Naviaux et. al.: Metabolic features of chronic fatigue syndrome

[Gijs]

Always the optimist!

Haha, No Sidereal, i am just realistic after 20 years. I have seen many ' breakthroughs'. I don't think the Naviaux findings will be replicated. Why? Because they used a very small 'special' cohort which is not representative, you will see. Also why do women (80%) have this metabolic state of Dauer and not more men? It does not make any sense too me. But let me be wrong.

@Ben, Thanks, but i think it isn't independent replication.

 

[Ben H]

Haha, No Sidereal, i am just realistic after 20 years. I have seen many ' breakthroughs'. I don't think the Naviaux findings will be replicated. Why? Because they used a very small 'special' cohort which is not representative, you will see. Also why do women (80%) have this metabolic state of Dauer and not more men? It does not make any sense too me. But let me be wrong.

@Ben, Thanks, but i think it isn't independent replication.

I mentioned independant replication in the bottom of my post. Hansons already partly contributes to this. This will come with NIH funding.

The study Is being replicated as we speak. Whether the findings will be, we shall see, but I am confident. They findings already have been partially replicated in Hansons study-but I am awaiting the full paper.

The people on the cohort were not a 'special' cohort at all-they were severely affected patients.
All CFS patients met the 2015 IOM, Canadian, and Fukuda diagnostic criteria for CFS.

So they are the most accurate representation of ME/CFS you can currently get, without a biomarker. Not 'special'-just specific. There is a study planned looking at the moderately ill. This still requires funding.

The research suggested all patients had this dauer state. Where are you getting the 80% from? The metabolomics results gave a sensitivity of identifying ME/CFS va healthy controls of 94 and 96% for male and females respectively. Thats unbelievable for a 'first go'.

Men and women are different biochemically so I don't think it is suprising there are differences in affected metabolites. But there were a significant number of similarities and identical affected metabolites. Its all in PNAS :

http://m.pnas.org/content/early/2016/08/24/1607571113.full


B

 

[Simon]

I'm not sure about that Simon. I'm pretty sure that a p value of 0.15 does mean that there's a 15% likelihood that it's due to chance.

Let me try to explain. p<0.15 is a 15% chance the data could have occured by chance, as you say. Q<0.15 is subtly but critically difference and is used all the time in genomics and gene expression, for instance. It means that you would expect 15% of the reported findings to be false positive, but not the other 85% ie it's highly enriched for true positives. Depending on the sample size, the p value will be smaller, but it will be way under P<0.05 in this study.

Nb if you correct p values to give NO false positives (what you want in normal studies), in a gemomics study you'd end up with a vanishigly small p value and miss all the real positives. Genomics studies are designed with both a discovery phase and a later validation phase, that only considers positives from the discovery phase (to weed out the false positives) There are fun courses on this if you'd like to know more.

Added (since weiredly people seem to be reading this)
Q values are part of a method called FDR, for False Discovery Rate. While p values control the chance of getting a single (or ANY) false positive(s), FDR (Roosevelt stats) instead control the rate (i.e. the proportion) of false positives.

 

[Sidereal]

Haha, No Sidereal, i am just realistic after 20 years. I have seen many ' breakthroughs'. I don't think the Naviaux findings will be replicated. Why? Because they used a very small 'special' cohort which is not representative, you will see. Also why do women (80%) have this metabolic state of Dauer and not more men? It does not make any sense too me. But let me be wrong.

@Ben, Thanks, but i think it isn't independent replication.

I understand your point of view. I'm a jaded realist who has been sick as long as you. But this time it's different. There have never been breakthroughs before, only nonsense peddled as a breakthrough. This, on the other hand, is an actual game-changer.

 

[Simon]

What would be freakin' awesome is if someone did a metabolomics study pre and post exercise challenge, showing objective abnormalities (metabolism crashing even further) during the PEM state, say 24-48 hrs after exertion. This sort of study would be the stuff of nightmares for CBT/GET pushers.

I think that's exactly what the NIH are planning as part of its study (only not just metabolomics).

 

[Sean]

I understand your point of view. I'm a jaded realist who has been sick as long as you. But this time it's different. There have never been breakthroughs before, only nonsense peddled as a breakthrough. This, on the other hand, is an actual game-changer.

Yep.

Been sick over 30 years, my whole adult life, seen too many false starts and promises to count.

But I am more optimistic about how things are currently playing out than I have ever been.

It isn't just one or two things. A whole lot of factors are starting a long overdue swing back in our favour.

In particular, I never doubted the game would fundamentally change once enough senior biomed researchers started taking a serious interest. Which they are now.

 

[Sidereal]

@Sean, my thoughts exactly.

 

[Hutan]

If this hypometabolic state is indeed something that has been conserved in both human and nematode genes because it has some utility, then I would expect we would see it occurring in mammals. It won't be just us and the nematodes.

I wonder if vets have ever seen something like an ME outbreak when a disease affects a group of primates or other mammals.

Sometimes vets know things doctors don't. Maybe less psychobabble to distract.

 

[Gijs]

@ Sidereal, I hope you are right. I also would like to know which medicine these cohort are using if they do it can influence the metabolic state. I like to know if they are on a diet etc.. I can not read this kind of information in the study.

