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

ScottTriGuy

Stop the harm. Start the research and treatment.
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1,402
Location
Toronto, Canada
epigenetic signalling which must occur as part of the regulation of human hypometabolism.

I am so not of the science brain, so epigeneticist Will De Vega plain explained it to me - here's an excerpt of his reply, maybe it informs your statement?

Will is presenting his ME research on epigenetics and glucocorticoids at the IACFSME Conference in October:

"Thanks so much for sharing this study. I'm actually aiming to submit in that journal (PNAS) so it's good to know that they're likely going to be receptive to our study as it will follow up the findings of this paper.

... it does show the tight interaction between metabolism and epigenetics. All in all, their findings actually nicely compliment my previous (PLOS ONE paper) and our upcoming findings as we do find differences in the epigenetic signatures of metabolic processes.
"

Sounds very exciting to my untrained ears!
 

ballard

Senior Member
Messages
152
Bear and NIH.jpg
 

valentinelynx

Senior Member
Messages
1,310
Location
Tucson

Art Vandelay

Senior Member
Messages
470
Location
Australia
I have high LDL and low HDL.

My mother, who also suffers from ME/CFS, has very high LDL. What's so unusual, is that she's abnormally skinny and avoids eating any fats.

I'm wondering if her high LDL might be her body's response to some sort of chronic inflammation, which is what a lot of the current medical literature now seems to indicate.

Any thoughts on this?

My cholesterol levels were normal before I got sick and doubled after I came down with ME.

If you dig beyond the "cholesterol is bad for you" discussions, there's some interesting literature out there about cholesterol:

Cumulative evidence suggests that lipoproteins may also prevent bacterial, viral and parasitic infections and are therefore a component of innate immunity. Lipoproteins can also detoxify lipopolysaccharide and lipoteichoic acid. Infections can induce oxidation of LDL, and oxLDL in turn plays important anti-infective roles and protects against endotoxin-induced tissue damage. There is also evidence that apo(a) is protective against pathogens. Taken together, the evidence suggests that it might be valuable to introduce the concept that plasma lipoproteins belong in the realm of host immune response.
http://www.ncbi.nlm.nih.gov/pubmed/20377753

Lipoproteins play important roles in the process of removing toxic bacterial cell wall constituents including peptidoglycans and lipoteichoic acid, and lipopolysaccharide (endotoxins), all of which can contribute to bacterial sepsis and septic shock.12) In addition, lipopoteins scavenge the main pathogenic component of the cell walls of Gram-negative bacteria; endotoxins (which are released during immunopathology) are rapidly bound by LDL cholesterol.13) 14) Another example: Staphylococcus aureus-toxin, a toxin produced by most pathogenic Staphylococcus strains and causing damage to a wide variety of cells, is bound and almost totally inactivated by human serum and purified LDL.
http://mpkb.org/home/tests/lipids#laboratory_evidence
 

Wolfiness

Activity Level 0
Messages
482
Location
UK
And what is that first picture supposed to be? (Sorry I don't know how to post it right now). A woman puzzled by why anyone would think this disease is psychiatric? Is she wondering why they interviewed this Macintosh dude?

:D
He's also in The Telegraph's article www.telegraph.co.uk/news/2016/08/30/scientists-find-signature-of-chronic-fatigue-syndrome-in-blood-w/, saying "It is difficult to know whether the changes reported are a cause or an effect of CFS." We all know how vexatious it can be when people confuse cause and effect.
 
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Sasha

Fine, thank you
Messages
17,863
Location
UK
I had trouble getting that information, too, in a specific way. Generally, Naviaux is saying that severity correlates to metabolomic results (which could be obtained through bloodwork), and I presume he means some kind of aggregate score for overall severity of symptoms, but I did not see how severity was measured.

In Table 1, he gives patients'/controls' average Karnofsky performance scores - it's a disability scale developed for cancer (to assess patients' ability to cope with chemo). 100 = normal, 0 = dead.

Wikipedia said:
  • 100 - Normal; no complaints; no evidence of disease.
  • 90 - Able to carry on normal activity; minor signs or symptoms of disease.
  • 80 - Normal activity with effort; some signs or symptoms of disease.
  • 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).
 
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15,786
Yes, more accurately it's a hibernation in hell, ravaged by unrelenting insomnia and all manner of extreme physical symptoms. Not the sweet and peaceful kind of hibernation.
Or maybe a partial or incomplete dauer state, due to the human versions of the relevant genes being only around 35% similar to the nematodes in some cases and missing in others. Non-essential biological functions shut down, but without the nice long nap :p

I still don't understand the cholesterol part and I think your article supports the idea that PWC's have low cholesterol (but I have very high cholesterol and have all my life even as a child) so would this imply I do not have ME/CFS? I am still not sure myself so am curious.
Cholesterol levels mostly depend on genetics. The impact upon cholesterol from an acquired disease might very well be smaller than the genetic impact.

Also are SED rates and cholesterol connected? My SED rate is six and was never as low as many PWC's report.
ESR can be raised for different reasons. High levels can be in response to many problems, so it's a very non-specific test: "The ESR is increased in inflammation, pregnancy, anemia, autoimmune disorders (such as rheumatoid arthritis and lupus), infections, some kidney diseases and some cancers (such as lymphoma and multiple myeloma)." (Wikipedia)

It's only low for these reasons: "The ESR is decreased in polycythemia, hyperviscosity, sickle cell anemia, leukemia, low plasma protein (due to liver or kidney disease) and congestive heart failure." (Wikipedia)

Contrary to what some people repeatedly say on this forum, ESR is not low in the research involving ME/CFS patients. Depending on the criteria used, it's typically normal or elevated compared to controls.
 

