PoetFire wrote:Hi Colin. Thanks for posting. It is a privilege and we are most grateful to you for taking the time to communicate with us. At this stage in the history of TMAU we are better off talking direct with the researchers. Most Drs still haven't heard of it. I noticed your name in early FMO3 genetic papers. Do you still work on FMO3 research ? I guess genetics rather than FMO3 itself is what your work is based around ?
A couple of questions I had were :
What % of the population do you think is potentially 'at risk' of genetic TMAU (of some sort) when you include those who don't have obvious severe mutations ? There was a paper by Dr Cashman where some ladies who were carriers of common variants could dip in FMO3 function at menstruation. I wondered if some considered 'carriers' could in fact be at risk of TMAU 'incidents' etc. Do you think 1% is too high an estimate ?
Also, Mallory is rallying the troops to try and raise awareness amongst the population and politicians to get research going. Would you have any advice as to how we should go about getting research going or any other suggestions how we can get society to do something about genetic TMAU ?
Thanks for the welcome. Working on FMO3 at that time was very exciting particularly as there was a significant element of (healthy) competition driving us on - 7-day weeks were the norm. My research has migrated into different areas since then but I've always been interested in how the field has moved forward. With the creation of this UK site I thought I'd offer support and answer questions where I can.
As to your questions: as you know primary TMAU occurs when two 'inactive' FMO3 genes are present that results in no FMO3 enzyme function and thus no TMA oxidation capacity in the liver. As well as these so-called loss-of-function forms of the FMO3 gene there are other forms which code for an FMO3 enzyme that has a reduced ability to oxidise TMA. These forms are called decreased-function forms. An individual who has inherited one loss-of-function FMO3 form and a 'normal' one (a heterozygote) will have a reduced amount of functional FMO3 enzyme and thus may occasionally have problems in oxidising TMA especially if they have eaten something that leads to the production of a large amount of TMA in the gut and/or their already reduced FMO3 capacity is further lowered which can you happen, as you say, at menstruation. The same situation can occur for individuals inheriting either loss-of-function and decreased-function forms of even two decreased-function forms. So TMAU can be viewed as more of a spectrum of odour severity, sometimes occasional, depending on the FMO3 forms inherited and other factors such as dietary load of TMA precursors. As to how common these cases are is difficult to tell but probably more common that we think.
As to further raising the profile of the condition forums such as this do a great job and help make more dietary advice and councelling available which wasn't before. I've seen the idea of emailing MPs, etc and that must be a good way of lobbying for further support.
HTH