Rest periods and can CFS people get really well?

[Mij]

@Gingergrrl He initially diagnosed me with post viral fatigue syndrome (I did not have PEM at that time), when I relapsed he suspected MS because I did not fit the normal symptoms of ME patients. I went for all the vascular tests etc to rule out MS. I did not fit the normal symptoms of most ME patients he saw.

 

[SDSue]

Can we be cured? I believe no at that this point of time. My experience has shown me that even if we became well with a 100% remission, we are still at high risk of getting ME/CFS back... all it may take is to catch another virus!! be in a car accident, have a vaccination or whatever.. if the wrong trigger point comes up again. You can find yourself back to square one with having to deal with ME/CFS all over again.

This! Even though I've had small improvements, I am very, very fragile. It's scary enough to keep me pacing like crazy.

This shopping trip can be the only time I get out of my house in a week (so a social thing for me too.. I get to "see" people doing their shopping etc. I get to say "thanks" to a checkout person).

At doctor's offices it's the same. Most of the time, all I can muster is a quick "thanks" as my brain doesn't yet work well when I'm out and about. Even so, it makes me feel human.

I could easily loose all my home support services if they deemed me to be being "lazy"

I'm sure you've thought of this, but could you wear a HR monitor set to go off just below your anaerobic threshold so they could have some tangible reason that you have to sit?

 

[Kimsie]

Regarding antioxidants. It looks like lipoic acid will reduce NADPH. It is common with antioxidants? I guess the same goes for Q10 (and anything that has to be reduced), unless you take ubiquinol. However, it feels like ubiquinone does give me energy. So now I'm confused whether antioxidants are good or bad for ME/CFS.

I think you mean lipoic acid uses NADPH to reduce other things. NADPH is already the reduced form. Lipoic acid uses NADPH when it works as an antioxident, just like glutathione, as far as I can tell, so it is a wash as far as NADPH is concerned but it seems pretty confusing.

But it is also used in the pyruvate dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex, so it affect energy production that way.

CoQ10 is an electron acceptor from Complex I, which is one of the complexes known to create superoxide, so if you have more of it, I guess that Complex I will be less likely to create superoxide because the electrons would leave the complex more quickly the normal way. This does not consume NADPH, which is good.

If you have a lot of CoQ10 in the mitochondria membrane, there will be more of it to transport the electrons to functional complex III's, so it does push the electron transport chain and it would give you more energy. When we tried it the energy advantage only lasted a short time, does it keep working for you?

 

[adreno]

I think you mean lipoic acid uses NADPH to reduce other things. NADPH is already the reduced form. Lipoic acid uses NADPH when it works as an antioxident, just like glutathione, as far as I can tell, so it is a wash as far as NADPH is concerned but it seems pretty confusing.

Yes, NADPH is used for the reduction of LA -> DHLA, as explained in the citation. So I assume the same is the case for the reduction of ubiquinone -> ubiquinol. But as you say, it is confusing, because both LA and Q10 is involved in energy production is other ways. Perhaps this is why LA is often paired with carnitine, which increases ATP.

The thing is, increasing energy will by itself increase ROS. So, more NADPH means more oxidative stress. This is why I said that there might be adaptive reasons for the energy reduction in ME/CFS. Energy production is reduced to avoid excessive ROS (which is already high in ME/CFS).

As a minimum, I think it is required to increase antioxidant intake when trying to increase ATP.

 

[taniaaust1]

This! Even though I've had small improvements, I am very, very fragile. It's scary enough to keep me pacing like crazy.

At doctor's offices it's the same. Most of the time, all I can muster is a quick "thanks" as my brain doesn't yet work well when I'm out and about. Even so, it makes me feel human.

I'm sure you've thought of this, but could you wear a HR monitor set to go off just below your anaerobic threshold so they could have some tangible reason that you have to sit?

I like that statment you made that "it makes me feel human". Yeah!!

I go into the RED aerobic exercise zone on hearing a heart rate monitor on just putting on a pair of jeans!! or my jumper on. By the monitor, that's way overdoing it for me hence I gave up real fast with that monitoring. By that I shouldnt be doing ANYTHING.

I had been going to do what some here have done and try to stay under a certain range, it was a huge disappointment as I had to rule out that idea in my case.

