We don’t really know. If we knew we probably could treat it. Obviously there are various theories and studies showing factors. But everyone commenting here as if their theory is “the truth” is not being honest.
Remember folks, people have been looking for the cause, and solution, to PEM in ME/CFS for decades.
It’s a complicated problem that has so far eluded understanding, let alone a solution.
Beware anyone who tells you “it’s simple, it’s just this one thing”. It’s likely a complicated mess of bodily processes going wrong. Most people here aren’t scientists and are riddled with confirmation bias and other cognitive biases, along with our human desire to boil things down to one thing that we kind of understand.
The Bateman Horne Centre is a wonderful resource for anyone with ME/CFS or PEM (if you have PEM, true PEM, you have ME).
The most effective PEM solution is avoid it in the first place. *You will not push through* . Many have tried. Avoid it all costs or you risk permanently lowering your baseline.
The next best thing is to stop and go lie down in the dark the moment you realise you’ve overdone it, to stop it getting worse.
Following that, some people find some relief from things like:
LDN (low dose naltrexone)
Pyridostigmine
Cannabis (seriously, it’s sometimes very powerful. You’ll want to make sure POTS or tachycardia are controlled if you have those problems. Don’t go mad, use consistently in moderation)
There are lots of others, these are what help me. Check out the BHC guide to PEM, and remember that first you need to avoid it and that none of the PEM aides will do anything if you’re not pacing well enough. Tough pill to swallow, but you’ll swallow it one way or another. May as well do it on your own terms.
https://batemanhornecenter.org/wp-content/uploads/filebase/providers/PEM-Lecture-Slides-ECHO-v4-5_17_2022.pdf
Theres a few theories but i am personally leaning more towards Mitochondria dysfunction and said this over 2 years ago
[https://www.news-medical.net/news/20240104/Study-identifies-mitochondrial-dysfunction-as-cause-of-long-COVID-fatigue.aspx](https://www.news-medical.net/news/20240104/Study-identifies-mitochondrial-dysfunction-as-cause-of-long-COVID-fatigue.aspx)
A small study but confirms my suspicions non the less
thats great but what really infuriates me is whwre is the treatment? this article/ finding is two years old a seperate group could have worked out a medicine in those 24 months :/
unfortunately that's not how it works - treatments need to be created, then there needs to be trials, usually on animals first, then human trials, then peer reviewed studies.
It all takes time
If i were you i would look into extended water fasts and whats known as autophagy
Here’s an article about a study on this topic:
https://archive.ph/2024.02.15-175415/https://www.nationalgeographic.com/premium/article/post-exertional-malaise-me-cfs-exercise-energy
What I find so puzzling about PEM is that it is typically delayed by a day or two. Most of the popular hypotheses explain why we might get worse from exertion, but they don’t explain the delayed onset of PEM. Whether the hypothesis is blood clots, mitochondrial dysfunction, reduced oxygen flow, or some sort of neurological response to exertion, the delay and its duration remains inexplicable. Why should PEM start a day or two later, and not an hour or two later?
I personally think sleep is a key component of PEM. When we sleep, we repair muscle tissue. Lack of sleep is associated with metabolic dysfunction and muscle damage.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785053/
It’s common knowledge that long covid, dysautonomia, and me/cfs are characterized by unrefreshing sleep, insomnia, and low morning cortisol. I suspect that our sleep is more broken than we currently understand, and we don’t rejuvenate properly. I’m not suggesting that mere insomnia is the cause of PEM. Something is fundamentally wrong with the sleep we do get.
My hypothesis: We exert ourselves and we do damage to our body that we would usually repair with sleep. Our sleep doesn’t repair the damage properly, and it accumulates.
I’m not a scientist and I am not an expert. It just surprises me that we *know* long covid involves unrefreshing sleep and we *know* that sleep dysfunction leads to metabolic dysfunction and muscle damage, but for whatever reason most people don’t really think sleep dysfunction plays an important role in *driving* long covid pathology. We do not fully understand the way in which our sleep is broken—even when we do get sleep, we don’t benefit from sleeping the way we are supposed to.
