The Great NIH Exercise Initiative: A Boon for Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia?

[dejurgen]

Progress is good, but I see nowhere that they'll study what happens with the brain/brainchemistry. That worries me a bit as studying the chemistry of our muscles alone (if that would be the design of the study) might obscure the complexity of our disease and yield yet another excuse to say we're perfectly fine. Maybe I'm a bit negative now.

Another major part not studied yet is the effect of poor neuron mithochondrial functioning on body motion. The brain works as a huge neural net. In Artificial Intelligence, deep neural nets are often used. They are a simplified form/mimicking of what happens in our brains. What is important here is following:
* Neural nets need large amounts of training, equivalent with human learning
* Once trained, the accuracy of performing a learned action is very sensitive to the exact strength of the neurons.
* Mytochondria of neurons going to Dauer/CDR may well equate to neurons losing their strength.
* The above may lead to a severe drop of precision in brain functioning and calculation power.
* Complex movements require huge amounts of computational power. There is for example no single human-moving-like robot in the world that can climb a set of different stairs. There ain't a robot with human-like hands that can peel an apple neither. Both are still too computational complex.
* Overexerted neurons may therefore quite likely lead to inability to do task precise and/or fast. That was exactly what happened at my biggest worsening ever: I did not know anymore how to walk around my bed or to stand up from the table. I had to relearn it and it took minutes the first time what should have taken seconds. I had to decompose the task in smaller less complex tasks. Less complex tasks are exponentially cheaper to perform computation wise so that remained OK. I for example could still put on my socks standing on one feet. This happens to be a sequential list of simple tasks so computationally very cheap.
* Overexerted neurons should also be very poor at the complex process of recognizing for example visual objects. Again, we are very poor at recognizing details in what we see fast enough. This leads to poor reaction time and sensory over stimulation: if we for example mis a car coming too close in time, the brain must reprocess all information even faster as there is no time left to avoid a dangerous accident. The already weakened brain must work in emergency mode and pull all reserves on a daily basis. That is a recipe for frequent fight-or-flight.
=> As no-one seems to study the effect of varying/diminishing neuron strength from a neural network viewpoint on mental and physical performance I'd like to see it done sooner than later. One may be tempted to think that for example a 20% drop/variation in neuron strength may only lead to a 20% drop in performance but that could be very very much more detrimental.

 

[dejurgen]

What I'd like too see studied too is:
* The impact of our poor blood flow and it's relation too our very poor ability to exercise. Let's start with people with 60 to 70% of normal blood volume. People with such low blood volume are mostly found in ER, trying to make it to the next morning. One shouldn't expect people with both ME and low blood volume to be just fine at exercise so studying the effect of low blood volume on exercise may be hard but badly needed. Maybe looking if people without ME but with poor exercise tolerance tend to have lower blood volume might be a starting point.
* Many studies show that people with ME have remarkably larger drops in blood flow through the brain (and in muscles?) after exercising compared to healthy people. Even a moderate difference should amplify in the hair vessels, as according to general fluid theories constricting should have a far stronger effect on the finest vessels compared to the bigger arteries and veins. So blood flow may swing wildly in our hair vessels in our brains and muscles during and after exercising. It may well be strong enough to be an almost "tidal" effect of lack of perfusion and reperfusion leading to strong inflammation and reperfusion injury as well as increased blood clotting in already constricted vessels. As reperfusion is often even more damaging then the prior lack of oxygen itself, daily reperfusion should be devastating if it actually occurred.
https://en.wikipedia.org/wiki/Reperfusion_injury
and "Restoration of blood supply to ischemic tissues can cause additional damage known as reperfusion damage that can be more damaging than the initial ischemia." according to https://en.wikipedia.org/wiki/Ischemia
Note that reperfusion relates to inflammation, oxidative damage, lactate acidosis and hydrogen sulfide (mentioned in a theory by a doctor on this site), see first link.
* For ME patients with low blood volume on top of the tidal effect, it's hard not to see blood flow in the hair vessels to come regularly to a near halt. Studying that in a lab should be feasible on a moderate budget.

 

[Hezza]

Twenty-five percent of the people who answered the poll were "total athletes" !!! That's a very high percentage. I loved exercise and did it frequently but I didn't put myself in that category..I hope someone does a real statistically based survey at some point

I also marked avid. But I did not exercise just for the benefits of exercise, what I did was strenuous work; full time volunteer construction in a developing country- which meant mixing concrete by shovel when electricity was not available, for example. That's after unloading by shovel pick up trucks carrying the sand & rock. Brut work was not the only thing- there was more finite work as well: setting tile, welding, laying block, forming concrete... Then there was my pay job: installing irrigation systems. Not bad for a 5'5" 105 lb girl.

I was in love with the sensation of feeling my muscles become stronger & more skilled as the different parts worked in unison to accomplish task after task. I loved physical work. The reward was not just a fit body but in construction you see immediate results of your labor. And when it is volunteer- you get all the feels emotionally as well. Did I mention I worked with the most amazing people in the world? We had just finished pulling 80 hrs in 6 days on site when I contracted dengue fever, the virus that brought me down.

