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Thursday, November 27, 2008

Interview with Dr. Robin Lachmann, PhD, MRCP, Consultant in Metabolic Medicine

Vanita, a Member of the TMAU Foundation in the UK interviewed Dr. Robin Lachmann, PhD, MRCP, Consultant in Metabolic Medicine, National Hospital for Neurology and Neurosurgery in London, on November 13, 2008. This very informative interview includes questions asked in this blog by sufferers upon Vanita's request. She presented us with this invaluable opportunity to bring forth our concerns regarding Trimethylaminuria, the testing process, and its management, so that she may present them to Dr. Lachman in this interview on our behalf.

Our most sincere gratitude goes out to Dr. Lachmann for his very generous and compassionate gesture in dedicating his very valuable time to help all the TMAU sufferers in the world understand the nature of this condition and its management. Our most sincere thanks go to Vanita for offering us the opportunity to raise these questions and for presenting them to Dr. Lachmann.

Dr Lachmann email :

Interview with Dr Robin Lachmann of London about trimethylaminuria, November 2008

Everyone that I have come across in the UK that has been tested by you praises your kindness and patience. By the time they come to know about TMAU and how to test, many have been through a long battle since body odour conditions are not so well identified.

RL: Thank you. I think that many people are just pleased that someone takes them seriously.

Do you offer any advice to people before they take the urine test?

RL: Yes we do, we send out a letter explaining a little bit about how TMAU works and why we want people to eat special foods before testing. We try and get the initial urine test done after we get a choline load. We don’t ask them to load up with choline tablets, but to follow a diet with lots of high choline foods before doing a 24 hour urine collection. We think this gives us the best chance of the right result, because we know that you can sometimes get false negative results. If you load up with choline and still get a negative result, then it is unlikely that TMAU is the diagnosis.

What is the process of the diagnosis?

RL: We ask people to make a 24 hour urine collection into an acidified bottle which they should be able to obtain locally. A sample from this gets sent off to Nigel Manning in Sheffield for analysis. This may not happen straight away because the tests only get run every month or two, so it often takes a while for the results to come back. In the meantime, we give dietary advice for people to try out while they wait for the results. For follow-up clinic visits we ask for urine specimens on the day, without choline loading, so we can see if the treatment has made any difference.

Equally if people are worried about odour at certain times, such as around menstruation, it is important to collect urine at that time, so we ask them to test at when their symptoms are at their worst.

Whenever we see a patient we have a dietician with us. At the moment we have a booklet with the choline content of foods, simplified from the complicated database available, and we are actually trying to work on some menu plans, which are coming along and should be available shortly.

What about those who get a negative result; what happens for them next?

RL: Just because someone tells you it’s not TMAU, that does not change your symptoms. Unfortunately, we cannot be as rational about the treatment we recommend. There must be other similar metabolic problems and other chemicals which cause odour, but as we don't know precisely what they are, it is much more difficult to suggest definitive treatment. Although there may well be dietary factors that contribute, we can’t really recommend a low choline diet if it’s not TMAU because the choline is what the bacteria turn into trimethylamine. One can give general advice and support and encourage people to try and find what works for them, but, unfortunately, without knowing what the biochemical basis is, you can’t really come up with any definite treatment. It’s more a matter of trial and error. It is also difficult to monitor those who cannot detect their own odour and, if they do not have trimethylaminuria, we cannot offer to monitor them using urine tests.
We are happy to go on seeing people with a negative test if they want to continue to come, but if you have tested negative for TMA after a proper choline load and 24 hour urine collection, then it is very unlikely that repeating it will give a different result.

I come across many who are desperate when they are waiting for a result and when they receive a negative result it causes a feeling of despair

RL: If we have tested after patients have loaded up with choline, or at times when their odour is severe, and get a negative result, then we have to accept it and move on from there to try and find other things that help. I think a number of treatments such as the copper chlorophyll tablets and other internal deodorants may work similarly for other conditions as well. Although not everyone with TMAU find those particularly helpful.

Testing in the UK , the only process I am aware of is being referred by your GP. Why do we not have the option to pay privately like in the US ?

RL: Our national health service has many advantages, but one of the disadvantages is that it may not be so easy to get yourself referred to a specific service like ours. Within the NHS you have to be referred to hospital by your GP as that’s how the hospitals' receive payment. There is no reason why your GP can not send the urine specimen off themselves, but they may not know who to send it to, or about choline loading, so asking to be referred to us is probably the better option. It is not a disease that many GPs will have heard of so there is not a lot of knowledge out there. Patients are often guided to myself or Nigel Manning via Information on the internet, and then need to get their GPs to refer them. I appreciate it is not straightforward especially if you are not in London .

I do not see TMAU patients privately. Our service is available on the NHS and I don’t think getting a referral should be an issue.

I have a few questions from the TMAU community which I would like to ask on their behalf:

For those who have tested positive, do you record what percentage of sufferers have a faecal/ammonia type odour as opposed to a fishy odour?

RL: It will be recorded in their notes, but we haven't collected that data. The ammonia and the fishy odour probably go together to some extent: the chemical structure of trimethylamine is like ammonia so it is not surprising that they smell similar. Many patients can not smell themselves and rely on feedback from others about exactly what odour they have.

In the article "Choline- and Betaine-Defined Diets for Use in Clinical Research and for the Management of Trimethylaminuria" the recommendations for Controlled Choline Diets for the Treatment of Trimethylaminuria include restriction of choline intake, vitamin supplementation with riboflavin and folate, restriction of dietary indoles and glucosinolates, drug treatment with oral antibiotics, and the use of laxatives. The latter two treatments are not feasible for long-term therapy.
Question: Using this 2004 article as a guide how does your recommendations compare? If different could you please explain because since 2004 things may be very different?

