The Netherlands and the U.K. have been the epicenter of biopsychosocial research (CBT/GET) into chronic fatigue syndrome (ME/CFS) for the past 20 years or so, but that is changing. In 2018, the Dutch Health Council asserted that “Scientific research on ME/CFS is needed to serve patients better”, and that the Minister of Health, Welfare and Sport should commission “a long-term, substantial research programme on ME/CFS“.
The Netherlands recently committed to spend 28 million euros (almost $33 million) on chronic fatigue syndrome (ME/CFS) research over the next ten years. It’s not a huge amount of money, but Dutch researchers have shown the ability to make a lot out of a little.
Back in 2014, RC Vermeulen was among the first to conclude that oxygen delivery to the muscles was impaired. Last year, Visser et al. used new technology to show that virtually everyone with ME/CFS exhibits a reduction in blood flows to the brain when they stand.
Now a Dutch team, led by E.G. Klaver-Krol and M.J. Zwarts and including Vermeulen, may have identified a key difference in the muscles between ME/CFS and fibromyalgia (FM).
Klaver-Kroll and Zwarts have been studying muscles issues in fibromyalgia and other disorders for years. In 2019, they found increased muscle membrane reactivity in FM and in 2012, muscle conduction issues in FM. Zwarts assessed muscle fatigue in post-cancer fatigue in 2015 (and didn’t find any).
With their FM findings under their belt, Klaver-Kroll, Zwarts and Vermeulen turned to chronic fatigue syndrome, and compared it to FM.
The Study
The study, “Chronic fatigue syndrome: Abnormally fast muscle fiber conduction in the membranes of motor units at low static force load“, used a non-invasive technique called surface electromyography to assess the electrical activity (muscle fiber conduction velocity) as small amounts of force were applied to the biceps muscle. If I have it right muscle fiber conduction velocity refers to the speed with which electrical activity results when force is applied to the muscle fiber. People with ME/CFS or fibromyalgia and healthy controls were included.
The authors reported that the pain in both ME/CFS and FM “particularly involves the muscles”. That was music to my ears as exertion typically produces muscle burning sensations and feelings of tight, contracted muscles that are impossible to ignore.
Fibromyalgia
“Negligible” levels of force were all that was required to produce a dramatic uptick in muscle membrane activity in FM.
A great deal of evidence suggests that something in the muscles in off in FM. The 2019 FM study “Fibromyalgia: Increased reactivity of the muscle membrane and a role of central regulation” produced a finding that seemed to astonish the researchers. They found that the largest increase in muscle membrane activity occurred when a “near negligible force” was applied to them.
That seemed to imply that the muscles were in a state of near activation, and just needed the slightest push to prod them into action.
That could be the result of two things: the muscle cells were being activated more quickly, or the membranes around the muscle cells were in a constant state of excitation. Since there was no evidence of increased muscle recruitment, the authors concluded that overly excited muscle membranes were the key.
Despite the fact that the muscle membranes were apparently itching to jump into action, the authors found no evidence of increased muscle activity overall. That suggested that the motor neurons in the central nervous system were feeding the muscles a steady stream of signals that was leaving them on high alert – but not quite pushing them into action.
Muscle studies are rarer in chronic fatigue syndrome (ME/CFS), but while the disease is more known for fatigue, muscle pain is common. This study’s unique feature was that it assessed muscle membrane functioning in both ME/CFS and FM. I’m fairly sure that nothing like this has been done before.
The Gist
- Surface electromyography assesses how quickly the muscles respond to force.
- Past studies indicate that the muscles in people with fibromyalgia respond very rapidly to “near negligible” amounts of force.
- The rapid response is believed to be due to something that’s akin to central sensitization: the muscles cells are being bombarded with signals from the central nervous system keeping them on high alert and causing them to respond immediately to even the smallest hint of activity.
- This study found that people with chronic fatigue syndrome exhibit increased muscle hyperactivity as well – but in a different way.
- Their muscles demonstrate unusually high levels of activation but at a higher level of force.
- Since aerobic muscle fibers are recruited first and anaerobic muscle fibers are recruited next, the authors believes the delayed jump in muscle activation seen in ME/CFS reflects their muscles hitting an anaerobic wall.
- This jives with exercise and other studies suggesting that the aerobic energy production pathways are damaged in ME/CFS. The jump in muscle activity seen in ME/CFS reflects muscle cells desperately trying to produce more energy.
- The authors suggested that while there may be overlaps, the primary muscle problems in fibromyalgia are due to central nervous system issues while those in ME/CFS are primarily due to problems with energy production.
Results
The membranes surrounding the muscle cells were more excitable in both ME/CFS and FM patients compared to the healthy controls, but there the similarities ended.
As in prior studies, the muscle fiber conduction velocity (MCFV) rose abnormally high when the slightest forces were imposed on the muscles of FM patients.
The muscle conduction velocity rose “sharply” in ME/CFS as well – but only when higher levels of force were applied. . The authors noted that these levels were “far above” those of the healthy controls. The people with ME/CFS, then, didn’t exhibit the excitable response at very low levels of force that the FM patients did. Their muscles were more excitable than the healthy controls but only when a particular level of force was reached.
