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

[Never Give Up]

OK sleeeeep. Bye guys!

Suuure.

 

[A.B.]

I think it will be difficult to achieve lasting improvement without removing the dauer trigger. The body isn't going to let outside intervention take it out of a needed survival state.

This might explain why so many things seem to help at least a bit for a short time and then stop working completely. The dauer state is intentional.

 

[Research 1st]

We are still in the very early days (yeah, after 30 some years and more) where NIH will have to admit they need to step it up.

I get worried about the suggestion of controlled nutrition as a treatment (mentioned a couple of comments up)- the last thing we need is to be told the problem can be fixed with a couple vitamins and yet another diet.

The researchers need to add the several layers that complicates things further: gene expression, blood-brain-barrier, brain abnormalities, co-morbidities (POTS), auto-antibodies, viral reactivation, NK cells, etc.

Something causes chronic innate immune activation in CFS - is this the CDR the Navieux paper is discussing maybe?. If it's never turned off, it'll become eventually damaged and perhaps (big if) you lose the ability to make antibodies to certain infections maybe also - so you test false negative on serology- Lyme anyone? But then you test positive on Cytokine tests using IFN-g to Borrelia (Elispot assays).

We know we're immune suppressed at the same time of not being so (on conventional tests). as we tend to zap everything we get, or least do at first......(e.g. length of disease changes the immune defense).

If we have low Lymphocyte ATP (White blood cell energy) maybe this is relevant to our immune problems? I'm yet to hear of someone with ME, ever test normal on this blood test.

Blood-brain-barrier. (BBB). Some PWME CFS have tested their Prion PrPC experimentally in the blood. The most severely affected reported absent PrPc (as do I) with less severe still being low, but not as low. One roll of PrPC is it protects the blood brain barrier. Theoretically, without PrPC you would have BBB compromised and allow infections to attack the brain with ease - is this why when we get viruses etc, we can get terrible symptoms (that doctors think we're imagining?). E.g Vertigo, Severe Headache - symptoms of Viral Meningitis, presumed psychogenic thanks to 'CFS' reputation as needing CBT/GET only.

Ideally we need an assay that measures CSF fluid for PrPc in CFS, and see what it shows, but as you know it's a painful procedure not without risk and classed as invasive.

So many questions, a few billion dollars in global research funding and we'd probably have it answered in 2 years.

 

[rosie26]

I think it will be difficult to achieve lasting improvement without removing the dauer trigger. The body isn't going to let outside intervention take it out of a needed survival state.

This might explain why so many things seem to help at least a bit for a short time and then stop working completely. The dauer state is intentional.

Thanks for expressing that so well. I agree. It's a very powerful problem that we have at root cause, can't see it staying quiet after all that I have experienced. Hopefully, we can get closer to the root cause to fix higher up stream.

 

[gregh286]

Autoimmune diseases can be reversed/cured by diet alone - look at Dr Terry Wahls and the folk with MS who are following her and taking part in the trials she is funding. A whole pile of folk with Hashimotos are doing the same, including me. Vast improvements on the autoimmune Paleo protocol. Not popular news here.

paleo diet is seen as starvation by human body. not exactly what is needed in a dauer state.

 

[consuegra]

http://cfspatientadvocate.blogspot.com/2016/08/robert-naviaux-metabolome-study-in-mecfs_29.html

 

[Art Vandelay]

They even make a speculative stab at directions for treatment..

Incremental improve-ments in NADPH production could theoretically be supported by interventions directed at folate, B12, glycine, and serine pools, and B6 metabolism (SI Appendix, Fig. S6)

I'm not sure if this is relevant but the Bioscreen researchers who were at Newcastle Uni (Australia) in the 1990s found some anomalies with animo acids in urine samples from people with ME/CFS. Included was serine and they found that some people responded well to serine supplementation.

Serine levels also mentioned in this study:

Five urinary metabolites were decreased in patients: acetate; alanine; formate; pyruvate; serine; valine and increased allantoin and creatinine.

I tried serine for a while and it improved my energy and brain fog but it also worsened my insomnia (which my specialist told me was very common in all his patients that had tried it). It was very expensive and hard to get in Australia back then, so I ended up giving up on it.

 

[Sean]

1. Tribunal ruling that PACE must release the data.
2. AHRQ downgrading its recommendations for CBT & GET
3. Naviaux et. al.: Metabolic features of chronic fatigue syndrome

A hat trick, a strike-out, and a trifecta, all rolled into one.