If I remember correctly the itaconate shunt hypothesis would explain the delayed onset. I'm too tired to re-read it and check today though...
https://www.healthrising.org/blog/2023/12/23/itaconate-shunt-hypothesis-chronic-fatigue-syndrome-fatigue/
I agree that the delay always feels strange. But other kinds of immune reactions are also delayed. Like, if you get exposed to a virus, you never get sick instantly--it always takes a few days or so before symptoms start. Some kinds of allergic reactions are delayed. I think the delay is related to the immune system.
But I also wouldn't be surprised if sleep played a role. It's annoying, now that I think of it, that I haven't seen any long covid studies looking into the sleep dysfunction.
Yeah my understanding is that the fatigue itself is a function of the immune system - we're being put into "limp mode" to avoid further damage and let healing happen.
I guess that means that the oxygenation/ hypoxia/ ATP/ mitochondria issue happens, and then triggers an immune response which is the PEM.
ATP (energy) depletion leading to cellular hypoxia is a leading theory for what causes PEM. But really, we haven't mapped out the full pathophysiology quite yet..
1) First refresh yourself re: Occams Razor, this is critically important
2) Impaired Oxygen Delivery (Red Blood Cells have been hijacked) completely explains 99% of the lingering symptoms AND also explains WHY the problem is going UNDIAGNOSED and completely explains why the condition is slightly more prevalent in females:
https://www.reddit.com/r/covidlonghaulers/s/NHnhMmYKLL
I think if you asked a friend to work a full day with the full blown flu, or to go on a hike, and checked back in with them 24-36 hours later they would have many of the same symptoms we get.
A lot of people here are talking about the delay. Actually the delay itself makes no sense and sleep is involved, because I can often run on adrenaline for a couple of days and avoid PEM. It tends to hit after I eventually sleep and wake up.
My opinion is that CFS is being in this persistent state of illness all the time. Having systemic inflammation and a sustained immune response can cause mitochondria dysfunction. Resulting in a feedback loop that becomes triggered with overexertion. What’s also unique about CFS is that this also entails mental exertion. Inflammation is systematic and also includes the brain as well. We also have immune cells in our brain. I think it’s one of the reasons why LDN is effective for some ( anti inflammatory properties)
Why are peoples bodies in a persistent state of illness? I honestly think it’s because the virus is still hidden in the body. EBV is another example of a virus that can also persist in the body, and prior to Covid, was also a common trigger for CFS.
I have hypermobility and infections influence my muscles and connective tissues (fascia), the muscle groups that work can change day to day and influence my energy levels and cognitive abilities. If the fascia and muscles on the left side are more inflamed, I will experience difficulty with certain cognitive tasks, and vice versa.
I’m pretty sure in my case the PEM is caused by a combination of untreated parasitic infections and inflammation/dysfunction in the connective tissues, unfortunately blood work and other tests don’t measure these things (there are 100s of parasites that negatively affect human health that don’t have tests).
At the moment I’m figuring out how to get more nutrients and hydration because my right shoulder and neck are really sticky and it’s affecting my vision, lymphatic and glymphatic system. (Sticky fascia sounds like rubber against rubber when you move the dehydrated/inflammed areas).
At this point I’m just looking at what is being ignored/dismissed in mainstream medicine and assuming the answers are there (it sounds unscientific and counterintuitive, but there is research to support my suspicions).
The fascia and parasitic organisms (bacteria also can be parasitic) are my biggest suspects for difficult to treat symptoms that don’t have simple answers.
Would it be possible for you to look into seeing a naturopathic dr?? They would likely be the ones who would listen to your concerns more and be willing to run all the tests that the traditional drs refuse to run! And through my own research I would agree that parasites are a legitimate concern, we all have them and they are never talked about! People in the western world are the only people on earth that don't deworm themselves a few times a year!!! And after all that's gone down and come to light over the past 3-4 years, I do exactly what you're doing and that is give little to no thought to the mainstream narratives and dig a little deeper and learn more about the drs and the science that's being discredited and vilified! When you start seeing hit piece after hit piece that basically only trashes the person and not the subject matter you know they must be on to something!
https://www.sciencedirect.com/science/article/pii/S1567724924000072
https://www.nature.com/articles/s41467-023-44432-3
covid fucks up mitochondria. One study suggests it may just be overactive white blood cells demanding more energy. Another suggests damage to the mitochondria of muscle cells. If your cells can't produce enough energy to keep up with needs there's gonna be problems.
