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

[Nielk]

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

They all came from one doctor's office.

Subjects in Naviaux/Gordon study were from Gordon Medical Associates practice, NOT OMI.
The OMF Big Data Study patients were from OMI. Ron's results are from Metabolon. Bob Naviaux's are from his own Mass Spectrometers at UCSD.

 

[Simon]

They all came from one doctor's office.

We don't have offices this big in the UK!
(map of patient locations, from the study)

 

[AndyPR]

We don't have offices this big in the UK!
(from the study)
View attachment 17158

Lol, that's a range of approx 700 miles - San Diego in the south up to Eureka (as an approximate position) in the north, and ignoring the outlier in Utah.

ETA: For UK people, John O'Groats to Land's End is some 800 odd miles as a comparison.

 

[Michelle]

1.) I can't remember now if someone mentioned this upthread (it's taken me days to read through it all!), but with regard to funding I would think the personalized medicine potential with this technology/data would make it a poster-child for funding through the new Precision Medicine Initiative (something I *think* Dr. Whittemore has mentioned in one of her recent talks/interviews). Though I had thought PMI got more $$ than I see it has upon closer inspection. Still...

I would be surprised if Davis and Co. haven't already thought of this. But it might be something for us to bug our congressmen and women about!

2.) I know I was skimming which, combined with the brain fog, means I miss a lot, but I can't remember why they singled out comparing/contrasting these results with diseases like depression and PTSD rather than/in addition to MS, Lupus, Cancer, Congestive Heart Failure, etc. To me, seeing what sort of metabolomic profile pops up with those diseases and comparing/contrasting that with ME/CFS would seem like the most important next steps to take research-wise (obviously after replication) in addition to @Sidereal 's excellent point about pre/post 2-day CPET.

Is the issue that they already know how this compares i.e. they already know those diseases have characteristics of hyPERmetabolic states?

 

[Tuha]

If you are looking for the big replication of Naviaux´s study, I think there is one good news. Lipkins team just got the first big donation to his microbiome study where he plans to do also metabolom study. So he could possibly validate Naviaux´s finding. We should try to do more publicity to this research and try to donate and to bring new donors. Now the next step should be to validate this hypometabolism findings from another independent group. Without fast validation everything will take longer.

here you can read more:
http://microbediscovery.org/2016/09/05/great-news-a-big-100000-donation-we-have-some-total-updates/

 

[Research 1st]

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.

RE: Gender difference:
I wouldn't worry as it it makes perfect sense, because autoimmune illnesses affect more Women than Men.

RE: It won't work out:
I agree, it won't work out as the cause of CFS, because the patients they are taking samples from sound like (Ben can correct me) ME sufferers who are long term sick and well diagnosed by experts, not by skeptics. Conversely, NIH/CDC will now just get a bunch of tired psych patients, sick for 1.6 years, and say they can't find anything - which is a half truth, because they can't find it, as they purposefully will chose 'fatigued' patients, without very long illness duration (opposite of Navieux/Davis).

So I agree with you, there is no cause to CFS (it's an estimated diagnosis) and for Naviux/Davis to get anywhere they will have to leaver themselves out of the 1000 diagnoseses in 1 of CFS, and go towards ME.

If from UK/Europe, the American researchers would have done this, and perhaps should have done this, and labelled their paper: ''Myalgic Encephalomyeltis'', instead, perhaps unwisely, they labelled their paper ''Chronic Fatigue Syndrome''.

Which now opens the flood gates, for Psych CFS patients, in the NIH paper (who know full well there are retroviruses) and it will ruin everything. The CDC diagnose CFS over the phone, and use people at the end of a phone as a legitimate 'CFS' patient. Outrageous, but that's how you do 'Science' with government bias, which is don't even bother physically examining the patient, and then put these random people, in 'research' to influence pro psychiatric agenda (mental and behavioural). Anything labelled ''CFS'' will always run this risk.

There are two ways out of this:

1)Accept 'they' won, and let them have their CFS, which never existed. Design a NEW disease label.
2) Fight them and prove the 'majority' of CFS is a Mito defect disorder (Navieu'x/Davis apparent aim?).

