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

[Mij]

When Acumen did a study of my mitochondria through Dr Myhill my cell membrane was described as normal.

Pam

Did you ever over exercise (aerobic) since becoming ill? I did for years and this what brought on PEM six years after becoming ill.

My oxidative stress test was "highly elevated" during the time of testing and I also had poor antioxidant status.

I wonder if a muscle biopsy would show anything.

 

[bertiedog]

@Mij Yes, I regularly over exercise as I am not one of the severely affected. I can walk for about 20 minutes maximum at a good pace but then my energy runs away especially as my blood sugar drops. I am positive my body cannot run on fats very well even though I eat quite a high fat diet (I am slim though).

The test through Acumen did show a problem within the cell, the ATP wasn't being produced as it should be and there was some sort of blockage. The comment was that the ATP was being rapidly used up which is exactly what I feel.

It's shopping that causes me PEM within about 30 minutes it really doesn't suit me at all. My legs start feeling like lead, my back starts aching badly and then I develop pain all over and just have to stop. Often it will trigger a migraine.

Pam

 

[Mij]

The test through Acumen did show a problem within the cell, the ATP wasn't being produced as it should be and there was some sort of blockage. The comment was that the ATP was being rapidly used up which is exactly what I feel.

Yes, this is what it feels like for me too. I had a much larger supply years ago but the constant overdoing diminished my ability to replenish quickly. Feels as though it's pretty much stuck there now.

 

[alex3619]

Females:
Fatty Acid oxidation ( how do I address this?)

This tells you the problem in very broad terms. To address it you would need specifics, and a doctor who understands the metabolic paths and associated paths, including regulation. A typical metabolic path involves multiple steps, multiple enzymes, multiple cofactors and at least one regulated step, which means a regulatory mechanism, though there can be more than one.

There are also effectively two paths by which fats are oxidized from what I recall. Which is affected? Both? You would need to know the specifics, as I said, in order to be clear about what might be attempted.

 

[Nielk]

This tells you the problem in very broad terms. To address it you would need specifics, and a doctor who understands the metabolic paths and associated paths, including regulation. A typical metabolic path involves multiple steps, multiple enzymes, multiple cofactors and at least one regulated step, which means a regulatory mechanism, though there can be more than one.

There are also effectively two paths by which fats are oxidized from what I recall. Which is affected? Both? You would need to know the specifics, as I said, in order to be clear about what might be attempted.

If this was a possibility, there would not be a growing obesity problem and the a huge diet industry.

There is currently no way to speed up metabolism of fats. If there was, we would know about it. It would cute obesity, heart disease and probably other diseases as well.

 

[mermaid]

Yes, this is what it feels like for me too. I had a much larger supply years ago but the constant overdoing diminished my ability to replenish quickly. Feels as though it's pretty much stuck there now.

@Mij

The test through Acumen did show a problem within the cell, the ATP wasn't being produced as it should be and there was some sort of blockage. The comment was that the ATP was being rapidly used up which is exactly what I feel.

It's shopping that causes me PEM within about 30 minutes it really doesn't suit me at all. My legs start feeling like lead, my back starts aching badly and then I develop pain all over and just have to stop. Often it will trigger a migraine.

Pam

Yes, this is what it feels like for me too. I had a much larger supply years ago but the constant overdoing diminished my ability to replenish quickly. Feels as though it's pretty much stuck there now.

Yes, I have a similar problem @bertiedog
When I had the Acumen test done I had a similar comment about my ATP being used up quickly. However I have improved over the years thankfully and can usually manage to walk about for a couple of hours now - that is unless I have a virus going on and then I struggle and like you tend to get migraine if I overdo things. I am a lot worse if made to stand though - much better if I keep walking.

edit note: sorry about all the quotes - just trying to get my head round how that thing actually works!

 

[Seven7]

. To address it you would need specifics,

Agreed I did more research and the kids that have this know early on. I did remember feeling like dying after heavy exercise, so I wonder if I have a mild block instead of a full blown issue. But as I read the symptoms they are spot on.

 

[rosie26]

Did you ever over exercise (aerobic) since becoming ill? I did for years and this what brought on PEM six years after becoming ill.