So I never was a gym rat- dislike gyms actually. (Where would I fit in the exercise category?) But I love physical activity that does double duty. I love to learn & accomplish. And I so miss this important part of who I am at heart.

 

[Cort]

U

I also marked avid. But I did not exercise just for the benefits of exercise, what I did was strenuous work; full time volunteer construction in a developing country- which meant mixing concrete by shovel when electricity was not available, for example. That's after unloading by shovel pick up trucks carrying the sand & rock. Brut work was not the only thing- there was more finite work as well: setting tile, welding, laying block, forming concrete... Then there was my pay job: installing irrigation systems. Not bad for a 5'5" 105 lb girl.

I was in love with the sensation of feeling my muscles become stronger & more skilled as the different parts worked in unison to accomplish task after task. I loved physical work. The reward was not just a fit body but in construction you see immediate results of your labor. And when it is volunteer- you get all the feels emotionally as well. Did I mention I worked with the most amazing people in the world? We had just finished pulling 80 hrs in 6 days on site when I contracted dengue fever, the virus that brought me down.

So I never was a gym rat- dislike gyms actually. (Where would I fit in the exercise category?) But I love physical activity that does double duty. I love to learn & accomplish. And I so miss this important part of who I am at heart.

Not bad at all for a 105 lb girl at all!

If you were doing strenuous physical activity every day or almost every day you would definitely be in the top category.

I loved the feeling of my body getting stronger as well.

 

[Cort]

What I'd like too see studied too is:
* The impact of our poor blood flow and it's relation too our very poor ability to exercise. Let's start with people with 60 to 70% of normal blood volume. People with such low blood volume are mostly found in ER, trying to make it to the next morning. One shouldn't expect people with both ME and low blood volume to be just fine at exercise so studying the effect of low blood volume on exercise may be hard but badly needed. Maybe looking if people without ME but with poor exercise tolerance tend to have lower blood volume might be a starting point.
* Many studies show that people with ME have remarkably larger drops in blood flow through the brain (and in muscles?) after exercising compared to healthy people. Even a moderate difference should amplify in the hair vessels, as according to general fluid theories constricting should have a far stronger effect on the finest vessels compared to the bigger arteries and veins. So blood flow may swing wildly in our hair vessels in our brains and muscles during and after exercising. It may well be strong enough to be an almost "tidal" effect of lack of perfusion and reperfusion leading to strong inflammation and reperfusion injury as well as increased blood clotting in already constricted vessels. As reperfusion is often even more damaging then the prior lack of oxygen itself, daily reperfusion should be devastating if it actually occurred.
https://en.wikipedia.org/wiki/Reperfusion_injury
and "Restoration of blood supply to ischemic tissues can cause additional damage known as reperfusion damage that can be more damaging than the initial ischemia." according to https://en.wikipedia.org/wiki/Ischemia
Note that reperfusion relates to inflammation, oxidative damage, lactate acidosis and hydrogen sulfide (mentioned in a theory by a doctor on this site), see first link.
* For ME patients with low blood volume on top of the tidal effect, it's hard not to see blood flow in the hair vessels to come regularly to a near halt. Studying that in a lab should be feasible on a moderate budget.

Great points again DeJurgen - Blood volume is definitely a major issue. I don't think its the only issue but the problem of getting blood to the brain and muscles could be the only issue. (I think more than blood volume is involved in that.)

There was that fascinating trial in which researchers eliminated the cognitive problems and other symptoms of POTS by using a drug that increased blood pressure and blood volume I believe.

I don't know why blood vessel and blood volume problems are better studied in this disease. I like Fluge's take that autoantibodies are whacking something in the blood vessels.

 

[Cort]

Lot of really fit people answered the survey...

 

[Katie]

Like others, I skied, swam, skated, hiked, biked, danced etc etc.
I too lost the majority of my friends partly due to natural attrition of just not being involved in sports activities any longer. It hurts, not just physically but emotionally too. This disease can rob everything, everything that we used to be.
I'm very excited about these newest studies. It will lead to further studies related to ME/FM and perhaps one day enlighten all of us who know it's not "all in our head".
I too pushed myself for years to keep my activity level up-and I ended up in a major crash and slow burn for the past 17 years.

 

[Katie]

U

Not bad at all for a 105 lb girl at all!

If you were doing strenuous physical activity every day or almost every day you would definitely be in the top category.

I loved the feeling of my body getting stronger as well.

Yup, I agree, I could be in the first category too as I was a nurse on very busy wards, ran my feet off most shifts, helping almost immobile patients up or move in bed etc. So that plus raising 3 kids on my own that I took camping, skiing etc. and my own stuff: both winter and summer sports plus swimming.
I am 5' tall and 105 pounds. Like Hezza.
I loved to be physically active-made me feel great-all those endorphin's floating around!
"The world was my oyster"

 

[dejurgen]

> Blood volume is definitely a major issue. I don't think its the only issue but the problem of getting
> blood to the brain and muscles could be the only issue.

I believe it is only one of many issues, making the total picture very complex but so many things seem to relate to it...

> There was that fascinating trial in which researchers eliminated the cognitive problems and other
> symptoms of POTS by using a drug that increased blood pressure and blood volume I believe.