2) is honorable, but will fail due to medico-politics, that I guarantee everyone, because of the cost of the compensation pay outs, when patients sue the NIH/CDC for mass neglect. This is why they want ME out of CFS, then the Americans can say, ''but you never had CFS'', ''You had this NEW 2018 disease, called ''X'', our CFS doesn't have Mito Dysfunction at all.

This way, they save billions of dollars law suit claims.
The British will do the same, but with ''ME''. Via the MRC, the British are desperate to make, ME into CFS and with the Socialised Health Care System in the UK (The Department of Health) have achieved this with an illness that doesn't actually exist, ''CFS/ME''. No disease exists with a forward slash, as it's confusing and thus dangerous, hence ''CFS/ME'' isn't coded, it's a political objective.

 

[justy]

Yeah, in addition to diet, taking (the proper) probiotics has been the other approach that's helped me the most. There's definitely something there. I don't think it's the root problem but it seems to help alleviate some of the symptoms at least.

But for others it does nothing. I am the opposite and feel MUCH better after eating a meal. strict diets do nothing for me and eating smaller portions or less leaves me with no energy. a decent sized meal adds on the pounds but gives me an instant energy boost. I don't know why this is.

 

[Research 1st]

If you are looking for the big replication of Naviaux´s study, I think there is one good news. Lipkins team just got the first big donation to his microbiome study where he plans to do also metabolom study. So he could possibly validate Naviaux´s finding. We should try to do more publicity to this research and try to donate and to bring new donors. Now the next step should be to validate this hypometabolism findings from another independent group. Without fast validation everything will take longer.

here you can read more:
http://microbediscovery.org/2016/09/05/great-news-a-big-100000-donation-we-have-some-total-updates/

The problem with this, is its dependent on the samples coming from patients with Organic CFS.

CFS = Chronic Fatigue and 4 or more symptoms, that is not Organic CFS.

So unless the patients are hand picked, by experts, the chances of getting any study replicated by someone like Lipkin, is about ZERO.

Lipkin found no inflammation in CFS, when other researchers find massive inflammation (Dr Montoya).

Who's work got published? Lipkin's. Whose work has been blocked from release since May 2014? Montoya's.

So there's your answer which way this is going, medico- politically.

 

[msf]

We don't have offices this big in the UK!
(from the study)
View attachment 17158

The question is whether there is a bias deriving from the way one doctor diagnoses illnesses - the geographical area covered is probably irrelevant. People have questioned KDM´s claims/research for the same reason, and his patients come from all over Europe.

 

[Research 1st]

But for others it does nothing. I am the opposite and feel MUCH better after eating a meal. strict diets do nothing for me and eating smaller portions or less leaves me with no energy. a decent sized meal adds on the pounds but gives me an instant energy boost. I don't know why this is.

Hi Justy

I'll try to have a guess to answer the last line of your reply, please excuse me if this is nonsense, but I like to try and help but that doesn't mean I can! What is evident, is you're describing an energy deficient state, we should also not forget both parties in polite disagreement could be correct as one patient has different problems, due to different acquired secondary diseases/syndromes and the primary problem could also be different (no test for ME, CFS).

So lets just focus on the individual, after all, we are all 'individually' unwell, with our own issues, but we also share them with others a lot of the time, hence I pounced on your problem!

I have heard from other PWME (severe) over and over again, namely they report:

1) Low blood sugar attacks randomly but don't have Diabetes or Addison's disease.
2) Low blood sugar only between meals never at night fasting
3) Must eat every few hours, or they get low blood sugar or feel 'terrible' (worse than normal terrible!).
4) Feel all of the above, but have borderline normal blood sugar when tested, so get ignored by medical profession.

I would say 4) is the most common complaint in PWME, aka Chronic Lyme, aka POTS, aka whatever...

