> the onset of ME/CFS is often associated with viral infections by patients
I can personally attest to this. I was an extremely energetic person (shooting straight out of bed in the morning, never requiring daytime naps or rests) until one specific week in April of 1996 when I had what I thought was a mild flu. The post-flu fatigue never really went away. I became acclamatised to it over the years and rarely notice it now (except times like this when I'm reminded that I'm significantly less energetic than the average person). I hope they find a treatment (if not a cure) for this soon. As I understand, some suffers are not as lucky as I am.
I recently had a minor cold that caused some sort of heart inflammation and could have exacerbated/triggered a latent heart rhythm issue. About 1-3 times a minute while resting, my pulse wouldn’t follow the normal rhythm (PVCs — could feel it too while pressing finger into the neck, without EKG).
It made me feel less energetic long after the inflammation subsided. I couldn’t identity anything specifically “wrong”. After having a cardiac ablation, I feel a lot better.
If you do, find a electrophysiologist, not a regular cardiologist. Asking the latter is like asking a plumber to find an electrical issue in your house.
I get where you're coming from (and it's great to be on guard for that!), but I think suggesting a specific diagnostic that can indicate a clear pathophysiology known to be associated with the symptoms they're experiencing is a little bit different.
Have done many over the past 25 years (we call them ECGs over here). All were normal. One suggested that I may have MVP (Mitral Valve Prolapse) at the age of 18, which I thought was the cause. But then more resent scans confirm that I don't suffer from MVP.
Interesting. I got a very weird illness last November and all I can say is that it wasn't COVID. Ever since, my energy levels have plummeted, I can't stop gaining weight, I've had worsening cognitive issues, and I've become intolerant to exercise(yes, the weight makes this worse).
Yeah I should try pumping up my D levels. I take 2,000 IU/day plus mid-day sun exposure but it doesn't hurt to try it. From what I've read, short term Vit D doses can be pretty high without causing an issue.
50K IU of Vitamin D per week would push many people into overdose range after a few months. Anyone taking high doses like this needs to also get blood tests to make sure they're not accumulating too much. Remember that it stays in the body a long time and therefore overdose can take many months or over a year to finally show up.
Vitamin D only really has dramatic effects in people who are severely deficient. Despite all of the influencers and podcasts claiming it's a miracle supplement and that we're all deficient, actual Vitamin D studies don't show much or any benefit outside of people who are significantly deficient.
But yes, if your Vitamin D is actually low then getting it into the normal range could have some dramatic effects.
Some doctors will prescribe short courses of Vitamin D as an almost-placebo when they can't find anything else wrong. It works quite well as a placebo for many people because podcast health influencers have been talking about it so much lately.
Tacking on for anyone alarmed or curious: The main distinction is fat-soluble versus water-soluble.
Fat-soluble vitamins (A/D/E/K) can accumulate in your tissues over time if you keep taking too much.
Water-soluble vitamins (such as C) are much easier for your body to filter and flush via urine. You could still overdose in the short-term, but a chronic accumulation is unlikely.
I wish this was true but I and other family members had rock bottom low vitamin D levels in lab tests. We supplemented until it rose to normal levels. None of us noticed any perceptible difference. Suppodedly this will prevent problems but it doesn't feel like anything has been fixed. I wonder how much is placebo.
One should get regular blood tests if possible for a lot of reasons... but supplementing with 50k IU Vit D per week is safe for almost everyone. Should take K1/K2 as well.
Not going to go into detail but there are several recent studies showing that daily intake of up to 50k IU is safe. The concerns over hypercalcemia, etc. were tied to much larger doses per day.
Apparently I had mononucleosis and my friends still tell me nowadays that I was sleeping all the time everywhere back then. I clearly remember something switching in my energy patterns around 17yo but it's hard to distinguish it from other possibilities like atypical depression or sleep apnea for instance or combinations.
"Seabiscuit" author Laura Hillenbrand wrote a disturbing (to me) essay entitled "A Sudden Illness" recounting the exact moment of the onset of her struggle with CFS. The apparent precursor infection was strep.
