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Professor Ron Davis's response to Naviaux study, including Q and A with Dr Naviaux

Sasha

Fine, thank you
Messages
17,863
Location
UK
I've just been reading an old thread that resurfaced in the past few days, in which @Kimsie put forward these ideas about mitochondria in the original post:

Kimsie said:
The majority of energy in the body is produced by oxidative phosphorylation, which is when the electron transport chain takes electrons and uses the energy it gets from the electrons to move protons into the intermembrane space of the mitochondria, and the ATP synthase enzyme uses the energy to release ATP. This energy of the protons in the intermembrane space can be referred to as the proton motive force. This proton motive force is also used to make NADPH through the NNT enzyme.
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I show the protons as dollar signs instead of H+ after they move into the intermembrane space because I think of them like money in the bank that you can spend for healing or for activity. (and I am from the USA)

The electron transport chain (ETC) is inhibited because it is full of iron-sulfur clusters, and iron-sulfur clusters are damaged by ROS, or reactive oxygen species, which include nitric oxide (NO) and hydrogen peroxide (H2O2) among others, i.e. oxidative stress. This is why you can't make enough ATP to have a normal life - the ETC is inhibited.

The ETC also produces ROS; this is normal. A healthy person can create enough proton motive force to make ATP andenough NADPH to get rid of the ROS, but a person with CFS can't. There are other pathways to make NADPH in the mitochondria, but NNT is the major one and probably normally produces about 50% of the NADPH.

So we have to keep ROS levels as low as possible to allow the body to produce ETC complexes (those are the ETC enzymes) with fewer damaged iron-sulfur clusters. Every minute of consecutive activity the ROS levels are increasing, and the rest breaks give the body a chance to lower the ROS levels. Long periods of consecutive activity will spike the ROS levels to a more damaging high.
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Of course this diagram is probably exaggerated, but you get the idea.

It takes a little over 2 weeks to replace most of the ETC clusters, so every 2 weeks we want to see an improvement in the function of the ETC clusters, and that means the electron transport chain will work a little better every two weeks, as long as the person does not increase activity levels which will draw the extra energy into ATP instead of NADPH!

How does NADPH get rid of ROS? NADPH is used to recycle GSSH back to GSH, or glutathione. So this is what is causing those low GSH/GSSH ratios. And the ratio you get when you are tested is the whole cell, not just the mitochondria, so you can be sure that your GSH/GSSH ratio in your mitochondria are worse than what the tests show.

This problem with glutathione is also why detox becomes such an issue.

So activity uses up the energy that could be used to fix the electron transport chain. By having frequent rests to allow the body to produce NADPH and lower ROS levels, the function of the ETC should improve over time, as long as the person doesn't use the extra energy for activity.

Total bed rest is unhealthy, so some activity is needed. If a person has a large enough window of activity, they can decrease their activity time somewhat to speed up recovery. A 6 hour activity day could be decreased to 4 hours spread out over the whole day in little increments. If a person is at 3 hours or less, they should probably not decrease their activity, but just try to keep the activity periods very short as much as possible.

There are other things that can be done to increase energy production such as supplements, which I talk about in other posts. The supplements will do no permanent good if the rest periods are not taken seriously.

Some people have had success with "aggressive rest therapy" in the past, although I've never seen it tied to a theory of a particular function of the mitochondria before. This isn't the thread to discuss this as a therapy - that should be on the original thread, and we should keep in mind that this is the Q&A thread for Dr. Naviaux - but I would like to ask if Kimsie's ideas fit in at all with Dr. Naviaux's thoughts about how the mitochondria are operating in the cell danger response and if the sort of intense rest, based on the principles that Kimsie suggests, is likely to be of any help (that is, not just "loads of rest" but alternating very short periods of activity with periods of rest, with timings based on what might be the underlying biology).

All this biological stuff is way over my head and I feel like a kid on the beach holding up a seashell and saying, "Is this an octopus?" but I hope my question makes sense. :)
 

Mij

Messages
2,353
"There are other things that can be done to increase energy production such as supplements, which I talk about in other posts. The supplements will do no permanent good if the rest periods are not taken seriously."