Recently I've learnt I've got antibodies to multiple adrenal receptors (as well as Muscaranic Acetylcholine, not
to be confused with Acetycholine Muscle antibodies found in Myasthenia Gravis), and apparently, this has the potential to target multiple organ sites, including the pancreas and so the immune system may effect insulin levels, in subsets of ME CFS POTS Chronic Lyme etc (possibly the same condition, or subsets of it). If this is correct, it would be possible PWME (with autoimmune subset of adrenergic type) may be getting some kind of episodic autoimmune insulin release, hence they don't have 'true' chronic hypoglycemia which is consistent and will randomly show up on a test, however, you'd need to rule out the conventional before the unconventional. Also I think on repeat testing, you'd still catch a 'glimpse' of what is happening, it just won't be consistent - hence no diagnosis or explanation of this Addison's of the brain, we have, although you can have a look at the list below to have a go at seeing what you can find.

From what you describe (classic ME) it sound as if you have a metabolic disorder in which your body cannot untilise fat stores for fuel. Perhaps in addition to ME, or masked by Growth Hormone deficiency/Pituitary disorder on top of ME.

*Have you had a Fasting Glucose test? (any GP can arrange this).
*Have you had a Glucose Tolerance test?
*Have you had an ATCH stimulation test? Low Cortisol is associated to hypo's.
*Have you had a Growth Hormone Stimulation test? Low GW is associated to hypo's.
*Have you measured your Carnitine, Free Carnitine, Carnitine Ester? My was very low - essential for Mitochondria/Muscle
*Have you measured your Q10? (Others have suggested this already I think, I don't want to steal their thunder!).
*Have you measured your Essential Fatty Acids? Deranged EFA's increase Arachandonic Acid. I found this
out by testing mine (I have uncontrolled Asthma) and my AA is massively elevated (Fatty Acid deficiency derived inflammation). AA is associated to Leukotrines, which Montelukast blocks.
*Have you measured your Long Chain Fatty Acids? Mine are all deficient, one was almost zero.
*Have you measured your Very Long Chan Fatty Acids? -Deficiency can cause random hypo's in adults.

So if you're 'running on empty' (probably as you have so many infections as well), when you eat, you'll feel better as your body is probably useless at using energy from fats and glycogen reserve from muscle and basically everything
to do with staying alive regarding the respiratory chain switching over, hence your body tries to protect you, by making you massively weak, metabolically to keep you alive, hence you literally cannot exercise but don't have 'heart disease' -when tested, if at all, because that's not the reason you get SOB/Tachy/dizzy from exertion.

It would make sense to me, food, gives you carb energy rush, and then even without chocolate or cans of coke, your insulin goes potentially too high and you need to eat again. In terms of known energy disorders of an immune kind, autoimmue Thyroid disease occurs in ME (replicates some CFS symptoms). By the way you can have a Thyroid Goitre, due to chronic inflammation on an ultrasound, and not be hypothyroid either.

I'm the same as you, with what you describe as I'm sure lots of us are.

Blood sugar control in myself, was wrecked the second I got this condition, mildly, when I could still exercise.
It didn't take 30 years to do this to me, it did it immediately to the extent my GP thought I was Diabetic as did a Diabetic Nurse...except I'm not. I've also had Ketones in my urine, despite not being Diabetic and not starving myself like an Anorexic either. So something complex goes on inside us.

How about yourself? The same perhaps some familiar similartiies?

Certainly If I don't eat food every few hours once awake (which makes me really ill as I have severe Dysautonomia, so eating is actually hell), I freak out anyway, anxiety symptoms, go freezing cold (cuddle a heater to warm up). This is interesting as panic symptoms occurs in 'true' hypo's as the body uses hormones (flight of fight) to try and put your blood sugar up in an emergency situation or you go into a coma a die (real risk of Brittle Diabetes). Also it's much worse with a virus, which is interesting as that's what people with Diabetes also report (exacerbation of blood glucose control during infection). How many times have we seen patients in Hospital with a blood sugar of 40/50 because they got a 'germ' and they end up on a drip for a week or so, monitored.

