Geoff’s Narration
The GIST
From viral persistence to complex immune studies, to tissue sampling, to assessing heavy-duty immune treatment trials and large treatment trials, long-COVID researchers are doing things the ME/CFS community has wanted to happen for decades.
Including an exercise stressor has proved so valuable in ME/CFS that it is now considered a core research practice.
On the flip side, long-COVID researchers have acknowledged that early on, they could have paid more attention to ME/CFS and post-infectious disease findings.
Health Rising’s Quickie Summer Donation Drive is On!Even now, though, the long-COVID field is mostly ignoring the most effective tool in the ME/CFS research playbook – adding an exertion stressor to a study to get at core elements of the disease.
Exertion Intolerant Disease
From the beginning, ME/CFS has been characterized by an intolerance of exertion. Its closest historical antecedent – neurasthenia – was described as producing chronic mental and physical exhaustion, easy fatigability after minor effort, and poor concentration, etc.
The ME/CFS field learned over 20 years ago that adding an exercise stressor wasn’t just helpful – in many cases, it was mandatory. The normal baseline results, which perplexed patients, doctors, and researchers – and gave rise to psychological interpretations of the disease – were quickly replaced by penetrating insights once an exertion stressor was applied.
Exertion studies show that people with ME/CFS are often running on empty.
Adding exercise stressors made sense and, in fact, was probably inevitable. It was the ME/CFS field, after all, that introduced the term “post-exertional malaise” to the medical field in 1991. Komaroff’s 1996 study documented the unique exertion challenges people with ME/CFS face when it found they were significantly more functionally impaired than people with congestive heart failure, type II diabetes mellitus, heart attack, and multiple sclerosis. The Institute of Medicine’s 2015 report underscored the core role exertion plays when it proposed calling the disease “systemic exertion intolerance disease (SEID)“.
Never before had a disease been so characterized by an inability to tolerate exertion. Never had it been so necessary to understand what happens during and after exertion. Using exercise studies to help understand ME/CFS was an innovation that was waiting to happen, and it didn’t take long.
The Workwell Foundation’s 2-day ME/CFS exercise test results sealed the deal. The results may have shocked exercise physiologists, but they didn’t shock people with ME/CFS. The idea that exercise one day inhibited one’s ability to generate energy the next day flew in the face of decades of research but made perfect sense to people with ME/CFS.
Using an exertion stressor enabled researchers to get at core factors in the disease.
Beginning in the late 1990s, ME/CFS researchers began using exercise stressors to understand HPA axis functioning and cytokine levels. During the 2000s, brain imaging and gene expression studies revealed abnormal patterns of brain activation and blood-flow regulation, and a dramatic upregulation of stress, sensory, and immune genes.
It was if a curtain obscuring ME/CFS had been pulled away. By the 2010s, using an exertion stressor to better understand ME/CFS had become a core ME/CFS research design feature.
Exertion is such a core feature of ME/CFS studies that, in an attempt to spare ME/CFS patients the effects of intense exercise, Canadian researchers have been using an inflatable cuff to mimic the changes produced during exercise.
Recent studies indicate that adding exercise greatly expands our understanding of ME/CFS. They include a gene expression study that found increased platelet activation, a proteomic study that demonstrated metabolic impairments, immune overactivation, and ER stress response, a urine metabolomic study that uncovered a dramatically diminished metabolic response, and a plasma metabolomics study that highlighted changes in lipid and energy-related pathways.
The Failure to Engage Findings
Some ME/CFS exercise studies suggest that a failure to engage on a molecular level plays a role.
Exercise studies are producing fundamental insights into the pathophysiology of ME/CFS that are, despite the enormous funding gap between the two diseases, arguably far outstripping what we’ve learned about long COVID. Consider the findings suggesting that, besides being dysregulated in a number of ways, ME/CFS patients’ systems are simply failing to engage on a molecular level when stressed by exercise.
- Gene expression – Exercise produced “altered functional gene networks” in healthy controls but produced no significant changes in ME/CFS patients.
- circRNA – Exercise produced an increase in circRNA in healthy controls but not in people with ME/CFS.
- Metabolites – Exercise produced an explosion in altered urine metabolites (n=400) in healthy controls, but produced no significant change in ME/CFS patients’ metabolites 24 hours after exercise.
- Proteins – Exercise produced reduced protein production in extracellular vesicles 15 s after exercise, reduced protein expression (63 vs 178), and a delayed increase in proteins in ME/CFS patients.
One Study
Exercise produced many results that were opposite to expectations.
Check out the dramatic changes – all abnormal – that exercise produced in Che’s recent ME/CFS study “Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS“. It found that exercise produced:
- Increased citrate levels
- No change in phosphate levels
- Elevated analytes in the S100 family and Class B/2 signaling pathways
- Increased levels of C1R and complement factor H-related protein 4 (CFHR4)
- Reduced acyl-carnitine levels
- High tri- and diglyceride levels
- Higher than normal linoleic acid and possibly high 12,13-diHOME levels
- Elevated ORN:CIT and ARG:CIT ratios prior to exercise; reduced ORN:CIT and ARG:CIT ratios after exercise
- Lower KYN: TRP ratios before exercise; increased KYN: TRP ratios after exercise
- Kynurenic acid (KYNA) to KYN KAT) activity ratios higher before exercise and decreased after exercise
- Higher levels of retina-specific copper amine oxidase (AOC2) and copper homeostasis protein cutC homolog (CUTC)
- Reduced pre- and post-exercise levels of tetranectin (CLEC3B).
These findings suggested that exercise disrupted the citric acid cycle, impaired beta-oxidation of fatty acids, impacted the urea cycle energy production cycle, produced lipid abnormalities, disrupted the extracellular matrix homeostasis, worsened gut dysbiosis, activated the complement system, knocked the redox system off balance, and dysregulated tryptophan-serotonin-kynurenine pathways.
Long COVID
Post-exertional malaise (PEM) is considered a core symptom in long COVID and is being used by the RECOVER and NIH-funded studies to differentiate the ME/CFS-like long-COVID cohort from other types of long COVID. Numerous cardiopulmonary studies have also documented a similar cardiovascular response exists in ME/CFS and long COVID.
In some areas, the small ME/CFS field is outstripping the much larger long-COVID field.