I just saw its impossible in my case if Im to do a thing. just imagine.. get out of bed and take off night gown and being in the red (extreme exercise area) so laying down for 20mins and then trying again.. getting as far as t-shirt this time.. way way over again.. so laying down another 20 mins.. etc etc. Getting a drink..being way over.. going to the loo being way over. The simpliest thing usually sends me in the highest range for exercise. High aerobic level.

I guess that is making it super hard for me to get any better and one of the reasons why Im getting worst... my body is doing what it thinks is intense aerobic exercise much of the time if I do things

My BP can be at over 190 (nearly 200) on one minute of being on my feet (the hospital monitoring saw that). Still the disability service ignores how sick I are and expect me to help. Disability service has ignored my doctors and what they've said. Im now taking legal action for ME/CFS discrimination against the state service for them refusing to believe Im sick due to having ME/CFS (which they believe is just a psych issue and arent prepared to believe otherwise. In my state (Sth Australia) NOONE is getting disability support services for ME/CFS)

Im going to fight it out in court thou I dont have a clue how Im going to get there. The state service is attempting to cause the court to drop the case before it even gets there saying they arent discrimining as they do give me a little bit of help "for Aspergers".

anyway, back to thread subject.

 

[lansbergen]

CoQ10 is an electron acceptor from Complex I, which is one of the complexes known to create superoxide, so if you have more of it, I guess that Complex I will be less likely to create superoxide because the electrons would leave the complex more quickly the normal way. This does not consume NADPH, which is good.

What if the infection causes Mn-SOD2 dislocation and is depleted?

 

[SDSue]

I just saw its impossible in my case if Im to do a thing. just imagine.. get out of bed and take off night gown and being in the red (extreme exercise area) so laying down for 20mins and then trying again.. getting as far as t-shirt this time.. way way over again.. so laying down another 20 mins.. etc etc. Getting a drink..being way over.. going to the loo being way over. The simpliest thing usually sends me in the highest range for exercise. High aerobic level.

I'm so sorry to hear this. I was this way for a brief time, and it was horrid. I think the LDN has helped stabilize my POTS and OI, but who knows. I hope you find an answer.

Im going to fight it out in court thou I dont have a clue how Im going to get there. The state service is attempting to cause the court to drop the case before it even gets there saying they arent discrimining as they do give me a little bit of help "for Aspergers".

Yikes! When, some fine day, ME/CFS is respected and supported, along will come another disease to be abused by the psychs. The definition of insanity is doing the same thing repeatedly and expecting a different result. By their own definition, they are the ones who are insane!!! (That just made my day lol )

 

[Kimsie]

Yes, NADPH is used for the reduction of LA -> DHLA, as explained in the citation. So I assume the same is the case for the reduction of ubiquinone -> ubiquinol. But as you say, it is confusing, because both LA and Q10 is involved in energy production is other ways. Perhaps this is why LA is often paired with carnitine, which increases ATP.

The thing is, increasing energy will by itself increase ROS. So, more NADPH means more oxidative stress. This is why I said that there might be adaptive reasons for the energy reduction in ME/CFS. Energy production is reduced to avoid excessive ROS (which is already high in ME/CFS).

As a minimum, I think it is required to increase antioxidant intake when trying to increase ATP.

Yes, I have realized just a few days ago that increasing energy increases ROS, and that the NAD recipe from my other threads is actually counterproductive if activity is increased along with the NAD recipe. And pretty much everyone increases activity when they feel themselves having more energy.

However, your statement that more NADPH means more oxidative stress is not true when the person does not increase their activity, and their activity level is low. Let me show you why.

The energy produced by the electron transport chain is in the form of protons (H+) in the intermembrane space of the mitochondria. This can be referred to as the proton motive force. That energy can be used to release ATP or it can be used to make NADPH. Each NADPH will neutralize 1 ROS.

Each electron going through the ETC produces 4-5 protons. Some fairly small percentage of electrons slip out of the ETC and make ROS, but many of them make 2 protons before they slip out, because a lot of the electrons that get out, get out at complex III, after they already made 2 protons at complex I. Each electron that gets out at complex III will neutralize 1 ROS made from electrons that escaped from complex I, in addition to neutralizing their own ROS.

On top of that, each ATP takes 3 protons, but each NADPH takes 1 proton. So if a person does not increase activity when they increase energy production, they will be able to have a net decrease in ROS. Here is an illustration to help people understand this confusing explanation.