Different kinds of motor neurons are associated with different kinds of muscle cells. During exercise, the slow motor units linked to aerobic muscle fibers are activated first and then the motor units regulating anaerobic muscle fibers are activated next. The authors proposed that the hyperactivated motor neurons in ME/CFS were associated with the activation of thicker, more anaerobic muscle fibers.
Then they pointed a finger at the early entry into anaerobic energy production that various exercise studies have found in ME/CFS: the people with ME/CFS were quickly blasting through their aerobic capacities and running into an anaerobic wall.
Next came a key question: could the amplified motor conduction times seen in ME/CFS have been due to muscle disuse or deconditioning? The answer to that couldn’t have been clearer. Deconditioning would have produced the opposite result – reduced muscle fiber conduction, not the increased muscle fiber conduction they found.
Similar Symptoms – Different Causes?
Fibromyalgia
The studies from this Dutch group suggest that FM and ME/CFS are both similar and different. Dramatically increased levels of muscle activation are seen in both.
In fibromyalgia, abnormally high muscle conduction velocities occur at very low force levels. This appears to result from a constant stream of signals from the central nervous system that’s leaving the muscle membranes in a constant state of near activation.
The authors suggested that a process similar to central sensitization was underway in FM patients’ muscles. Either the muscles were being fed too many signals to activate or the inhibition system designed to keep them in check was not working. Either way, the central nervous system was throwing the muscle activation system out of whack.
Evidence of a kind of hyper-excited muscles in FM goes way back. A 1989 study, “Evidence of neuromuscular hyperexcitability features in patients with primary fibromyalgia”, found that the muscles in FM tend to stay in an activated state long after a task has finished. It also found evidence of twitchy muscles which failed to relax or calm down between contractions.
Mental exertion was all it took to activate the trapezius muscle in FM in one study.
Other studies suggest problems with inflammation, reduced energy production, reduced blood flows and high levels of oxidative stress may be present in FM patients’ muscles.
It’s surprising, given how rich the research on muscle problems in FM is, that this aspect of the disease is not better known.
Chronic Fatigue Syndrome (ME/CFS)
The results jive with those from Workwell’s two-day exercise studies which indicate that people with ME/CFS hit the wall after blowing through their limited aerobic energy production capacity.
In ME/CFS, the abnormally high muscle conduction velocities seen in FM occur only after more force is applied to the muscle. While the authors stated that central nervous system activation may be involved in ME/CFS, they more pinned the blame on a breakdown in aerobic energy production and a subsequent quick entry into anaerobic energy production.
For years, two-day exercise studies have documented that people with ME/CFS are quickly blowing through a broken aerobic energy production – and finding themselves fatigued and in pain as their anaerobic energy tries (and fails) to keep up.
Some exercise studies do suggest that problems with energy production are present in FM, but it’s pretty clear that people with FM can generally tolerate more exercise than people with ME/CFS. This is the first study I’ve seen that might explain why. In FM, the central nervous system appears to be the chief culprit. In ME/CFS, a broken aerobic energy production systems is.
Here’s to more biological Dutch research!
Thanks Cort, as usual an excellent report on science I never heared of before.
“The authors proposed that the hyperactivated motor neurons in ME/CFS were associated with the activation of thicker, more anaerobic muscle fibers.”
Lately, I’ve been looking upside down on the issue of our muscles going very quickly into anaerobic functioning. Maybe that is the goal rather then a dysfunction. Sure, it isn’t a healthy response. Yet, it still may be a symptom due to the body attempting to prevent something even worse.
What are we talking about?
Since long, Issie has been working on the idea that excessive glutamate can cause the brain neurons (in ME patients) firing at far too high speed. That easily can create a hyper brain buzzing of activity and flashing thoughts and senses, but it all being rather unsynchornised and chaotic. That would easily lead to very high brain energy usage while creating a hyper but confused mind and sensory overload. What’s worse, the brain neurons risk to damage themselves in a process called glutamate excitotoxicity. That can permanently kill neurons.
Such uncoordinated overly buzzing brain can not only make thinking more on the edge, but muscle activation too quick and movements uncoordinated. We recently extended that idea with the “spinal cord escalator idea”, seeing good reason why an overexcited and inflamed brain can pass that inflammation downstream to the tissue like muscles and organs by having inflammation, oxidative stress and excessive levels of glutamate leak along the spinal cord to these tissue. Inflammation of inflamed tissue could equally well flow upward along the spinal cord to the brain, more precisely the brain stem where so many nerves start and end. The combination of the downward path and the upward path have potential to create a vicious circle.
Now we have stumbled on another likely odd mechanism: the inflamed brain, using so much energy so often, needs an increased supply of energy and oxygen. That means an increased amount of glucose (as few other sources of energy pass the brain blood barrier) and increased blood flow. Yet, other studies point to our brains having reduced blood flow at base and even less after exertion. And our RBC seem to be rather stuborn when it comes to release oxygen to the tissues.
A higher need for energy and oxygen and a poorer blood flow towards the brain combined with reduced oxygen release from the RBC isn’t an ideal combination to say the least. So, chances are reasonable our brains depent more on anaerobic energy usage then the brains of healthy people. That would mean an even bigger need to send plenty of glucose to the brain, for providing bits of energy per molecule of glucose converted to lactate. Research has found increased lactate levels (at least at times) in our brains too.