I have gone well over my limits for so many years. Just raising my arms up is going over my limits. And it is not surprising that I have suffered severe ME and still get thrown into severe bouts of ME. If I had been financially better off it would have helped in that I could have paid for help. I can remember mowing lawns in my severe years - absolutely awful and felt dreadful - I paid badly for it.

It will be interesting to see how the body feels and how much repair happens when we eventually do get some treatment. Hoping it is in the next few years.

 

[Mij]

There is currently no way to speed up metabolism of fats. If there was, we would know about it. It would cute obesity, heart disease and probably other diseases as well.

What do you mean by this? I was under the understanding that fats don't make us fat as previously thought.

 

[alex3619]

There is currently no way to speed up metabolism of fats. If there was, we would know about it. It would cute obesity, heart disease and probably other diseases as well.

This has been known to be incorrect since the 1930s. The fastest way to lose fat is a high fat diet, but energy controlled. Its not known if its healthy though, there has been almost no research on this. The second fastest is a higher protein diet, especially with higher fat. There are problems with both these approaches however. These findings are confirmed by the extensive biomedical research on arctic and antarctic exploration. However this does not, at any time, imply its easy to do. Arctic explorers really get this effect kicked up by immersing themselves in extreme cold, for example. With their metabolism already biased toward burning fat by shifting to a high fat diet, their fat metabolism increases again with the cold.

Increasing fat metabolism and losing weight are not quite the same thing. Doing this safely with sick people is completely not researched so far as I know.

 

[Sea]

Agreed I did more research and the kids that have this know early on. I did remember feeling like dying after heavy exercise, so I wonder if I have a mild block instead of a full blown issue. But as I read the symptoms they are spot on.

It is not necessarily so that kids who have this know early on, if by "this" you are referring to a fatty acid oxidation disorder (FOD). Not all countries or states do newborn screening and of those who do there is no standard as to what is included and what isn't. There are mild and severe forms of FODs so there are children with a mild form who either have not had newborn screening or managed to pass it and therefore do not know they have a condition which can result in metabolic crisis given certain conditions. Also many adults have one of these disorders and are undiagnosed.

 

[bertiedog]

When I had the Acumen test done I had a similar comment about my ATP being used up quickly. However I have improved over the years thankfully and can usually manage to walk about for a couple of hours now - that is unless I have a virus going on and then I struggle and like you tend to get migraine if I overdo things. I am a lot worse if made to stand though - much better if I keep walking.

That's good to know that you have improved what do you put that down to? I had a period of about 6 weeks earlier this year when my energy was amazing but I don't know what switched it on and later switched it off again, very frustrating. Actually those 6 weeks weren't really normal though because my brain was very hyper and hardly switched off which wasn't very pleasant but it was brilliant to be able to do physical stuff without problems. I was actually looking for things to do which involved using my body.

Also like you when I get a virus (which can be very frequent with me) I can only manage around 10 minutes before the ATP is all used up and I have to stop. I have been like this since 2000 so find it very hard to believe I will ever be able to have a more normal life but am very interested in the latest research showing a hypo metabolic state. This seems to be even more impressive because its coming from 3 different sources.

Pam

 

[Sidereal]

This has been known to be incorrect since the 1930s. The fastest way to lose fat is a high fat diet, but energy controlled.

This myth of fat burning advantage for low carb high fat diets has recently been shown to be completely false in two metabolic ward studies. Metabolic ward studies are the highest quality evidence because subjects are housed in a unit where food intake and energy expenditure are controlled.

Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity

In this first study (2015), a very low fat diet (<7.7% of total calories) resulted in more fat loss than the low carb high fat diet where fat was 50% of total calories. However, the study was criticised for being too short duration and not low carb enough perhaps to allow for "ketoadaptation".

Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men

In this two month metabolic ward study (2016), patients on the low carb ketogenic diet (80% fat, 5% carb) lost fat mass slower than on the high carb (where 25% of total calories came from sugar!) diet. The slight transient increase in energy expenditure in ketosis was due to transient loss of lean tissue (wasting of water and muscle).

You can watch a short video here where Hall explains the findings of the second study in an accessible way.

 

[alex3619]

low carb high fat diets has recently been shown to be completely false in two metabolic ward studies.

Thank you for those links.