My doctor gave me such a drug too. It made my head better but my legs much worse. After stopping the medication the better head remained in part and it took half a year to get my legs back to the state before the treatment. I believe *forcing* the pressure to a constant higher state was problematic.

He gave me this meds after I discovered that many times daily !gently! and short series of losing up my tight neck and shoulder muscles removed some and severely reduced most OI related symptoms including general pain, pain shoots, brain fog as long as I stay well under my envelope, walking completely folded... and that for over a year now. I'm still severely ill but my quality of life has gone up from terrible to almost can do.

I believe these exercise do basically the same as the meds but it leaves the body more ability too increase the pressure *only* when it is desirable rather then always. So I believe it increases "regulation range" rather than shifting to another fixed gear.

> I like Fluge's take that autoantibodies are whacking something in the blood vessels

That's what triggered me into this view. I see two potential links so far:

A) Strong exercise significantly increases peroxide production by the cells in all healthy human beings. Strong ROS and oxidation is reported often in relation to our disease. Recent research reported that peroxide likely attracts white blood cells to the site of peroxide release. And triggered white blood cells release large respiratory bursts with ... peroxide. So white blood cells could work as an amplifier of a ROS runaway.

B) I am looking into this other one more now. According too https://en.wikipedia.org/wiki/Reperfusion_injury

"Activated *my addition: due to repurfusion injury* endothelial cells produce more reactive oxygen species but less nitric oxide following reperfusion, and the imbalance results in a subsequent inflammatory response. The inflammatory response is partially responsible for the damage of reperfusion injury. White blood cells, carried to the area by the newly returning blood, release a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage. The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the plasma membrane. Damage to the cell's membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling to turn on apoptosis. White blood cells may also bind to the endothelium of small capillaries, obstructing them and leading to more ischemia."

-> I feel that that describes my disease quite well.

Select breathing techniques in response to what happens to my body helps me. It's still difficult to find reproducibility and coherence in it, but so far I guess it helps to boost respiration efficiency at times of local ischemia.

As the described obstruction should be focused in the smallest hair vessels, larger vessels and surrounding tissue should be far less effected. That could explain both lack of oxygen at one place whilst having at the same time too much in other places. I experienced more then once a very severe feeling of lack of breath whilst having an oxygen high at the same time. It could also explain how some cells could consume plenty of oxygen while we have at the same time local lactic acidosis.

It could also explain the odd delayed and long lasting increase of lactic acid after exercising in our blood some researchers reported: it would be happening after local hair-vessel constriction and blocking so hypoxia would occur later in the exercise and last long. This local blocking and obstruction would force anaerobic functioning and produce lots of lactic acid. The supposed respiratory burst would signal other exhausted cells to go very quickly into CDR.

It would also cause massive damage to the blood hair vessels. That could lead to continuous blood loss and hence low blood volume. Or, it could also necessitate the body to lower blood volume and pressure to prevent very dangerous brain hemorrhage due to damaged brain hair vessels with could also show up as brain inflammation.

If some of this "B" process would happen, it would cause quite a lot of debris and blood clotting. I experienced that my legs could be hit far worse than my head doing only brain activity. It felt like "it sunk to my legs". Debris could do so. It would be one more reason to lower blood volume and pressure. The slower the blood flow, the easier debris sinks to the bottom protecting the far more difficult to repair brain from damage due to debris blocking hair vessels. Men may have the advantage of have more leg muscles and be able to repair them at an increased rate compared to women. This may work somewhat protective. Muscles could potentially be scarified to take some of the damage away from the brain.

Also, when hit worst by this disease, it feels like if my muscle are like tens to hundreds of layers torn apart from each other !painfull!!!. It resembles the pain of thousand of micro "dried blood clots sticking to tissue and making a healing wound" *EDIT scabs seems to be the correct translation of what I tried to describe END EDIT* be torn from the surrounding tissue. That may actually do as the link says: "Damage to the cell's membrane" in combination with the toxic radicals and a weakened immune system may force the cells to go into CDR. One of it's main functions after all is to harden up the membrane. That would both decrease pathogen access and the hypothetical hair vessel blood loss.

It could shed some light on the contradicting findings of us having both too active and too exhausted immune systems: reperfusion injury could cause daily strong activation of the white blood cells but leave them too exhausted to deal with pathogens.

All of this would quite a lot resemble sepsis, a state CFS has been compared with several times recently.

A last link is blood sugar levels. I had much neuropathic pain. 2/3 of people having neuropathic pain have it due to diabetics. My blood sugar levels are quite normal. However, the main advantage a low sugar / moderate carb diet gives me is less of this pain. Eating significantly higher sugar and even carb loads then usual seems from time to time to lead to a spike in neuropathic pain. Diabetic pain in diabetics is mainly caused by poor blood flow and related damage in hair vessels due to too thick blood. Now if we have in general more constricted hair vessels and even worse after exercise and if the hypothesized reperfusion damage would be there (far rougher hair vessel surface due to scars) then the effect of blood sugar levels would be amplified in us at times of exercise and happen at far lower then diabetic sugar levels. That may be in part why many of us are reporting issues with carbs and worse sugar.