Despite the similarities between the two diseases, I found just six long-COVID studies that used exercise to explore other aspects of long-COVID pathophysiology. Three were done by researchers who had worked with ME/CFS researchers or who had been funded by ME/CFS groups.
The findings were strikingly similar to those found in ME/CFS: lipid dysregulation, a shift towards glycolysis, problems with fatty acid metabolism, inflammation, blood vessel dysfunction, impaired muscle bioenergetics, and mitochondrial dysfunction.
Adding a new component – exercise – to a research study is not easy, but it is now routinely being done in ME/CFS and is an opportunity not to be missed. Indeed, more commonly including exertion stressors in long-COVID studies could conceivably shorten the search for answers by years. The possibilities are enormous.
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This is an impressive study just out on long covid and menstruation. This very much sounds like what my daughter experiences.
https://www.nature.com/articles/s41467-025-62965-7
It’s great to see this study. This is a subject, which after CDC studies showed a huge uptick in gynecological problems in ME/CFS, sorely needs more exploration.
Really interesting. My ME was gradual onset from puberty. Big problems with menstruation right from the start – such a relief when I reached the menopause. For a long time I’ve felt that the big hormone changes at puberty caused my ME and have definitely made it worse over the years. Sorry to hear your daughter is going through similar problems.
I came down with it when I was 17. In the six months prior to it I had:
– stressful life experiences
– multiple vaccinations prior to a trip to South East Asia
– an unidentified viral / bacterial illness on the trip
And then add in the hormonal stuff (I had quite late puberty)
I think all these things contributed to my CFS.
I guess being a male I am lucky I don’t have the further complication of menstruation
Thank you for sharing your symptoms improved with menopause, Kajo! Helps to know!
Ouch! That’s painful to hear that just 6 Long Covid studies used exercise to explore a disease affected so drastically by exercise!! 3 had ME/CFS researchers involved. Meaning it’s really only 3 research groups that used their own rational thinking.
Especially when $1.2 billion was handed over in the US alone to Long Covid researchers. It almost makes me think a bit of fraud or utter ignorance and incompetence was happening
One would think astute and curious researchers would have at least had the gumption to look at the scientific literature for past similar symptom clusters (so easy to do in the internet era by typing them in your search bar). As they would have found a lot of research had already been done, and they could have used that information to help guide their own research further.
I bet many Long Covid patients who are here reading this, have done exactly that, i.e. searched their the symptoms and found they fit ME/CFS perfectly.
But not the Long Covid researchers, they didn’t bother doing that, instead they took the money and squandered it on what they arrogantly assumed were new studies, but had already been done by ME/CFS researchers years ago.
Many of those studies also had proven many things not to be a cause of ME/CFS. Meaning starting a study for Long Covid using hunches (they didn’t know had already long been debunked) was just wasting funding… but no worries for the Long Covid researchers, they still were paid handsomely.
In my view the Long Covid Recover initiative was a complete waste of money. And then not. Why?
(Part of comment deleted – conspiracy mongering not allowed on this website).
You nailed! It’s all about the $$!
It is still a VERY early attempt, made as a result of reading (two papers linked in) this blog. So it is nothing more then brainstorming but I felt the need to write it down in the forum now to get the idea out for sure. Waiting till perfection could result in failing to share anything. There is plenty of chance of errors and I haven’t proofread it yet. I am exhausted now.
However, I feel I may have connected a fair number of so far separate dots and have done it possible quite well.
The title says it all. The third comment, posted below, is the not so short summary.
Title: Linking Exercise, Immune activation, Pain and PEM flares and Connective tissue degradation AND female dominance
https://www.healthrising.org/forums/threads/linking-exercise-immune-activation-pain-and-pem-flares-and-connective-tissue-degradation-and-female-dominance.6964/
(Now actually how exercise creates the needed immune activation to produce copious amounts of ROS is not in that post, but I am working on it and confident that steps happens. Here is the consequence of such immune activation of importance.)
(With more info and citations to research on the forum posts):
not so short summary:
The shorter version, still not proofread and with a rather fatigued brain :):
The first major part comes from the paper:
Title “Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS”
=> Figure 1 shows a number of responses to different immune stimuli. It sort of looked to me at first sight that TLR2/TLR4 activators hammer ME/CFS cells a lot more then a simple viral part does. Yet for some activators there is only modest evidence for TLR2/TLR4 activation but it shows T-cell activation.
=> Figure 2a shows glucuronic acid to be a major elevated plasma metabolite (out of nearly 1000) at rest in ME/CFS and even more so 24 hours after exertion.
=> Combining both plus remembering that glucuronic acid can cause quite a bit of joint pain, I combined those.
=> Glucuronic acid turns out to be quite a potent TLR2/TLR4 activator. TLR2 and TLR4 are receptors that are common on many types of cells, including macrophages (and there brain variant called microglia) and B-cells.
=> Interesting, the paper says that naloxone, a TLR4 antagonist much like LDN reduces the inflammatory effect of glucuronic acid.
=> Glucuronic acid is a part of the molecule hyaluronic acid. That in turn is an important part of all sorts of connective tissue including tissue surrounding our blood vessels and giving it good support.
=> Humans have about 15 grams of hyaluronic acid, of which each day about 5 grams is turned-over / renewed. That raises the question how glucuronic acid in ME/CFS plasma could be so elevated *if that elevation came from breakdown of the hyaluronic acid in our connective tissue* if it already has such high percentual turnover in healthy people.
=> Hyaluronic acid is a long chain of [N-acetyl-d-glucosamine and d-glucuronic acid] building blocks after each other, each linked by a single atom to each other.
=> Hyaluronic acid is like a long wire. Cut it in a hundred smaller pieces, and each of the pieces is still a wire with the properties of a wire. All pieces are just smaller.
=> A paper details that hyaluronic acid, with its high renewal rate, can be broken down enzymatically (and in an ordered fashion) as well as through oxidative stress (ROS).
=> Oxidative stress always breaks it on the glycoside bond according to the paper, leaving “entire” but smaller pieces of hyaluron after cutting it in parts. The parts are not modifed by ROS, only the length of the chain is modified. This leaves most of the properties of the small parts of hyaluronic acid still intact.
=> Hyaluronic acid also has a strong proven effect on TLR2, TLR4, B-cells and T-Cells. In fact, there is a dedicated receptor called the CD44 receptor for hyaluronic acid on immune cells.