 

[Mij]

I had a period of about 6 weeks earlier this year when my energy was amazing but I don't know what switched it on and later switched it off again, very frustrating. Actually those 6 weeks weren't really normal though because my brain was very hyper and hardly switched off which wasn't very pleasant but it was brilliant to be able to do physical stuff without problems. I was actually looking for things to do which involved using my body

I've had those days and weeks too. I once varnished my whole bedroom floor! I can't attribute it any supplement I took though but it does give us hope that it can turn around a bit even though it doesn't last.

I also have frequent viral/immune activation issues but it's odd how I'm not always disabled (less energy production) or negatively affected by it, it's always different. I guess it depends on the culprit.

 

[mermaid]

That's good to know that you have improved what do you put that down to? I had a period of about 6 weeks earlier this year when my energy was amazing but I don't know what switched it on and later switched it off again, very frustrating. Actually those 6 weeks weren't really normal though because my brain was very hyper and hardly switched off which wasn't very pleasant but it was brilliant to be able to do physical stuff without problems. I was actually looking for things to do which involved using my body.

Also like you when I get a virus (which can be very frequent with me) I can only manage around 10 minutes before the ATP is all used up and I have to stop. I have been like this since 2000 so find it very hard to believe I will ever be able to have a more normal life but am very interested in the latest research showing a hypo metabolic state. This seems to be even more impressive because its coming from 3 different sources.

Pam

@bertiedog Well I have been chipping away at things for around 7 years now, trying things as you do, and some have helped and some have not. I began with Dr Myhill's tests (25%) and took most of the supplements, changed my diet a lot, and tried to pace, but began to lose heart as no noticeable difference, after a year, so reduced the supplements due to cost.

Then I tried other things (e.g. acupuncture - no use really apart from getting crush on man doing it; LDN - could not tolerate re gut, and did some odd things to my brain; plus a few other odd things that I didn't pursue long).

Then in 2013 I paid out megamoney to see private GP in London who works in similar way to Dr Myhill. He did same tests which showed I had improved somewhat, (41%) and other tests called Lymphocyte Sensitivity test (Acumen Lab again) which showed 3 main things affecting my immune issues. I did my best to cut them out. Also began supplement regime again, and did some other tests re my gut which was v problematic (upper gut re dyspepsia and pain), and also began methylation supps, and had organic acids test done too.

I have been pretty consistent with the supplements since then, whilst adding a few of my own from time to time, and recently have begun increasing some like magnesium and the NAC. About 2 years ago I began to notice some improvements re my immune issues (very frequent viruses) and also could even see it in my standard blood tests (FBC) as lymphocytes had normalised, plus some of the other things like monocytes etc.

At around that time I also began to go to a medical herbalist as well, and I think her herbal mix has helped a lot over time. I also use Oil of Oregano. I am also managing the constant issues I get with the stomach pain re foods and try very hard to keep it under control by controlling my diet and using Slippery Elm tabs. All of this helps me to maintain a kind of homeostasis if that's the right word here....

As a result I have noticed that I can sustain more - most of the time. I easily go over my limits though and then will slip back and get the migraine aura which drain me for a few days. Not so much the viruses now, though except this week! However even with the virus I have functioned better than before.

Big thing too is I am retired (2 years now) so a definite factor in my mental well being over time. I am able to volunteer for 2 hrs for Oxfam (behind the scenes), run a monthly rag rugging group, do almost all my own gardening, and even belong to a dance/theatre group (with limitations and it's for disabled people). I also advocate for my son who has severe mental health issues (does not live with me).

This is probably all TMI. In fact only last year I went down a big hole mentally so this is all very recent this year. I even went to see a psychologist in the CFS unit, as a result.

Like you, I am very interested in the new research. It's difficult to believe that I will ever be totally OK but as you can see, I am doing well for now (I also have had a detached retina op only 5 weeks ago which has put me back and maybe accounts for getting the virus as I tend to overdo things a lot).

 

[Lolinda]

The low sphingolipid profile in CFS appears to be an adaptive response that is opposite to the increased sphingolipids observed in metabolic syndrome (11) and the acute cell danger response (CDR) (7) and ultimately may represent a fundamental response to oppose the spread of persistent viral and intracellular bacterial infections.