Our brains can produce some amount of energy by converting proteins into bits of energy too. Metabolic research however has shown that we tend to be low on blood protein too.
So it seems when our brains go on a wired frenzy, they often may need plenty of both glucose and amino acids and use much of it in a low energy yielding anaerobic process.
That is where the muscles come in. The liver has some glycogen storage, from which it can produce glucose to release to the brain. It is said to be able to store about 100 grams of it. The muscles can store up to 4 times as much, 400 grams. However, the muscles can’t release glucose to the blood stream. They lack the transporters to do so.
So, when the brain is craving for plenty of glucose, the smaller liver storage may get depleted faster then desired. Or it may not be able to convert glycogen to glucose fast enough. Or… there are a few more ways this could be insuficient at times.
When the brain really needs more glucose (and the liver can’t easy enough produce plenty of ketones), then the body quickly will have to turn to salvaging tissue for taking out the protein from it. As you can imagine, that is a rather harsh option on those tissue. So the body preferably will do that to “more repairable” tissue. Think about skeletal muscle and in second place connective tissue. There is plenty of protein in both.
Still, with muscle glycogen storage depots being four times as large as the livers storage, it’s a bit a shame the muscles can’t deliver glucose to the blood isn’t it? That holds even more for us, as most of us are crippled enough to be unable to move enough every and each single day to make a dent in those rich glycogen (if filled, of coarse) stores.
Now if there would only be a way to release that glucose. Well, actually there is, under conditions that is. Muscles are very well known to produce lactate from glucose quickly when working anaerobically and then dump plenty and plenty of lactate in the blood. Well, if that pathway isn’t broken, the liver excels at recycling that lactate to glucose. OK, the process is fairly inefficient. For each glucose converted to lactate the muscles receive 2 ATP. It does cost the liver however 6 ATP to recycle lactate back to glucose. But hey, if the alternative is to destroy skeletal muscle and connective tissue (EDS like?) to salvage enough proteins to save the brain… then it may be a fair price to pay.
All of a sudden, me waking up shivering and shaking violently with my limbs in the middle of the night makes a whole lot more of sense. Blood sugar at night can drop rather low. Blood flow gets worse. My brain feels like being in really bad trouble. If it are mainly my anaerobic (fast) muscle fibers shaking that hard, they convert plenty of glucose to lactate. The shaking and shivering is a good sort of pump to pump out that lactate to the blood and get it to my liver. The liver then can work extra hard to try and convert it to glucose for my brain. That does put a very high burden on my liver and on my breathing, especially if the brain needs plenty of it as it uses much of the glucose in an anaerobic and poorly efficient way. So me waking up and breathing like a horse in the middle of the night when I do that suddenly makes a lot more sense too…
So, our muscles going very quick into anaerobic mode: a bad dysfunction or an attempt to save our brains?
Part of the answer may be in this quote from what Cort wrote:
“Evidence of a kind of hyper-excited muscles in FM goes way back. A 1989 study…evidence of **twitchy** muscles which failed to relax or calm down between contractions.
**Mental exertion** was all it took to activate the trapezius muscle in FM in one study.”
Is interesting you write this Dejurgen because as I read Cort’s blog I wanted to ask if anyone else here has very high calorie requirements?
I need to eat a lot of calories for my size and regularly consume more calories than my 6 foot 2 husband. As unhealthy as sugar is for me, I need it to avoid muscle shakes and weakness. Chocolate is my go to.
One of the first things that happened to me when I got sick over 25 years ago was significant weight loss along with IBS. My weight stabilized with time but I still need to eat very regularly to avoid low blood sugar. Oddly, during occasional periods of better health, my blood sugar stabilizes, I don’t need to eat as many calories and can go for longer without eating. This usually happens when I am under little to no stress for an extended period of time. I am a pretty easy going person by nature but any stress just seems to tip my body into imbalance. I swear my parasympathetic nervous system doesn’t switch on properly.
As I enter middle age I am concerned about the impact of my sugar intake and lack of movement on my heart health. In all other ways my diet is extremely healthy but sugar is a problem. It helps with energy but causes its own side issues.
Would you happen to have some sort of gluten intollerance? That can damage your gut wall and with it increase food malabsorption. That includes malabsorption of fat. That can lead to fatty stool and low vitamine D levels as vitamin D, like A, E and K, are fat soluble. So if you can’t absorb fat will you will lose those callories and much of the vitamines the fats carry.
As I suspected, there are multiple reports of Celiac disease (but one form of gluten intollerance) possibly impacting blood sugar regulation.
https://gluten.org/2019/10/17/diabetes-and-celiac-disease/
“Celiac disease can cause unstable blood sugar control.”
I didn’t quickly found more scientific literature and don’t have the spare energy to do so now.
Note: while I show negative on gluten antibody tests I do have clear trouble with it. Long after I became aware of that, a genetic test confirmed me to be at high risk for celiac disease. It appears I haven’t got that but some undefined gluten trouble.
