OMF study: Targeted analysis of seven selected tryptophan-melatonin metabolites: Simultaneous quantification of plasma analytes...

[Alvin2]

Got this email the other day, the full name of the study and its link:

Targeted analysis of seven selected tryptophan-melatonin metabolites: Simultaneous quantification of plasma analytes using fast and sensitive UHPLC-MS/MS

https://www.sciencedirect.com/science/article/pii/S1570023225000728

This seems to be about the design of a new analysis tool, but not any ME/CFS results (you have to build the base before you can build the tower).
They do mention in their press release:

This new method developed by the team allows researchers to simultaneously separate and quantify tryptophan metabolites, including serotonin, N -acetylserotonin, tryptamine, 6-sulfatoxymelatonin, hydroxymelatonin, melatonin, and N -acetyltryptamine. These metabolites are important in the context of ME/CFS because they have implications for hallmark symptoms of the disease: sleep disturbance and brain fog.

I want to try and research each metabolite and what effect it might have on cognition, has anyone here already done this and can share?

 

[Wishful]

Why do they keep studying plasma for this sort of thing? Local levels in the brain should be far more important (but of course, far more difficult to measure). How much of an effect on brain function do levels in plasma have compared to local levels? Isn't 95% of the serotonin in the brain produced locally?

 

[Rufous McKinney]

BUMP THREAD

 

[Alvin2]

Why do they keep studying plasma for this sort of thing? Local levels in the brain should be far more important (but of course, far more difficult to measure). How much of an effect on brain function do levels in plasma have compared to local levels? Isn't 95% of the serotonin in the brain produced locally?

Because its much, much harder to measure in the brain. Measuring metabolites is time honoured way to collect useful data.

 

[Wishful]

Because its much, much harder to measure in the brain.

It's much, much easier to invent ridiculous treatments than it is to figure out a disease and find an effective treatment.

Measuring metabolites is time honoured way to collect useful data.

Has that actually collected useful data on highly localized brain disorders? Some do produce significant markers in serum, but I'm pretty sure others don't. Time-honoured don't mean useful for all tasks.

 

[Wishful]

I should also add that there's a risk that people will say "We did the time-honoured approach and didn't find anything, so there's no point in wasting more funding on it."

 

[Alvin2]

It's much, much easier to invent ridiculous treatments than it is to figure out a disease and find an effective treatment.

This is a tangent. For any disease you need to understand what you are doing before you can address it. Medicine sometimes gets lucky and happens upon a treatment, but that is uncommon.
Of course for us little money is put on our condition since we are considered worthless and easily forgotten.

Has that actually collected useful data on highly localized brain disorders? Some do produce significant markers in serum, but I'm pretty sure others don't. Time-honoured don't mean useful for all tasks.

Why yes, many things in medicine have come from measuring metabolites. Medical research is extremely complicated and accessing the brain without causing permanent harm to the patient is very difficult to accomplish. Hell i remember reading about a team that developed several metabolite assays to measure brain changes and response to medications in Parkinsons.
You are correct that directly accessing the brain would be ideal, however it is a very dangerous thing to do and thus difficult get approval for because its not only costly, there are many ethics considerations at hand.
Of course if your a billionaire you can ask for volunteers, lie to them, destroy their brains and lives and the government looks the other way.

I should also add that there's a risk that people will say "We did the time-honoured approach and didn't find anything, so there's no point in wasting more funding on it."

Again this is a tangent, governments dismissing us will do so based on ideology. They can rationalize it till the cows come home, and will use whatever convenient reason they wish.

 

[Wishful]

Why yes, many things in medicine have come from measuring metabolites.

I meant specifically neurological disorders. I just checked schizophrenia: "A review of these studies revealed several potential metabolite signatures of schizophrenia including reduced levels of essential polyunsaturated fatty acids (EPUFAs), vitamin E and creatinine; and elevated levels of lipid peroxidation metabolites and glutamate. Further research is needed to validate these biomarkers and would benefit from large cohort studies and more homogeneous and well-defined subject groups." In other words, no definite metabolites found in serum so far.

I expect there are neurological disorders that do release metabolites into the serum. I just don't see TRP metabolites as likely to make a significant change in serum, since there are plenty of other body functions that produce large amounts. If, for example, ME increased QUIN levels in brain cells, isn't that likely to result in only fractional percentage changes in serum (QUIN doesn't cross the BBB), while an infection somewhere else in the body would significantly increase serum QUIN).

I wonder whether this is a case of specialists in a specific area (TRP metabolites in serum) managing to get funding for research that isn't really appropriate for their specialty. Measuring CSF instead of serum might not even help, since the elevated levels might not show up in CSF. From wiki: "In fact, the amount of quinolinic acid found in the brain of HAND (HIV) patients can be up to 300 times greater than that found in the CSF."

While the improvement in technology may be impressive, that doesn't mean it's the right tool for studying ME.

 

[Alvin2]

I meant specifically neurological disorders. I just checked schizophrenia: "A review of these studies revealed several potential metabolite signatures of schizophrenia including reduced levels of essential polyunsaturated fatty acids (EPUFAs), vitamin E and creatinine; and elevated levels of lipid peroxidation metabolites and glutamate. Further research is needed to validate these biomarkers and would benefit from large cohort studies and more homogeneous and well-defined subject groups." In other words, no definite metabolites found in serum so far.

I expect there are neurological disorders that do release metabolites into the serum. I just don't see TRP metabolites as likely to make a significant change in serum, since there are plenty of other body functions that produce large amounts. If, for example, ME increased QUIN levels in brain cells, isn't that likely to result in only fractional percentage changes in serum (QUIN doesn't cross the BBB), while an infection somewhere else in the body would significantly increase serum QUIN).

I wonder whether this is a case of specialists in a specific area (TRP metabolites in serum) managing to get funding for research that isn't really appropriate for their specialty. Measuring CSF instead of serum might not even help, since the elevated levels might not show up in CSF. From wiki: "In fact, the amount of quinolinic acid found in the brain of HAND (HIV) patients can be up to 300 times greater than that found in the CSF."

While the improvement in technology may be impressive, that doesn't mean it's the right tool for studying ME.

I'd love to see more research tools become available, don't think i am arguing that we have all that we need.
However we should also bear in mind that we have not even reached the apex of current technology, never mind new technology.