=> The paper says that long strands of hyaluronic acid are more anti-inflammatory, and short strands of hyaluronic acid more pro-inflammatory.
=> Simple geometry says that it is VERY likely that one long strand of hyaluronic acid likely can’t bind to / activate more then a few immune cells total. Hundreds or thousands of pieces of hyaluronic acid, still maintaining most of the properties of the longer strand, can easily be dispersed and activate much more immune cells. As they are very small fragments, they can spread quickly all over the body.
This leaves healthy versus ME/CFS. Weakened cells and immune systems can, in ME/CFS, trigger a strong immune response (also) near connective tissues. With too much oxidative stress and/or too few anti-oxidant defenses, that risks to quickly break down parts of the *already weakened* / “cheesehole” connective tissues into copious amounts of small pieces of hyaluronic acid and glucuronic acid, spreading as the splinters of a splinter bomb throughout our bodies and triggering immune cells all around the body. Overdoing it in one part of the body, activating such breakdown of connective tissue, could spread the fragments in minutes all around the body creating inflammatory flares from ankles over gut to brain and leaving connective tissue damage (including weak blood vessels) as a “residue gift”.
=> One long strand of lineary chained hyaluronic acid in good health versus hundreds or thousand of fragments of glucuronic acid containing molecules formed from it under heavy ROS / immune activation
Now take the other linked paper:
Title: “Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients”
The most upregulated metabolite, among about 250 analyzed, in urine is 11-ketoetiocholanolone glucoronide.
=> I haven’t been able to check yet, but that sounds a lot like a variant of (or something easily converted into) etiocholanolone glucuronide. Now etiocholanolone produces, together with UDP-glucuronyltransferase (easy enough made from UDP and glucuronide IMO) something that is much more soluble in water and hence can be removed out of the plasma and dumped into urine.
=> Etiocholanolone hence sounds as a rather good thing to clear this (at excessive amounts) highly inflammatory glucuronide from our bodies.
=> Etiocholanolone is one of the main breakdownproducts of testosterone, and it is known as an inhibitory neurosteroid, improve GABA effectiveness and be anticonvulsant.
=> When binding available etiocholanolone to glururonic acid to try and excreed it, there is less etiocholanolone available increasing brain hyperexcitability and convulsions / spams as seen in ME/CFS when crashing. Also: men obviously have much more of it then women to start with.
=> Then why do men still have a chance to get down with ME/CFS, FM, connective tissue disorders if they have so much more of this protective etiocholanole? My best guess at the moment is that ethiocholanole only clear one component of the “fragmentation bomb” I theorize: glucuronic acid. The other thing hammering the immune system, plenty of small fragments, probably can only be removed if hyaluronic acid first is broken down into glucuronic acid and glucosamine. Only then can the other “fragment” be removed quickly in men.
=> In simpler words: It may take plenty of time for women to clear out both glucuronic acid and hyaluronic acid “bomb fragments” hammering the immune system while men only / mainly have to deal with excess hyaluronic acid “bomb fragments”. Both can hammer the immune system and create a vicious circle (by hammering the immune system to break down more connective tissue that produces more “bomb fragments” that can hammer the immune system more… Since both glucuronic acid and hyaluronic acid trigger the immune system in similar *but somewhat different* ways, it is reasonable to see a different immune activation profile in women versus men on top of the increased vulnearbility for this vicious circle.
=> Etiocholanolone, a breakdown product of testosterone, binds to glucuronic acid (the highly problematic molecule in this hypothesis) and removes is into the urine. Hence having more testosterone can dampen a quick rise in collagen / hyaluronic acid breakdown due to ROS due to immune activation VICIOUS circle A LOT FASTER, helping to explain the big gap in prevalence among men versus women for ME/CFS, FM and Connective tissue disseases.
I think I figured out another important piece of the puzzle:
The two main elevated plasma metabolites in ME/CFS at rest are Wikipedia(Methyl-α-D-galactose) and glucoronic acid according to the https://pmc.ncbi.nlm.nih.gov/articles/PMC12408823/ paper with title “Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS”
Looking at https://en.wikipedia.org/wiki/File:Methyl-alpha-D-galactose.svg and holding https://en.wikipedia.org/wiki/File:Glucosamine_Structural_Formulae_V.1.svg next to it, it looks like that:
a) The NH2 group in the bottom middle of glucosamine has been replaced by an OH group.
b) The OH group in the bottom right has been replaced by an OCH3 group.
a) looks close to a deanimation. See https://en.wikipedia.org/wiki/Deamination.
In a deanimation, a common biological reaction, ammonia is removed and in the wikipedia example water is added. Here an NH2 group is removed and and OH group is added. Mathematically:
NH2 – NH3 + H2O = -H + H2O = HO = OH group
In English: have an NH2 group, do what deanimation reactions would do (remove ammonia and add water or -NH3 + H2O) and you have just enough atoms left to add an OH group in the place where you removed the NH2 group.
b) looks a lot like a methylation reaction. For example in the Electrophylic Methylation part of https://en.wikipedia.org/wiki/Methylation, you replace in every example an OH group by an OCH3 group, just as in this molecule.
Then there is the left top OH arm that bends the other way in both molecules, but it is present in both at the same position. That is a conformational change that is also common in biochesmistry.
=> The 1-methyl-galactose looks to have high chance of being a degradation product of glucosamine.
=> As written in previous post, it also is a potent immune activator.
=> It will, in this hypothesis, be also part of cleaning up the hyaluronic acid fragments. So there will be plenty of it (as seen in figure 2a)
=> Another important thing: the 1-methyl-galactose levels where NOT increased 24h after exercise compared to healthy controls. They do not even show up on figure 2b. That is important and rather remarkable. It IMO indicates that both in healthy controls and ME/CFS 1-methyl-galactose is likely elevated (need to look into raw data, didn’t yet, exhaustion…) (as I presume that exercise does not let dissapear the excess seen in ME/CFS at rest; since fig2b shows ratios, it then makes sense that it raised in healthy controls 24h after exercise to match ME/CFS levels ?as part of normal inflammatory response to exercise?)
=> If correct assumption (need to verify), then ME/CFS patients are not efficient at cleaning out the remaining 1-methyl-galactose after some long time of rest.
=> That may point to increased continuous (or at least every day) destruction of hyarulonic acid / connective tissue due to increased immune activity and decreased oxidative stress defenses. Plus possibly decreased glucosamine / 1-methyl-galactose clearance rates.