Here is me in dauer:

Here is me in dauer, before Naviaux et al. ...

Here is me in dauer, after Naviaux et al. ...

For a day or two, at least, before I am all dauered out, again.

 

[hixxy]

@Rever

In particular it will end false lines of research given a few years. It will also help narrow the range of research, give us much better targets to focus on, and far fewer potential therapeutic targets.

It is unfortunately a very expensive biomarker. Not sure how useful it will be unless the price of Metabolomics can be brought down.

 

[hixxy]

I tried serine for a while and it improved my energy and brain fog but it also worsened my insomnia (which my specialist told me was very common in all his patients that had tried it). It was very expensive and hard to get in Australia back then, so I ended up giving up on it.

Serine shows as high in the paper, not low.

 

[Gingergrrl]

I've been trying to understand "dauer" and Googled it but still not sure exactly what it means. What would be the best translation or most similar word in English?

 

[brenda]

paleo diet is seen as starvation by human body. not exactly what is needed in a dauer state.

Dr Kruse says that we need to eat carbohydrates (but not grains) in the summer but not winter so maybe we need to time it when we attempt to come out of the dauer state at the start of summer as part of correcting the circadian cycle. There are methods of doing that in his protocol which involve cutting blue light at night, rising with the sun getting out in the sun for natural ight on our skin and in our eyes and it has really done a lot for me.

 

[hixxy]

I've been trying to understand "dauer" and Googled it but still not sure exactly what it means. What would be the best translation or most similar word in English?

Hibernation

 

[A.B.]

I've been trying to understand "dauer" and Googled it but still not sure exactly what it means. What would be the best translation or most similar word in English?

A state of resistance in harsh conditions.

 

[Gingergrrl]

Thanks @hixxy and @A.B. and I get it now.

 

[A.B.]

Fever was once thought to be a disease, and doctors tried to reduce the body temperature of patients.

Then it was discovered that fever was a defense strategy against infections.

CFS was once thought to be a behavioural disorder, then it was discovered to be a defense strategy against ...

 

[Janet Dafoe]

@Rever


It is unfortunately a very expensive biomarker. Not sure how useful it will be unless the price of Metabolomics can be brought down.

Ron, Laurel Crosby and colleagues are working on that! Stay tuned!

 

[hixxy]

Fever was once thought to be a disease, and doctors tried to reduce the body temperature of patients.

Then it was discovered that fever was a defense strategy against infections.

CFS was once thought to be a behavioural disorder, then it was discovered to be a defense strategy against ...

... against death.

 

[Marco]

Does this explain my constant urge to collect nuts?

I'm having problems with this theory - its all so speculative and non-specific.

I suspect an element of expectation bias here.

Naviaux is obviously interested in these highly conserved metabolic processes, went looking expecting to find something consistent with the cell danger response and instead found a pattern of metabolites 'consistent' with another highly conserved metabolic process that most of us have never heard of.

But leaving aside false positives/correcting for multiple comparisons, is it really likely that anyone can specifiy with any accuracy exactly which metabolites will be down/upregulated in nematodes in this dauer state (dauer states - good name for a band) never mind in humans (where hibernation doesn't appear to be part of our behavioural repertoire)? 'Consistent with' is much too wooly.

Being highly conserved suggests a temporary state (to be conserved you have to pass on your genes so have either bred prior to hibernation and are still able to protect/raise your offspring during hibernation (unlikely) or the hibernation state passes once the environmental stressor is gone. The more interesting question is why PWME enter this state (if they do) and why they don't leave it. As an evolutionary conserved mechanism we all should be susceptible so why just PWME. Genetic vulnerability? If so why don't we all develop ME/CFS as infants when we first encounter environmental stresssors?

Then there's the issue of cause and effect. You test a group of people who spend a lot of time in a state of semi-hibernation and their metabolic profile is suggestive of a state of hibernation. Did they use healthy but sedentary controls?

I've yet to read the full paper - maybe they address these issues so apologies if they do.

 

[trishrhymes]

Wow! I haven't read everyone's comments yet, but have done a 'speed read' of the scientific paper to get the gist. Wow! I feel like throwing a party. Proof at last that I'm not malingering!

Come and join me at my hibernation party! No graded exercises (or any other sort) allowed.

Seriously, I wonder whether anyone has done any research to see what happens to animals in the hibernating state if they are roused and forced to exercise. PEM perhaps??