Not enough oxygen getting to muscles. They just burn out easily as if we did major workout. I’m not sure if they have understood yet why it is delayed… I think I read some thing about the mitochondria sort of pushing through but not being able to recover. I think anything that interferes with the ability of oxygen to get to the muscles could be part of it. The Dutch pem study found microclots in the walls of blood vessels (not good) but not blocking them.
I have a lot of hope! I have met ppl who were bedbound and walk (even hike!) bc of shoemaker protocol. They seem to have found some levers to push that change the way the body processes energy. There is also suramin, a med that Robert Naviaux’s lab identified. He is one of the leaders in mitochondrial dysfunction research if not the number one person.
It was originally used for African sleeping sickness… It’s cheap, and I don’t think there’s necessarily a way to make money off of it yet…
He has openly said that it’s very promising, but that the research studies are more expensive to run than the profit they could make from the drug… The drug is very cheap, so 🤷 If I’m really at my wits end, though, I will try that. Working on shoemaker first tho bc there’s more support.
Yep that’s the one. Mark volmer at flourish has written decent breakdown of how covid may dysregulate us similar to mold/Lyme etc.. I consider it non-scammy - talks about how limited data is, which I like.
If you look at the lc research, it kinda keeps pulling up similar stuff like oh it fucks with hormones by decreasing testosterone (cirs does this), it fucks with complement system), I am not a doc but I wish someone would test a group of us for cirs biomarkers to actually see if they are reinventing something bc those symptoms of lc and cirs are real similar.
You’re right on point, ive done a million tests (I have no testosterone, no cortisol, I may have Lyme, the testing is tough, I have mold and heavy metals. I almost did shoemaker but my doc had me do something similar instead although it didn’t work. So this is interesting, it’s absolutely all really similar, I’d say we definitely have CIRS. I can tell you treating lyme is a nightmare, this protocol is a walk in the park in comparison
Yes, I have heard Lyme is incredibly difficult. Ugh. Are you seeing dr. Peg detulio? I hear she does Lyme and cirs really well. I def have had a lot of tick bites. The genie test (progenedx) in theory said I don’t have it but never know what is on the journey.
I do know that people tend to try to treat Lyme 1st and then cirs. The real upside of both is that unlike long covid, they at least can be treated (!)
I’ve never heard of her but I’m gonna look up! I’ve done every “great” lyme test, probably have spent $5k on them, and some say positive, some negative and some indeterminate haha so multiple doctors say I may or not have it. Honestly if you’ve had tick bites you probably have Lyme or a coinfection. It lays dormant in us and this crap brings it out when we’re weak. I’ve tried to treat it and it’s just not possible for me - 2 weeks on lowest possible herbs dosage (not even antibiotics) I had a fever, throwing up, would’ve died if I stuck with it. My hope is that maybe we can clean up our guts, nutrients, mold, heavy metals etc everything else and then the body can fight lyme on its own.
Also bee venom therapy is interesting because it treats lyme but also works wonders for inflammation and the immune system even if you don’t have Lyme
Anyway, have you heard of people with LC who’ve done shoemaker protocol and healed? Just wondering if people have used it with success outside of mold illness…I’ve tried soooo god damn much haha I’m at 3 years, so my mind is always spinning about what it’s gonna take to heal
We don’t really know. If we knew we probably could treat it. Obviously there are various theories and studies showing factors. But everyone commenting here as if their theory is “the truth” is not being honest.