If there are so many *plausible* links to 1 issue, then I feel it may be more then a coincidence.

 

[Katie]

> Blood volume is definitely a major issue. I don't think its the only issue but the problem of getting
> blood to the brain and muscles could be the only issue.

I believe it is only one of many issues, making the total picture very complex but so many things seem to relate to it...

> There was that fascinating trial in which researchers eliminated the cognitive problems and other
> symptoms of POTS by using a drug that increased blood pressure and blood volume I believe.

My doctor gave me such a drug too. It made my head better but my legs much worse. After stopping the medication the better head remained in part and it took half a year to get my legs back to the state before the treatment. I believe *forcing* the pressure to a constant higher state was problematic.

He gave me this meds after I discovered that many times daily !gently! and short series of losing up my tight neck and shoulder muscles removed some and severely reduced most OI related symptoms including general pain, pain shoots, brain fog as long as I stay well under my envelope, walking completely folded... and that for over a year now. I'm still severely ill but my quality of life has gone up from terrible to almost can do.

I believe these exercise do basically the same as the meds but it leaves the body more ability too increase the pressure *only* when it is desirable rather then always. So I believe it increases "regulation range" rather than shifting to another fixed gear.

> I like Fluge's take that autoantibodies are whacking something in the blood vessels

That's what triggered me into this view. I see two potential links so far:

A) Strong exercise significantly increases peroxide production by the cells in all healthy human beings. Strong ROS and oxidation is reported often in relation to our disease. Recent research reported that peroxide likely attracts white blood cells to the site of peroxide release. And triggered white blood cells release large respiratory bursts with ... peroxide. So white blood cells could work as an amplifier of a ROS runaway.

B) I am looking into this other one more now. According too https://en.wikipedia.org/wiki/Reperfusion_injury

"Activated *my addition: due to repurfusion injury* endothelial cells produce more reactive oxygen species but less nitric oxide following reperfusion, and the imbalance results in a subsequent inflammatory response. The inflammatory response is partially responsible for the damage of reperfusion injury. White blood cells, carried to the area by the newly returning blood, release a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage. The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the plasma membrane. Damage to the cell's membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling to turn on apoptosis. White blood cells may also bind to the endothelium of small capillaries, obstructing them and leading to more ischemia."

-> I feel that that describes my disease quite well.

Select breathing techniques in response to what happens to my body helps me. It's still difficult to find reproducibility and coherence in it, but so far I guess it helps to boost respiration efficiency at times of local ischemia.

As the described obstruction should be focused in the smallest hair vessels, larger vessels and surrounding tissue should be far less effected. That could explain both lack of oxygen at one place whilst having at the same time too much in other places. I experienced more then once a very severe feeling of lack of breath whilst having an oxygen high at the same time. It could also explain how some cells could consume plenty of oxygen while we have at the same time local lactic acidosis.

It could also explain the odd delayed an long lasting increase of lactic acid after exercising in our blood some researchers reported: it would be happening after local hair-vessel constriction and blocking so hypoxia would occur later in the exercise and last long. This local blocking and obstruction would force anaerobic functioning and produce lots of lactic acid. The supposed respiratory burst would signal other exhausted cells to go very quickly into CDR.

It would also cause massive damage to the blood hair vessels. That could lead to continuous blood loss and hence low blood volume. Or, it could also necessitate the body to lower blood volume and pressure to prevent very dangerous brain hemorrhage due to damaged brain hair vessels with could also show up as brain inflammation.

If some of this "B" process would happen, it would cause quite a lot of debris and blood clotting. I experienced that my legs could be hit far worse than my head doing only brain activity. It felt like "it sunk to my legs". Debris could do so. It would be one more reason to lower blood volume and pressure. The slower the blood flow, the easier debris sinks to the bottom protecting the far more difficult to repair brain from damage due to debris blocking hair vessels. Men may have the advantage of have more leg muscles and be able to repair them at an increased rate compared to women. This may work somewhat protective. Muscles could potentially be scarified to take some of the damage away from the brain.

Also, when hit worst by this disease, it feels like if my muscle are like tens to hundreds of layers torn apart from each other !painfull!!!. It resembles the pain of thousand of micro "dried blood clots sticking to tissue and making a healing wound" be torn from the surrounding tissue. That may actually do as the link says: "Damage to the cell's membrane" in combination with the toxic radicals and a weakened immune system may force the cells to go into CDR. One of it's main functions after all is to harden up the membrane. That would both decrease pathogen access and the hypothetical hair vessel blood loss.

It could shed some light on the contradicting findings of us having both too active and too exhausted immune systems: reperfusion injury could cause daily strong activation of the white blood cells but leave them too exhausted to deal with pathogens.

All of this would quite a lot resemble sepsis, a state CFS has been compared with several times recently.

