Firmicutes 70%, Bacteroidetes 26%.
My own opinion, not enough known of the gut flora for me to have an opinion.
This post more a 'for your information' post, rather than any 'breakthrough'.
Perhaps others should try stool DNA testing.

The new Phillips/Shephard TMAU-FMO3 overview paper mentioned a 2012 paper which they seemed to have great credence for. The research in the paper proved TMA could be produced from choline by certain gut bacteria flora phyla (Firmicutes, Actinobacteria, and Proteobacteria) but not from Bacteroidetes.

Quote from Phillips/Shephard/Fennema paper

Free choline is absorbed throughout the small intestine and is subsequently integrated into cell membranes or actively taken up by the liver, where it can be converted to betaine, phosphocholine, or lecithin (Zeisel, 1990). High amounts of choline may exceed the absorptive capacity and pass through to the large intestine, however, where it is metabolized to methylamines by microbial action (Zeisel et al., 1983). Choline is a quaternary ammonium compound containing a trimethylammonium moiety. Thus, it can act as a precursor for TMA (Zeisel et al., 1989; Chalmers et al., 2006). The bacterial conversion of choline to TMA involves the cleavage of the carbon-nitrogen bond of choline, producing TMA and acetaldehyde (Hayward and Stadtman, 1959). Craciun and Balskus (2012) proposed that a glycyl radical enzyme CutC (EC 4.3.99.4), encoded by the bacterial choline utilization gene cluster (cut), might act as a choline TMA-lyase to catalyze this initial step in choline degradation (Fig. 1). This was confirmed by demonstrating that deletion of cutC in Desulfovibrio desulfuricans abolished the ability of the organism to produce TMA from choline. Bioinformatics analysis revealed cutC homologs in 89 bacterial genomes. The homologs are not distributed evenly among the major bacterial phyla of the human gut, being present in Firmicutes, Actinobacteria, and Proteobacteria spp. but absent from Bacteroidetes (Craciun and Balskus, 2012). Table 1 shows bacteria known to be associated with formation of TMA via choline degradation.

This is the paper they refer to :
Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme

Firmicutes and Bacteroidetes seem to make up the bulk of the gut flora. There seems to be different opinions on what that % make-up should be for a healthy gut.

Ubiome suggest the healthy gut should have about 70% Firmicutes and 30% Bacteroidetes.

My own Firmicute/Bacteroidetes ratio :
I have tested with Ubiome 4 times.
In 3 samples my Firmicute was slightly higher than normal. Bacteroidetes was slightly lower.

My view on the knowledge of the human gut flora :
I would suggest if you compare it to the history of USA, it may be around the year 1620. Perhaps I'm wrong, but my impression is so little is understood of the gut flora (Oct 16). I'm hoping technology has caught up and we will be at around year 1900 in the next few years.

My view on my own results :
I will not be excitedly trying to alter my firmicute/bacteriodetes ratio, though may look around for info. It seems that bacteroidetes are not the type usually put in 'probiotics'. Possibly partly as they are so 'sensitive' (and die easy in oxygen). Possibly there is no 'bacteroidetes' probiotic on the market. The general view seems to be taking 'prebiotics' is the best hope of feeding bacteroidetes.

Perhaps others can do the stool DNA test :
Since the stool  DNA test is relatively cheap, and sometimes they do special offers (e.g. 3 for 1), perhaps others with systemic body odor/halitosis can do the test and mention anything they want about the results in the comment section of this post.

Stool DNA test suppliers :
Ubiome (choose citizen science)
American Gut (also 'UK Gut')

These are the 2 best known suppliers. Thankfully, they are consumer health friendly, and not health learning obstacles as is the case with normal DNA tests, urine tests etc. The spirit of the testing would be that it may be not very useful, but perhaps will be in hindsight.    

What's this to do with systemic body odor ?
My own view is that most cases of SBO are probably due to enzyme weaknesses, probably the bulk of which are due to sub-par FMO3 enzyme function. But I also think gut dysbiosis will be a common factor in 'FMO3 body odor', probably as part of the syndrome, and perhaps often the 'tipping point'.

Currently TMAU is the only acccepted form of systemic body odor. My own view is that 'FMO3 body odor' can mean smelling of any FMO3 substrate rather than just TMA, and many of the volatiles produced in the gut are probably FMO substrates. Although this paper was about TMA, perhaps bacteroidetes can't produce other FMO3 substrates, but who knows.

