Plan for Christmas boat trip in York, England

York boat trip : Are you interested

Claire, who appeared on the TV Show 'This Morning' to raise awareness of trimethylamuria, has come up with the idea of a boat trip on the river Ouse in the beautiful historic city of York in north England. The plan is to book the trip that will last around 3 hours for around Christmas time. It should be about £30 per person.

You can see her post on the tmau.org website forum :
York boat trip for tmau people
Example boat trip company

Those who go to meetups find them very therapeutic, pilgrimage-like.

TMAU Foundation website

TMAU Foundation website

We are pleased to make you aware of the TMAU Foundation website. The TMAU Foundation, a non-profit charity, has for many years been working to help those with TMAU. The website is not fully completed yet.

Note from Maria:
My congratulations goes out to the web designer of this site and everyone who contributed to its creation. My favorite section is the Home tab on the main menubar, which has 3 subsections, Trimethylaminuria, Food Guidelines, and Choline Chart. I am most certainly bookmarking this site because it is bound to have much valuable information on TMAU. Congratulations to everyone involved with this very important organization - one of the oldest, if not the oldest TMAU sufferer founded organization.

María

ISBOR Breath Odor Research conference is underway : May 25 - 28

The bi-annual ISBOR Conference is underway in Salvador, Brazil. ISBOR is the international society for breath odor research. The impression was that interactivity with the internet would be provided for this conference, but it seems not to be the case.

ISBOR
ISBOR conference May 25-28 Salvador, Brazil 

Update on TMAU story to appear in British newspaper

We reported earlier that someone was bravely appearing in the best-selling British newspaper The Sun about their trimethylaminuria (TMAU) this Tuesday or Wednesday. The story did not appear, but a Sun photographer was at the volunteer's home on Sunday, so it does seem the story will be going ahead.

NORD TMAU Fund research proposals deadline was 20th May : 'Several' applications submitted

It is our understanding that 'several' applications were submitted for the research grant made available via the NORD Fund, which was around $30,000 raised by the body odor/halitosis community, mainly through the hard work of the website rrr.tmau.org .

The application date closed on 20th May. Now it is a case of waiting until they decide who wins the bid around September. At least we can be sure that some sort of modest TMAU research will take place some time after September.

Thanks to everyone who donated. You can be glad to know it was worthwhile. Over the last few years very little TMAU research has been conducted.

23andme.com DNA test not as thorough for FMO3 testing as hoped

In a previous post it was suggested that the 23andme.com DNA test may be a good way of DNA testing for FMO3 variants/mutants inexpensively. However, it seems that the number of FMO3 SNPs checked for is not as comprehensive as hoped. It checks for 56 FMO3 SNPs in total. Of those, only 17 are at codons with known variants/mutants. Most of the others seem to be to do with FMO3 introns (introns will be discussed in a later post) and about 5 are currently unlisted for any information.

It tests for 17 variants/mutants, out of about 50 known variants/mutants. Most of the 17 are common polymorphisms/variants, but the rarer more severe mutants are not checked for.

The variants, mutants tested for are at the codons listed below (an FMO3 protein is made up of 532 codons)

82, 147, 158 ,205
,239 ,257 ,277 ,285
,302 ,305 ,308 ,360
,362 ,486 ,502 ,503 ,510

This does not include the codons known to have rarer known variants/mutants (about 300 ?) such as at codon :

32, 37, 51, 52, 58, 61, 64,
66, 114, 143, 148, 153, 187
197, 198, 199, 201, 223, 237,
238, 314, 387, 388, 394, 415
434, 470, 475, 492, 500

So it looks like the 23andme.com genetic testing service is currently not suitable for FMO3 DNA testing other than for the more common FMO3 variants. It should be also kept in mind that much more is still to be learnt about FMO3 genetics, and even a comprehensive test is currently still capable of a 'false negative' result. For example, little is known of the FMO3 introns (all the testing and research mostly involving the exons), as explained in this post