=> Methylation is often part of processing chemicals to remove them as waste from the body. Methylation also requires good working mehtylation pathways and enough coblamin (vit b12)
=> The two main metabolites increased (in this research) in ME/CFS at rest versus in healthy people have both a rather strong chance to be break-down products of hyaluronic acid. Hyaluronic acid is found in connective tissue and ROS can break down the glycoside bonds leaving plenty of small fragments of glucuronic acid and 1-methyl-galactose as observed to be the two dominant markers found out of a thousand metabolites in plasma. Plenty of hyaluronic acid fragments, glucuronic acid and 1-methyl-galactose have proven rather strong influence on multiple parts of the immune system. They are small molecules that can be made in very large numbers from a single strand of hyaluronic acid. One of these three components can be cleaned up a lot faster with a breakdown product of testosterone, a hormone obviously higher in men then women. All of this fits ME/CFS and its connection to FM, connective tissue disorders and even migraine being more prominent in women. The symptoms of plenty of hyaluronic acid fragments, glucuronic acid and 1-methyl-galactose show good overlap with what is seen in ME/CFS, FM and connective tissue disorders.
Quote” => Another important thing: the 1-methyl-galactose levels where NOT increased 24h after exercise compared to healthy controls. They do not even show up on figure 2b. That is important and rather remarkable. It IMO indicates that both in healthy controls and ME/CFS 1-methyl-galactose is likely elevated (need to look into raw data, didn’t yet, exhaustion…) (as I presume that exercise does not let dissapear the excess seen in ME/CFS at rest; since fig2b shows ratios, it then makes sense that it raised in healthy controls 24h after exercise to match ME/CFS levels ?as part of normal inflammatory response to exercise?)”
This may sound as if this methabolite, that also can hammer the immune system, reacts the same in healthy controls versus ME/CFS 24h after exercise. This is not entirely true however:
a) A healthy person may indeed experience a part of the symptoms we have when exhausting himself far too much. He may for example get excruciating pain, loose limb coordination, get brain fogged and feel like and effectively risk falling to the ground on the spot somewhere halfway when stubornly keep trying to finish an iron man (one of the most ridiculy harsh endurance sports ever) without training for it. We may get that when trying to walk 100 meters at a snails pace or going up one flight of stairs. The level of combined effort and time of effort at which this happens for producing the same amount of metabolite is orders of magnitude different.
b) When stopping the effort in a), both healthy controls and ME/CFS patients can take quite some time to recover. The drop in load on all tissue cells excluding the immune cells however massively drops in the healthy person going from stubornly attempting to finish an iron man. With it, the body only mainly sees “aggression” from the immune system remaining during recovery. Getting up from rest to go to the toilet or make a cup of coffee barely breaks this rest. With us, stopping this snails pace 100 meter walk barely (percentage wise, at least in comparison to the healthy person going from exhaustion to rest) decreases the load on much of our tissue cells when going from exhaustion to rest. The “aggression” of the upregulated immune system alone can upregulate the stress and danger signals send from all those non immune tissue cells into the body, compounding with the “aggression” of the upregulated immune system to keep the vicious circle going. Even a small effort like going to the toilet can break our rest and is hard to avoid.
Both differences, a) and b), are enough to cause healthy people recovering to normal health versus us keep being stuck at a very low level of performance and wellbeing. That is also seen in the continued upregulation of glucuronic acid in ME/CFS versus healthy controls at rest.
This view also tells why it seems a rather bad idea to get back to full activities too quickly after an infection (a common pattern in many people) or exhausting oneself again and again before being sufficiently recovered (IMO a likely way into gradual onset ME/CFS, especially when already having slumbering health and immune issues).
Now I am back to trying to recover from this mental marathon effort. I more then feel it and it will take some time.
Another part:
I am on a roll (and my sleep is broken for the night). I may have got a new angle on the low blood volume paradox:
When I crash, I always need to pee plenty. And I easily tend to (over)breathe even more. Many people / doctors consider both a wrong reaction. The body “should” hold more water and correct via the renin-angotension system and reacts “wrong and paradoxal” and patients “should learn to breath better because there breathing makes them worse”.
But: https://link.springer.com/article/10.1134/S0006297906060113
Title “pH-dependent regulation of myeloperoxidase activity”
Note: myeloperoxidase is an enzyme formed by (among others) neutrophils and neutrophil extracellular traps (NETS). It transforms relatively weak oxidant H2O2 into very potent (and highly damaging / inhibiting to mitochondrial respiration) HOCl or hypochlorous acid.
Saying “It is shown that at neutral pH MPO had higher affinity to peroxidase substrate guaiacol: at pH 7.4, chloride ions did not compete with guaiacol up to the concentration of 150 mM. At acidic pH, chlorinating activity of MPO dominates” and “Thus, in the presence of phenolic peroxidase substrate, MPO chlorinating activity can be displayed at acidic pH only. It can lead to elimination of hypochlorite production in normal tissues at neutral pH (7.4) and its enhancement in phagosomes where the pH range is 4.7–6.0.”
=> If there is plenty of H202 (“basic oxidative stress molecule”), then presence of myeloperoxidase can produce copious amounts of much more aggressive HOCl or hypochlorous acid. HOCl is often formed in bleach and is highly effective at killing micro-organisms. Copious amounts of it all around our body would be pretty harsh.
=> Now it seems that much of that *might* be prevented by trying to get the liquid in our body (blood plus other water all around the body) less acid / more alkaline and just getting it to neutral or slightly alkaline would already inhibit HOCl production a lot.
One way to do that is: expelling CO2 as well as possible, as that slightly increases acidity. Basically: hyperventilate at rest, hyperventilate like a horse when crashing when the immune system kicks in one more extra gear (and lactic acid potentially is bilding up to increasing blood and tissue acidity).
It gets even better: while removing acidity from the blood and body fluid might be the “goal” of hyperventilating, increased alkalosys incourages the kidneys to try and secrete bicarbonate and dump it in the urine. In order to try and maintain ion balance, that’ll require dumping sodium in the urine too. Combined extra NaHCO3 or sodium bicarbonate should be dumped in urine. That may not be easy to detect in tests, as that’ll simple draw water from the blood into the urine (diluting the extra sodium bicarbonate). And it’ll decrease blood / water content.