Yes debsw, I seem to have a much higher energy need, compared to how I used to be. However just glucose doesn’t work – I tried that – food like peanuts, chocolate, chocolate chip cookies, that have fat and sugar work best. However, I’m also intolerant to these foods now, so I have a dilemma. Also, currently it’s my brain that runs out of energy, not my muscles. This is an ongoing issue for me. How to obtain energy, without setting off my immune system.
I’ve found Gatorade to help quickly and miraculously get me out of bone crushing episodes of my most severe fatigue…I avoid most sugar, but felt that whatever my body was doing to itself had to be worse than the sugar’s effect to stabilize something in my body…Coconut water helps too, but not as effective.
Per Cort’s writing, I tried the WHO formula for rehydration, and that seems to help too.
I think, like you Jessica, that I know the sugar isn’t good but the lack of it seems to be worse – I don’t function – particularly my brain. Howevrr too much causes some sort of side effect – immune/inflammation? Somehow, I believe, the mechanism for keeping my brain glucose level steady is faulty or set too low. It just doesn’t kick in, when it needs to, to keep me functioning optimally so I have to consciously intervene, fairly crudely. Ginger biscuits/cookies are the current fuel.
Thanks for your replies Dejurgen, Tracey Anne and Jessica. Sugar sounds like it might be a double-edged sword, helpful and harmful at the same time.
Dejurgen, yes I do suffer from non-celiac gluten intolerance and have been gluten free for nearly 20 years. I felt a lot better when I first removed gluten from my diet but the ME/CFS relapsed again a couple of years later. Thanks for the link.
Tracey Anne, I also do best with a combination of fat and sugar and find concentrated sugar too sickly, but during bad relapses I get a lot of relief from Gatorade just like Jessica. I hope your ginger biscuits keep helping!
“most of us are crippled enough to be unable to move enough every and each single day to make a dent in those rich glycogen (if filled, of coarse) stores”
This has a mirror side: if we can move so few due to exercise intollerance, our muscle glycogen stores (if we don’t have a glycogen storage diseasse) will likely be most of the time near full.
That in turn would make them basically ineffective to help buffer the strong influx of glucose from meals and hence ineffective to stabilize blood sugar peaks. Once the storage is full, few can be added on top of it.
With a calloric intake of 2000 KCal a day and 60% of it being carbs in a common diet, 1200 KCal a day is carbs, mostly broken down to glucose and fructose. That equals to roughly a bit less then 300 grams of carbs a day. With 4 gram of glucose in all of our blood, a single meal would multiply that amount far too much. Insulin must be secreted to reduce the blood sugar levels rise.
One way to reduce and contain that rise is to store glucose as glycogen in the liver (100 gr of storage) and muscles (400 gr of storage). If that muscle glycogen storage would be near full before the meal (due to our muscles needing and using few glucose), then near 4/5th of the total glycogen storage would be near unusable to top off the strong rise in blood sugar levels.
The remaining options to top off nefarious high blood sugar peaks?
* build fat from excess sugar in both the liver (risk for non alcoholic fatty liver disease) and the mithochondria
* just try and burn glucose fast with no real use, creating heat and oxidative stress
* make digestion worse so uptake would be reduced; good for feeding yeast and bad bacteria in the gut
* dump glucose in the urine; to find sugar in the urine isn’t known as a good sign to say the least
So, having too few (ability to) exercise could keep the muscle glycogen stores near full and with it severely hamper the bodies ability to reduce blood sugar peaks. Too high blood sugar peaks have a whole series of inflammatory side effects like glycolisation of protein and RBC (strongly diminishing to destroying their function).
Less ability to quickly store glucose in the glycogen stores also needs higher insuline peaks. High insulin peaks are reported by plenty of research to be very inflammatory. Needing to form plenty more fat (including triglicerides) to reduce blood sugar levels quick enough isn’t good long term neither.
So, also looking at it that way *some* increased production of lactate in our muscles (to make more room in our glycogen stores before a meal comes in) isn’t a bad idea either. Once more, this symptom might be part of a mechanism to try and prevent worse.
Notice I wrote *some* increase in lactate production. Too high levels can overwhelm the liver and be nasty too.
Fascinating Cort!
Can you clarify something for me? What is the relationship between the research suggesting aerobic energy pathologies and existing theories of ME as fundamentally a “central sensitization disorder”? Does the former undercut the latter? I’m wondering because the sensitization theory is still prominent in some of the best ME clinics we have here in Canada, as is the corollary assumption that ME and FM are similar on a basic pathophysiological level. But central sensitization, or at least my limited understanding of it, has long seemed inadequate to explain my core ME symptoms.
David, this is a digression, but you state: “…in some of the best ME clinics we have here in Canada…” I live in Montreal, and there is not a single clinic in Montreal. I have also lived in Toronto, and there was not a single ME clinic there either. There were a few single practice doctors who know only a little. I also know Ottawa well, and there were two doctors there, but no clinic. Are you in Western Canada, perhaps? And would you be so kind as to let me know where these clinics are. And have you had some success in these clinic, even marginal. Thank you in advance. Best wishes.