A last link is blood sugar levels. I had much neuropathic pain. 2/3 of people having neuropathic pain have it due to diabetics. My blood sugar levels are quite normal. However, the main advantage a low sugar / moderate carb diet gives me is less of this pain. Eating significantly higher sugar and even carb loads then usual seems from time to time to lead to a spike in neuropathic pain. Diabetic pain in diabetics is mainly caused by poor blood flow and related damage in hair vessels due to too thick blood. Now if we have in general more constricted hair vessels and even worse after exercise and if the hypothesized reperfusion damage would be there (far rougher hair vessel surface due to scars) then the effect of blood sugar levels would be amplified in us at times of exercise and happen at far lower then diabetic sugar levels. That may be in part why many of us are reporting issues with carbs and worse sugar.

If there are so many *plausible* links to 1 issue, then I feel it may be more then a coincidence.

Ok WOW. I'll have to read this a couple of times to make sure I have your hypothesis straight.
However, when you explained the neuropathy that happens with diabetes, then I got it.
Your description of the "hair vessels" is perfect and really makes a whole lot of sense.
Sugar and carbs in my diet (except for vegetables) always lead to an increase in symptoms. Sometimes I feel I must check again, like at Christmas time with all the sweets around, but I do suffer for it later and need to "detox" all over again.

 

[SuziRider]

Phil, here is my thinking. There are literally thousands of myokines, metabolites, immune cells and molecules that ebb and flow for several days after an execise. If they can pinpoint particular molecules, we have something physical to pursue, and knowing the culprit molecules may point us precisely what/where to look. For example, if the symptoms track only normal inflammatory myokines and lukocytes, we could further pursue with confidence the hypothesis that CFS/FMS is a hypersensitivity to inflammation, rather than the inflammation itself or hypometabolism. And studying the singaling pathways for those molecules may reveal the ultimate cause.

The top CFS/ME/FM researchers are following Dr. Martin Lerner's theories that the inflammation, cellular dna changes/ATP production malfunctions are all viral based. A lowered immune system from a physical, emotional, or chemical stress lets those dormant viruses smolder and create havoc in our bodies. The effects of the energy-hungry hypothalmus running at half-speed is the only common system, otherwise the various lurking viruses seem to affect everyone differently. The Epstein-Barr ('Mono') virus, carried by 96% of the US population, and CMV (80%) also seem to be common underlying factors.
The current standard tests for those carrying EBV only cover around 6 strains out of dozens, show Positive (you have Mono and are contagious) or negative (it is dormant), but nothing for those people who are inbetween; They dont show the actual viral load. Dr. Montoya says the average of his CFS patients is around 60.
At Kaiser California, out of 1500 doctors, they have none that know anything about diagnosing and treating CFS. Lab tests all coming out Normal & morning fatigue (instead of feeling energized) seem to be the surest sign of CFS! But isnt every other adult tired? And drinking morning coffee?

None of the medical establishment's available Lab tests show signs of CFS, but they do exist. Usually CFS is misdiagnosed as depression, Hashimotos, or just plain laziness.

I just wish they would have the ATP Profile test (Acumen Labs in the UK), Reverse T3 (are the cells using the thyroid, or is it inert?), and more detailed viral load tests, giving doctors the information they need.

Boosting the immune system through good nutrition (& a lot of phytonutrients) and feeding the Kreb's Cycle (per Dr Lerner's Protocol, which is also followed by many others like Myhill and Teitelbaum) to build ATP are the best solutions to date.
Getting viral loads tested at a research hosptial and prescription anti-virals for those that are active (like Valtrex for EBV), is great, but difficult. Dr. Montoya has a 2 year waiting list.

As for athletes trying to recover from CFS, I have read stories of Olympic Athletes competing again after a couple years. None detail how they did it. However, they are young and less 'Long Term' CFS sufferers. Studies have shown that CFS is different in more long term (fairly severe > 1 year) cases when they split the CFS people into subgroups.

As an ex National level powerlifter and a bicyclist myself, I would like to see exercise (beyond going up the stairs!) and recovery from CFS/FM addressed more thoroughly.

Once my energy levels increase a little more, and the brain fog decreases, I hope to start a website just for athletes with CFS. No one seems to be addressing this.

 

[SuziRider]

> Blood volume is definitely a major issue. I don't think its the only issue but the problem of getting
> blood to the brain and muscles could be the only issue.

I believe it is only one of many issues, making the total picture very complex but so many things seem to relate to it...

> There was that fascinating trial in which researchers eliminated the cognitive problems and other
> symptoms of POTS by using a drug that increased blood pressure and blood volume I believe.

My doctor gave me such a drug too. It made my head better but my legs much worse. After stopping the medication the better head remained in part and it took half a year to get my legs back to the state before the treatment. I believe *forcing* the pressure to a constant higher state was problematic.

He gave me this meds after I discovered that many times daily !gently! and short series of losing up my tight neck and shoulder muscles removed some and severely reduced most OI related symptoms including general pain, pain shoots, brain fog as long as I stay well under my envelope, walking completely folded... and that for over a year now. I'm still severely ill but my quality of life has gone up from terrible to almost can do.

I believe these exercise do basically the same as the meds but it leaves the body more ability too increase the pressure *only* when it is desirable rather then always. So I believe it increases "regulation range" rather than shifting to another fixed gear.