Possibly the lungs (hyperventilating) and kidneys (dumping (sodium-)bicarbonate) counteract each other by both being unaware of each others goal. One decreases acidity and one tries to restore it (or better said reduce excess alkality, not increase acidity above the neutral point). But that may not be an error. Doing so seems to be the better way to draw excess CO2 from every bit of liquid outside the blood to first in the alaklic blood and then bind it to sodium to dump it in the urine. IF so, decreasing blood acidity wouldn’t be the only goal. Decreasing all tissue acidity would be the goal.
In light of the “collagen destruction” hypothesis, that would make sense as that would reduce immune cells that travelled from the blood into the connective tissue to have lower HOCl production as well and HOCl is likely very effective at destructing hyaluronic acid:
https://pubmed.ncbi.nlm.nih.gov/9641257/
with title “Degradation of hyaluronic acid, poly- and monosaccharides, and model compounds by hypochlorite: evidence for radical intermediates and fragmentation ”
saying “The detection of increasing yields of low-molecular-weight radical adducts from hyaluronic acid and chondroitin sulphate A with increasing HOCl/ClO-concentrations suggests that formation of the initial nitrogen-centered species on the N-acetylglucosamine rings, and the carbon-centered radicals derived from them, brings about polymer fragmentation.”
Rough translation: there seems to be strong indication that HOCl in reality breaks down long pieces of hyaluronic acid (a polymer of smaller building blocks) and creates radical intermediates and fragments from them. Radical intermediates counds like ROS, and fragments like the above described “hyaluronic acid, glucuronic acid and 1-methyl-galactose fragmentation bomb”. And hyperventilating to get body fluid acidity down and peeing CO2 bind in sodium bicarbonate out might reduce the formation of HOCl.
All that seems to make good sense , now for treatment/solution to help with all that! My muscles never recover fully, have stayed sore now for two years solid,
but get extremely weak, fatigued and sore about 24-36 hours after I exert myself…I guess we call that a
crash, and like clockwork I have noticed a pattern of increased frequency to urinate in that time period.
Not qualified to assess your hypotheses but want to pay tribute to your research and analytical drive. What an intellectual push! I hope you re able to spend a few days resting. When you are recovered it would be fascinating to hive mind whether your dot joining could throw up any possible avenues of treatment attack.
Thanks for your comment. Appreciate it!
I think clinical researchers can find quite a few treatment options in it *PROVIDED THE HYPOTHESIS IS CLOSE ENOUGH* easily enough. Problem is that I see quite a potential for complications / serious side effects by blocking some of those pathways (or blocking them too strongly in order to try and defeat the dissease rather then only milder a bit).
For that reason, I am not going to discus those options here. Some people might try and experiment if they can get similar effects with what they can get their hands on, and take way too high risk. What would work and how to best dose and administer it NEEDS good clinical research I feel.
First the hypothesis needs validation and corrections. Then there IMO are somewhat straithforward treatment options IMO. The real hard work is then doing all the research to make it safe and reliable and find combinations that fullfill that demand. Still, IF the hypothesis would provide a good new angle at this, it helps a lot to better know what to look for.
How do you think all this fits in with hypocapnia (low blood CO2)?
I don’t have the cognitive ability to follow your posts here, but the bit about hyperventilating caught my eye. It’s something I’ve been trying to understand recently. (Agree that it’s much more likely to be a physiological response rather than “patient has suddenly forgotten how to breathe correctly”).
Researchers at U of Calgary are currently conducting a study to see if CO2 supplementation *helps* POTS…and I wonder if it might be helpful in ME too. As in, can it help offset hypocapnia? Can it help rebalanced blood pH?
(Side note: I don’t think the idea of CO2 supplementation is necessarily at odds with what your rationale. Still trying to untangle my thoughts on this, and figure out how it might all fit together)
CO2 in watery liquid (blood) forms H2CO3 (bicarbonate, the stuff that make water sprankle when you add much more to it then what is in our blood). It also gives sprankling water a refreshing taste. That is not only the sprankling effect it adds, but also the slight increase in acidity.
In our blood, more CO2 makes blood slightly more acidic. But during crashing, ME/CFS patients have the chance to already have increased lactid acid (saying it makes things more acidic) and (hypothesis here) the chance it increases the fairly potent HOCl (hypochlorous acid) part of oxidative stress in their body.
So during crashing (mainly onset PEM) patients have a natural habit to hyperventilate more, as the bodies attempt to reduces blood and fluid acidity a bit (within normal range!). That happens to be in sync with the need to try and do damage control.
More CO2 however also helps with removing oxygen from the RBC and transport it to the tissues. So less CO2 reduces tissue oxygenation. Like so many things, even our possible natural remedies have side effects.
As to what CO2 supplementation does for POTS, I’ll leave it to that study. Personally I’d be reluctant to use it during an ME/CFS crash however if they did not test that.
If CO2 supplementation could help hypnocapnea? That should increase it. Help? Less sure.
In air it is about 400 ppm (parts per million). That is 0.04%. In order to increase it in the blood you’d have to increase it in the air you breathe a whole lot. That’ll require a rebreather or other “space man” type of equipment. That’s not convenient in everyday use. And there are studies that (if I remember correct) increasing CO2 to about 5% shows significant side effects even in healthy individuals, like severe headaches and loss of focus and brain clarity.
That should increase *blood CO2*, I meant to say.
https://en.wikipedia.org/wiki/Glucuronidation:
“Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds.[1]”
=> So binding to glucuronide is a common way to make “waste”, polutants or metabolites more soluble in water and easier to remove by urine and feaces. It removes many androgens and glucocorticoids (like anti inflammatory cortisol related molecules). Here we say glucoride removes the excess of something else.
=> But when glucoride itself is in excess, the other molecules can be scooped up “too early”, before their “end of use time”. So excess glucuronide has the potential to scoop up and remove still usefull androgens and glucocorticoids. According to the 1000 plasma metabolite study, tesoterone metabolites seem to be particularly suited to do that, more then female hormones (IF the test studied those, didn’t check yet).
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Now an attempt at another ME/CFS mistery: often very strong *temporary* progress during pregnancy
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https://pubmed.ncbi.nlm.nih.gov/22371261/
Title “Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice”
Saying “In humanized UDP glucuronosyltransferase-1 (hUGT1) mice that express the entire UGT1 locus, the maternal hepatic UGT1A genes are dramatically induced 12-14 days after conception.”