Hi Perrier,
Such is the state of things in Canada and in most cities in the U.S.. There is the Environmental Health Clinic in Toronto – https://www.womenscollegehospital.ca/care-programs/environmental-health-clinic/ – but it’s small (and seems to be getting smaller over time) and I’m not surprised that you haven’t heard of it. It’s a shame as there are some good, knowledgeable doctors there.
Stay tuned, though, for a way to find more doctors coming up.
Thank you Perrier,
You’ve saved me from having to post the exact same question.
Cort,
The last I’ve heard, the Women’s College Environmental Clinic will see you *one time* (with perhaps a follow up or two, but NO ongoing treatment). They also have an 18 month waiting list. That’s IF your GP will even consent to order the many blood tests they require as a prerequisite to getting on the waitlist (many won’t, ask me how I know).
It’s a considerable stretch to describe them as an ME clinic.
Perrier is correct; there is effectively no ME treatment (or even physicians willing to treat ME patients unless you’re willing to pay privately) anywhere in Canada – at least that I’m aware of. I hope to be proven wrong.
In fact, there are several Canadians who dial in to the monthly Bateman Horne MECFS support calls – even though I’m pretty certain BH’s funding was never intended to cover out-of-country patients. BH deserve huge credit for doing that, and its Canadian support group callers owe them (and feel) a huge debt of gratitude.
Canada likes to brag about its ‘world class’ (free) health-care, but its stigmatization and abandonment of Canadian MECFS patients (in every province) is shameful.
All this on top of the fact that it’s illegal (well, at least forbidden) for Canadian MECFS patients to donate blood. Odd restriction for a ‘disease’ that is still considered by the medical establishment as psychological in origin, no?
My sincere apologies for the rant; this touched a nerve.
The EHC is an ME/CFS clinic but one which it is practically impossible to get into. (I know someone with ME/CFS who has been going there for years.) My understanding is that it was never big and has been steadily cut back, and is now very small – hence the very long wait times. It in no way has the capacity to serve even a small percentage of the MECFS patients in Toronto. The situation in Canada as in the states and elsewhere regarding treatment is that good treatment is very, very hard to find. If I gave the impression that it’s not I apologize.
https://www.womenscollegehospital.ca/care-programs/environmental-health-clinic/
My mistake. The person I was referring to is seeing a doctor associated with the EHC. She is not seeing her at the EHC and only had 2 apps there. I don’t know if it’s possible to have more appointments there. The doctor she is seeing is not taking patients.
I agree that it is difficult to see how central sensitization can explain the exertion findings in particular. I think more must be involved. I suppose it is possible that the brain shuts down aerobic functioning (somehow) in order to reduce pain and fatigue but that’s a pretty far reach. Clauw did however show that central sensitization might be leading the small fiber neuropathy- so who knows.
In general, though, the energy production problems seem quite distinct from CS. Maybe some others have some ideas about this. At some point all of this will need to be tied together.
Unfortunately them blaming ‘sensitisation‘ is their lazy response to diseases they can’t actually treat with their outdated psychological techniques.
Psychology and psychiatry have epically failed in this area.
My advice to anyone facing a clinician suggesting psychobabble treatments or simply being dismissive, even a snide remark, is to tell them you are considering laying a complaint with their governing medical authority.
Doctors are terrified of being investigated as it’s a huge audit and scary as they can get into serious trouble. My friends are doctors and all say they never want a complaint against them.
Yet for the patient the complaint process is a very easy to do.
The more people like us that complain, the more doctors will educate themselves about ME/CFS and FM. We need to join forces with Long Haul Covid patients and help them not be dismissed with this gaslighting nonsense either.
In Canada you can complain to ‘The College of Physicians and Surgeons’
https://www.cpso.on.ca/Public/Services/Complaints
In the US the ‘Federation of State Medical Boards‘ can help patients lay a complaint.
https://www.fsmb.org/contact-a-state-medical-board/
In the UK contact the ombudsman or phone them to lodge a complaint 0300 061 0614
http://www.ombudsman.org.uk
I agree that it’s hard to blame everything on central sensitization – and it is a very real thing. Studies show that pain nerves stay reactive longer than usual in FM, that they react more quickly to stimuli than usual, and they react to stimuli that they shouldn’t be reacting too. Studies also demonstrate that the pain inhibition pathways are inhibited and that the pain enhancing pathways are more activated. The pain processing system in FM is really on edge.
I don’t know the ins and outs of all this but Younger’s description of microglial cells responding to the slightest stimuli with pro-inflammatory cytokines that put the nerves in a hyperactive state sounds a lot like central sensitization to me.
I guess time wil
Perrier and Anne,
Just to clarify, when I say “best clinic in Canada,” I only meant that they are “best” relative to what little we have. I don’t know of any clinic that would compare to the Bateman Horne Center or the Institute for Neuro-immune Medicine, for example, and that’s a shame for people like us.
One that mentions sensitization explicitly is BC Women’s Hospital’s Complex Chronic Disease Program. They are definitely an ME clinic in that they exclusively treat ME/FM/Lyme. I also know someone with POTS and ME who has been helped very much by them. I guess it goes to show that you can still do a reasonably good job as a clinician even if you subscribe to an someone dubious underlying theory of the illness you’re treating.
