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

[Gingergrrl]

i agree with you @alex3619, the Karnofsky scale is useless for ME.

I agree with you and when I read the scale in this thread, it was challenging to give myself an exact number. There are things that I am able to do with ease that some on PR cannot do yet there are other things (like walk without wheelchair) that I cannot do at all. I am not housebound at all b/c I have a motorized wheelchair and I have a portable wheelchair and my family or friends push me in it. But if I did not have the wheelchair or a strong support system, I would be 100% housebound. So there there many nuances like you said. I could not physically unload a dishwasher to save my life but I could spend 5-6 hours on the phone advocating to straighten out an insurance error or helping my daughter with homework and this does not tire me. My mind is ready to go but my body does not cooperate.

 

[Kati]

Yes, current scales, and I mean all of them, miss the nuances. Its why evaluations get it wrong so often, and not just for ME. SF36 tries to get around this by breaking issues down into different subscales, but I don't think even that is enough. Just the physical subscale is far too subtle to be captured by any simple linear scale.

The problem I see with SF-36, right off the bat, starts with the question ' in general my health is good'. This is very subjective. Patients with ME may think, well, I never catch a cold, so in general, yeah, my health is good, I just have an energy problem. Answering my health is really poor- does that mean I am over reacting? Do you compare your health status to a palliative patient, in which case your health might be quite good? I suspect that just with this question, there is a lot of interpretation bias with our patient population.

 

[alicec]

I was able to quickly skim the paper when it first came out but haven't had the chance to read in detail and follow the discussion until now.

I don't want to go over ground that has already been discussed but would like to make a few separate points.

I must emphasise the ground breaking nature of the research. It is NOT, as @serg1942 and @Gijs have implied, more of the same, or some type of confirmation of studies that have gone before.

This study (and those we understand are in the pipeline) are orders of magnitude different with capacity to dramatically increase our understanding of the disease as well as providing a robust diagnostic along with likely treatment options.

I was impressed with the initiative shown in this post; the calibre of the science is such that it may well draw in others from right outside the field, who may add some unexpected insights.

I'm going to take the opportunity to plug The Microbe Discovery Project.

I agree. This is another initiative of such quality that we can also look forward to significant advances in understanding and thus potentially treatments.

Congratulations to @JaimeS for your analysis and the unifying concept of lipid rafts. I'm so pleased Naviaux acknowledged your contribution - it was masterful.

I think this hypometabolic state can be both protective and maladaptive. The original invocation of the response may well be protective but being permanently stuck on could well be an aberration. The researchers appear to think the latter since they are working on ways to unstick it.

 

[M Paine]

Could someone post a quote or link to the Naviaux comments regarding lipid rafts? Was that in the Q&A thread?

 

[alicec]

Could someone post a quote or link to the Naviaux comments regarding lipid rafts? Was that in the Q&A thread?

Here is his comment

Hi Jamie,
Please contact me at naviaux@ucsd.edu or call my cell (XXX-XXX-XXXX) sometime next week after the buzz dies down a little. I would like to talk.
You did a nice job explaining the implications of the sphingolipids for CFS biology. I had to cut 80% of our sphingolipids results and discussion to meet PNAS page limits. Some of this got relegated to the supplemental online material.
Kudos to you for a very nice job.
Sincerely,
Bob

Here is the link to the article.

 

[frog_in_the_fog]

There is no doubt we have some highly knowledgable members here on PR. I enjoy reading the play by play analysis, these are exciting times for us.

I truly feel empowered to make the best treatment choices for myself thanks to all the great people here on the forums.

I agree that the way forward is to continue research in all areas that show promise, as our conditions may vary as widely as the treatments that seem to work for us.

We each have our own story, yet here we are, all gathered together fighting for a common cause. As with other conquered once mysterious illnesses of the past, only progress through diligent research will take the mystery out of cfs/me; thus opening the door for the development of new more effective treatments, that will finally bring an end to our suffering.

 

[Marco]

If present, shouldn't this hypometabolic state show up as a reduction in total calories consumed/produced? Isn't this one of the test to be included in the big NIH study?

 

[trishrhymes]

Hi folks,
This thread is such a rich source of ideas and things to follow up. Thank you everyone.

After reading the Naviaux paper I feel I have a glimmer of what is being found - my background knowledge is not sufficient for me to understand all the details of the biochemistry/physiology involved, but I can get the gist and see how groundbreaking it is.

Thanks also for the stuff about lipid rafts - another fascinating piece. Something else to learn about.

And thanks for the links to the research on hibernation in animals - I'm off now to sofa-surf my way through some of the papers on this. Even if it's not relevant, I'll enjoy learning about it.

I know my knowledge and foggy brain won't enable me to make any useful contribution to the research, but I'm very much enjoying what I'm learning.

And of course, I'm hopeful that it will one day lead to new treatments. Patience!!!

 

[Jenny TipsforME]

I had lots of questions and comments in my head while reading this thread but mostly they've evaporated before I got to the end. :thumbdown:
A couple of thoughts left are:

It made me think of this video

about how to fix sleep (from 18min maybe relevant)
Gominak is puzzled about how animals are able to hibernate when mammals need frequent replenishing of B vitamins.
It goes into talk about vitamin d, precise b vitamin levels and the microbiome. IIRC the theory is that if your microbiome is appropriately balanced it can provide the relevant b vitamins.

I wonder what being in a hibernation like hypometabolic state but expected to be active, lacking microbiome diversity and b vitamin imbalance might feel like? Does that feel like ME?