Each ATP you don't use allows you to get rid of 3 ROS.

I hope this explanation is clear. If it isn't, ask questions and I will try to explain better.

 

[Kimsie]

...Im now taking legal action for ME/CFS discrimination against the state service for them refusing to believe Im sick due to having ME/CFS (which they believe is just a psych issue and arent prepared to believe otherwise. In my state (Sth Australia) NOONE is getting disability support services for ME/CFS)

Im going to fight it out in court thou I dont have a clue how Im going to get there. The state service is attempting to cause the court to drop the case before it even gets there saying they arent discrimining as they do give me a little bit of help "for Aspergers".

anyway, back to thread subject.

This is why the cysteine/sulfate test is needed so badly. It will be an objective blood test which can lend support to the fact that the person with CFS has a real illness, and the illness isn't caused by being out of shape or lazy or anything like that. When we can prove that some people have to have total bed rest to improve, and the government will save a lot of money by giving it to them (bed rest) so that they will be able to do things for themselves later, they will be more likely to give people the help they need. (Many people are not so bad off that they need total bed rest, I think taniaaust is in that state at this point, from what she says.)

 

[Kimsie]

What if the infection causes Mn-SOD2 dislocation and is depleted?

This is something I would have to think about. Do you have any tests showing that your SOD2 is depleted? What is SOD2 dislocation? Does it escape from the mitochondria? I can't find this on the web. Tell me some more, if you don't mind.

If the SOD2 is depleted then the only thing I can think of off the top of my head is manganese supplementation.

 

[Mary]

@Kimsie I didn't even try to read all the science in your post b/c I know it is over my head, but wanted to comment on this part. For me, if I have a day or even a few hours that I can breathe better or have more energy, I always feel the need to do something. I feel a sense of accomplishment and relief when I get something done and if I am able to do something with family or friends, I feel better psychologically that I was able to participate. It is so hard to rest in those rare moments that I am able to do something. And what I "do" is still a fraction of anything that I did in my former life.

How do you force yourself to rest if you have a rare moment of feeling better?

@Gingergrrl - I had the exact same reaction when Kim first proposed resting more - I rest so much already and when I do have a rare moment of feeling better, I want to do things so badly. Then I read this article she linked for me: http://treatcfsfm.org/detail-69-Experiences-with-Pre-Emptive-Rest.html and I began to understand that frequent resting could actually enable me to do more things, not less (though Kim stresses NOT to increase activity level just because I might feel better). And I began to understand that we need the rest to heal. Kim explained that if we're active, we have to have ATP for energy, and thus will not be making NADPH to heal. Our bodies will do one of those two things. - make ATP or NADPH and that's why resting is so important, and the frequent resting will help limit damage and promote healing. Read the article linked - it motivated me to try the pre-emptive resting which goes against everything in my nature!

Mary

 

[adreno]

I hope this explanation is clear. If it isn't, ask questions and I will try to explain better.

Thanks, I understand your explanation, but have no way to tell how correct it is. I need someone with better biochem knowledge, @alex3619 could you take a look at #48?

 

[lansbergen]

This is something I would have to think about. Do you have any tests showing that your SOD2 is depleted? What is SOD2 dislocation? Does it escape from the mitochondria? I can't find this on the web. Tell me some more, if you don't mind.

If the SOD2 is depleted then the only thing I can think of off the top of my head is manganese supplementation.

You can search the forum and no I do not and will not take mangnanese. The immunemodulator I use is also a superoxide scavenger.

 

[alex3619]

Thanks, @adreno.

This is a complex topic, and I probably can't do justice to it. Its something I would like to see answered empirically, as all the theory does not necessarily give us a good picture. I may be able to say more in a couple of days when I get my new computer, this one has major limitations on how I use the net.

Increasing ATP production will lead to increased ROS. I am not sure that if energy is not used it will make much of a difference, due to the dynamics. Ramping up NAD etc may help energy production. On the other hand with more energy around the body may have more capacity to make more antioxidants. So provided there are no other major deficiencies, such as methylation problems or mineral deficiencies, then the body should (theoretically) cope. There are lots of potential caveats here though.

The problem with simple pathway analysis is that there are complex dynamics and feedback loops, and these can change everything.