Kalliope

Senior Member
Messages
367
Location
Norway
I haven't been able yet to read through all the comments, so forgive me if this has already been discussed, but could the "dauer effect" be an explanation to why we don't always observe the expected muscular atrophy in ME-patients bed bound for long periods?
 

msf

Senior Member
Messages
3,650
Please could someone explain this apparent contradiction to me, I'm finding it hard to understand:

In the Open Medicine Foundation article it states:

http://tinyurl.com/z6sgbbh

"This result supports the controversial idea that while infection is often the initiating event for ME/CFS, it does not contribute to the ongoing illness."

However, the Naviux paper itself states (at the bottom of page 3):

“The low sphingolipid profile in CFS appears to be an adaptive response...and ultimately may represent a fundamental response to oppose the spread of persistent viral and intracellular bacterial infections”.

Not sure how to reconcile those two statements?

Yes, some of us are quite puzzled by this. We have been discussing it in the usual spirited manner in this thread: http://forums.phoenixrising.me/inde...nd-a-with-dr-naviaux.46520/page-5#post-757528
 

natasa778

Senior Member
Messages
1,774
Lipids-Naviaux.png



Just to say, for the record ;), that my money is on (endogenous) retroviral proteins messing up cellular membrane and causing all this.

"It is well documented that lipids in both the viral and cellular membrane play an important role in retroviral replication; these lipids include cholesterol, sphingolipids and certain phospholipids...."

Described here in great detail The Role of Lipids in Retrovirus Replication

What is most pertinent imo is that some retroviral proteins, including endogenous RV ones, will be chronically expressed and embedded in the host cellular membrane even in the absence of active infection and viral replication.

The 'two-hit infectious hypothesis' could fit nicely with viral pseudotyping, and other types of virus-to-virus interactions (like EBV and HERV) where most of the action happens to take part on host membrane.


@anciendaze any thoughs?
 
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Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
Can`t help theorizing around these findings..

After some thought I think the most likely reason for these abnormalities, is also the most simple: It is a downstream effect to keep us from using our sick bodies more actively than it can manage.
or possibly, our metabolism is directly affected by disease mechanism X
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I haven't been able yet to read through all the comments, so forgive me if this has already been discussed, but could the "dauer effect" be an explanation to why we don't always observe the expected muscular atrophy in ME-patients bed bound for long periods?
This is a good question and occasionally we speculate about why the deconditioning and muscle atrophy is much less than you would expect. I think its possible, but we lack proof, that our metabolism is resistant to deconditioning such as muscle atrophy. Indeed the point of a dauer effect seems to be to slow down damaging impact on the body. It also prevents the body from increasing capacity on demand. However I am not sure it protects from bone deconditioning.
 

Kalliope

Senior Member
Messages
367
Location
Norway
This is a good question and occasionally we speculate about why the deconditioning and muscle atrophy is much less than you would expect. I think its possible, but we lack proof, that our metabolism is resistant to deconditioning such as muscle atrophy. Indeed the point of a dauer effect seems to be to slow down damaging impact on the body. It also prevents the body from increasing capacity on demand. However I am not sure it protects from bone deconditioning.
Thank you @alex3619 for your comment. I've also heard from carers of long term bed bound ME-patients, that skin and hair seems to take care of itself and don't really need that much attention in comparison to others in need of nursing. Don't know if that is a general observation or relevant..
 

mermaid

Senior Member
Messages
714
Location
UK
Thank you @JaimeS for your ME Action blog re the study. As a non scientist I will need to read it several times, but there are some things I can understand better already by reading it.

Are you able to enlarge at all on the 'Women, but not men, generally had disturbed fatty acid and endocannabinoid metabolism'? I am specifically interested in the fatty acid side of things as on the very day the study came out, I had just written off to my GP to tell her that I had been researching Fatty Acid Oxidation Disorder in particular with reference to problems with Carnitine. (ha ha - sounds more impressive than it is with my science ignorance, but my GP once said I knew more about the thyroid than she did). I have requested a blood test from the NHS as another member on PR has helped me a lot to understand more than I did. They often test babies I believe, but not adults so much.

I had a blood test done some years ago when I was at an ME low point with Dr Myhill, and had the lowest serum Carnitine score she had ever recorded. She pointed me towards taking Acetyl-l-Carnitine but I was unable to, due to horrendous stomach pain from it, but in spite of that my score increased by quite a bit in 4 years, though was still below the range. I have evolved my own method for transdermal Acetyl-l-Carnitine but don't know how much it's doing (I dissolve A-l-C into transdermal magnesium with DMSO and plaster it on my legs and feet, and put long support socks on top)

I don't know if this is an issue I may have always had even pre ME days, as I had some symptoms as a small child which indicate I might have (frequent sickness, GP saying that my brother and I had problems with absorbing fats, rough skin on upper arms).

My overall ME symptoms have improved a lot in the past year, mostly via herbal medicine I believe, but I am l left with the basics of lack of stamina, and symptoms kicking in if I overdo too much but I have been able to extend activity more than I did before.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Or maybe a partial or incomplete dauer state, due to the human versions of the relevant genes being only around 35% similar to the nematodes in some cases and missing in others. Non-essential biological functions shut down, but without the nice long nap
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?