23andme do update their SNP testing chip occasionally, so in future it is possible it will be more thorough for FMO3. But FMO3 seems a low priority to them so it is unlikely, and if you have already used their service you would need to retest

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pubmed list of FMO3 SNP's

Body Odor person's story to appear in popular UK newspaper 'The Sun' next week

A brave member of the body odor community will appear in the best-selling national newspaper in the UK; The Sun either next Tuesday or Wednesday. This will be a result of the agencies who were recently looking for TMAU stories to sell to the media. This is another major public appearance for a body odor story, greatly raising awareness further. We are all indebted to these brave pioneers. They follow brave media heroes of the past, some examples from our hall of heroes are given below :

Hall of Heroes :

Camille's TMAU story on ABC News Primetime in 2006
Cheryl appearing on popular medical show 'Mystery Diagnosis' in 2009
Tammy who appeared on a popular mid-morning USA TV show in 2007; and along with Cheryl Fields and others appeared on a 10news story about TMAU in 2008, and also on a Komo News TV story in 2007 (shown above)
Gary's TMAU story on the BBC 'One Show' ; a primetime BBC evening show in 2010, as well as local BBC radio and the Yorkshire Post

Claire talk of her TMAU on 'This Morning', the most popular mid-morning chat show on UK TV in 2010
Michelle's TMAU story on 'Embarrassing Bodies' ; a popular medical UK TV show in 2010
The 3 volunteers that were on 'Help I smell of Fish' BBC documentary on UK TV in 2007
Arun Nagrath, who appeared on a discussion about body odor and halitosis on BBC Radio World Service in 2006

All have bravely helped us get closer to treatment and cures for the taboo subject of systemic body odor and halitosis, as well as other forms of BO/halitosis. Thank you

TMAU body odor story on Embarrassing Bodies now on their youtube page

The story of the brave lady who appeared on the UK TV programme 'embarrassing bodies' is now available to view on the TV channel's official youtube page. It has been available elsewhere on youtube for a while, but it is good to see TMAU feature on an official youtube channel, and hopefully will lead to greater awareness. The video seemed to demonstrate the usefulness of monitoring TMA levels on the TMAU diet protocol to boost trust in the diet protocol. It seemed her TMA level went down from 45 umols to 15 umols, which unfortuntaely is still a bit above Sheffield Children Hospital currently set 'high limit' for TMA, but was a lot less than 45 umols.

They have published the story in 3 parts. In 2 months it has over 6,000 views. Thanks again to Michelle for appearing :

MEBO Research's commitment to transparency

It's that time of year again, and MEBO Research must submit its Annual Returns in England, where it is registered as a Not For Profit Limited by Guarantee Company and in the United States as a 501(c)(3) Public Charity.

As noted in its website, MeBO has committed to practice,

Transparency : All moneys received, fund balances, planned and actual spending activities will be disclosed on this website and/or English and Spanish blogs.

In fulfillment of this declaration, MeBO will periodically share information about it's financial dealings with varying types of reports. Even though MeBO is not obligated to do so, as the Founder of these two companies that were established specifically and exclusively to represent the needs of our international community of sufferers, I have chosen to make the financial dealings transparent from the onset.

When I established these two companies with the aim of making them Charities, I envisioned them to be built upon a "Self-Directed Team" concept. This way, no one person is indispensable and all are replaceable, beginning with me. Even though the Self-Directed Team approach is "more risky," than a company sole run from "top to bottom," it is my preferred method because if anything should happen to me, my successor would easily be able to pick up where I left off and continue with the smooth operations of this organized international effort.

MEBO Research is operated, financially and otherwise, by sufferers and for sufferers who volunteer their time and treasure to achieve the goals described in MeBO's website. Each person who considers himself or herself part of this international community would hopefully then be encouraged to be creative with new ideas to meet MeBO's Mission Goals, and to proactively brainstorm and pursue ways to achieve them, or to provide positive ideas to modify or replace these goals with better ones.

