Kati
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Naviaux et. al.: Metabolic features of chronic fatigue syndrome
- Thread starter A.B.
- Start date
Thanks. I've only glanced over it but not sure it is all there. Seems to be fewer than the 612 metabolites mentioned, and I don't see any Karnofsky performance scores or any key to which metabolites belong to which pathways.
M Paine
Senior Member
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Yes, this confused me also.
I counted 226 Positive ION, and 223 Negative ION entries.
They mention in the methods:
So perhaps they truncated the data to exclude metabolites for which sampling was not sensitive enough to measure in all test subjects
Well ... I understand most of the words ... it's just the way they go together I need to work on
I should know better than to reply (semi) seriously to this but 1 in 20 (95% confidence) looks pretty good, consider how this compares to the position patients currently find themselves in re diagnosis.
I wonder whether this is simply one laboratory test or the result of a number of tests for metabolites (techie point), one laboratory test is cheaper possibly $300 ish.
I'm wondering if the accuracy will decrease in the larger study, but maybe with more laboratories running this test (Mass spectrometry) then alternative (better) biomarkers may be found (e.g. by Maureen Hanson).
Haven't had a look at the raw data yet.
I wonder whether this is simply one laboratory test or the result of a number of tests for metabolites (techie point), one laboratory test is cheaper possibly $300 ish.
I'm wondering if the accuracy will decrease in the larger study, but maybe with more laboratories running this test (Mass spectrometry) then alternative (better) biomarkers may be found (e.g. by Maureen Hanson).
Haven't had a look at the raw data yet.
I've looked very briefly at the method used.
They seem to have provided sufficient information for others to replicate this - good.
Viability - In terms of working this up into a diagnostic test if/once they confirm the target metabolites in a larger study then theoretically they may simply look for these which may speed up the time taken for each test (40 minutes in the current method). Even if each test takes 40 minutes and 20% are reference standards and 20% of potential output is lost for maintenance; this still looks viable at $300 per patient [price of statutory (i.e. Government) Mass Spectrometry test] since it would return possibly $2.5 million a year gross (check the sums). I think they said the instrument cost $1 million.
Excuse the back of the fag box approach but currently this seems to stack up as a possible diagnostic test; what we need now is the larger study looking at conditions which are clinically similar e.g. Lyme's disease, Gulf War veterans (and depression?). The fact that there may be a benefit for those with other diseases may help to get this funded by NIH etc.
Please try to get the larger study supported by your Government particularly the bigger players USA/Europe etc. E.g. by contacting your local elected representative/elected health representative. Also, consider trying to get those with an interest in Lyme's disease etc to push for the larger study.
Also, maybe the folks at the Open Medicine Foundation would consider a spin off company to carry out testing on a cost recovery basis.
They seem to have provided sufficient information for others to replicate this - good.
Viability - In terms of working this up into a diagnostic test if/once they confirm the target metabolites in a larger study then theoretically they may simply look for these which may speed up the time taken for each test (40 minutes in the current method). Even if each test takes 40 minutes and 20% are reference standards and 20% of potential output is lost for maintenance; this still looks viable at $300 per patient [price of statutory (i.e. Government) Mass Spectrometry test] since it would return possibly $2.5 million a year gross (check the sums). I think they said the instrument cost $1 million.
Excuse the back of the fag box approach but currently this seems to stack up as a possible diagnostic test; what we need now is the larger study looking at conditions which are clinically similar e.g. Lyme's disease, Gulf War veterans (and depression?). The fact that there may be a benefit for those with other diseases may help to get this funded by NIH etc.
Please try to get the larger study supported by your Government particularly the bigger players USA/Europe etc. E.g. by contacting your local elected representative/elected health representative. Also, consider trying to get those with an interest in Lyme's disease etc to push for the larger study.
Also, maybe the folks at the Open Medicine Foundation would consider a spin off company to carry out testing on a cost recovery basis.
Jill
Senior Member
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- Auckland, NZ
Cheney reviewed the naviaux paper. He will hv told them I expect
Thanks Jill, references to hormones is beginning to ring a bell.
The Naviaux paper used Mass Spectrometry to look at blood metabolites. The Naviaux paper seems to point the way forward i.e. find biomarkers in blood (accessible sample); this will enable you to test whether a treatment such as growth hormone works.
In terms of hormones in ME/CFS was this a research area that Jonas Bergquist was interested in i.e. looking at hormones using Mass Spectrometry?
The problem is how to get these studies funded; e.g. the UK Government funded PACE rather than the type of biochemical studies demonstrated to work by Naviaux, Hanson and Bergquist etc.
I suggested that possibly a not for profit company could be established to deliver ME/CFS biochemical diagnostic testing, using Naviaux's method (my previous post), e.g. by the folks in the Open Medicine Foundation. If it generated profits then these could e.g. be used to evaluate possible treatments.
In the meantime I'd suggest that folks try to influence their elected representatives, and public funding bodies, to support Naviaus's etc biochemical research (I recall my failed attempts but others may have more success).
ZeroGravitas
Senior Member
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- UK
Man, I'd really love to know Naviaux's thoughts on this newly published study!: "Elevated Energy Production in Chronic Fatigue Syndrome Patients" - http://www.jnsci.org/files/html/2016/e221.htm
Yes, elevated... They report finding 250% more ATP in blood mononuclear cells (PBMCs), with all of that coming from synthesis outside of the mitochondria. Also finding normal looking mitochondria, other than a slight (but significant) increase in number and density of their cristae (strongly indicative of raised energy requirement).
Result seems utterly counter-intuitive. Is it a trustworthy and meaningful result? Or even expected for someone in the know, like Naviaux? If true, does it mean that we're using, loosing or just sitting on that extra energy store? (Could extracellular ATP signaling, or something related, be draining this additional production, I wondered? Probably nonsensically.)