Strep, in particular Streptococcus pyogenes, is really fascinating, and is potentially implicated in a lot of things. It's capable of what's called molecular mimicry, where a virulence factor called M protein cross-reacts with host antigens, causing autoantibodies to attack your own tissue, i.e. autoimmunity [1].
S. pyogenes has been implicated in other autoimmune disorders like psoriasis [2], which we know can be triggered by strep bacteria. In psoriasis, we have some evidence that it may set off a kind of bogus vicious cycle where a type of T-cell called a tissue-resident memory T-cell is "programmed" by an initial bacterial infection, but gets into a confused state where inflammation keeps going even long after the bacteria are physically gone. With other disorders, PANDAS [3], the cross-reactivity causes strep affect the brain and cause neuropsychiatric symptoms.
In some cases, strep bacteria are thought to linger in the body even long after a symptomatic infection, hiding in biofilm or in reservoirs like the tonsils, occasionally re-emerging to cause an immune response, similar to the Epstein-Barr virus. I would not be surprised if strep turns out to be the ultimate cause of some illnesses like ME.
Interesting! Earlier this year my spouse fell mildly ill and was diagnosed with strep (throat). She was given a high-strength anti-biotic that had two or, maybe three initial large doses followed by about 20 smaller doses. She felt better for a couple weeks but soon fell ill again. She was diagnosed a second time with strep. She was prescribed a wider spectrum antibiotic with a longer course of 28 days which seemed to do the trick.
Viral infections can also induce narcolepsy. I'm not sure if that's what did it to me, but I developed symptoms in my 40s and it was a few years after a bout of what I think was meningitis.
I managed to get through a bad flu infection in late 2003, but my health steadily declined over the next 5 years to the point where I could not get out of bed two or three days per week. Like, crawling on the floor to get out of bed exhaustion.
I've been tested and evaluated for lots of things. Fortunately, not a dire progressive disease like multiple sclerosis or Parkinson's.
Unfortunately, I have not been able to substantially improve energy level in a sustained way. There are times when I can gain momentum for about three weeks but then there's a collapse. If I push it, I've had vital signs go awry and it's enough to scare the emergency medical personnel who are called when I pass out... and then a few hours later, nothing worse than severe fatigue.
I wonder how far away we might be to sorting it all out, things you shouldn't be doing after a viral infection, or environmental factors that we will discover, or if we will be able to understand this at all without a more fundamental rework of medical understanding.
This is a finding more about cellular fatigue and might explain what fatigue actually is. The root cause of ME/CFS and Long Covid Fatigue is almost certainly a chronic infection in tissue without much detectable presence in fluids making it difficult to identify and treat.
It is an interesting finding since some treatments for ER stress exist and are worth testing. It's also somewhat linked to the Itaconate shunt theory that Robert Phair at Stanford has been investigating for the past year.
It's probably not COVID hiding in the tissues? I wonder whether injection of genes by the virii result in altered DNA producing broken proteins. Is 23andMe data of sufficient quality to test altered DNA?
23andme looks for specific single nucleotide polymorphisms (SNPs) so it’s completely unsuitable for looking for this kind of DNA alteration that could be anywhere in the genome.
Whole genome sequencing of some kind, preferably one of the newfangled long-read technologies such as Oxford Nanopore or Pacbio, would be best for looking for novel insertions into the genome.
However, this is likely to be a fool's errand in this case, because this kind of sequencing normally assumes that we can take a sample of many cells from the body, and that all those cells have the exact same DNA changes. If you have a mutation that is induced in a parent or the single-figure-cell stage of embryo development then that will be true, but for DNA modification by a virus in an adult it will not be. Each cell will have a different insertion. Now, there are some techniques that can sequence the DNA from a single cell, but they don't give quite as good quality data, and because you'd be wanting to sample a good number of cells to see what the distribution of insertions is, it will likely also be very expensive.
It totally could be. Viral persistence is a strong suspect. HIV hides in "sanctuary" tissues. Other viruses and bacteria probably can evade the immune system in certain types of tissue.
* Virus' have a high failure rate - many infected cells never go on to multiply.
* However, those infected cells may also not still perform correctly.