The other one I was thinking of is indeed the Environmental Health Clinic in Toronto, which borrows some of it’s info sheets from the BC clinic. It certainly has its limitations (long waitlist, 3 total visits per person with a one-year timespan, not exactly cutting edge, etc.) and is clearly underfunded. But it’s definitely an ME clinic worth considering. A lot may depend on the particular doctor who is assigned to your care, but in my case the clinic was invaluable. I got things from it that I would not have gotten anywhere else, including:
-a formal diagnosis
-very specific advice on pacing (e.g. specific brands of heart rate monitors and how to use them for ME purposes), diet and exercise
-a referral to one of the top cardiologists in Ontario for treating orthostatic intolerance (diagnosed me with POTS, offered several natural and pharmacological treatments, was willing to prescribe Mestinon at my request)
-a referral to a sleep doctor familiar with ME and FM, who’s also wiling to experiment
-a reference letter which enabled me to win my appeal of my disability tax credit application
-the opportunity to try experimental drugs like LDN
-most importantly, a 15-page initial consult report that has made it impossible for my family doctor and other specialists not to take me seriously (This is one of their main goals: to help your GP better understand and manage our complex chronic needs.)
There’s also an impressive ME clinic in Calgary run by Elanor Stein, which Cort has mentioned a few times recently in the blog. (Don’t be fooled by her being a psychiatrist…she’s the real deal!) I subscribe to here newsletters and can tell you that she’s one of the best in the world at persuasively distinguishing between ME and primary psychiatric conditions like major depression and generalized anxiety.
Unfortunately, I don’t know much about clinics in Quebec or Atlantic Canada, only the impressive research group in Montreal. But I know that there are ME-friendly clinics out there. They’re just not easy to find.
One strategy that I’ve used to find ME-friendly doctors in Ontario is to compile a list of doctors who have completed fellowships/residencies at known ME clinics is North America and then check to see if they’ve moved on to a family practice (or other relevant specialty) in your area. Again, not easy to do but I have found a couple using this strategy (e.g. Dr. Sarah Selke in Toronto, who used to work at the EHC, then joined a family practice that included treating people with ME. Not sure where she’s practicing at the current moment, however.)
Sorry about the length of this reply. Hope it helps.
One additional note about getting your GP to refer you to these clinics in the first place. I find that doctors are willing to do a lot more for you when you make things as easy as possible for them. My family doctor at the time didn’t take ME seriously, but when I printed out the EHC referral form myself, filled out as much as I could, and brought it to him, he was willing to do the tests and send it. You may also need to follow-up with both your doc and the EHC to make sure the process was done correctly, add you name to the cancellation list, etc. (I can’t tell you how many times a doctor’s office has screwed up a basic referral, consult notes, test requisition, etc.)
I realize that this is not how healthcare is supposed to work, and it’s especially unjust for ME patients who don’t have the energy to self-advocate. But at some point we (Canadian ME sufferers) need to face the fact that our public system is ridiculously inefficient. We can’t afford to assume that anything will get done if we don’t take matters into our own hands and become our own medical secretaries. This is true not only for ME patients but for many with chronic health issues.
Interesting article/ findings as always. I have OA and FM in my neck and upper back and have lived with chronic pain for 4 years now. Your website is very helpful, Thank you for putting it together.
Cort, the abstract speculates CNS deregulation for the muscle membrane hypersensitivity. Did the authors say something different, separate from the paper?
That’s interesting. I didn’t read the abstract. I did note in the blog that the authors did not rule out that the central nervous system may be involved in ME/CFS. I think that’s where the line “Central neural deregulation may contribute to these effects” comes from.
It was definitely not, though, the thrust of the paper. The line before that is the key but it’s hard to decipher. “The sEMG pattern in CFS patients suggests a disturbed, hyperactivated muscle membrane in the force-generating motor units, with their intermediate (and possibly type-2) muscle fibers.” Those muscle fibers refer to anaerobic muscle fibers.
Sometimes abstracts end up a bit weird. I wonder if the journal editors made them put that CNS part in.
Here’s what they said about the cause in the paper.
Interesting. I didn’t read
“The sEMG pattern in CFS patients suggests a disturbed, hyperactivated muscle membrane in the force-generating motor units, with their intermediate (and possibly type-2) muscle fibers.”
in the free to read abstract. Damned paywalls.
Another brick for the idea that it are the (at least half) (the intermediate) anaerobic to full anaerobic (the type 2) muscle fibers that twitch… in order to produce lactate ?as a desired intermediate for both energy for the liver and a source of gluconeogenis (production of new glucosis) for the liver?
The liver can use that lactate as a good source of aerobic energy production for its own use by turning it in pyruvate too and so make its own glycogen stores last longer.
Not sure if it’s related but when I have an MRI I can’t relax – not due to claustrophobia but my muscles feel on the edge of spasming or contracting. Like super twitchy. The technologist said a small % of people feel like that- more sensitive muscle reaction?
DO the researchers speculate on the causes of the issues they have found in CFS?
I see they speculate on ‘central neural disregulation’. I am a university lecturer so I will have access to the paper and have a read and report back if there is anything particularly interesting.