So something in our brains isn't working properly, and then this links to the fact the brain had an independent insulin/glucose system from the periphery, then that's interesting in a complex, multi systemic disease like ME. Why? When someone takes a your blood glucose, they aren't sampling your brain circulation glucose supply, which I suspect, in ME, is something to do with it, mixed with a dysautonomic nervous system response by it, or to it occurring. From memory brain glucose metabolism in some CFS papers(or was it ME?) is abnormal, and that's laying under a scanner and not typing on the net for 5 hours on no food and walking around using your body either.

Finally, for those interested, I should add dehydration can cause a feeling of hunger, starving hungry, (before low BP sets in and the sweating and passing out) when actually you are dehydrated. You'll know this is the case, as when you re-hydrate, only then will you feel thirsty, and also you'll take a long while to pee despite drinking 1 litre or so straight down.

I get caught out a lot with this, because at first I was thirsty all the time, but since I've gotten more sick, I have no memory to remember to drink. This 'forgetting to drink', is also seen in stroke and dementia patients.

 

[gregh286]

But for others it does nothing. I am the opposite and feel MUCH better after eating a meal. strict diets do nothing for me and eating smaller portions or less leaves me with no energy. a decent sized meal adds on the pounds but gives me an instant energy boost. I don't know why this is.

insulin release = arteriole vasodilation = fuel to cells.

 

[cman89]

Apart from general health benefits can anyone see why hgh is often a very effective treatment for cfs in relation to these findings?

Kind of. HGH and IGF-1 signaling are involved in the knocking out of "dauer" state for some organisms.

 

[actup]

This way, they save billions of dollars law suit claims.

@research1st, "sovereign immunity" laws in the US make it very difficult to sue the federal government and permission to do so must be granted by a govt office set up for that purpose- who could have guessed?

http://www.nolo.com/legal-encyclopedia/suing-government-negligence-FTCA-29705.html

 

[Lolinda]

I just read the Naviaux study: Hey, this is my story how I got out of ME!!
The study mentions: bile, B12, cholesterol, purines, arginine, branched chain amino acids, gut bacteria, phospholipids, sphingolipids. These describe my path out of ME:

1. Bile production:
Some B12 etc intervention led surprisingly to sudden and extreme bile flow, accompanied by immediate improvements: I could think clearly again. Brain fog gone. Next day, I marvelled at stool vividly colored by green bile and red blood. Will never forget that view...

2. Tons of cholesterol, purines and amino acids:
At the peak of my ME my body finally kinda forced me to eat only salad and fat for a week. This led to a surprising change: My digestion recovered and I started eating lots of meat. I didnt tolerate it before at all. So, I switched to a very low carb high meat paleo diet: lots of healthy fats, meat and salads. In 2 weeks I got from unable to walk up stairs or lift a bag to carrying a 30kg backpack. In the beginning, my ME pains in the muscles increased. I never forget the worst day, sitting in front of my baffled GP, begging him in misery to please heeeeeeeelp. From previous experiences with killing bad microbes in the gut, I knew this was bacterial die-off. Without carbs, many bugs die. Fortunately, there was no turning back at that point, I had to continue, so sick I was. And then I got betterment.

3. phospholipids and sphingolipids:
The body produces these from choline. And there is a third product from choline, which is arguably even more important: acetylcholine. The whole parasympathic nervous system and parts of the sympathicus run on acetylcholine. Unfortunately, even Naviaux cannot measure it unless the patients kindly donate their brains . So let's take Naviaux' measurements of low phospholipids and sphingolipids as a surrogate for low choline products in general, in particular low acetylcholine. Look up here the patent description for Parasym Plus to learn what one can profit from increasing the neurotransmitter acetylcholine. Concretely in me: While 1 & 2 essentially resolved my ME, several issues remained. Among them: gastric emptying, SIBO and sympathetic overactivation. Taking choline first led to excessive effects, good and bad, from moderate supplemental doses. My conclusion: I must have been so low on choline that every tiny bit caused a huge effect on my poor system. My first attempt to increase choline by food failed into digestive misery. Transdermal choline in small doses worked. Gastric emptying better, bouts of resting sympathetic overactivation resolved, and for SIBO currently first signs of improvement. Details

 

[Gingergrrl]

Recently I've learnt I've got antibodies to multiple adrenal receptors (as well as Muscaranic Acetylcholine, not to be confused with Acetycholine Muscle antibodies found in Myasthenia Gravis),

I was just curious, if you are comfortable sharing, did you do this test (the one I bolded) through Cell Trend Lab in Germany or in your own country? I am hoping to do 3-4 tests through them but am waiting to hear back from them with some additional info. For whatever reason, this test is not available in the US. Were there any specific treatment suggestions given to you after learning of this antibody? I suspect that I have this antibody but do not have proof yet.