> I like Fluge's take that autoantibodies are whacking something in the blood vessels

That's what triggered me into this view. I see two potential links so far:

A) Strong exercise significantly increases peroxide production by the cells in all healthy human beings. Strong ROS and oxidation is reported often in relation to our disease. Recent research reported that peroxide likely attracts white blood cells to the site of peroxide release. And triggered white blood cells release large respiratory bursts with ... peroxide. So white blood cells could work as an amplifier of a ROS runaway.

B) I am looking into this other one more now. According too https://en.wikipedia.org/wiki/Reperfusion_injury

"Activated *my addition: due to repurfusion injury* endothelial cells produce more reactive oxygen species but less nitric oxide following reperfusion, and the imbalance results in a subsequent inflammatory response. The inflammatory response is partially responsible for the damage of reperfusion injury. White blood cells, carried to the area by the newly returning blood, release a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage. The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the plasma membrane. Damage to the cell's membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling to turn on apoptosis. White blood cells may also bind to the endothelium of small capillaries, obstructing them and leading to more ischemia."

-> I feel that that describes my disease quite well.

Select breathing techniques in response to what happens to my body helps me. It's still difficult to find reproducibility and coherence in it, but so far I guess it helps to boost respiration efficiency at times of local ischemia.

As the described obstruction should be focused in the smallest hair vessels, larger vessels and surrounding tissue should be far less effected. That could explain both lack of oxygen at one place whilst having at the same time too much in other places. I experienced more then once a very severe feeling of lack of breath whilst having an oxygen high at the same time. It could also explain how some cells could consume plenty of oxygen while we have at the same time local lactic acidosis.

It could also explain the odd delayed an long lasting increase of lactic acid after exercising in our blood some researchers reported: it would be happening after local hair-vessel constriction and blocking so hypoxia would occur later in the exercise and last long. This local blocking and obstruction would force anaerobic functioning and produce lots of lactic acid. The supposed respiratory burst would signal other exhausted cells to go very quickly into CDR.

It would also cause massive damage to the blood hair vessels. That could lead to continuous blood loss and hence low blood volume. Or, it could also necessitate the body to lower blood volume and pressure to prevent very dangerous brain hemorrhage due to damaged brain hair vessels with could also show up as brain inflammation.

If some of this "B" process would happen, it would cause quite a lot of debris and blood clotting. I experienced that my legs could be hit far worse than my head doing only brain activity. It felt like "it sunk to my legs". Debris could do so. It would be one more reason to lower blood volume and pressure. The slower the blood flow, the easier debris sinks to the bottom protecting the far more difficult to repair brain from damage due to debris blocking hair vessels. Men may have the advantage of have more leg muscles and be able to repair them at an increased rate compared to women. This may work somewhat protective. Muscles could potentially be scarified to take some of the damage away from the brain.

Also, when hit worst by this disease, it feels like if my muscle are like tens to hundreds of layers torn apart from each other !painfull!!!. It resembles the pain of thousand of micro "dried blood clots sticking to tissue and making a healing wound" be torn from the surrounding tissue. That may actually do as the link says: "Damage to the cell's membrane" in combination with the toxic radicals and a weakened immune system may force the cells to go into CDR. One of it's main functions after all is to harden up the membrane. That would both decrease pathogen access and the hypothetical hair vessel blood loss.

It could shed some light on the contradicting findings of us having both too active and too exhausted immune systems: reperfusion injury could cause daily strong activation of the white blood cells but leave them too exhausted to deal with pathogens.

All of this would quite a lot resemble sepsis, a state CFS has been compared with several times recently.

A last link is blood sugar levels. I had much neuropathic pain. 2/3 of people having neuropathic pain have it due to diabetics. My blood sugar levels are quite normal. However, the main advantage a low sugar / moderate carb diet gives me is less of this pain. Eating significantly higher sugar and even carb loads then usual seems from time to time to lead to a spike in neuropathic pain. Diabetic pain in diabetics is mainly caused by poor blood flow and related damage in hair vessels due to too thick blood. Now if we have in general more constricted hair vessels and even worse after exercise and if the hypothesized reperfusion damage would be there (far rougher hair vessel surface due to scars) then the effect of blood sugar levels would be amplified in us at times of exercise and happen at far lower then diabetic sugar levels. That may be in part why many of us are reporting issues with carbs and worse sugar.

If there are so many *plausible* links to 1 issue, then I feel it may be more then a coincidence.

Neuropathic Pain (pain the the nerves) is often from an internal shingles virus. CFS people and diabetics often get it due to their lowered immune system. Colitis is similar, when the virus is irritating the nerves to the guts. It comes and goes.
Your blood pressure varies with the needs of the body. It is self regulating (aka controlled by God, who is very smart and does everything for a reason), and so try to figure out WHY it is too high or too low and address that issue, instead of artificially changing it and messing up your kidneys and brain.
Low blood pressure and heart issues (shown by a constantly low HRV score, independent of exercise) (see EliteHRV.com for general info on HRV) can be from the EBV living semi-dormant in the Vagus nerve. It messes up the HPA axis.