The loss of electrons is indeed why we get reactive oxygen species though. See for example: http://jp.physoc.org/content/552/2/335.full

It should not matter if there is more ATP around. Its the rate of activity in the electron transport chain that matters. However that rate of activity relates directly to energy expenditure. So its how much we do, and put demand on the electron transport chain, that matters most.

There are other sources of oxidative and nitrosative stress predicted in ME though, including failed NO synthesis leading to peroxynitrite. This ties in to B12 metabolism. Other sources include immunological activity.

Increasing NAD (and CoQ10) might indeed improve energy capacity. Its how much of that we use that determines the ROS, not how much ATP is hanging around, from what I see. As we improve our metabolic rate is likely to increase, which will automatically increase our ROS. However a faster metabolic rate will boost our capacity to make and recycle antioxidants.

So its fair to say that during improvement its a good idea to take it easy, but I agree we are likely to want to do more ... I have a huge list of things I want to do. CoQ10, lipoic, C, E and dealing with methylation will help; a lot. So will peroxynitrite scavengers.

On SOD, there are lots of people with low SOD. Progeria is a genetic SOD disorder. There is medical interest in creating SOD enhancing drugs, but I have not been following this research. Funny enough I had a chance to work on a PhD in this area when I was doing my biochem, but I had to decline as at about that point I realized my health was crashing again.

A big caveat to all this though is that we still do not really know what is wrong with the mitochondria in us. There is some evidence that one or more mitochondrial transporter proteins is not working right, largely from Myhill's research. If this is the case then the usual dynamics we are counting on may not fully apply. As usual, my mantra, we need more research.

However, as a caveat to the caveat, what counts is this - does it work? I use my lemon rules as a heuristic simply because reality often trumps theory. Its why science requires testing. For a patient this comes down to trying a protocol to see if it tastes like a lemon or not. Sometimes, even with all the theory, there is no other way available to us to be sure if something works or not.

 

[Gingergrrl]

@Gingergrrl - I had the exact same reaction when Kim first proposed resting more - I rest so much already and when I do have a rare moment of feeling better, I want to do things so badly. Then I read this article she linked for me: http://treatcfsfm.org/detail-69-Experiences-with-Pre-Emptive-Rest.html and I began to understand that frequent resting could actually enable me to do more things, not less (though Kim stresses NOT to increase activity level just because I might feel better). And I began to understand that we need the rest to heal. Kim explained that if we're active, we have to have ATP for energy, and thus will not be making NADPH to heal. Our bodies will do one of those two things. - make ATP or NADPH and that's why resting is so important, and the frequent resting will help limit damage and promote healing. Read the article linked - it motivated me to try the pre-emptive resting which goes against everything in my nature!

@Mary I read the article but not sure how it applies to me as it seems the people they quoted can travel or go on walks or even exercise (and then alternate these activities with rest.) I am nowhere near that level and get short of breath walking across the room. I still cannot lift anything over my head, carry anything, bend down to pick things up, etc, and am almost positive now that I have orthostatic intolerance.

I don't take long naps b/c I am not actually sleepy or tired (on most days) and most of my worst symptoms are autonomic dysfunction. Even when I sleep for 9-10 hours straight, as soon as I stand up to brush my teeth or put my meds together, I am short of breath. So if I added 15 min of rest, I am not sure how it would help my particular case? I also don't know what NAGPH is?

I don't mean to sound negative and I like the idea but if I rested any more, I would not be able to spend any time with my family (which is already limited) or prepare for a trip to see my cfs MD. I am finding that increasing fluids and electrolytes along with magnesium are more helpful to me than resting b/c when I sleep too long, I get dehydrated and lately this includes getting really shaky, dizzy, and in most severe state, severe tachycardia.

 

[Kimsie]

@Mary I read the article but not sure how it applies to me as it seems the people they quoted can travel or go on walks or even exercise (and then alternate these activities with rest.) I am nowhere near that level and get short of breath walking across the room. I still cannot lift anything over my head, carry anything, bend down to pick things up, etc, and am almost positive now that I have orthostatic intolerance....

I don't mean to sound negative and I like the idea but if I rested any more, I would not be able to spend any time with my family (which is already limited) or prepare for a trip to see my cfs MD. I am finding that increasing fluids and electrolytes along with magnesium are more helpful to me than resting b/c when I sleep too long, I get dehydrated and lately this includes getting really shaky, dizzy, and in most severe state, severe tachycardia.

