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:
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.
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.
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.
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.