This may be helpful at the beginning of illness but I found that years into the illness you can rest until the cows come home and it will not increase energy production. I rest to prevent PEM and becoming worse.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
This may be helpful at the beginning of illness but I found that years into the illness you can rest until the cows come home and it will not increase energy production. I rest to prevent PEM and becoming worse.

@Kimsie's ideas are interesting because they're less about tons of rest and more about keeping bouts of activity very short (and then resting). So, based on his ideas about the mitochondria, there's a huge difference between being active for half an hour and resting for three hours (the "tons of rest" model), and being active for 10 mins and resting for ten mins (the "ETC cluster" model).
 

Mij

Messages
2,353
@Sasha hmm . . . ok, the way I was interpreting this was that if you limit activities/keep them short, that long term it would increase energy production over all
 

Chris

Senior Member
Messages
845
Location
Victoria, BC
Somewhere there is a great short paper by one of those Western researchers who did the first 2 day VO2 Max tests that included a graph showing that we used our anaerobic system for the first 2 mins or so of exercise, and then shifted over to our broken aerobic systems. I find I can jump onto my rowing machine and row 200-250 metres in about 58-70 seconds at a fair pace and not trigger any PEM--I can do this maybe 2 or even 3 times a day on a good day. It does tone my body a bit, and I enjoy it, while thinking of the days some 10 years ago when I could reel off 5-6,000 meters at a better pace and feel a bit tired but great and relaxed. Ah well....

And I find I can walk about 9-10 mins, rest 15, and return at a slightly slower pace, and not suffer serious PEM, though I do have to restrict my activities for a few hours afterwards, or suffer the consequences.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
@Sasha hmm . . . ok, the way I was interpreting this was that if you limit activities/keep them short, that long term it would increase energy production over all

Yes, that's the idea - as long as you intersperse those short periods of activity with total rest.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
@Countrygirl--sorry! I was just trying to say that I think Kimsie's advice is very good, and fits well with my experience; and thanks, @Sasha, for bringing this thread forwards--I am working my way through it and finding it very interesting.

Thanks, Chris - glad you had good experience with it.

I've started a thread specifically on Kimsie's ideas (and the implications of Dr. Naviaux's work for resting schedules) here:

http://forums.phoenixrising.me/inde...the-implications-for-resting-schedules.46826/

so that we don't take this one off-topic. I suggest we continue discussing this over there and leave this one for people to ask Dr. Naviaux more questions. :)
 

SGR

Messages
42
God bless these scientists and their families!

My question is if the mitochondrial balance is tilting in favor of the resting, likely in response to cellular defense, which makes sense to me, why on earth can't I sleep? That would be healing, wouldn't it? What an evil disease! Thank you.
 

ghosalb

Senior Member
Messages
136
Location
upstate NY
God bless these scientists and their families!

My question is if the mitochondrial balance is tilting in favor of the resting, likely in response to cellular defense, which makes sense to me, why on earth can't I sleep? That would be healing, wouldn't it? What an evil disease! Thank you.
I believe Dr. Naviaux has said that one needs more energy to relax than react....may be, since we do not have lot of energy, we can not relax and hence can't sleep.
 

paolo

Senior Member
Messages
198
Location
Italy
@Ben Howell

We know that mycotoxins are harmful for bacteria, and we also well known that mitochondria were bacteria, long ago.

So, could mycotoxins have a role in both mitochondria hypometabolism (Naviaux et al, 2016) and intestinal flora reduced diversity (Giloteaux et al, 2016) that we see in ME/CFS?
 

SGR

Messages
42
I believe Dr. Naviaux has said that one needs more energy to relax than react....may be, since we do not have lot of energy, we can not relax and hence can't sleep.

Thank you @ghosalb - so maybe I should "run around" reacting to things, then I will feel better- ha! Probably not that easy...although I will try taking a nightime dose of d-ribose.