Discussion already in this thread - http://forums.phoenixrising.me/inde...n-in-chronic-fatigue-syndrome-patients.47443/
Yes, elevated... They report finding 250% more ATP in blood mononuclear cells (PBMCs), with all of that coming from synthesis outside of the mitochondria. Also finding normal looking mitochondria, other than a slight (but significant) increase in number and density of their cristae (strongly indicative of raised energy requirement).
Result seems utterly counter-intuitive. Is it a trustworthy and meaningful result? Or even expected for someone in the know, like Naviaux? If true, does it mean that we're using, loosing or just sitting on that extra energy store? (Could extracellular ATP signaling, or something related, be draining this additional production, I wondered? Probably nonsensically.)
Discussion already in this thread - http://forums.phoenixrising.me/inde...n-in-chronic-fatigue-syndrome-patients.47443/
Occasionally the counter-intuitive can herald new insights.
It cannot really be extra energy, else people with ME/CFS would be eating like horses and/or skinny as rakes. Tentatively suggests the 'extra energy', might be energy diverted from somewhere else? Which sort of fits.
Actually, I seem to remember that in answer to a question that it was identified that some of the metabolomic readings were downregulated and still others upregulated. So, having some extreme value (either low or high) seems similar to what was reported in the Naviaux study.
I have been reading the other thread, but don't have any ability to follow it well enough to offer any improvement to the discussion. I do, however, have some background in another medical process (blood clotting factors) enough to know that the body tends to have a lot of checks, counter checks, counter actions involved in anything that would be considered a complex process. In the blood clotting process if one process is blocked, there are other processes that attempt to correct the issue (sometimes to a benefit, sometimes in blood clotting to a detriment causing blood clotting issues).
And while I have no 'worthy' information ... it does make one wonder that if the metabolics are attempting to 'adapt' or 'handle' either a block or whatever it is that's causing the issue.... is basically self adjusting now to a state we don't really want as opposed to self adjusting to a state that is more towards what we expect when we feel healthy. I know in this thread, it was suggested that the 'self adjusting' might account for why some treatments seem to provide benefit, but only for a short time period...and then they help less over time.
If, in fact, our body is tired and it does have the right signals going... it may up regulate the production of certain types of energy factors. Whether those are usable (or blocked) or viable (which seems like studies have found they are ok in and of themselves).... or otherwise not being directed to where we need it.... well, that's the puzzle.
Jonathan Edwards
"Gibberish"
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Counter-intuitive results tend to be more reliable because they are not just made up to confirm what the researcher assumed would be the answer in the first place. And poor scientists tend not to publish findings if they are counter-intuitive because they are frightened by them.
Kati
Patient in training
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It sounds like Lawson et al. published in parallell with Naviaux et al. without one another knowing about the other's publication, because there is no mention or reference of each other's work.
I would also be very curious to know what they have to say about each other's work, and comments from our experts interested in that area of work.
I would also be very curious to know what they have to say about each other's work, and comments from our experts interested in that area of work.
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When the ANS is in 'overdrive' energy production is also. It is like driving in a car to fast the gastank will be very quick out of fuel. This can explain both studies. ME is like an abnormal (stress) reaction to a normal stimulus. Such as firing a nuclear bomb on a mosquito. The moment of blooddraw is very importent.
Could this mean that rather than ME/CFS suffers being unable to process the available energy fast enough, there may instead be some 'parasitic' mechanism stealing the available energy away from where it is needed, and self regulation mechanisms strive to make up the shortfall, with limited success?
Maybe akin to driving a car with the brakes stuck partly on.
Yes, indeed the parasympathetic nervous system (brakes) is broken.
Doing this on my phone so limited opportunity to lift text etc.
There's a great electron microscope image showing the altered "cystis" or whatever they're called (possiby Figure 1(d)). Can this be used to diagnose patients? Also, can it be used along with the Naviaux metabolic study to improve confidence in diagnosis? We understand that there is to be a bigger metabolmics study, so possibly testing electron microscopy (as well as metabolmics) would be useful.
In terms of what this study reveals, it's confusing and interesting. Possibly the body using a workaround (comments above re blood clotting) possibly interesting insight re signalling (comment above re parasympathetic nervous system). Fluga and Myla (Norweigan retuximab group) findings may help to understand this (see other blog on this new paper).
Excuse cryptic comments.
We need to see this translated into benefit for patients I.e. a diagnostic test; even if it has to be self funded in the short term.
There's a great electron microscope image showing the altered "cystis" or whatever they're called (possiby Figure 1(d)). Can this be used to diagnose patients? Also, can it be used along with the Naviaux metabolic study to improve confidence in diagnosis? We understand that there is to be a bigger metabolmics study, so possibly testing electron microscopy (as well as metabolmics) would be useful.
In terms of what this study reveals, it's confusing and interesting. Possibly the body using a workaround (comments above re blood clotting) possibly interesting insight re signalling (comment above re parasympathetic nervous system). Fluga and Myla (Norweigan retuximab group) findings may help to understand this (see other blog on this new paper).
Excuse cryptic comments.
We need to see this translated into benefit for patients I.e. a diagnostic test; even if it has to be self funded in the short term.
Leopardtail
Senior Member
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The most obvious thing jumping out at me as that most PWME I know have elevated Cholesterol where this study shows low. That seems surprising.
The purine stuff seems entirely constant with previous studies on ATP synthesis and Ribose levels but inconsistent with Myhill et Al's work showing elevated Adenosine.
Some expected results, some puzzling. I had low Cholesterol with mild ME high once it became severe.
Leopardtail
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I noticed that too 80 of 84 from CA.