Cure to anything viral based (including so called 'auto-immune' diseases that show viral anti-bodies) is building up the immune system. This is accomplished by eating healthy, 20-25% protein, with a lot of phytonutrients), and taking a lot of magnesium (+1000mg/day, or as much as tolerated), selenium (200-400 mcg/day), CoQ10 (ubiquinOL form, 100-200 mg), d-Ribose 5gm scoop 3x/day in coffee, green tea, or food), iodine (Iodoral, 12.5mg tablet), Vit D3 (10, 000 IU/day, unless you have a good leg tan or blood levels over 60, then 2000 IU/day, per Dr. Mercola), Vit K2, plus electolytes potassium +chloride to help the blood vessels and heart do their job. If you often have headaches, try using extra pink or gray sea salt, or drink salty organic broths. Avoid processed table salt. Use Epsom salt baths and magnesium lotion or 'oil' (skin spray) if oral Mag. irritates your guts. The extra magnesium will also help with any headaches, leg cramps, constipation, osteoarthritis, and low energy (ATP). Take Omega3's, and use Olive oil, grass-fed butter ('Kerrygold', etc.), coconut oil, or MCT oil (not vegetable oil PUFA's).
If you also add L-Carnitine, then you are also doing and enhanced version of Dr.Lerner's widely used CFS/FM protocol.
Of course, take a high quality 'optimized' Vit/Min combo, too. Hint: If you can buy it at the grocery or CVS, it is in the bottom 20% in terms of quality. Check with your Natureopathic/ Holistic doctor for recommendations.
Try it for 3-6 months and see what results you get. Severe shortages of any of those nutrients may show Positive changes in just a couple weeks. Others come every month or two as the body recovers.
After a year on it, I have gone from a 1 to a 4.5 on the CFS 0-10 Energy Scale, and can now bicycle 25-30 flat miles with a group 2-3x/wk. It took 6 months on the Protocol to notice a noticeable change (suddenly in August I could do small hills, too, OR do two easy flat 20-25 mile rides 2 days in a row.).

Normal people as beginners to road cycling (which is 3x easier than walking) can improve 10% each ride or two, and do a Metric Century within 3 months of starting to bicycle regularly, and a full Century (100 miles) a month or two later. It takes me 4-6 months to improve 10%.

 

[dejurgen]

Boosting the immune system through good nutrition (& a lot of phytonutrients) and feeding the Kreb's Cycle (per Dr Lerner's Protocol, which is also followed by many others like Myhill and Teitelbaum) to build ATP are the best solutions to date.

I would like to add another cheap one: many pathogens including viruses and bacteria enter through either skin, mouth or nose. Avoiding easy access of new ones significantly reduces the pressure on the immune system over time. Lesser entry of new pathogens leaves more resources to gradually reduce existing ones or suppress retroviruses like Epstein-Bar, cold sores Herpes... that multiply and increase the problem each time they get the chance (opportunistic pathogen behavior).

Simple things like:
* Taking preventive medicine like Broncho Vaxom or equivalent does reduce my inherited strong vulnerability to the common cold a lot. It does however work really good for some to not at all for others. Not having a very strong cold half the time from September to February is quite big on removing pressure on the immune system. That is an "old" trick for me from before my CFS. Always consult your doctor first!
*** Ones that I started over the last year ***
* Using paper tissues (only once and throw away) over textile reusable ones. It appears to be "common knowledge" that it helps to reduce infection rates from common colds and the flue.
* Use herbal infusions with mild cleaning properties like sage and not just drink it but move it around mouth and throat. Note: even herbal infusions must be used with care and limited in duration; consult your doctor.
*Use seasalt spray for your nose early when a cold is starting to show up.
* Traditionally milk whey has been considered mildly antiseptic and I know several non-CFS people who report clear benefits of it. I find it helpful too. Rinse mouth and throat with it. There is a possibility of being allergic too it; consult doctor again. Some products do only contain the proteins. I believe the full product with lactic acid is needed as it is considered to help with sugar levels and digestion. Not that much solid evidence but many good reports and low side effects if not allergic.
* Don't allow your skin to "break". Don't scratch; Don't scratch acne (bacterial spread). Keep finger nails short as long they don't inflame and clean them if you still scratch some time. Don't bite the skin next to your nails. Use good razor blades so you don't cut yourself. Protect lips and skin from cold and apply potions here needed.
* Consume regularly moderate amounts of garlic, onion, crest as they have antibacterial and or antiviral properties.

It all are quite simple measures that did not gain me anything at first but I did keep doing and refining this. A few months ago I started to finally get results. Cold sores, acne and skin damage is reduced by about a factor of three compared to a year ago. It is now at the lowest in years and approaches pre-CFS times. Maybe not all of it works, but the total package does yield good results for me. None of it may fight the hard pathogens like EBV, but by not exhausting the immune system while fighting opportunistic pathogens I believe it is stronger to defend against those ones. Having less opportunistic infections may well lower the CDR as well, potentially reducing sickness depth.

 

[dejurgen]

Try it for 3-6 months and see what results you get. Severe shortages of any of those nutrients may show Positive changes in just a couple weeks. Others come every month or two as the body recovers.
After a year on it, I have gone from a 1 to a 4.5 on the CFS 0-10 Energy Scale, and can now bicycle 25-30 flat miles with a group 2-3x/wk. It took 6 months on the Protocol to notice a noticeable change (suddenly in August I could do small hills, too, OR do two easy flat 20-25 mile rides 2 days in a row.).