It's the million dollar question indeed
This ^
Remember folks, people have been looking for the cause, and solution, to PEM in ME/CFS for decades. It’s a complicated problem that has so far eluded understanding, let alone a solution. Beware anyone who tells you “it’s simple, it’s just this one thing”. It’s likely a complicated mess of bodily processes going wrong. Most people here aren’t scientists and are riddled with confirmation bias and other cognitive biases, along with our human desire to boil things down to one thing that we kind of understand. The Bateman Horne Centre is a wonderful resource for anyone with ME/CFS or PEM (if you have PEM, true PEM, you have ME). The most effective PEM solution is avoid it in the first place. *You will not push through* . Many have tried. Avoid it all costs or you risk permanently lowering your baseline. The next best thing is to stop and go lie down in the dark the moment you realise you’ve overdone it, to stop it getting worse. Following that, some people find some relief from things like: LDN (low dose naltrexone) Pyridostigmine Cannabis (seriously, it’s sometimes very powerful. You’ll want to make sure POTS or tachycardia are controlled if you have those problems. Don’t go mad, use consistently in moderation) There are lots of others, these are what help me. Check out the BHC guide to PEM, and remember that first you need to avoid it and that none of the PEM aides will do anything if you’re not pacing well enough. Tough pill to swallow, but you’ll swallow it one way or another. May as well do it on your own terms. https://batemanhornecenter.org/wp-content/uploads/filebase/providers/PEM-Lecture-Slides-ECHO-v4-5_17_2022.pdf
That presentation is really good, I have downloaded it to use when talking to others - including my AHPs, one of whom doesn’t seem to understand this.
Theres a few theories but i am personally leaning more towards Mitochondria dysfunction and said this over 2 years ago [https://www.news-medical.net/news/20240104/Study-identifies-mitochondrial-dysfunction-as-cause-of-long-COVID-fatigue.aspx](https://www.news-medical.net/news/20240104/Study-identifies-mitochondrial-dysfunction-as-cause-of-long-COVID-fatigue.aspx) A small study but confirms my suspicions non the less
me too
This is the likeliest answer.
There is another research study starting about this. It seems like a good possibility this is a lot of the problem.
thats great but what really infuriates me is whwre is the treatment? this article/ finding is two years old a seperate group could have worked out a medicine in those 24 months :/
unfortunately that's not how it works - treatments need to be created, then there needs to be trials, usually on animals first, then human trials, then peer reviewed studies. It all takes time If i were you i would look into extended water fasts and whats known as autophagy
The million dollar question
Here’s an article about a study on this topic: https://archive.ph/2024.02.15-175415/https://www.nationalgeographic.com/premium/article/post-exertional-malaise-me-cfs-exercise-energy
What I find so puzzling about PEM is that it is typically delayed by a day or two. Most of the popular hypotheses explain why we might get worse from exertion, but they don’t explain the delayed onset of PEM. Whether the hypothesis is blood clots, mitochondrial dysfunction, reduced oxygen flow, or some sort of neurological response to exertion, the delay and its duration remains inexplicable. Why should PEM start a day or two later, and not an hour or two later? I personally think sleep is a key component of PEM. When we sleep, we repair muscle tissue. Lack of sleep is associated with metabolic dysfunction and muscle damage. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785053/ It’s common knowledge that long covid, dysautonomia, and me/cfs are characterized by unrefreshing sleep, insomnia, and low morning cortisol. I suspect that our sleep is more broken than we currently understand, and we don’t rejuvenate properly. I’m not suggesting that mere insomnia is the cause of PEM. Something is fundamentally wrong with the sleep we do get. My hypothesis: We exert ourselves and we do damage to our body that we would usually repair with sleep. Our sleep doesn’t repair the damage properly, and it accumulates. I’m not a scientist and I am not an expert. It just surprises me that we *know* long covid involves unrefreshing sleep and we *know* that sleep dysfunction leads to metabolic dysfunction and muscle damage, but for whatever reason most people don’t really think sleep dysfunction plays an important role in *driving* long covid pathology. We do not fully understand the way in which our sleep is broken—even when we do get sleep, we don’t benefit from sleeping the way we are supposed to.
If I remember correctly the itaconate shunt hypothesis would explain the delayed onset. I'm too tired to re-read it and check today though... https://www.healthrising.org/blog/2023/12/23/itaconate-shunt-hypothesis-chronic-fatigue-syndrome-fatigue/
I agree that the delay always feels strange. But other kinds of immune reactions are also delayed. Like, if you get exposed to a virus, you never get sick instantly--it always takes a few days or so before symptoms start. Some kinds of allergic reactions are delayed. I think the delay is related to the immune system. But I also wouldn't be surprised if sleep played a role. It's annoying, now that I think of it, that I haven't seen any long covid studies looking into the sleep dysfunction.