The ideas I wrote in the first comment may also offer an opportunity to bring the post-infectious and non infectious onset ME cases closer together.
A strong infection creates a strong surge in energy use and with it glucose and amino acid consumption of the immune cells. If the infection (or the immune response) is too strong or lasts too long, then the body may have to turn on its muscles and connective tissues in order to keep the fight going while saving the brain from starvation. “Sickness behavior” helps us to not (feel the desire or will to) squander energy, glucose or amino acid on physical or mental activities.
Such strong infection also tends to cause a lot of debris (by breaking down pathogens and own tissue as collateral damage) and or plenty of antibodies. A strong surge in antibodies in the blood can have it clot, further reducing oxygen and energy provisioning.
Covid is a good example of that: it has a very strong immune response, costing plenty of energy, glucose and amino acids and in many cases it causes massive antibody buildup creating blood cloths.
As such, virusses such as covid and EBV can IMO trigger strong persistant brain inflammation without having the need to infect the brain itself: it hampers the brains supply of blood, energy and oxygen a lot for a long time (including after the infection has cleared).
When not pacing long enough after every trace of the infection has gone completely out of the body, one increases the energy load on a body that already has to turn quickly to anaerobic mode (due to lingering impaired blood flow from the assault). That increases the need to pull reserves out of skeletal muscle and connective tissue. That however is still damaged and in need of repair. Repair is an inflammatory process by nature.
So, either sporters returning too quickly to train again or office workers doing a demanding job too fast after the infection has been cleared out from the body are at risk triggering that dreaded ME vicious circle. The pathogen *no longer needs to be in the body* to cause (near) permanent damage.
Prolongued poor blood flow after the infection (to clear out all the debris and due to many capilaries being damaged during the infection) is enough to keep us long after the infection has cleared at risk. Some Covid patients have those clear “dark spiders” of clogged capillaries filled with dark clotted blood showing on their skin. Such *isn’t* a detail. It spells “very poor blood flow”, increasing the need to provide these areas with anaerobic energy a lot and increasing the need for the immune system to mount a highly inflammatory response to either try and “eat” the clots (spanning entire capillaries!) or worse ditch / eat the entire capillaries and replace them with new ones. That is when the very inflammatory Wikipedia(Vascular_endothelial_growth_factor) needs to kick in.
In adition, such poor blood flow will decrease limb temperature and with it increase blood thickness, further strengthening the vicious circle. The body wide oxidative stress involved in this highly inflammatory clean up phase will impact mitochondrial functioning (by blocking key enzymes) and RBC oxygen release (both further driving towards body wide anaerobe energy consumption).
Such strong infections also have the potential to weaken the neck muscle and connective tissue, as they hold protein ready to be pillaged too. That may explain the idea of ME patients with neck trouble that some virusses “can eat neck connective tissue”. Here again, the infection does not need to be in the neck itself.
Antibody mediated food sensitivity can do something similar. Even without a leaky gut, food in the gut can create a massive production of antibodies on the other side of the gut, to be dumped in the global blood flow. No undigested food particles even need to leak into the blood. I read a research paper describing that this process can be that powerfull that it can coat the kidneys filtration system with antibodies that much that filtering largely falters.
For those having non antibody mediated food sensitivities, that seems to go by the innate immune system. That can create plenty of debris too. And it can damage or blunt the Wikipedia(Intestinal_villus). That impairs food absorption, makes the gut more sensitive to new and other food and is a highly inflammatory process creating plenty of debris and needing plenty of energy, glucose and amino acids to repair it… on a daily basis if left untreated. Once a person becomes intollerant to near all food, treatment becomes rather challenging to say the least.
And that is where pacing, doing less and less to allow the body better to rest, can only do so much. If one is intollerant to more food then one can count, the gut will undergo this highly inflammatory process several times each day. When one can’t stabilize blood flow and glucose and oxygen provision (and get the brain in a calm low energy usage state) enough during the night, one will go through a dangerous stage risking to starve the brain every night. One can pace both body (housebound) and mind (bad brain fog, vision going grey), but from a point on those other daily stressors far dominate the stress the few remaining activites we do. We sure still need to pace a whole lot, as exercising or thinking with highly inflamed muscles or brains is a very bad idea. But it is no longer enough to turn our disease around and reach better health with it. We only can prevent it getting worse by pacing.
Dropping the last thought (my previous comment was more structured but got lost in the send process, very tired now):
The idea that muscles in first place and connective tissue in second place forms a buffer against ME/FM/… sort of is indicated by those less vulnerable to it:
Children, having a biological need to be able to grow fast. They have high growth hormones.
Men, having much more testosteron that is well documented to help build and repair (repair almost equals re-grow) muscle a lot better.
Both hormones have been used with some mixed success in treatment of ME patients. Some return to fair health with it, others not. Supplementation can only adress one aspect and has its own side effects.
I remember studies done many years ago by Dr.Ben Natelson’s research group that showed a problem in energy (ATP) production within the mitochondria. I was intrigued by this, because the study was conducted by an exercise physiologist. I got sick 6 months after completing an MS in Exercise Physiology. My opinion then (and now), was that researchers needed to be examining why we cannot do aerobic activity. (I have CFS, not fibro). I did not see any follow-up research. I believe, just my opinion, that there is a cellular metabolic issue with production of energy.