In play English meaning IMO: pregnancy increases (parts of) the womens body to “add, glue” glucuronic acid to plenty of other molecules.
=> Whatever the purpose of that, that IMO has the potential to get rid of a lot extra glucuronic acid to “somehwere”, wherever that is. That could / might include synthesizing hyaluronic acid anew for the womb and growing baby but I am not sure about that yet.
Still: https://pmc.ncbi.nlm.nih.gov/articles/PMC6120812/
Title “Cervical hyaluronan biology in pregnancy, parturition and preterm birth”
Saying ”
ROLE OF HA IN THE CERVIX DURING PREGNANCY AND PARTURITION
HA Synthesis
The enzyme responsible for HA synthesis, hyaluronan synthase (Has), is encoded by three genes termed Has1, Has2, and Has3 [14, 15]. The expression of Has2 is critical in development as mice with a global targeted mutation in the Has 2 gene die on gestation day 10.5 due to cardiac defects [16]. In contrast mice lacking Has1 and Has 3 are viable with no essential role in development [17]. The development of a floxed Has2 allele provides a valuable tool for assessment of Has2’s role in the adult mouse [18]. Has1 and Has3 expression is low to negligible in the nonpregnant and pregnant cervix of women and mice [11]. In contrast, Has2 expression is induced at term in women and in mice on gestation day 15 with peak expression during cervical ripening on gestation day 18. Consistent with the expression of Has2, the HA content in the mouse cervix increases from 7.4 nmol/mg dry wt in nonpregnant to 24.6 nmol/mg dry wt on gestation day 18 [19]. Thus during term ripening on gestation day 18 the total GAG content more than doubles with HA comprising 71% of total GAGs as compared to nonpregnant in which HA comprises 51% of total GAGs.”
=> So more hyaluronic acid production during pregnancy (potentially scooping up excess glucosmaine and gluuronic acid molecules quickely as that are the building blocks of hyaluronic acid.
=> Also of note: I recently found a paper that showed that female blood volume significantly rose during pregancy (already able to explain some of the variance in disease behavior) and it seemed percent wise a lot greater then the weight gain during pregnancy (resulting in more blood volume per kg of woman plus growing baby). Too tired to look title of that one up.
Now, it seems that increased blood volume might be a side effect of less hyperventialation to get CO2 out and acidity down as there is less need to tame the immune system IF pregnancy would reduce free floating hyaluronic acid plus glucuronide plus glucosamine fragments after each exertion.
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Also a weaker link with glucuronic acid and the female cycle
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https://pmc.ncbi.nlm.nih.gov/articles/PMC5990994/
title ”
The Use of Estrone-3-Glucuronide and Pregnanediol-3-Glucuronide Excretion Rates to Navigate the Continuum of Ovarian Activity”
=> See figure1: some female hormones bound to glucuronic acid are excreted up to 10 fold during certain days of the female cycle, potentially getting rid of a significant amount of excess glucuronic acid. In women with ME/CFS, FM, connective tissue this opens the path to stronger fluctuations during the cycle then healthy women too as more glucuronic acid in the plasma *could* increase this process. But depending on the bottlenecks, it could go the other way around too. As a man I have no experience with ME/CFS plus cycle variation. Still, the increased removal of glucuronic acid bound to sterols during part of the cycle still seems to hold for all woman.
Note to self: NOW REST AND STICK TO IT!
For people asking: but what about one of the last promissing hypothesises, the itaconate shunt hypothesis? Is this completely different or another total different hypothesis?
I would say it is quite compatible. (modestly) Increased itaconate is observed in early research in ME/CFS [need to find reference, name of researcher, too tired now]. Monocytes, like macrophages, microglia and even more so dendrites produce copious amounts of itaconate when triggered by TLR4 (and TLR2?) agonists / activators. “Letting explode a hyaluronic acid fragmentation bomb” will spread copious amounts of small molecules excelling at triggering TLR2 and TLR4 receptors. Hence these monocytes would likely be able to produce plenty of itaconate and some itaconate will spill into the bloodstream and non-immune cells.
In addition, the itaconate *shunt* requires coblamin (vitamin B12) to remove a slow degrading itaconate metabolite “capturing, trapping” CoA and making CoA unavailable for the Krebbs cycle of our mitochondria. That (in combination with clearing metabolites of this “fragmentation bomb”) has potential to be part of the PEM timeframe / cascade.
Now metabolizing plenty of glucosamine fragments to 1-methyl-galactose (IF that was indeed the source of it and the pathway) for processing and excretion would require a methylation step and a large amount of methylation effort. That also require coblamin (vitamin B12).
Combine both, and vitamin B12 risks to drop in blood, and have to “divide its workings” amoung two simultaneous happening “PEM related pathways”. More stress on vitamin B12 / the methylation pathway reduces clearance of an itaconate / CoA intermediate (not sure the name now, will look up later). That would ty up CoA longer extending needed CoA availability recovery time in the mitochondria.
On the other hand, this extra load on vitamine B12 / methylation pathways due to need for clearing itaconate metabolites would slow down break down excess (TLR2 and TLR4 triggering) glucosamine levels by slowing methylation to 1-methyl-galactose IF that were the needed pathway. Being low on ATP wouldn’t help either.
=> So both hypothesises seem to be complementairy, not competing.
Dejurgen, unfortunately I cannot follow most of your posts but I really appreciate what you’re doing. Thank you.
I was wondering if you happen to know anything about the thymus. A doctor recently recommended I try this: https://www.inmunyvital.com/. Also known as Biomodulina T, it seems that this has been shown to help boost T-cell production in older cancer patients (and so help decrease inflammation): https://www.sciexplor.com/articles/2972-4759-2024-02-01-2. But if T cell hyperproliferation is an issue in me/cfs, it doesn’t make sense to me that this approach would also be helpful for me/cfs patients. Then again, I don’t even know how to tell the difference between an immune system in overdrive and one that’s become exhausted 🙃
This doctor is not an me/cfs expert. They apparently got this idea from someone they recently met at a conference, not sure to what extent that person knows about me/cfs or LC.
I couldn’t find anything about this here on Health Rising or in the long list of patient-reported treatment experiences in the recent PNAS study.
Any ideas?