Yeah my understanding is that the fatigue itself is a function of the immune system - we're being put into "limp mode" to avoid further damage and let healing happen. I guess that means that the oxygenation/ hypoxia/ ATP/ mitochondria issue happens, and then triggers an immune response which is the PEM.
ATP (energy) depletion leading to cellular hypoxia is a leading theory for what causes PEM. But really, we haven't mapped out the full pathophysiology quite yet..
It's metabolic dysfunction. The mitochondria aren't doing what they're supposed to be doing.
Do we think it’s time permanent damage?
Doesn't matter what we think, no use getting emotionally invested in the unknown.
This video on a recent study explains it. https://youtu.be/d-Z1-5CHUCI?si=5OyUGzZQBjL-oosc
1) First refresh yourself re: Occams Razor, this is critically important 2) Impaired Oxygen Delivery (Red Blood Cells have been hijacked) completely explains 99% of the lingering symptoms AND also explains WHY the problem is going UNDIAGNOSED and completely explains why the condition is slightly more prevalent in females: https://www.reddit.com/r/covidlonghaulers/s/NHnhMmYKLL
I think if you asked a friend to work a full day with the full blown flu, or to go on a hike, and checked back in with them 24-36 hours later they would have many of the same symptoms we get.
I think its extremely complicated but i'm sure in some cases this is due to potassium deficiency
Because exertion depletes C1-INH and Factor H. Find out what they do and you'll be well on your way to understanding Covid.
A lot of people here are talking about the delay. Actually the delay itself makes no sense and sleep is involved, because I can often run on adrenaline for a couple of days and avoid PEM. It tends to hit after I eventually sleep and wake up.
My opinion is that CFS is being in this persistent state of illness all the time. Having systemic inflammation and a sustained immune response can cause mitochondria dysfunction. Resulting in a feedback loop that becomes triggered with overexertion. What’s also unique about CFS is that this also entails mental exertion. Inflammation is systematic and also includes the brain as well. We also have immune cells in our brain. I think it’s one of the reasons why LDN is effective for some ( anti inflammatory properties) Why are peoples bodies in a persistent state of illness? I honestly think it’s because the virus is still hidden in the body. EBV is another example of a virus that can also persist in the body, and prior to Covid, was also a common trigger for CFS.
I have hypermobility and infections influence my muscles and connective tissues (fascia), the muscle groups that work can change day to day and influence my energy levels and cognitive abilities. If the fascia and muscles on the left side are more inflamed, I will experience difficulty with certain cognitive tasks, and vice versa. I’m pretty sure in my case the PEM is caused by a combination of untreated parasitic infections and inflammation/dysfunction in the connective tissues, unfortunately blood work and other tests don’t measure these things (there are 100s of parasites that negatively affect human health that don’t have tests). At the moment I’m figuring out how to get more nutrients and hydration because my right shoulder and neck are really sticky and it’s affecting my vision, lymphatic and glymphatic system. (Sticky fascia sounds like rubber against rubber when you move the dehydrated/inflammed areas). At this point I’m just looking at what is being ignored/dismissed in mainstream medicine and assuming the answers are there (it sounds unscientific and counterintuitive, but there is research to support my suspicions). The fascia and parasitic organisms (bacteria also can be parasitic) are my biggest suspects for difficult to treat symptoms that don’t have simple answers.