Since the annual returns report for the English company is "short and sweet" this year and it seems to be a good snapshot of the year's financial activity, I have determined that it is a good report to make public. All personal information of donators has been replaced with a number code for confidentiality purposes. Click on this link to see this document. The international community is most grateful to all the donators for their very generous contributions towards making this dream come to fruition, one step at a time.

I am currently still working on the US annual returns, and will try to find a "snapshot" financial report to share with the community in the near future.

María


María de la Torre
President and Chief Executive Officer

A Public Charity

www.meboresearch.org
maria.delatorre@meboresearch.org
MEBO's Blog (English)
El Blog de MEBO (español)

FMO3 Genetics class : part 1

It is hoped readers may be interested in a series of posts about the technical side of Trimethylaminuria (TMAU), especially genetic TMAU. Genetic TMAU is deemed to be caused by a deficiency (of some degree) of the flavin mono-oxygenase Isoform 3 enzyme (FMO3). It seems the deficiency can be generally constant or can be only at certain times, such as menstruation, depending on the variant causing it.

A simplistic way to think of the genetic building of FMO3 is to think of the FMO3 protein being made up from a series of 532 amino acids in a particular sequence. An analogy to use would be a ladder with 532 rungs. If at any rung (codon) there is a fault (variant), it can cause problems depending on the expected severity of the variant. Also, a nonsense mutation is where the building of the rungs is stopped completely at a certain rung, leaving an unfinished 'ladder' to be turned into the FMO3 protein.

At each rung in the ladder, the person can potentially have a variant on one side (heterozygous) or both sides (homozygous), or be completely normal.

A common 'variant' in humans is known as E158K. It is estimated that perhaps 50% of the population are at least heterozygous for this variant. It means at rung (codon) 158, the amino acid should be glutamic acid (E), but instead is lysine (K). On it's own, this is such a small error that no negative effect on FMO3 function is expected even if the person has variant E158K on both sides (homozygous) of rung 158.

Another common variant is E308G. Using the ladder analogy again, this is a common variant at 'rung' 308. It is meant to be lysine (E), but instead is glycine (G). Again, whether the person has one copy (heterozygous) or 2 (homozygous), it is such a minor fault that normal function is predicted.

However, it now seems expected that if someone is at least heterozygous for both the above variants on the same side, i.e., on the same chromosome, from the same parent, there is predicted to be a loss of function to some degree, e.g., 80% TMA to TMAO conversion, rather than over 95%. Possibly this combination may make up most cases of genetic TMAU - they would likely be 'mild' genetic TMAU cases.

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The table of symbols for amino acids
Table of human FMO3 allelic variants (to be updated soon)

E158K estimates (at least one copy) in USA population :
Caucasian 40%
African-American 40%
Hispanic 33%
Asian 14%

E308G estimates (at least one copy) in USA population :
Caucasian 19%
African American 5%
Hispanic 9%
Asian 16%

2.5% of Caucasians are estimated to have one copy of both E158K and E308G (known as a haplotype), but as long as they are not on the same chromosome then no loss of function is currently predicted.

UK : Smart Nutrition website back up

Smart Nutrition Website

Recently we announced that MeBO Research had managed to arrange a way for people to access the trimethylaminuria urine test performed at Sheffield Children's Hospital via Smart Nutrition UK. This means people can test directly for £170, which is the cheapest in the UK (£249 via Medichecks and was £190 via the now defunct Mullhaven lab).

Unfortunately the Smart Nutrition website went down the week we made the announcement. We are now informed it is back online.

More details about this service can be seen in the original post

UK : 2 journalists looking for TMAU volunteers for media stories

UK: looking for an 18-40 year old TMAU female who has not appeared in a TMAU media story before

The concept of systemic body odor has almost no awareness in society, including in the medical community. The only systemic body odor with a 'foot in the door' is trimethylaminuira (TMAU). Systemic body odors and halitosis are of course still a major 'unknown' taboo in society. So, anyone who volunteers to raise awareness through the media can safely regard themselves as a hero.