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By sysbodyodor

fecal body odor, gut dysbiosis, metabolic/systemic malodor, my results, possible future therapy, stool dna, systemic body odor, systemic malodor syndrome, TMAO-CVD, tmau, TMAU research

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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 

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By sysbodyodor

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

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Mint Breathometer ... to detect stinky breath

Mint Breathometer app and device to detect halitosis.
Available in USA from 30th Sept 2016 (can pre-order now).
$100.

The systemic/metabolic body/breath malodor community usually cannot smell themselves when they smell, so I have thought a phone based 'odorometer' is as essential as therapies and 'clinical' tests. I have looked around for leads and found no company to view it is likely profitable. This was frustrating as I figure the 'bad-breath vanity' market for say 'halitophobia' would be as big as mouthwash, and quite often they may check for some 'volatiles' that may be common to the main type of  systemic body odor (e.g. mercaptans, hydrogen sulfide etc).

It was inevitable that phone breathometers would come along, although this 'version 1' breathometer seems the first one and only one available. Perhaps it has also taken the technology up until now to catch up with the concept, and even now it's probably pretty new and probably subject to many changes until the tech matures.

links :
Breathometer site
Indiegogo : where Mint breathometer started
Mint Breathometer article in Techcrunch
article in Venturebeat (9/16)

Charles Yin is the 'tech entrepreuer' who owns the company. So far he found riches in 2 tech companies (selling them. Not sure if they are still around). Now he doesn't need money.

He appeared on 'Shark Tank' looking for funding for a 'phone alcohol breath sensor', which all 5 sharks gave money for (a bit worrying imho. I would want the publicity but not their stake). A 'breath alcohol phone sensor' sounds not very interesting to me, as there are so many small breathylyzers around.

It seems now they have dumped the 'alcohol breathalyser' and are focusing on detecting all kinds of volatiles that may be related to health. And as I say, the halitophobia vanity market is probably huge and this seems their current focus.

Philips
It seems that Philips are now involved, meaning the tech will have unlimited funding/research, and this means it's probably a long-term part of their oral healthcare strategy.

Relevance to Systemic Body Odor
My own feeling is that those with SBO tend to emit the volatiles through every part of our body, and the breath is probably a good indicator. Some feel they have Systemic Malodors only through their breath. Personally I feel my main problem is SBO, but even then there may be a higher than normal amount of volatiles in my breath when smelling.

The SBO community needs a sensor device as much as therapies, clinical tests etc, and currently this seems the nearest to the aim of a portable sensor for SBO. It looks like it tests for the common VSCs they look for in 'traditional localized halitosis'. I am sure one or more of these will be common in SBO (suspects like sulfides).
And at the moment this is really the only sensor on offer.

Foodsniffer
This device became available about 2 years ago. Again starting on indiegogo (possibly to test the market) then going 'professional'. This is meant to tell you if food is spoilt, about to spoil, or fine. I bought one and it does seem to sense something (e.g. I tried over a bin). It was also pretty good tech overall imho (bluetooth, nice app, well made device).
But I have little to no confidence in it to monitor SBO (as it wasn't intended to).

Mint Breathometer worth buying for SBO ?
For SBO, I would put this down as an 'exploratory gamble buy' that may obviously not be useful after a day or 2 (for SBO monitoring). But currently we have no choice so I'm thinking it's better than nothing.
It's on the right trajectory for SBO, but not quite designed for SBO. Personally I think the 'SBO' market itself will be huge (my estimate, 1% population 'at risk', or would at least buy a sensor). The 'halitophobia' market will be even bigger. I would guess almost everyone worries about halitosis.            

         

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By sysbodyodor

crowdfunding, malodor sensor, metabolic malodor, metabolic/systemic malodor, systemic body odor, systemic malodor syndrome

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Exome testing for systemic body odor

Exome test for $399 (beta price, summer 2016).
Direct to consumer (not NY or FL).
Genos (based San Francisco).
A 'beta phase' price offering that may increase. 
This might be a good affordable way of testing your coding genes rather than just 1 gene (e.g. FMO3).

Exome testing for systemic body/breath odor
My guess is that FMO3 enzyme flaws will be responsible for most cases of systemic/metabolic body/breath malodor. But, I may be wrong, or it may be more complex than that (e.g. compounded enzyme faults acting together to create a bigger flaw).

So for that reason I still consider the genetics of systemic body/breath malodor to be unknown, and any testing would need to be very exploratory and broad. Currently DNA testing is still at an early stage and the main limitation for most is probably cost.

Genos Exome testing ($399 'beta price' Summer 2016)

Genome : this is your full DNA code including all the junk.

Exome :  this is the 'coding part' of your DNA, so the most important. About 3% of genome / about 24,713 genes. 

