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

[AndyPR]

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?

Bear-ly able to do anything?

 

[lansbergen]

apparently prions do this too guys.

And prion infection will not be found in blood. Even if one looks at the right place one can only test for the pseudo marker.

 

[Forbin]

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?

It would feel like you were being attacked by a bear.

 

[Simon]

Are there any statistics experts following this who able to comment how rock solid this evidence is ? The sample sizes are on the low side and number of items measured very high, can we confidently rule out a fishing expedition ?

Yes (though with any small sample it may not replicate)

>Methods

Data Analysis.
Metabolomic data were log-transformed, scaled by control SDs, and analyzed by multivariate PLSDA, PCA, t test, univariate ANOVA with pairwise comparisons, and post hoc correction for multiple hypothesis testing using Fisher’s least significant difference method in MetaboAnalyst (56), or the FDR method of Benjamini and Hochberg (57).

.... Sets of 5–15 metabolites were selected manually from the top 60 significant metabolites as candidate diagnostic classifiers using two multivariate methods: RFs (58) [random forest] and linear support vector machine (SVM) implemented in MetabolAnalyst (56). .. Classifier robustness was estimated by repeated double cross-validation (rdCV) (59) and permutation testing 1,000 times in MetaboAnalyst.

Confidence intervals for the ROC curves were calculated by bootstrap resampling. Sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and number of misclassifications (60) were estimated by conventional 2 × 2 contingency table analysis and P values calculated by Fisher’s exact test in Prism.

 

[jaybee00]

Looking at the Karnofsky scores, most of these subjects were probably severe CFS cases, no?

What is mean by active work? If you are a 70, you are not working?

• 70 - Cares for self; unable to carry on normal activity or to do active work.

• 60 - Requires occasional assistance, but is able to care for most of their personal needs.

• 50 - Requires considerable assistance and frequent medical care.

• 40 - Disabled; requires special care and assistance.

• 30 - Severely disabled; hospital admission is indicated although death not imminent.

• 20 - Very sick; hospital admission necessary; active supportive treatment necessary.

• 10 - Moribund; fatal processes progressing rapidly.

• 0 - Dead

In the Naviaux paper, the controls were at 100, but the CFS means were 62 (males) and 54 (females).

 

[Tuha]

It will be also interesting to see if NIH will finally fund prof. Davis and his team. We were always listening that he doesnt have a hypothesis - now he got very interesting results and he can create many interesting hypothesis.
Dont we have an information that NIH will put 20 mil. USD to prof. Davis?

 

[JaimeS]

Are you able to enlarge at all on the 'Women, but not men, generally had disturbed fatty acid and endocannabinoid metabolism'?

Fatty acid metabolism issues are HUGE. Too huge to go into every detail. However, this on endocannabinoids may be of interest:

Energy balance and metabolism
The endocannabinoid system has been shown to have a homeostatic role by controlling several metabolic functions, such as energy storage and nutrient transport. It acts on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. It has also been implied in modulating insulin sensitivity. Through all of this, the endocannabinoid system may play a role in clinical conditions, such as obesity, diabetes, and atherosclerosis, which may also give it a cardiovascular role.[43]

 

[ScottTriGuy]

Fatty acid metabolism issues are HUGE. Too huge to go into every detail. However, this on endocannabinoids may be of interest:

Perhaps self-delusionally, I attribute my not being sicker to indica cannabis.

The more they find about its effects that aren't part of the obvious user experience, the more medicinal uses we'll get.

 

[Tom_Nightingale]

Coming from an evolutionary perspective, it's hard to believe that such a state is a "mistake", that hypometabolism is unhealthy.

Coming from a conscious, emotional perspective: WHAT THE HECK IS YOUR "PLAN", BODY!

A part of me wonders whether an aspect of modern life is sabotaging the "off switch" for this adaptive response. My best thought on this so far has been that such a hypometabolic state would be so debilitating, that the organism would not be able to procure resources from the environment like food, water, even oxygen. This is essentially like starvation.

Might the "off switch" be something so extreme as a level of metabolites or other molecule that is only achieved in a state of extreme starvation, thirst or even hypoxia?

Living in a post-industrial Western country, I've never experienced anything close. If anything, I'm a gluttonous organism relative to my ancestors. I don't even have to work hard to acquire a tremendous abundance of nutrients. With PEM or CFS, I would in short order be starving from inability to procure food if I were a human being just a blink of an eye ago in evolutionary time.

I wonder if being well fed/hydrated, even being in a temperature controlled environment is getting in the way of the CFS "off switch"...

Though that does sound a lot like death.... So there's that. But would an evolutionary adaptation persist to that point? I doubt it, unless there's some super-organism type of strategy going on (sloughing off of the weak/sick so the healthy won't be burdened). It's a dark theory, but maybe the light through the keyhole shines when it's dark

 

[mermaid]

Fatty acid metabolism issues are HUGE. Too huge to go into every detail. However, this on endocannabinoids may be of interest:

Thank you @JaimeS for that. Was just hoping that there might be a clue for me, but I didn't realise the fatty acid metabolism issues were so big. I had better read up more on the subject then!

