OMF claim that Naviaux has replicated 77% of the metabolic pathway abnormalities found in his 2016 publication via Facebook

Andy

Andy

Retired committee member
The pertinent bit from their Facebook post
The latest news is great news: 23 of 30 (77%) of the metabolic pathway abnormalities found in the first study were validated by this follow-up study, despite large differences in clinical practice and geography between the two patient cohorts. These results add support that this metabolic signature can distinguish ME/CFS patients from healthy controls. Dr. Naviaux believes this metabolic signature is telling us that ME/CFS results from the persistence of a ‘dauer’-like metabolic program, leading to an energy conservation state mediated by the cell danger response (CDR).
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Why have we so many possible biomarkers yet nothing translates into real world medicine? I know studies need to be replicated but how come we never seem to move on one step further? I am glad to hear of Naviaux's replication study but it doesn't seem like something that could be transferred to doctor's office/hospitals.
 
Sounds promising, though of course we'll need to await the paper to see if the consistency is between specific metabolites or just between metabolic pathways. They seem fairly confident though as I don't think the OMF would put this out unless they thought it would be publishable shortly.
 
Sunshine3 said:
Why have we so many possible biomarkers yet nothing translates into real world medicine? I know studies need to be replicated but how come we never seem to move on one step further?
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I think replication allows the research take a step forward, a massive step forward potentially as it could mean more researchers focus on a smaller area.

In the past there were plenty of one- off studies which were never replicated, that doesn't help anyone move forward.

Sunshine3 said:
I am glad to hear of Naviaux's replication study but it doesn't seem like something that could be transferred to doctor's office/hospitals.
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I think they are still in the exploratory phase, but if that is successful the next step will be treatments. Everything has to start somewhere so who knows how far this could lead.
 
Chris said:
The question I always ask myself regarding Naviaux's hypometabolic hypothesis which evokes a kind of constant low energy state is - how does it account for those huge swing downwards and drastic drops that occur during crashes?
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I think the basic hypothesis is that when one overdoes limited energy supply the CD-R is triggered further to shut body down more to conserve more energy
 
Time to bring our old friend back. :slugish:

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Is 77% a lot? I'm a total layperson and was rather disappointed that they weren't able to completely replicate the results. :) I hope they won't lose further 30% with every new study on this. :nerd:
 
Joh said:
Time to bring our old friend back. :slugish:

Is 77% a lot? I'm a total layperson and was rather disappointed that they weren't able to completely replicate the results. :) I hope they won't lose further 30% with every new study on this. :nerd:
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The difficulty with, and one of the reasons I'm wary of, metabolomic (and microbiome) studies is that they're so wide-ranging that one is bound to get chance results. Plus there seems to be a wide intertemporal variation as well - it really depends on what time of day you take the samples, what the subject has been doing, what they've been eating etc etc. A 77% replication rate would be a pretty good hit rate, I think. (As said above: if the 77% relates to the same metabolite - I would be far more sceptical if it turns out 77% refers to the same pathway only, given the number of metabolites that can make up a given pathway).

Put me down as very cautiously optimistic.
 
Joh said:
Is 77% a lot? I'm a total layperson and was rather disappointed that they weren't able to completely replicate the results. :) I hope they won't lose further 30% with every new study on this. :nerd:
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A preliminary study would usually be fairly inconclusive, due to smaller number of patients and looking at a larger range of metabolites. Generally, such a study would be unlikely to have statistically significant results if correcting for making multiple comparisons.

A replication study would only look at the significant results from the first trial, so it would be making far fewer comparisons. That makes it a lot easier to see if there is a real difference between patients and controls, even after correcting for the number of comparisons being made. And based on the description of this study from last year, it's entirely a replication study so the results should be a lot more reliable (though we have to see the paper to know for sure). Plus they have 50% more patients than the first study, which increases its power to find significant differences as well.

23% of the initial study being likely false positives wouldn't be bad at all ... it's actually pretty impressive, I think, since they were looking at a ton of metabolites from what I recall. Depending on the methodology used in this paper, they wouldn't be likely to "lose" more significant results with further replication.
 
I think Dr. Davis said in London that they found differences between Naviaux data and the big data study, and that was probably a sample collection issue (hopefully).

These are the differences with Maureen Hanson, though it is a pilot study. We´ll see….

Naviaux vs Maureen.jpg
 
Chris said:
The question I always ask myself regarding Naviaux's hypometabolic hypothesis which evokes a kind of constant low energy state is - how does it account for those huge swing downwards and drastic drops that occur during crashes?
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Maybe there are mechanisms working in opposition? The cell defence mechanism trying to shut things down, and normal cellular operation trying to carry on regardless? Whenever you have complex systems with opposing forces at work, there is the potential for over- and under-swings, as regulatory systems under- and over-compensate. But just an engineer's notion, I have no medical knowledge.
 
Dr. Chris Armstrong’s team in Australia has done metabolomics studies using two types of machines, the kind Naviaux uses, Mass Spectrometry (MS) as well as a machine which does Nuclear Magnetic Resonance (NMR). Armstrong said it is ideal to be able to use both as each excells in a different way. MS is more sensitive but also shows more variability if using too small samples, for instance, but NMR is more reliable. I got this from a piece Cort Johnson about Armstrong’s work on 11-10-16. I am sure Naviaux’s team would know about the pluses and minuses of their machine, and probably designed things to correct for any shortcomings, but these questions may be worth getting clarification on.

Those more knowledgable than I about such machinery and study designs would be better able to comment.
 
Chris said:
The question I always ask myself regarding Naviaux's hypometabolic hypothesis which evokes a kind of constant low energy state is - how does it account for those huge swing downwards and drastic drops that occur during crashes?
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When asking the ME body to perform at normal levels of exertion, there’s a lot of fallout, such as more oxidative stress, more lactic acid in the brain and muscles causing brain fog and aching, more work for the liver to process the products of anaerobic metabolism (Hope I have this vaguely right.) The ME body can produce and deal with a slow stream of energy but a stronger one, an overload on its capacity, will create stress effects and trash products, so to speak, which then add to the work it has to do to restore the only form of homeostasis it has going, the lower set kind.
 
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