I would like to state again that when I wrote the original post, I was thinking mainly of people who have a reasonable window of activity to work with, such as 3 hours or more. By activity I mean anything except bed rest. I have not tried to work out anything for the more affected people at this time. I am still working on figuring out and implementing this for my sons.

 

[Gingergrrl]

I would like to state again that when I wrote the original post, I was thinking mainly of people who have a reasonable window of activity to work with, such as 3 hours or more. By activity I mean anything except bed rest. I have not tried to work out anything for the more affected people at this time. I am still working on figuring out and implementing this for my sons.

@Kimsie do you mean three hours of straight activity or three hours split throughout the day? Are you saying three hours should be the goal?

I am struggling more with just eating and drinking right now and having weird episodes that are different than PEM and either dehydration or not eating enough?

 

[Mary]

@Mary I read the article but not sure how it applies to me as it seems the people they quoted can travel or go on walks or even exercise (and then alternate these activities with rest.) I am nowhere near that level and get short of breath walking across the room. I still cannot lift anything over my head, carry anything, bend down to pick things up, etc, and am almost positive now that I have orthostatic intolerance.

I don't take long naps b/c I am not actually sleepy or tired (on most days) and most of my worst symptoms are autonomic dysfunction. Even when I sleep for 9-10 hours straight, as soon as I stand up to brush my teeth or put my meds together, I am short of breath. So if I added 15 min of rest, I am not sure how it would help my particular case? I also don't know what NAGPH is?

I don't mean to sound negative and I like the idea but if I rested any more, I would not be able to spend any time with my family (which is already limited) or prepare for a trip to see my cfs MD. I am finding that increasing fluids and electrolytes along with magnesium are more helpful to me than resting b/c when I sleep too long, I get dehydrated and lately this includes getting really shaky, dizzy, and in most severe state, severe tachycardia.

Gingergrrl - you don't sound negative. I think Kim was referring to people like me - I can manage 3 to 4 hours of light activity a day. So usually my day ends at noon or 1:00 and I do nothing, except maybe light cooking, the rest of the day/evening. So if I broke up my morning activities with plenty of resting, my day would lengthen because of rest periods and also I'd probably crash less and eventually would be able to do more. But your case is quite different than mine.

Have you had testing like Nutreval done? Something that measures amino acids and everything? Nutreval testing revealed some important irregularities for me, like low leucine and glycine, and copper, among other things. It might be helpful for you if you haven't done it already.

 

[Kimsie]

You can search the forum and no I do not and will not take mangnanese. The immunemodulator I use is also a superoxide scavenger.

I haven't found anything yet about what you are talking about, but while I was searching for it, I got onto a post about B12 and SOD and following that line from study to study I have come up with some new information that I have never seen. I have to look at it some more tomorrow, but I decided it can't hurt to take some extra B12 tonight. It looks like maybe B12 would help with the ROS and a way I hadn't thought about before.

What immunemodulator do you take?

 

[taniaaust1]

Yes, I have realized just a few days ago that increasing energy increases ROS, and that the NAD recipe from my other threads is actually counterproductive if activity is increased along with the NAD recipe. And pretty much everyone increases activity when they feel themselves having more energy.

However, your statement that more NADPH means more oxidative stress is not true when the person does not increase their activity, and their activity level is low. Let me show you why.

The energy produced by the electron transport chain is in the form of protons (H+) in the intermembrane space of the mitochondria. This can be referred to as the proton motive force. That energy can be used to release ATP or it can be used to make NADPH. Each NADPH will neutralize 1 ROS.

Each electron going through the ETC produces 4-5 protons. Some fairly small percentage of electrons slip out of the ETC and make ROS, but many of them make 2 protons before they slip out, because a lot of the electrons that get out, get out at complex III, after they already made 2 protons at complex I. Each electron that gets out at complex III will neutralize 1 ROS made from electrons that escaped from complex I, in addition to neutralizing their own ROS.

On top of that, each ATP takes 3 protons, but each NADPH takes 1 proton. So if a person does not increase activity when they increase energy production, they will be able to have a net decrease in ROS. Here is an illustration to help people understand this confusing explanation. .

I once did have a brain which would of been able to understand that. I cant get my brain past the brightly coloured jelly beans in the diagram.. complete mental overload. I used to really enjoy biochemistry at collage too and may of even got a credit in it.

Im so glad that some here can follow