For many of us big fluctuations are a feature of our ME (almost remitting-relapsing). Do we nearly snap out of this hypometabolic state and then a new threat makes the body remember the previous strategy? My relapses have always been accompanied by what appears to be a new virus (over doing it causes setbacks and PEM but not dramatic relapse).

 

[Jenny TipsforME]

Another thought: one of the experts in POTS said that it is fairly common to get temporary POTS when you have flu (presumably this is adaptive to get you to lie down and rest). Animals other than us also get POTS. Do animals get POTS while in hibernation mode to encourage rest?

 

[trishrhymes]

Exploring stuff on hibernation, I found this, which seems to precisely describes how my legs have felt from the beginning of my ME - still able to do short bursts of normal walking, then feeling that I had to sit down suddenly or my legs would collapse having completely lost muscle power (nothing like de-conditioning).

In ground squirrels during hibernation:

'These findings in hind limb skeletal muscles suggest that, although maximal contractile power output is maintained in torpor, there is both suppression of ATP production capacity and reduced fatigue resistance.'

That's the final sentence from the abstract of a paper about muscles in ground squirrels comparing them in summer and during hibernation: http://www.ncbi.nlm.nih.gov/pubmed/23531815

Just thought I'd share it. I'm now a hibernating ground squirrel!

 

[Jenny TipsforME]

@trishrhymes yes it is a really odd feature to be able to walk normally a few metres and then not. I've tended to think this is more POTS than ME but there isn't a clear distinction. It looks very different from someone with MS trying to walk.

 

[Neunistiva]

Exploring stuff on hibernation, I found this, which seems to precisely describes how my legs have felt from the beginning of my ME - still able to do short bursts of normal walking, then feeling that I had to sit down suddenly or my legs would collapse having completely lost muscle power (nothing like de-conditioning).

In ground squirrels during hibernation:

'These findings in hind limb skeletal muscles suggest that, although maximal contractile power output is maintained in torpor, there is both suppression of ATP production capacity and reduced fatigue resistance.'

That's the final sentence from the abstract of a paper about muscles in ground squirrels comparing them in summer and during hibernation: http://www.ncbi.nlm.nih.gov/pubmed/23531815

Just thought I'd share it. I'm now a hibernating ground squirrel!

It's certainly interesting but Dr. Naviaux said the metabolic signature is more similar to dauer than hibernation

I wouldn’t use the term hibernation to describe chronic fatigue syndrome. Humans do not hibernate. Hibernation is just one of a handful of hypometabolic states that has been studied in different animals. There are many others that go by names like dauer, diapause, torpor, estivation, caloric restriction, etc. Many environmental stresses will trigger hypometabolism in humans. In our experience, the metabolic signature of dauer is more similar to CFS than some of the other hypometabolic states that have been studied.

So we don't really have similarities with metabolic signatures of hibernating squirrels. And to think that we have similar physical experience of it seems even more of a stretch.

 

[Jenny TipsforME]

This is all I've found re animal hibernation and heart rate so far

During the first part of entrance into hibernation, heart rate
and blood pressure were irregular. Bradycardia often occurred
for a few seconds followed by tachycardia, with a concurrent
decline and rise in blood pressure (Figs. 1 and 2a). As the
entrance into hibernation proceeded, the pattern of the heart
rate became more regular, and the fluctuations in blood pressure
became less pronounced.

358 BULLETIN : MUSEUM OF COMPARATIVE ZOOLOGY Vol. 124
It doesn't say if tachycardia on trying to stand. It does mention animals change posture a couple of times an hour

 

[Jenny TipsforME]

It's certainly interesting but Dr. Naviaux said the metabolic signature is more similar to dauer than hibernation

So we don't really have similarities with metabolic signatures of hibernating squirrels. And to think that we have similar physical experience of it seems even more of a stretch.

I don't think @trishrhymes was being entirely literal! There was an element of humour in her post.

Creatures that experience Dauer are quite different from us so there does seem to be some value in looking at what happens in mammal hibernation. It is another type of hypometabolic state.

 

[trishrhymes]

You're absolutely right to correct me, Neunistiva. I wasn't suggesting we are in the exactly the same physiological state as ground squirrels, simply being amused/bemused by the parallel I saw in this aspect of another creature in a hypometabolic state.

As you say, Jenny, I wasn't being entirely literal. I must be more careful to point this out in future.

 

[Avengers26]

Hi @JaimeS or any one else,
Is there any "possible" actionable information that can be derived from this paper. I just finished reading it. It seems phosphatidylcholine phospholipids were low but DHA was high. Tyrosine/Phenylalanine & Riboflavin metabolites were decreased, Arginine was increased, BCAA metabolic intermediaries were decreased etc. etc.
Am I oversimplifying this or Is this practically useful info "at this time"?

 

[JaimeS]

Hi @JaimeS or any one else,
Is there any "possible" actionable information that can be derived from this paper. I just finished reading it. It seems phosphatidylcholine phospholipids were low but DHA was high. Tyrosine/Phenylalanine & Riboflavin metabolites were decreased, Arginine was increased, BCAA metabolic intermediaries were decreased etc. etc.
Am I oversimplifying this or Is this practically useful info "at this time"?

You are not. And I've got an idea: that's what I'll write my next bit on.

I will do my best to write about actionable stuff from this article and from this concept in general when I reach 10% of my fundraising goal. That info will go out to everyone, but people who donated will get to see it first. Good incentive?

 

[Chris]

Just a quick note on "actionable stuff"--I would guess most of us are on some form of fish oil for DHA/EPA--but if our DHA is high and phospholipids are low, a switch to krill oil might --might--be a small improvement?

 

[JaimeS]

...I am $5 from that 10% Chris.

But seriously, I'm not sure about the krill oil.