Gene : the exome is made up of all the important gene's coding part.

SNP/mutation : this is the sole faults in a gene. you can have a few in a gene (compounded)

Until recently probably testing a single gene (e.g. FMO3) would be the most affordable, but obviously limited to that sole gene. Genomic testing will someday become the norm but is still too expensive. But Exome testing is now getting to a price that it probably makes sense to do Exome testing rather than single genes. A bit like getting the whole box of sweets rather than having to pick one.

Exome testing direct to consumer (DTC) :
DTC genetic testing can be difficult to access due to the traditional set-up of the health system (probably worried about money loss rather than health). 23andme tests a range of variants but it's a pretty random list. Also they have been 'crippled' by the FDA since 2012.

Genos exome testing :
Genos look like they may have found a way to offer dtc Exome testing without the FDA clamping down (for now).

I like the look of Genos Exome test because (but I could be wrong) :
Looks the cheapest exome test at the moment ($399, beta price).
Is a US Venture-backed startup (one investor is BGI) based in San Francisco.
Sequencing service is currently performed at a CLIA certified referral lab located in USA.
Similar set-up to 23andme.
Saliva sample.
Other reasons (can download raw data, delete account and data, I own data)

Why I may Exome test for systemic/metabolic malodor :
I already have my FMO3 code (which cost me about the same as this Exome test). But so little is known about systemic/metabolic (same meaning) breath/body odor that I do not want to rule any gene out.
In particular, I am interested in the broad-spectrum 'detox' enzymes. This would be the the 'oxidizer' enzymes (alongside FMO3) such as the CYP450 enzymes, and the conjugation/'phase 2' enzymes such as sulfation, glucorinidation etc. These enzymes often alter drugs (pharmakinetics).
My bias would be to look at the 'oxidizers' but I may be wrong. That's what's good about exome/genome testing.

We have 1,000s enzymes but it seems to me the enzymes above are the only real 'broad spectrum' enzymes that alter many different compounds. If someone smells of 1 thing, then I would guess it could be any enzyme, but when you can smell of many different (unpleasant) things then my guess it is one (or more) enzyme that alters many different compounds.

So for reasons of price compared to single gene testing, the scope of genes tested, and other reasons, this is why I may Exome test at some point (until genome testing becomes cheaper), and at the moment Genos would be my likely lab to test with.

Final thought
So now I don't suggest doing the single gene test for FMO3 anymore. Probably for the same price (or cheaper) and without the hassle of a standard CLIA lab's traditional procedures, you can now test FMO3 and all the other important genes in an EXOME TEST.

Keep in mind the $399 price will probably not last long, but in general DNA testing prices are continuing to fall.

Note :
I am no DNA expert, so ...
Genos exome test may not meet my expectations.
You will need to read more about them yourself.
I haven't done this test.

Update Nov 2016 : 
Genos contacted me to correct something. I said they were owned by Chinese company BGI.
They replied :
'Actually, Genos is a venture-backed startup.  BGI is one of our investors, but we are not owned by BGI.  The headquarter of Genos is located in San Francisco, CA, USA.  Our sequencing service is currently performed at a CLIA certified referral lab located in USA as well.'  

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By sysbodyodor

FMO3 DNA saliva test, systemic body odor, systemic malodor syndrome

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Metabolomic Profiling for Systemic Body Odor

This post is meant to be thought provoking.

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

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

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

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

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

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

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

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

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

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

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

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

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

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By sysbodyodor

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

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FMO3 codon 285 'silent mutation' : N285N

The DNA code for FMO3 is a 1596 nucleotide sequence (532 x 3).
This 532 x 3 nucleotide sequence creates a 532 amino acid sequence which creates the FMO3 protein.

codon	3-nucleotide code	resulting amino acid
283	gta	valine
284	ttt	phenylalinine
285	aac	asparagine (N)
286	gat	aspartic acid

Silent codons
Often a wrong nucleotide inserted can mean an incorrect amino acid created in the codon sequence.
FMO3 example : the common substitution at codon 158 results in E158K. It should be an E but came out a K (E stands for glutamic acid, K for lysine). Many people have this common mutation (estimates : 20-40% caucasians). It is currently regarded as 'benign' on it's own, but this may in future turn out to be wrong.

However, there are also substitution mutations where the wrong nucleotide is inserted but the resulting amino acid is correct. They are known as 'silent' (presumably as they are presumed not to affect function).

FMO3 example : N285N  (N = asparagine)

N285N turns out to be a seemingly common 'silent mutation' in ethnicities.

The question is, can 'silent' mutations affect function ?