 

[halcyon]

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....

It's not too far fetched. I lived smack in the middle of where most of these patients were from. I probably would have been in this study had I wanted to pay the outrageous office visit fee that they charge. Large parts of the county are served with drinking water from the Russian river. Parts of the next county south are also served from this source. This river has had large amounts of sewage dumped in to it on multiple occasions. The last occasion was reported within a few days of when I came down with ME. Something like 100,000 gallons of raw sewage ended up in the river.

 

[Groggy Doggy]

It's not too far fetched. I lived smack in the middle of where most of these patients were from. I probably would have been in this study had I wanted to pay the outrageous office visit fee that they charge. Large parts of the county are served with drinking water from the Russian river. Parts of the next county south are also served from this source. This river has had large amounts of sewage dumped in to it on multiple occasions. The last occasion was reported within a few days of when I came down with ME. Something like 100,000 gallons of raw sewage ended up in the river.

Just Googled the incident with the 100,000 gallons of raw sewage on feb 2014, sept 2015 story of toxic algae, and aug 2016 story of Anatoxin-a.

 

[JaimeS]

I *think* Dr. Whittemore has mentioned in one of her recent talks/interviews). Though I had thought PMI got more $$ than I see it has upon closer inspection. Still...

I would be surprised if Davis and Co. haven't already thought of this. But it might be something for us to bug our congressmen and women about!

She definitely has talked about this as a potential place from which to get funding -- good memory @Michelle !

The CDC diagnose CFS over the phone, and use people at the end of a phone as a legitimate 'CFS' patient.

pics or it didn't happen... though with the CDC my question is more along the lines of "how long ago was this?"

-J

 

[JaimeS]

They all came from one doctor's office.

The question is whether there is a bias deriving from the way one doctor diagnoses illnesses - the geographical area covered is probably irrelevant. People have questioned KDM´s claims/research for the same reason, and his patients come from all over Europe.

I think there is definitely a good argument for diagnosis bias being a factor, as well as geography.

A factor not mentioned so far is that after a certain amount of time in practice, the patients who come to see the same physician grow more and more homogeneous, maybe because the treatment plan they recommend tends to improve QOL for a specific subset of patients, and those are the ones that keep coming back... maybe just because a friend describes their condition and the listener says, "I have a friend with just those symptoms and he went to Dr so-and-so."

I've heard many clinicians of varied backgrounds remark on this without understanding beyond hypotheses why/how it had happened.

-J

 

[Kati]

I think there is definitely a good argument for diagnosis bias being a factor, as well as geography.

A factor not mentioned so far is that after a certain amount of time in practice, the patients who come to see the same physician grow more and more homogeneous, maybe because the treatment plan they recommend tends to improve QOL for a specific subset of patients, and those are the ones that keep coming back... maybe just because a friend describes their condition and the listener says, "I have a friend with just those symptoms and he went to Dr so-and-so."

I've heard many clinicians of varied backgrounds remark on this without understanding beyond hypotheses why/how it had happened.

-J

Interesting comment, and I also think that. But it is well known that each ME expert had a certain way of practicing, and the patients know it. What patients believe their illness is due to would influence who they would see. For instance, enterovirus, Dr Chia. Lyme, KDM. If patients wants to be treated a certain way, then certain physicians would meet these needs. DR Peterson: Ampligen, Vistide. dr Montoya, Kogelnik Valcyte. DR Enlander, GC-maf.

So in some ways, there is self-selection also going on.