Nashville meetup: Nigel Manning's paper & handout

HANDOUTS DISTRIBUTED AT THE NASHVILLE 2010 MEETUP

1. ‘TMAU – diagnostic testing at Sheffield Children’s Hospital’ by Nigel Manning, Principal Scientist, Sheffield Children’s Hospital,Sheffield, England
2. Nashville Meetup Handout: Links and references to Body Odor/Halitosis related professional journals, organizations, papers, and blog posts
3. Pedigree of Service Dog at Nashville Meetup by Pawsibilities Unleashed, Pet Therapy of Kentucky, Inc.
   

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Due to the broad spectrum of substrates oxidized by FMO3, TMAU1 patients may suffer from adverse reactions with many drugs including codeine, tamoxifen, ketoconazole, nicotine, cimetidine, ranitidine and phenothiazine

As previously mentioned in a post in this blog, we have received a paper, which we discussed at length on Sunday at the Nashville Meetup, written by Nigel Manning, Principal Scientist, Sheffield Children’s Hospital,Sheffield, England entitled, ‘TMAU – diagnostic testing at Sheffield Children’s Hospital’. All TMAU urine tests in the UK, Ireland, and some from other parts of the world are done in his lab. Nigel wrote this paper specifically for our meetup, and I wanted very much to discuss it with everyone on Saturday so that we may all learn from it. However, since I was sick, Glenna was kind enough to go over it on Saturday, and we discussed it again on Sunday when I was able to participate as well. More about our discussion of this paper will be forthcoming on another post.

In this six-page paper, Nigel explains to us the formula he uses to arrive at either a Primary TMAU or a Secondary TMAU diagnosis. In the US, only the Primary TMAU diagnosis is used.

Nigel explains in his paper that the liver enzyme FMO3 not only oxidizes TMA, but in addition, oxidizes a wide range of substrates including many drugs. He explains,

Due to the broad spectrum of substrates oxidized by FMO3, TMAU1 patients may suffer from adverse reactions with many drugs including codeine, tamoxifen, ketoconazole, nicotine, cimetidine, ranitidine and phenothiazine. Hypertension may result from ingestion of red wine and cheese (and chocolate), which produce the neurotransmitter tyramine, another FMO3 dependent compound. Many people suffer from migraines associated with tyramine containing foods and perhaps FMO3 deficiency may explain some of these cases, but overall this demonstrates the adverse medical consequences of TMAU1 as well as the odour related psychosocial aspects.

Nigel also elaborates on the condition diagnosed as Secondary TMAU (TMAU2). He defines this diagnosis as being an acquired form of TMAU where TMA excretion is high even though FMO3 activity is normal.

Most TMAU2 patients produce too much intestinal TMA due to excessive bacterial growth of TMA-generating species. The TMA burden is so great that FMO3 oxidation produces large amounts of TMO but (in most cases – but not all) is still unable to oxidize enough TMA to prevent an excess…

…TMA itself is generated in the large intestine by bacterial degradation of compounds such as choline (high in liver, eggs and beans/peas), carnitine (meat) and TMO [TMA-oxide] from seafood (TMA from fish ‘spoilage’ has been attributed to several species of Vitrio and Shewanella bacteria)…

In this paper, Nigel provides us with three graphs,

1. TMA testing- urines analysed at Sheffield Children’s Hospital: of 1,150 urines tested from 716 individuals from 1997 tP 2009, of which 379 results indicated significant TMAU.
2. Free Trimethylamine v Free TMA / TOTAL [%] – end of 2009 n = 716: This graph is a summary of samples analysed from 1998 to 2009 – TMAU1 and TMAU2 differentiation by the ratio of Free TMA to Total TMA (TMA+TMA-oxide). Free TMA normal range 1-11.
3. A case of choline load to aid diagnosis in a case of TMAU (results indicated a treatable TMAU2)

In the Discussion section of his paper, Nigel discuses the treatment of both TMAU1 and TMAU2 and the types of odours associated with these conditions,

…the type of odour is often difficult to describe, but ranges from ‘chemical’ to faecal’. ‘Rotten fish’or ‘ammonia-like’ is not always mentioned, but TMAU seems to have become a focus for all malodours, possibly due to awareness of the disorder, the availability of a test and the possibility of a diagnosis.

A significant cohort of sulphurous or faecal odours have been reported by individuals who contact the laboratory. This may be another enterobacterial problem, but although Shewanella species are known to produce both hydrogen sulphide and TMA, we have yet to measure an increased TMA or TMO as a secondary marker for enterobacterial overgrowth in these cases.

FOR ADDITIONAL INFORMATION, see Parts 1 & 2 of Nigel Manning's interview for this blog, along with other experts' interviews.f