In the UK a the moment, 2 journalists are looking for TMAU volunteers to do articles on. At this stage, it is not known what medium the stories will appear on.

Natalie Lisbona at centralfeatures.com is looking for an 18-40 year old TMAU female who has not appeared in a TMAU media story before. If you want to find out further details or apply you can contact her through her website : centralfeatures.com TMAU media story opportunity

Update from Natalie :
Ideally it will be for a magazine and a newspaper but never say never to TV.
If it's a younger woman, in her 20's, it opens up more media potentials for us but obviously it depends on who comes back to you.Yes they will get paid, again depending on the publication and if they appear in more than one then obviously the fee doubles.
I will also put any support group into the article as a way of thanking you for your help, just please let me know the details.
Kindest regards
Natalie

Also, the forum owner of tmau.org has been contacted by a different journalist looking for a TMAU volunteer. Details can be seen on the tmau.org website

Any volunteers should remember they are relying on the journalist as to how the article turns out, and it is a risk. It is not known if a fee is given.

New paper suggests common FMO1 variants are associated with nicotine dependence

In humans, FMO1 is the major FMO in fetal liver and adult kidney and intestine

The blog always has an interest in research into any of the flavin-monooxgenase enzymes, since FMO3 is associated with genetic trimethylaminuria. There are currently 6 isoforms of FMO3 discovered in humans (FMO1-6), with five of them thought to play a role. FMO3 is thought to be the only one linked to genetic TMAU. But so little is known about the FMO enzymes, with FMO3 being the most researched.

This new paper looks at variants in the FMO1 enzyme. For context, a quote about the function of human FMO1 can be read in this 2005 paper, with this quote from it :

In humans, FMO1 is the major FMO in fetal liver and adult kidney and intestine. The human is a very interesting species with respect to developmental regulation of FMO1 and FMO3. FMO1, the major FMO in liver of most adult mammals, is expressed at relatively high concentrations in human fetal liver, but shortly after birth, expression is reduced to almost zero; the signal for termination of expression is related to the parturition and not to gestational age (Hines & McCarver, 2002; Hines et al., 2003). FMO1 may play an important role in extrahepatic drug metabolism in humans as well as in the liver of the fetus exposed to numerous potential xenobiotic substrates in utero. Currently, there are ~20 allelic variants of human FMO1 described by Furnes et al. (2003) and Hines et al. (2003) and the GeneSNPs database. The enzymatic activity of some of the FMO1 variants are given in Table 4. Based on the work of Hines et al. (2003), some of these allelic variants are probably rare alleles (H97Q, I303V, I303T, R502X) and may not contribute significantly to interindividual differences in FMO1 expression. On the other hand, a much more common variant (FMO1*6) caused by a C→A transversion in the upstream promoter region (−9,536), may impact FMO1 expression as it renders a Yin Yang basal promoter incapable of binding YY1 (Hines et al., 2003). The allelic frequency ofFMO1*6 is 13, 11, and 30% in African–Americans, northern European–Americans, and Hispanic–Americans, respectively (Hines et al., 2003).
2005 FMO paper : Krueger & Williams

NEW FMO1 PAPER : NICOTINE DEPENDENCE

Nowadays, geneticists are often looking at enzymes for possible health related issues. Whether it is wiser for readers to wait until a trend occurs in research papers is up to each reader. In this paper, they did seem to choose the 3 main groups of families of enzymes likely to handle nicotine detoxification. Their conclusion is that out of these groups of enxymes, common FMO1 polymorphisms (variants) seem to be linked with nicotine dependence. It is of interest that Dr Cashman has previously found that a part of nicotine will be detoxified by FMO3.

NEW PAPER : Common polymorphisms in FMO1 are associated with nicotine dependence

Abstract

BACKGROUND:

Cigarette smoking and other forms of tobacco use are the leading cause of preventable mortality in the world. A better understanding of the etiology of nicotine addiction may help to increase the success rate of cessation and to decrease the massive morbidity and mortality associated with smoking.