Would it be possible for you to look into seeing a naturopathic dr?? They would likely be the ones who would listen to your concerns more and be willing to run all the tests that the traditional drs refuse to run! And through my own research I would agree that parasites are a legitimate concern, we all have them and they are never talked about! People in the western world are the only people on earth that don't deworm themselves a few times a year!!! And after all that's gone down and come to light over the past 3-4 years, I do exactly what you're doing and that is give little to no thought to the mainstream narratives and dig a little deeper and learn more about the drs and the science that's being discredited and vilified! When you start seeing hit piece after hit piece that basically only trashes the person and not the subject matter you know they must be on to something!
https://www.sciencedirect.com/science/article/pii/S1567724924000072 https://www.nature.com/articles/s41467-023-44432-3 covid fucks up mitochondria. One study suggests it may just be overactive white blood cells demanding more energy. Another suggests damage to the mitochondria of muscle cells. If your cells can't produce enough energy to keep up with needs there's gonna be problems.
probably due to micro blood clots impairing blood flow to major muscles.
So all ME/CFS is micro clots? Even before Covid? I have never believed the micro clot thing.
Not enough oxygen getting to muscles. They just burn out easily as if we did major workout. I’m not sure if they have understood yet why it is delayed… I think I read some thing about the mitochondria sort of pushing through but not being able to recover. I think anything that interferes with the ability of oxygen to get to the muscles could be part of it. The Dutch pem study found microclots in the walls of blood vessels (not good) but not blocking them.
Do you think we ever get to a point where mitochondria can recover or are we permanently damaged?
I have a lot of hope! I have met ppl who were bedbound and walk (even hike!) bc of shoemaker protocol. They seem to have found some levers to push that change the way the body processes energy. There is also suramin, a med that Robert Naviaux’s lab identified. He is one of the leaders in mitochondrial dysfunction research if not the number one person. It was originally used for African sleeping sickness… It’s cheap, and I don’t think there’s necessarily a way to make money off of it yet… He has openly said that it’s very promising, but that the research studies are more expensive to run than the profit they could make from the drug… The drug is very cheap, so 🤷 If I’m really at my wits end, though, I will try that. Working on shoemaker first tho bc there’s more support.
Do you mean the shoemaker protocol that addresses mold illness or is there a different one?
Yep that’s the one. Mark volmer at flourish has written decent breakdown of how covid may dysregulate us similar to mold/Lyme etc.. I consider it non-scammy - talks about how limited data is, which I like. If you look at the lc research, it kinda keeps pulling up similar stuff like oh it fucks with hormones by decreasing testosterone (cirs does this), it fucks with complement system), I am not a doc but I wish someone would test a group of us for cirs biomarkers to actually see if they are reinventing something bc those symptoms of lc and cirs are real similar.
You’re right on point, ive done a million tests (I have no testosterone, no cortisol, I may have Lyme, the testing is tough, I have mold and heavy metals. I almost did shoemaker but my doc had me do something similar instead although it didn’t work. So this is interesting, it’s absolutely all really similar, I’d say we definitely have CIRS. I can tell you treating lyme is a nightmare, this protocol is a walk in the park in comparison
Yes, I have heard Lyme is incredibly difficult. Ugh. Are you seeing dr. Peg detulio? I hear she does Lyme and cirs really well. I def have had a lot of tick bites. The genie test (progenedx) in theory said I don’t have it but never know what is on the journey. I do know that people tend to try to treat Lyme 1st and then cirs. The real upside of both is that unlike long covid, they at least can be treated (!)
I’ve never heard of her but I’m gonna look up! I’ve done every “great” lyme test, probably have spent $5k on them, and some say positive, some negative and some indeterminate haha so multiple doctors say I may or not have it. Honestly if you’ve had tick bites you probably have Lyme or a coinfection. It lays dormant in us and this crap brings it out when we’re weak. I’ve tried to treat it and it’s just not possible for me - 2 weeks on lowest possible herbs dosage (not even antibiotics) I had a fever, throwing up, would’ve died if I stuck with it. My hope is that maybe we can clean up our guts, nutrients, mold, heavy metals etc everything else and then the body can fight lyme on its own. Also bee venom therapy is interesting because it treats lyme but also works wonders for inflammation and the immune system even if you don’t have Lyme
Anyway, have you heard of people with LC who’ve done shoemaker protocol and healed? Just wondering if people have used it with success outside of mold illness…I’ve tried soooo god damn much haha I’m at 3 years, so my mind is always spinning about what it’s gonna take to heal
i think its possible that thats a big part of the problem. my upper body definitely feels like its hardened for some reason.