@ Ben, I read the Hansons findings differently. It didn't confirm the findings of Naviaux, like spingholipids. That was a very significant finding. I mean with 80% the ratio woman/men with ME.

 

[lansbergen]

I wonder if vets have ever seen something like an ME outbreak when a disease affects a group of primates or other mammals.

I saw it in my large animal group and as I treated them early in the disease process with the immunemodulator it did not get as bad as I got.

 

[trishrhymes]

If this hypometabolic state is indeed something that has been conserved in both human and nematode genes because it has some utility, then I would expect we would see it occurring in mammals. It won't be just us and the nematodes.

Interesting idea. I guess hibernation has parallels, as already suggested. Otherwise, as an illness state rather than a species wide adaptation, I guess it would be harder to find.

I can imagine a wild animal with ME would struggle to survive, either starving or being eaten, and a farm animal would soon be disposed of as unproductive. Not sure about pets - how would you tell?

 

[halcyon]

I wonder if vets have ever seen something like an ME outbreak when a disease affects a group of primates or other mammals.

 

[Simon]

The chat talks about different methods to analyze the blood, but to me, the cohort differences are most significant; Naviaux's folk were in such a small geographic area.

That made me laugh - they were from all over California. If you live in Britain, that's not such a small area.

 

[Ben H]

@ Sidereal, I hope you are right. I also would like to know which medicine these cohort are using if they do it can influence the metabolic state. I like to know if they are on a diet etc.. I can not read this kind of information in the study.

@ Ben, I read the Hansons findings differently. It didn't confirm the findings of Naviaux, like spingholipids. That was a very significant finding. I mean with 80% the ratio woman/men with ME.

Thats why waiting for the full paper is sensible. But from the podcast/ graphs it did confirm many of the same metabolomics which is significant. It did not use the same method as Dr Naviaux which could account for the spingholipids and it did not measure near as many metabolites iirc. Im all for replication and independant replication, its a necessity.

Has that 80% even been substantiated?


B

 

[JamBob]

I mean with 80% the ratio woman/men with ME.

Hypothyroidism (another form of hypometabolism) is 10 times more common in women than in men.

 

[Hutan]

http://www.institutferran.org/documentos/cfs_horses_2000.pdf

CHRONIC FATIGUE SYNDROME IN HORSES: DIAGNOSIS AND TREATMENT OF 4 CASES
2000
AUTHOR:
Walter Tarello, veterinary surgeon

I've seen this paper before - not sure about the arsenic as treatment but there are some interesting snippets of information in there.

These two animals were examined at a riding school in Aosta (Northwestern Italy) in late October 1992. They had taken ill at the beginning of August, and no clinic improvement had followed previous treatments.

Symptoms consisted of chronic weakness and easy fatigability after moderate physical effort, with difficulty in carrying out their work. The animals did not feed well,

......
Symptoms and signs, in horse #1 and #2, were compatible with those of the initial stage of Borna’s equine encephalomyelitis, caused by an RNA virus [24]. However, the second stage of this sickness is characterized by a rapid, acute worsening of the neurological disorders, and death. In these horses, instead, the illness had had its onset three months before, followed by some worsening of the symptoms but in a chronic course.

 

[Gijs]

Hypothyroidism (another form of hypometabolism) is 10 times more common in women than in men.

That is mostly autoimmune and well known.

 

[JamBob]

That is mostly autoimmune and well known.

The present study doesn't rule out autoimmunity though.

 

[JaimeS]

That made me laugh - they were from all over California. If you live in Britain, that's not such a small area.

True! But it is mostly the same coastline of the US. You're right to say that geographically, it's a huge area, but for example all of these people would have been exposed to very similar oceanwater contamin....

[stops self]

[checks self before wrecks self]

....I'm not really 100% sure about that!

-J

 

[KME]

I keep thinking about this question - if you could wake a hibernating bear, and keep it awake, but the hibernation process did not stop, how would it feel?

I would like to see that bear's reaction if told to get on a treadmill.

Or to stop catastrophising.

(The nematode worm's reaction might be pretty good too, if subtle by comparison.)

Joking aside, I think this is the absolutely crucial implication of this study's finding that ME/CFS/SEID is a hypometabolic disease. If people are in a hypometabolic state, doing normal activities will damage them. Doing activities that are challenging for those who are normal metabolically, such as exercise, will be dangerous. Right? Otherwise wouldn't animals have evolved to get more active during times of environmental challenge? Oh look, says the toad, drought and famine are coming: time for some aerobic exercise to help me adapt.

I'm so enthused by this research. Makes such a lot of intuitive sense. I particularly like that it explains (not explicitly) how generally we with ME don't die (with extremely sad exceptions) although we can teeter on the brink for a long time, and how some improve and even recover, even after long periods of illness. I can completely understand that someone's body might just un-dauer itself, either spontaneously or in response to some change in the biochemistry caused by a treatment.

The switch idea also appeals - that mitochondria are turned off rather than broken. I made an initial complete-except-full-on-exercise recovery initially, and it felt like a dimmer switch gradually being turned up. I didn't have to do anything, just wait it out and function just returned gradually. Then I relapsed (due to full-on-exercise) and it felt like an on-off switch went firmly to the off position. It hasn't budged in 6 years.

Huge thanks to all the researchers and to all the bloggers for communicating these important findings to patients.