At the moment, who knows ? . We have to assume mainstream experts will currently say no (?)

Common 'silent mutations' in the FMO3 gene coding region:
codon 147
codon 285 (N285N)

My own FMO3 'coding faults'
You can have faults in the coding part of your FMO3 DNA, but also faults in the non-coding parts (introns, promoter region, exon parts that do not code).
Ignoring my non-coding parts (as I don't have the info), I know the most important part : my own 532 coding sequence.
Note : Your 'coding region' can be 'normal' but you can still have TMAU due to faults in the non-coding region.

I carry 3 common SNP's :
E158K
N285N
E308G

FMO3 is about efficiency :
Bad analogy : 100m runner. Say a runner has small handicaps, e.g. broken arm. This may not effect his run much (say 94% normal). Whereas a broken leg may make the run 20% normal. It's the same idea with most FMO3 faults. They may affect function minimally, or you may have a few compounded small gene faults which may drag you down to 85% sometimes. FMO3 should be working at say 95%+.

So at the moment I am presuming my 'small faults' combine to affect FMO3 function either to a small % or perhaps intermittently. Personally I always feel lousy (e.g. migraine) and suspect it may be to do with FMO3 function as FMO3 is regarded as one of the group of heavy-duty 'detoxifier' enzymes (in the case of FMO3, to detoxify abundant small sulfides and amines of a certain structure). It seems not that much is known of the 'detoxifier enzymes', with the main group (the CYP450's) being identified as the main players, and FMO3 regarded as lesser players ... but perhaps this will later prove to be incorrect,

The main reason for the post was to point out the notion of 'silent' SNP's.

Commonality of N285N :
This paper from 2006 mentions N285N and it's commonality in some ethnicities.
2007 FMO3 paper :
Identification and Functional Analysis of Common Human Flavin-Containing Monooxygenase 3 Genetic Variants

Summary :
N285N silent mutation is currently regarded as having no effect on the efficiency of FMO3 enzyme function, and is quite common. It will most likely not be listed in a clinical FMO3 gene test as they tend to list only mutations they feel may have an affect. To see if you have N285N, you would need a copy of your full 532 codon FMO3 code (or at least, any variations from 'normal' listed).

What has this to do with systemic body odor ?
My own current belief is that FMO3 enzyme may be implicated in most cases of systemic body odor. SBO is not currently a properly documented disorder, with only TMAU being given as a diagnosis of the SBO concept ... perhaps a gross underdiagnosis.

Other links :
2006 paper : silent mutations
2014 article : silent mutations
Stanford 2015 article
Codon amino acid abbreviation code list
The main different types of mutations in a gene
wikipedia : FMO enzyme family

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By sysbodyodor

fmo3, FMO3 reference, systemic body odor, systemic malodor syndrome

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P&G TMA-blocker will be stronger than DMB

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

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

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

Full article : Statnews April 2016

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

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

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

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

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

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

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

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By sysbodyodor

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

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How much DMB for TMAU ?

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

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

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

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

The estimate is generally from this overview paper : link

Acronyms

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

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

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

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

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

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

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

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

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

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

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

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By sysbodyodor

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

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Exome/Genome Consumer Test list

To me, it's getting to the point where it's possibly economically and future-proofing best to Exome or Genome test rather than test for single genes (partly or fully) or groups of genes. And Direct to Consumer (no need for Dr, health professional and their fees etc)

So here is my list ...

Aims :
Exome or Genome testing
Direct to consumer
Note : For health-related testing the advice seems to be to go for 30x coverage at least

my List : Exome / Genome Consumer Test companies

COMPANY	EXOME / GENOME	COMMENT
Full Genomes link	Exome 33x $775 Genome 30x	Other links : ISOGG Facebook
Veritas Genetics link	Genome 30x  £999	Other links :

update : 19 May 16

Exome is about 1.5% of the Genome.
But Exome is the CODING PART, whereas rest of Genome is junk / promoter region etc.
But you can have faults in the junk part which can affect the gene coding.

Main reasons for choosing Exome or Genome
Exome is the coding part, and probably cheaper to do
Genome includes everything, and perhaps in future more will be known and you will already have your full data.

FMO3 :
Readers will be aware I currently suspect FMO3 enzyme as the main suspect for most cases of Systemic Body Odor. FMO3 coding part would be included in both Exome and Genome testing.

FMO3 gene code : 532 amino acid sequence (532 codons from 1596 (532x3) Nucleotides) plus stop codon at codon 533.

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By sysbodyodor

fmo3, FMO3 DNA saliva test, genetics, systemic body odor, systemic malodor syndrome, tmau test

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