I found some potentially more relevant studies:
History of Biomodulina T
https://www.sciencedirect.com/science/article/abs/pii/S1567576923004885?via%3Dihub
Restoration of immunity in older adults
https://www.scielosp.org/article/medicc/2020.v22n3/54-56/
https://www.scientificarchives.com/article/biomodulina-t-modulates-lymphocyte-compartments-in-institutionalized-cuban-geriatric-patients
Helps contain C-19 (opinion article)
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.606447/full
https://www.massgeneral.org/news/press-release/study-reveals-unexpected-importance-of-the-thymus-in-adults
https://www.scielosp.org/article/medicc/2020.v22n3/54-56/
I cannot assess their quality myself, but FWIW Cuban doctors are generally among the best in the world.
Hi Shika,
Despite the commonly held idea that our (ME/CFS patients’) immune systems are underperforming, a rather large subgroup hasn’t had a meanigfull infection (beyond that nasty new Covid virus) in years. That’s a better track record then most healthy people have.
It seems a lot that parts of the immune system are overperforming, others not underperforming but inhibiting. Even cells of the same type can IMO do a bit of both too much and too few.
For the immune system to be able to do that, it seems like a small marvel where everything needs to get in place to fend of some sort of danger while inhibiting (in order to reduce excess damage from the immune system itself) without putting the patient at risk of dying of infection. It’s like a perfectly balanced house of cards. Try and push it in the direction you think it should go most often backfires.
So personnaly I try and avoid to interfere directly with any immune process, but go the long and challenging way to try and identify and reduce the external things I have some grip on like food intolerances.
Hi! Thank you so much for replying.
What you’re saying makes sense to me too. I used to get significantly more respiratory infections. Obviously venturing outside much less nowadays has something to do with that, but I do think an overactive immune system likely plays a role too.
A few months ago I decided to try the PEM Buster tip here of using paracetamol preventatively on some days. After doing this only a handful of times I had noticeably more energy overall.
Then I caught a flu, possibly Covid (much less likely given current infection trends here but not impossible and I didn’t manage to test). Even during the three days or so I had a fever, I had more energy than a month earlier. That was an odd experience.
So my guess is that the paracetamol likely did dial down one part of my immune system, which freed up energy and also made me more susceptible to infections again. But who knows, it could also be coincidence, maybe the increase in energy was the result of eating more antioxidants (like chia seeds) for half a year.
Anyway, thanks again for your reply and your work to try to further understanding of this illness!
Thanks for sharing your observation.
As I remember that paracetamol can deplete glutathione levels, something ME/CFS patients are said by many to be short on already, it asks for some carefull consideration. The thing is: glutathione is needed to detoxify paracetamol: https://en.wikipedia.org/wiki/Paracetamol_poisoning
“Liver damage results not from paracetamol itself, but from one of its metabolites, N-acetyl-p-benzoquinone imine (NAPQI).[6] NAPQI decreases the liver’s glutathione and directly damages cells in the liver.[7]”
So I long considered paracetamol a no go for me with ME/CFS and FM. But thanks to searching for a reply to you I found an unlikely other part of the story here:
Now the typical metabolic route explained goes from paracetamol -> (highly liver toxic) NAPQI.
But: https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/paracetamol-glucuronide
“UDP-Glucuronyl transferases conjugate 52%–57% paracetamol become paracetamol glucuronide and hepatic sulfotransferases conjugate 30%–44% paracetamol become paracetamol sulfate, a nontoxic conjugate, and are then excreted through urine. About 5%–10% paracetamol can be metabolized oxidatively into highly toxic metabolites, N-acetyl-p-benzoquinone imine (NAPQI) via the hepatic microsomal cytochrome P450 enzyme system particularly by CYP3A4 and CYP1A2,9, 10 CYP2E1.11 NAPQI is detoxified by glutathione catalyzed by glucuronyl s-transferase and excreted in urine. A small amounts (5%) of paracetamol is excreted in unchanging form.12, 13”
In Fig 1 in https://pmc.ncbi.nlm.nih.gov/articles/PMC6062253/, it shows that some other metabolites also are removed by glucuronidation. So likely total removal of paracetamol metabolites makes up an even larger percentage then 55% even in healthy people.
In the long above hypothesis, we would produce much more glucuronic acid then healthy people especially during crashes, removing even more paracetamol that way… or removing more (in this hypothesis) a lot of pain and inflammation causing excess glucuronic acid.
That may help explain why paracetamol is useless to me (male) in flares, since my testosterone would catch the main excess of glucuronic acid and leave me “only” with the two other hyaluronic acid inflammatroy components. Maybe *in the specific case of ME/CFS and FM flares* women might fare far better with paracetamol then men? It would be intersting to know.
IMPORTANT WARNING: https://pubmed.ncbi.nlm.nih.gov/31873866/
“For some drugs (e.g. paracetamol, metoprolol), women are at significantly higher risk of adverse effects.”
For people low at glutathione already (ME/CFS, FM), that might be extra tricky. Counting on my vage hypothesis for self experimenting is something I STRONGLY advice against. Still, it might be worth a clinical trial for finding if it worked that way and what would be an optimal AND safe dose. CAN CAUSE HEAVY LIVER DAMAGE!
Note to Shika: Would you want to post your above comment on the forum so I can reply to it? Don’t want to quote you there without. Note that I wrote the above comment in the assumption your name is female.
https://www.healthrising.org/forums/threads/linking-exercise-immune-activation-pain-and-pem-flares-and-connective-tissue-degradation-and-female-dominance.6964/
Can you link where you found this paracetamol tip? Maybe I can find some more info in it? Meanwhile I’ll try and find much safer alternatives.
Quercetin, Green tea catechins (Epigallocatechin Gallate and others), Curcumin, Resveratrol, Sulforaphane (Broccoli and Cabbages).
Some have poor bio-availability, like curcumin. It depends on personal basis as well.
Another interesting find:
https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-024-02011-8
“UDP-glucuronide glycosyltransferases (UGTs) play a crucial role in detoxification by combining with endogenous and exogenous chemical to eliminate them from the host [14]. However, it has been observed that several UGTs mediating glucuronide metabolites can bind to proteins in gut epithelial cells and lead to toxic effects”
“Here, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea.”
=> If I understand well, glucuronidation is a good mechanism to remove many toxic components from the blood by the liver BUT the same process could become toxic to the gut epithelial cells. That is hypothesised to be a cause of IBD in many patients with bile problems.