Is this then related to the wired and tired phenomenon? Because I do feel like I'm hyper reactive to sensory input.
 
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Strawberry

Senior Member
Messages
2,107
Location
Seattle, WA USA
Sorry if this isn't kosher, but I have a question for the doctors if I may @Ben Howell . I have had years of muscle stamina issues, I am wondering if this is the mitochondrial hallmark of this disease? For instance, when I used to water ski or play on my seadoo I would come in with my legs visibly shaking badly, and I would have to immediately lay down on the dock. Shaking as if my legs were made of jello. Everyone thought it was weird, but I just thought it was because I really like to push myself beyond my means. I can now barely stand for more than 2 minutes. Is this CFS, or a MCAS issue? Or deconditioning? I would really like to know.

Thank you in advance.
 

hixxy

Senior Member
Messages
1,229
Location
Australia
Thank you @ghosalb - so maybe I should "run around" reacting to things, then I will feel better- ha! Probably not that easy...although I will try taking a nightime dose of d-ribose.

Is this then related to the wired and tired phenomenon? Because I do feel like I'm hyper reactive to sensory input.

I don't think @ghosalb worded that very well. The point is it takes plenty of mitochondrial energy output to keep the nervous system, both central and peripheral, from firing erratically. The "reacting to things" would be a manifestation of this erratic excessive firing.

Calm controlled energy, non nervous ("wired but tired") energy requires stable mitochondrial energy output.
 

SGR

Messages
42
I don't think @ghosalb worded that very well. The point is it takes plenty of mitochondrial energy output to keep the nervous system, both central and peripheral, from firing erratically. The "reacting to things" would be a manifestation of this erratic excessive firing.

Calm controlled energy, non nervous ("wired but tired") energy requires stable mitochondrial energy output.

Fascinating, @hixxy, thank you. Yes, it does feel out of control.
 

rosie26

Senior Member
Messages
2,446
Location
NZ
...although I will try taking a nightime dose of d-ribose.
I found ribose great in giving me a little bit more energy, it also eased pain in my hands within the first hour of taking ribose.

But, I stopped taking ribose about 2 years ago. I think ribose has contributed to making me sicker. It gave me energy and I used it. I didn't rest with that extra energy. I got jobs done that needed doing. I think ribose was a booster for me and activated my immune system by way of speeding processes up. So going against dauer effect? I don't know, it just feels that way to me. I won't be taking ribose again. I think it did me some harm but not sure.
 
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SGR

Messages
42
I found ribose great in giving me a little bit more energy, it also eased pain in my hands within the first hour of taking ribose.

But, I stopped taking ribose about 2 years ago. I think ribose has contributed to making me sicker. It gave me energy and I used it. I didn't rest with that extra energy. I got jobs done that needed doing. I think ribose was a booster for me and activated my immune system by way of speeding processes up. So going against dauer effect? I don't know, it just feels that way to me. I won't be taking ribose again. I think it did me some harm but not sure.

Oh, my @rosie26, I'm sorry to hear that. Yeah, I have to confess that I use it to travel to doctor appointments, so I might be borrowing from Peter to pay Paul. Thank you for the heads up.
 
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SGR

Messages
42
Sorry if this isn't kosher, but I have a question for the doctors if I may @Ben Howell . I have had years of muscle stamina issues, I am wondering if this is the mitochondrial hallmark of this disease? For instance, when I used to water ski or play on my seadoo I would come in with my legs visibly shaking badly, and I would have to immediately lay down on the dock. Shaking as if my legs were made of jello. Everyone thought it was weird, but I just thought it was because I really like to push myself beyond my means. I can now barely stand for more than 2 minutes. Is this CFS, or a MCAS issue? Or deconditioning? I would really like to know.

Thank you in advance.

@Strawberry, I just bumped a post from Camas, January, 2013 regarding mitochondria released by mast cells in the mast cell section, if you are interested. It's a study by Dr. Theoharides. I hope this information is not redundant to what you already know.