METHODS:

To identify genetic polymorphisms that contribute to nicotine dependence, our group undertook a genetic association study including three enzyme families that potentially influence nicotine metabolism: cytochrome P450 enzymes, flavin monooxygenases (FMOs), and UDP-glucuronosyl transferases.

RESULTS:

Several polymorphisms in FMO1 showed association in a discovery sample, and were tested in an independent replication sample. One polymorphism, rs10912765, showed an association that remained significant after Bonferroni correction (nominal P=0.0067, corrected P=0.0134). Several additional polymorphisms in linkage disequilibrium with this single nucleotide polymorphism also showed association. Subsequent in-vitro experiments characterized FMO1 as a more efficient catalyst of nicotine N-oxidation than FMO3. In adult humans, FMO1 is primarily expressed in the kidney and is likely to be a major contributor to the renal metabolism and clearance of therapeutic drugs. FMO1 is also expressed in the brain and could contribute to the nicotine concentration in this tissue.

CONCLUSION:

These findings suggest that polymorphisms in FMO1 are significant risk factors in the development of nicotine dependence and that the mechanism may involve variation in nicotine pharmacology.

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FMO : wikipedia

ISBOR bi-annual breath odor conference this month in Brazil

It's amazing to think it was 2 years ago that we mentioned the last ISBOR conference was happening in Germany. So that makes it time for the next conference, this time being held in Brazil on May 25-28. Apparently anyone is welcome to attend. There was no internet interactivity last time, but it says there will be this time, although nothing indicates this on the site at this point.

The ninth international meeting of the International Society for Breath Odor Research (ISBOR) 

at Bahia Othon Palace Hotel in Salvador, Bahia - Brazil. 

May 25-28, 2011

TMAU (Trimethylaminuria) urine testing in the UK for £170 and £177 in Europe

MEBO Research is pleased to announce an arrangement in the UK with Smart Nutrition to offer the trimethylaminuria urine test via mail order for £170 in the UK and £177 in Europe. Through Biolab Medical Unit, the test is sourced by the Department of Clinical Chemistry, Sheffield Children's Hospital where Nigel Manning, Principal Clinical Scientist, performs most if not all of the UK's TMAU tests.

One of the goals of MeBO Research is to make trimethylaminuria testing more widely accessible. In the UK, the only test source currently known of is Sheffield Children's Hospital through NHS. Unfortunately, NHS will not allow people to test directly (even for a fee), so we have been looking for ways to get around this obstacle, in order for people to test directly for a fee if they wish.

Through an arrangement with Biolab and smartnutrition.co.uk, we are now happy to offer the TMAU urine test for £170 (£177 in Europe), which is the least costly in the UK for those who wish to test directly. In the future we are looking for other sources and to bring the price down; however this is the best we can offer for now.

The test is available online here,
scroll down on the page to order your test:

A voluntary survey for MEBO Research is added to the form, so that MeBO can collate the anonymous data for future research (hopefully). Smart Nutrition has also kindly offered to donate £5 off the price to MeBO Research, as noted on their site. An anonymous copy of the results will also be sent to MEBO Research.

Smart Nutrition Website

Each customer will receive a PDF copy of their results directly from Smart Nutrition with a brief interpretation, as well as a PDF giving general information about TMAU. The founder of Smart Nutrition, Emma Wells, Dip ION, NTC, CNHC, is a Nutritional therapist, lecturer and health writer; and, she may also provide further consultation advice for a fee, to those who wish to do so. Emma was not aware of TMAU when we first contacted her in early 2011, but is has been researching and developing a nutritional program for sufferers, that we hope will also expand to include nutritional therapy for other types of body odor conditions. These consultations are not part of the arrangement with MeBO Research, but we mention it so people are aware of the service.

In the UK, it should be noted that the test can be done via the NHS without charge.

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