Congratz with the VERY impressive improvements. In order to get a better understanding I'd like to ask a few questions:
* Did you have a clear and strong viral onset of ME/CFS?
* Were you "short time" (up to 3 years) or long time ill?
* Did you change diet at the same time as starting the supplements? If not, what came first and what were the results?
* Might you have got food intolerances and not eat those products anymore? Other reports I heard of very fast and convincing improvements all had to do with food intolerances so far so there is some (you may have clues about it's likeliness) potential for overlap here. I can imagine intolerances weigh on the immune system and so work indirectly.

I did not take those exact supplements in those exact quantities, but I did take some of them for a prolonged time. I saw no clear improvement nor change at all and stopped after a few months each time due to not working / no budget to try if no clear benefit. Having a "cleaning" diet with loads of nutrients and moderate calories did however help somewhat. So do antivirals. Those seam to increase my resistance against the common cold as well, despite clearly not working against it. That likely is due to offloading the immune system so I do follow you but so far supplements don't seem to help me anywhere near they do help you. Keep on improving and reporting!

 

[Aidan Walsh]

Even with information from the cellular level, though, what are the chances that we will get to know more about "causes"? What is going on at the cellular level might just all be symptoms. We might just be getting incredibly well-informed about symptoms and not getting any closer to discovering the causes and the correct order of the cascade of effects.

At least we are now well beyond the "its all in the imagination" stage, if only all practitioners were getting the memo. Even so, in spite of the constant addition of information about what is wrong in the actual physical and nervous tissue of CFS and FM patients, there remains a "foot in the door" for the hypothesis that this still "all starts in the mind" or "the attitude". I have always said this is outrageous BS because I went down with FM from the point of being very confident in my physical prowess and thinking I was invulnerable because I kept myself so fit.

I was in denial for a long time, believing that my "lost form" was on the verge of being regained, after all, I was working very hard on it in the same ways that had worked to make myself very fit in the first place. I kept up a training regime of around 300 miles per week on the bicycle even into approximately the first 3 years of full-blown FM. The doctors kept saying there was nothing wrong with me (according to their tests) in spite of loss of fitness, inability to recover after exercise, all-over pain that had me writhing every few seconds in my waking existence, hydration issues, excessive urination, etc. Finally someone thought of checking those "tender points"....

At that point I started trying "something else" other than pushing myself! But it was 20 years until I discovered a multi-disciplinary protocol that wound the condition back. It was actually my mental determination to push myself - "no pain no gain" - that obstructed me all that time, from discovering that correct pacing was the most important key. So I have no patience at all with the argument that I still hear, that these conditions "start with a negative attitude" or some such arrogant cop-out from practitioners who don't want to admit "it is THEM who don't know enough to be able to understand this condition". Of course they see a lot of people who "believe they can't do" XYZ - those people actually can't do it, physically. Even if they used to do those things and more, and were proud of it - and damn well knew they lost the ability in spite of every honest effort on their part.

*To understand what Ehlers Danlos Syndrome Hyper-Mobility is it will explain what CFS is not & that is the problem with this entire illness it is EDS not so called CFS or the other thousand names it has been given over the years...All one has to do is look at the long list of people with all the multiple diagnosises

they are given it is all the same illness. Then I will hear People say I am not flexible or they never had the proper evaluation in any Doctor's Office for EDS done then when they are stiff they will say I do not have EDS but little do they know when one ages one becomes stiffer...The complications to EDS are so long & so

complex it took me 26 years to finally get diagnosed & Yes Syncope POTS Fibro CFS is all in EDS types & one can also have 'multiple' types of EDS involved plus some can have (HFI) as well they are even told they have fructose malabsorption but they do not they have Genetic (HFI) as well...How come the NIH is

not using the EDS Protocol on CFS ??? Doctors need to seriously wake up they are actually daft & cannot see EDS in patients...Majority very very high percentage of so-called Lymies have undiagnosed EDS types even Michael Jackson with all his Money in life never ever got properly diagnosed with EDS

HYPERMOBILITY...One cannot ever Cure any illness unless one knows what it is the term Fatigue is in countless illnesses 'fatigue' is not a Disease/Syndrome as they project & it is so easy for Doctors to throw people into a CFS waste-basket diagnosis label...Imagine any Doctor giving out a Medicine with Sucrose or

even Fructose-Sorbitol & telling the patient to eat bread or other items containing these ingredients would one expect any patient getting well if they had EDS & (HFI) combined??? If one has (HFI) you will never ever get better consuming these medicines/foods or Hospital procedures containing these

ingredients that is certain 100%, Quote from Dr. Rodney Grahame 95% of patients diagnosed with CFS/Fibro have 'undiagnosed' Ehlers-Danlos Syndrome he refuses to even use the term Myalgic Encephalomyelitis M.E. he knows its EDS not so called M.E. Labels. Popping Vitamins/minerals with any of

these ingredients is also a Death sentence so are countless medicines...Rheumatologists are needed so are Metabolic Genetic trained Doctors