IBD is common in ME/CFS, and I happen to have frequent diarrhea when overdoing it / crashing. Moments when glucuronic acid would be in excess. And https://en.wikipedia.org/wiki/Indole-3-carbinol, an,other (metabolite) from Broccoli / Cabbage would reduce that. Now I am lucky I do surprisingly well with broccoli despite being intollerant to plenty of food. Need to see where this goes.
I also found another lead in slowing hyaluronic acid methabolism through natural ways. Too soon to be sure, will look into it deeper.
Yes, in above hypothesis, removing more excess glucuronic acid would decrease TLR2 / TLR4 activation, causing less inflammation and pain but also reducing “standby high innate (macrophage) immune activation.
I always thought that since it is now known to harm people, they just say no to permanently damaging the study participants, most ME/CFS studies now include Post COVID Patients that meet criteria of ME/CFS, so subdividing isn’t really the case and I certainly don’t think they play against eachother.
One study indicated that even the 2-day exercise test – which not everybody is in shape for – doesn’t cause lasting damage.
Further to that point, the CPET is the metabolic equivalent of carrying 1 box of groceries up 1 flight of stairs.
Also, each test takes 8-12 minutes.
I’d strongly object this, did you read all of them and did they REALLY include ME/CFS patients with PEM, or did they find things none harmful because they weren’t testing the right audience. We all know someone who’s drastically decreased because of exertion, why risk ending up in a dark chamber… My main point stands ME/CFS Studies now include Post Covid Patients who meet criteria, so nobody is being left behind.
I think that you and Cort don’t talk of the same research. As it was seen since the beginning of the pandemic there is and still is a lot of Long Covid research going on that doesn’t take notice of ME/CFS.
These are very heterogenous patient groups that certainly include undiagnosed ME/CFS patients. And only god knows what these researchers want to find out.
The few smart one’s among them have figured out sooner or later that they can make their work easier and better by acknowledging ME/CFS and reading up its research literature.
In the meantime these people have become ME/CFS researchers themselves.
You speak of these folks. But Cort, when I get you right, you speak about those who are still researching Long Covid with the broadest criteria and believing that Long Covid is a distinct syndrome.
Hi Lina, ME/CFS and Long Covid are not the same. I have both.
A month after having Covid in 2023, I developed sudden A-Fib and high blood pressure. It turns out that this is not unusual.
“There is an increased risk of heart attacks and strokes after a COVID-19 infection, with a large study showing that people infected with the virus had double the risk of major cardiovascular events for up to three years, a risk that was significantly higher for hospitalized patients and more pronounced in those with non-O blood types.”
I have improved with the help of an excellent cardiologist, but then I got Covid again. This time, it affected my ability to walk and maintain balance. Nothing like anything I had during nearly 40 years of ME/CFS.
Covid also affected my hearing. Now, I can hear almost nothing in my left ear.
Complete hearing loss can be an outcome of Covid.
It is time to quit dwelling on PEM, when both ME/CFS and Covid can cause so much more. PEM is just the low hanging fruit that won’t get researchers into any trouble so it is easier to fund.
Hi Betty, I am one of those ME/CFS patients who advocates since several years that people stop talking about ME/CFS and Long Covid as if it were the same thing.
From what I’ve seen, this is in the short run dangerous or unhelpful for patients with Long Covid. Because just as you say many people with Long Covid don’t have PEM but they have other problems that they need help to.
I have read an article by such a Long Covid patient who was furious that her medical support team wouldn’t stop to teach her ME/CFS illness management and pacing when what she needed was something completely else.
On the other hand I have seen that there are many Long Covid people who have ME/CFS for several years but don’t know. Because they’ve received a Long Covid diagnosis fast they don’t realise that they have ME/CFS and they don’t receive the ME/CFS patient information and the support with ME/CFS management and pacing that they would need.
Since I am a 2017 ME/CFS patient I think that this is tragic but it doesn’t bother me personally. What does is that by not carefully distinguish between ME/CFS and Long Covid ME/CFS experiences a diagnosis creep and becomes again something that people think of not as a distinct syndrome – what it is – but rather like as of Long Covid as a random list of symptoms or as a spectrum.
This is very dangerous for ME/CFS research.
Hi Betty,
I also have had a fairly mild case of CF since 1999.
But it didn’t get really bad, with thorough PEM, until 2,
possible 3 (too early to test) cases of Covid.
So I too think I have both CF and Long Covid.
I know it sounds crazy but people do recover from these studies. The person at the heart of exercise testing for ME/CFS – Staci Stevens – has ME/CFS herself and has worked with many ME/CFS practitioners and researchers including Dan Peterson, Maureen Hanson, Betsy Keller and John Chia.
The study is below.
https://pubmed.ncbi.nlm.nih.gov/36984572/
Another good read, Cort.
Hope things are getting more settled for you.
They are getting better. Fire is basically out which means no more smoke which means no more driving hours to get out of it. 🙂 The sheep (another story) are gone too. 🙂
HealthRising does a phantastic job
Dr? phantastic or fantastic -)
Did any of these tests include a muscle biopsy to assess damage to the muscle sarcolemma, and if so, was any damage found?
Check out Rob Wust’s study.
You mean: Fireside Chat Series | Episode 24
https://www.youtube.com/watch?v=8i4iHaFlUiw&t=841s
Thanks
Hi dejurgen,
I am curious. Do you have ME/CFS and Long Covid or just ME/CFS?
ME/CFS, FM, and non POTS form of orthostatic intollerance. Plus plenty of intollerances and a number of allergies.
I have decided to stop dwelling on the “big picture” of ME/CFS and Long Covid and work on my individual symptoms.
I was doing pretty well with pacing and the antiviral Nexavir until I got Long Covid. Suddenly, I had high blood pressure and scary heart problems. These have resolved by upping my dose of Nexavir and seeing a wonderful cardiologist who didn’t load me up with heart and blood pressure meds.
Now I am working on the balance and walking problems post Covid. Yesterday, I started Physical Therapy. I was so happy when the therapist mentioned Long Covid without me bringing it up. He also asked about tinnitus which I have had through all of this.
He seems very understanding of the need not to overdo. I will let you all know how things work out.
I’m going to tell my friends who also have Chronic Fatigue
that if you don’t believe me, I’ll take you to CORT.
But then, seriously, with so many SYMPTOMS so well documented,
there must be some REMEDIES for them.
What are they, Cort, in simple language?