 

[MikeJackmin]

Not every trait which is preserved is adaptive. Some vestigial traits are not costly, or are only occasionally costly, and they can remain stable over time because other, more useful traits share some of the same pathways.

Another way to look at it is that our illness might be nature's way of eliminating this trait right now.

 

[Tom_Nightingale]

Not every trait which is preserved is adaptive. Some vestigial traits are not costly, or are only occasionally costly, and they can remain stable over time because other, more useful traits share some of the same pathways.

Hmm. Do you have an example that illustrates this in humans that is as inconvenient as CFS?

 

[MikeJackmin]

Hmm. Do you have an example that illustrates this in humans that is as inconvenient as CFS?

Well, consider the classic peanut or bee sting allergy that can kill you with an entirely unnecessary anaphylactic reaction. It's clearly maladaptive, but it's closely tied in with very useful functions, and not likely to go away any time soon. I think that just about any auto-immune disease might be in the same category.

 

[Gingergrrl]

• 50 - Requires considerable assistance and frequent medical care.

• 40 - Disabled; requires special care and assistance.

I am also confused re: the difference between how to interpret 40 and 50 on the scale. (The bolding is mine). In thinking about my own situation I definitely require considerable assistance and frequent medical care (50) but I also view myself as disabled b/c I use wheelchair 24/7 and require special care/assistance. I am not sure how to distinguish between "considerable" assistance vs. "special care" and assistance. In both scenarios, I require medical care b/c I am actively having a treatment every three weeks that is done at an infusion center. But if I were not having this treatment, then I manage my meds at home without medical care and go to appts as needed (which are much less frequently than before). Some of the distinctions between numbers seem vague to me!

Not every trait which is preserved is adaptive. Some vestigial traits are not costly, or are only occasionally costly, and they can remain stable over time because other, more useful traits share some of the same pathways.

Another way to look at it is that our illness might be nature's way of eliminating this trait right now.

This is very interesting and I am not sure if I view this trait (Dauer) as adaptive or maladaptive. Maybe it is nature's way of ultimately eliminating it (like you said above)? I was not able to have biological children and if having this illness was my destiny, and if there was any chance of passing it on to a child, then maybe this is why my fate led me to my step-daughter who I have raised as my own child for 4-5 years. I couldn't understand why we would find each other and then I would get so sick, but maybe this is why?

 

[frog_in_the_fog]

Not every trait which is preserved is adaptive. Some vestigial traits are not costly, or are only occasionally costly, and they can remain stable over time because other, more useful traits share some of the same pathways.

All I can say, if we evolved from hibernating mammals, we must still have that inactive code someplace in our dna. I surely feel like I am in some kind of hibernation cycle a good deal of the time.

http://blogs.scientificamerican.com/guest-blog/can-humans-hibernate-ask-the-dwarf-lemur/

 

[duncan]

Would this qualify as "sickness behavior" or hibernation behavior?

 

[alex3619]

I don't even have to work hard to acquire a tremendous abundance of nutrients.

Its easy to get an abundance of high energy foods, or macronutrients, for most in the Western World. However our ancestors probably ate far better in terms of micronutrients such as vitamins and minerals, but this might include small active molecules such as plant antioxidants. A huge percentage of the Western population, and nobody really knows the exact figure, is both overfed and starving, depending on whether you are talking about macronutrients or micronutrients.

Then there are all those weird modern chemicals, including trace radioactive isotopes etc., plus a growing elecromagnetic signal that might interfere with voltage gated ion channels. We are still largely in the dark with even identifying all the potential issues.

 

[Dr Speedy]

Looking at the Karnofsky scores, most of these subjects were probably severe CFS cases, no?

What is mean by active work? If you are a 70, you are not working?

• 70 - Cares for self; unable to carry on normal activity or to do active work.

• 60 - Requires occasional assistance, but is able to care for most of their personal needs.

• 50 - Requires considerable assistance and frequent medical care.

• 40 - Disabled; requires special care and assistance.

• 30 - Severely disabled; hospital admission is indicated although death not imminent.

• 20 - Very sick; hospital admission necessary; active supportive treatment necessary.

• 10 - Moribund; fatal processes progressing rapidly.

• 0 - Dead

In the Naviaux paper, the controls were at 100, but the CFS means were 62 (males) and 54 (females).

I wouldn't label 60 as severe; people who are severe like myself wished we functioned at the level

 

[Gingergrrl]

I wouldn't label 60 as severe; people who are severe like myself wished we functioned at the level

Agreed and my end goal/fantasy after the entire treatment path I am pursuing is done is to be a 60 or 70 (barring an actual miracle occurring)!

 

[KIO]

"Dauer": Does it mean that we're an evolutionary throwback to an invertebrate with a larvae stage of development?! We might be feeble but we are supreme at toughing-out and surviving harsh environmental conditions! Well... perhaps... (Or we would be if we were larvae!)

Forgive my frivolity. I am actually enjoying the paper, and taking it seriously. It's very interesting.

I have already heard, sick ME / CFS to say: "Maybe we are mutants ..." ;-)