RL: The article itself covers more then one thing, which is why it can be a bit confusing. They talk about choline and betaine defined diets. The clinical research they describe is not into trimethylaminuria. It is clinical research into sets of biochemical reactions in the body which involve the transfer of single carbon molecules, and both betaine and choline are important In these reactions. In FM03 deficiency/dysfunction, it is only choline that is important and betaine does not need to be restricted (nor increased). A lot of the information in the article is about low betaine foods, which is not relevant to trimethylaminuria. It has a long list of foods, very similar to the database we use for the low choline diet, but listing betaine content as well. As regards vitamins, I don’t think a low choline diet make you deficient in those. Indoles and glucosamines are not particularly relevant to trimethylaminuria. The low choline bits of the report are relevant, but the rest isn't.

We use antibiotics to try to get rid of the trimethylamine-producing bacteria in the gut and hope the ones grow back don’t produce trimethylamine. It is probably worth taking the antibiotics and then probiotics to encourage bacteria which don't produce TMA to grow back. In the UK we have not treated patients with laxatives.

Are most TMAU sufferers born with the deficient enzymes and symptoms?

RL: In our clinic, most of our patients were not born with symptoms and have secondary TMAU, but we only run an adult service and not paediatric. My colleagues at Great Ormond Street (paediatricians) do look after children with primary TMAU. Our patients tend to first develop symptoms later on, often about the time of puberty or early adulthood.

Is TMAU2 also hereditary? There is so much about Primary TMAU being genetic but no mention of Secondary.

RL: Primary trimethylaminuria is an autosomal recessive condition which means you would need to get an abnormal gene from both parents. Chances of both parents being carriers are very small, and therefore it is rare. We don't really understand the genetics of secondary TMAU but I cannot think of any of my patients where the disease has been passed on.

Can it result from (or produce) an overly acidic body, and does consuming baking soda or ACV safely help to alkalize it?

RL: I would not recommend taking large amounts of baking soda. It has been suggested to use alkaline body washes to remove TMA. Your skin pH which will not be changed by taking baking soda or alkalis. Your body is not overly acidic.

Have you come across any visible signs in sufferer's body (skin, lymphs, or otherwise)?

RL: No.

Is social or physical anxiety a cause or symptom of this?

RL: That's difficult to answer. People with TMAU get anxious and anxiety will make their symptoms worse. If you sweat or get hot when you are anxious, your odour will get stronger. I don't think TMAU causes anxiety, but it’s a matter of other people’s responses and how you interact with them.

Some have cut out choline in their diet which has caused nerve damage. Can we use a choline-bitartrate supplement to help meet the recommended daily choline intake amount 425mg? Not sure if we could better tolerate choline in a supplement form versus a food form? Do you have any advice on this?

RL: I am not aware that choline deficiency causes nerve damage. It’s not something that I have seen. There are some cases of patients who have been very sick on ITU and have been on intravenous feeds without enough choline who have developed ‘fatty liver’ which is entirely reversible. That would require severe choline deficiency and I have not seen that as a problem with patients on a choline-restricted diet.

Taking a choline supplement with a low choline diet would defeat the object of the diet.

Two researchers advised taking Cod Oil for Omega3, one was in UK. I thought Cod was one of the highest in Free Choline? Our diet is lacking good Omega3 any suggestions would be greatly appreciated.

RL: Omega 3 is good for your health, but fish oils are not recommended for those with TMAU, although there are other alternatives to fish oils that contain omega 3. A good dietician can advise on suitable omega 3 rich supplements. Cod liver oil contains all sorts of things other than omega 3s and comes from the livers of a lot of cod!

How does one know if they have mild, moderate, or a severe range by their results?

RL: Some people do have higher trimethylamines than others, particularly if loaded up with choline, but what really makes a difference to people is how bad their symptoms are and how it affects their life. Some people with higher levels can control them better than some with lower levels. For example (provided by individual asking question) a result showing TMA *42.3 umol/mmol creat (normal 2.5-10.9) shows high levels of trimethylamine in their urine at the time of testing, but these would be expected to change depending on diet, menstrual cycle etc etc.

Is there a difference between treatments of Primary and Secondary TMAU and prognosis?

RL: The treatment options available to you are the same.

I read some TMAU2 patients may have symptoms as a result of liver disease which results in a TMAU1-like pattern of excretion. Does this mean that those with TMAU2 are tested for other conditions on how they could have developed TMAU2, or to eliminate other causes?

RL: We always test peoples’ liver function in a routine blood test, since the FMO3 enzyme Is active in the liver, but have not come across any issues.

How does the UK research get funded? I know of NORD in the US , is there an organisation or charity that collects funding in the UK locally?

RL: There is currently no funding in the UK for clinical research on TMAU. There are people who work on FM03, but not specifically for patients with TMAU.

What is it that you personally do here at the University College Hospital ?

RL: I work with my colleagues in the metabolic unit looking after adult patients with inherited metabolic diseases. We have seen about 1600 patients of whom only 15-20 have TMAU. A lot of the other diseases we see are due to enzyme deficiencies and many are treated with diet, so it makes sense for us to see TMAU patients as well and I am sure the numbers of patients we see will continue to increase.

On behalf of the TMAU community, we really appreciate you agreeing to participate in this interview. Thank you very much!


Margaret H said...

Thank goodness there are people out there who can help and support us with this condition.

Many thanks,


Oct 28, 2012, 4:27:00 AM
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