I don´t suffer from fibromyalgia myself, but came across this devoted researcher the other day. Maybe there is something of interest in this article and the enclosed study. Best to all of you
https://news.ki.se/people-with-fibromyalgia-have-inflammation-of-the-brain
The idea that FM or ME are “central sensitization” is a completely inadequate concept. Of course sensitization is involved in both conditions, some say “sensitivity”.
Both conditions are homeostatic dysfunctions and the evidence that both conditions (even if they are different in some of their physiology) involve epigenetic dysfunction underlying the dys-homeostasis is now pretty clear. Every person with FM or ME knows that if they step outside their (idiopathic) boundaries they will suffer, usually for days. These boundaries include energy expenditure, muscle work, dietary regime, mental effort, sound levels, light levels, anxiety etc. All of these are bound by the “rules” of homeostasis.
To explain all these different symptoms and tolerances we must resort to fundamental explanations. We know many genes have been found to be “malfunctioning” producing faulty, insufficient or excess proteins in various systems including the immune system.
We know that there are faults in the gene switching or epigenetics, in particular hypo-methylation and hyper-methylation. This is in both conditions.
Even as far back as the 90’s we have known that “sub-sets” of people in both conditions have an auto-immune signature, much debated but as time goes on becomes more clearly true. The dissenters to this fact are wearing the wrong glasses – by which I mean they are not looking with the correct tools. For example:
Abnormalities or alterations in T cell function, natural killer cell cytotoxicity, cytokine production, mitogen stimulation and lymphocyte phenotypes have all been shown. All of these are consistent with an epigenetic dysfunction.
About 52% of people with ME/CFS have an IgG autoimmune signature in the form of antibodies to the nuclear membrane. In particular nuclear envelope protein lamin B1.
Sjogrens syndrome, similarly exhibits NE (nuclear envelope) autoantibodies seen on an ENA. ME/CFS disturbances do not appear on an ENA, this is because the level of IgG autoantibodies is much lower but still significant and can be seen using immunoblotting rather than immunofluorescence.This is why ANAs are not normally seen in ME/CFS. Immunoflurescence = wrong glasses)
Nuclear lamins play important roles in the organization and structure of the nucleus including the chromatin structure and function. If IgG auto-antibodies damage or impede nuclear lamin B1 expression then a number of key cell functions are disrupted, including apoptosis. In addition, many genes will be affected.
Now! Are we dealing with sub-sets of patients or are we dealing with sub-sets of experimental results? As you can see from the results of the studies on NE (nuclear envelope) it requires a special approach to see these. I think quite often disparities in results can be due to inadequate clinical data or restricted experimental variables. It may be that FM and ME are distinct pathologies but I think this is the wrong way to think about it. ME and FM are just labels of symptoms. It stands to reason that an epigenetic pathology will have many variations of expression. It certainly makes nonesense of the central sensitization idea.
My new doctor is an ND. His father, who works with him, has gluten intolerance that causes his hands to break out in a rash. I have had gluten intolerance since the beginning of ME/CFS although I found that I had no trouble eating wheat overseas. My doctor told me about a wheat flour called 00 from Italy. You can order it on Amazon. I made some delicious Hawaiian bread with it and did not have my usual gluten reactions. His father can eat bread made with it too without any reaction. I wouldn’t overdo it, but it is a real treat after eating dry, fairly tasteless gluten free bread for years. On that note, I can recommend a great book, The Gluten Free Gourmet by Bette Hagman. Every recipe I have made from this book is delicious, but they do require a some ingredients you may not have on hand.
Interesting points Betty. I remembered having seen recently one of the episodes of the dr. Kahn webminars where a speaker said preparation methods are key in food tollerance. He talked about fermenting beans and soy, soaking beans in water AND grinding flower slowly with IIRC limestone “deactivating” some of the hard to digest stuff.
So the difference may be in the milling method used. This scientific paper for example gives an overview comparing two different milling methods and its influence on the charactheristics of the end product https://www.sciencedirect.com/science/article/abs/pii/S092422441930980X
That is a very good point, deJurgen. Another factor may be in the harvesting process for wheat in large production farms in the U.S.
“Increasingly, glyphosate (a herbicide) is also sprayed just before harvest on wheat, barley, oats and beans that are not genetically engineered. Glyphosate kills the crop, drying it out so it can be harvested sooner than if the plant were allowed to die naturally.”
A third factor is the wheat varieties grown. Different types of wheat are grown overseas.
I wonder if there has been any study parameters on muscle types (slow vs fast twitch and super fast twitch fibers). I recently received my 23&me genetic reports and found out I have fast twitch fibers (like elite athletes). I tend to always feel like my muscles are fatigued even at rest- while the severe flare of pain all over starts 100% of the time – at two days (48 hours) post-physical activity. And I mean even the most simple activity’s like washing dishes for ten minutes. I do ten minutes if work and it takes my body 72 hours to recover. Sometimes much longer if I spend up to an hour of yard work- which causes “injury-type” pain- and is crippling.