Interesting. And worrysome for me: I supplement since weeks with choline. It took a while to get it right, but transdermal agp-choline in small doses works fine now since 2 weeks (experiences). So far wonderful effects (much better gastric motility and sympathetic overactivation reduced!). But could it be that I feed and multiply some intracellular bacteria or viruses? All my inflammatory markers (crp, esr, TNF, IL-6) were always low. Tons of viruses and bacteria tested: nothing. Until 2 years ago, I had a fullblown ME. At least I succeeded to work myself out of that (here is what I did), so I do not have ME any more (a small PEM is left. My remaining current main issues are POTS and some gastro probs). From the huge improvements I make on agp-choline currently, I conclude that I likely had (or still have) strongly reduced choline metabolism.

Did anyone have choline, sphingolipid or phospholipid levels tested? Which labs did you use? I am in Europe.
I searched a lot and found only phospholipids. Synlab does it.

 

[Forbin]

I apologize if the following has already been addressed a dozen times thusfar…

I have a question about the relationship between PEM and hypometabolism.

The "dauer" state to me evokes a static state with little fluctuations, whereas my experience of this illness is roller coaster like - from my baseline (very poor to begin with), then down into PEM, and back up to my baseline, and so on.

Would a crash in the context of Dr Naviaux's ideas simply be a process where I suddenly "hypometabolize" myself even more??

I am asking because PEM doesn't feel like a shut-down, but more like a sudden activation. Not a quantitative change but a qualitative one - I don't just feel "more" exhaustion than hours earlier, but rather as though a process of a different nature had kicked in (it lasts 3 days, happens almost every week …I never learn…), a process in which my metabolism, far from going quiet, seems to be "roaring" inside (heart pounding, ears ringing, increased insomnia, and above all, fever-like cerebral malaise that knocks me out)

Just speculating, but perhaps the answer has something to do with this study which found increases in the expression of certain genes following exercise:

Moderate exercise increases expression for sensory, adrenergic and immune genes in chronic fatigue syndrome patients, but not in normal subjects
Alan R. Light,1,2 Andrea T. White,3 Ronald W. Hughen,1 and Kathleen C. Light1

...but I don't know if this kind of expression would produce the symptoms of PEM, or if they might just be a marker of it.

It might also be interesting to see if the plasma cytokines and spinal fluid cytokines measured by Hornig, et al., increase subsequent to exercise. Maybe they don't - but, if they did, it might create an increased sense that one's immune system has "revved up" - as if you were fighting an bad infection. I could see that causing the symptoms similar to those you describe ("heart pounding, ears ringing, increased insomnia, and above all, fever-like cerebral malaise that knocks me out").

As I say, just speculation.

 

[adreno]

Interesting. And worrysome for me: I supplement since weeks with choline. It took a while to get it right, but transdermal agp-choline in small doses works fine now since 2 weeks (experiences). So far wonderful effects (much better gastric motility and sympathetic overactivation reduced!). But could it be that I feed and multiply some intracellular bacteria or viruses?

I believe the consensus is that the hypo-metabolic state is maladaptive (not helpful), so for now I would not worry about this.

 

[Lolinda]

I believe the consensus is that the hypo-metabolic state is maladaptive (not helpful), so for now I would not worry about this.

Much appreciated. That is actually, what I hope too, but I have seen also very credible voices against it. And I can support the voices against it by studies that some bacteria actually feed well on choline. Let me know if you wanna know more I dig it out. Most of all: if it was so easy then all people would simply resolve their probls by taking more choline, more B12, more cholesterin rich food, etc etc to supply exactly those things low as per Naviaux. There must be some hidden issue why it does not work for all or why it will work only short time, whatsoever... What is this issue? I worked out myself of ME by eating more B12, more cholesterin, etc etc by my high meat, high fat, low carb diet. But if it was so simple for all, then all would be healthy. Same for choline - If anyone is interested, here are all the details on my choline supplementation. My failures and my finally successful version. I am happy as a bird it works so well for me!
Just think of the 13000 members of PR! Why are there no masses leaving PR because their ME resolved? Do we really believe that these 13000 dont try all the time all sort of things, paleo, low carb, high choline, whatsoever? If it worked, people would have found it!

I was however unable to find any research sources that the hypometabolic state would be really maladaptive! Do you have any? Anyone?