* If you have a good chunk of your cells in your body no longer performing their function, yet not dying and making way for replacements either, everything isn't going to work as well.
That would explain why it is a wide range of viruses that can all cause fatigue symptoms, and also why parasitic and bacterial infections rarely cause the same.
Probably not a solution, but many people have reported benefits from fasting, which increases cellular autophagy which degrades disfunctional cell parts - and might play a role in programmed cell death, though the relationship is not clear.
Two sibling comments mentioned fasting. Adding more to that.
Prolonged fasting is known to clear away senescent cells. So that is the intervention which seems most promising here. Intermittent fasting can help the gut by giving it time to rest between meals, and it can improve insulin sensitivity because the body spends more time in a low insulin state. Maybe there are longer chains of mechanism there, but at first glance, they don't seem quite as relevant.
Last Thursday the Dutch News reported about findings at Amsterdam UMC of an enzyme IDO-2 that keeps being produced in long covid patients' cells. And that an experimental cancer medicine manufactured by Bayer and BMS can put a stop to this. It was brought as an 'important step' in long covid research (that nonetheless would take years to lead to any broadly available cure). Unfortunately the article didn't publish links to papers.
IDO2 is stimulated during any infection but ongoing IDO2 expression could come from an iron deficiency. Iron is the cofactor for TPH1 and TPH2 which turns tryptophan into serotonin. If that is not working the tryptophan will be turned into kynurenine by IDO1 and IDO2.
I'm esp. interested in any interaction with food. Because I get depression 4 days after I ate a food. I don't have any other symptoms than low energy and a sense of impending doom. Symptoms stay for 3 days then go away.
Started collecting the info in my github. I'm very interested if anyone has more ideas.
I'm on carnivore diet. I seem to tolerate almost only meat, plants only in small quantities. I did okay with 1 grapefruit/day for a while but that's come to an end.
I seem to be okay with fermented thyme.
Pepper is no good, swollen eyes, but chilly seems to be okay. Those are never consumed in big quantities, I could test with chilly capsules though and maybe I will.
Diet consists of Lamb, once a day, then some yoghurt or kefir in the evening. Some koffee and milk as well.
Haven't collected everything yet, maybe you find something that helps - or can add some. Trying to get diagnosis for leaky gut, it's a drag to get an appointment.
https://github.com/cutestuff/FoodDepressionConundrum
Histamine is a general inflammation-inducing chemical. That pain and rash you get when you touch a stinging nettle - that's caused by the stinging nettle literally injecting histamine into your skin.
Histamines affect a broad spectrum of body systems. One time I was really stressed about work, went to bed and started itching unbearably and had welts. Apparently I had broken out into hives, which I didn't recognize at first, then I took an antihistamine and within half an hour everything was back to normal.
Mast Cell Activation Syndrome would be the main one. Mast cells are an integral part of the intestinal epithelial barrier. When they become over-sensitive, even small amounts of dietary histamine (present in a large number of foods) can trigger GI and systemic symptoms. H2 blockers have shown some efficacy, as well as DAO supplements (which break down dietary histamine).
I'm constantly eating beef and occasionally cheese with no issue, so I haven't been thinking about histamine. I don't seem to react to cheese, other fermented milk or fermented meat or canned fish.
- Thiol intolerance (impaired sulfur metabolism) - could try molybdenum and maybe Boron supplementation (ask doctor if ok)
- High gut permeability („leaky gut“) -> undigested proteins enter blood stream -> autoimmunity (eg via viral mimicry; all kinds of viruses can do that, but COVID and EBV come to mind). Water fasting could help, maybe digestive enzymes
- Mechnical interaction, eg dysbiosis -> bloating -> cervical spine misalignment -> more bloating due to vagal nerve pinching (try massaging back of the neck vigorously to see if depression disappears for a while)
- Auto-brewery syndrome
All of those can be downstream issues of systemic issues, like hypothyroidism (which has been shown to be caused by microbiome metabolites; I wouldn’t just down the next best yogurt though, but look at studies around Bifidobacterium Longum, which looks promising; probably others too).
This has been found to be effective, although it has a huge list of potential side effects [0]. Anecdotally, among people with GI problems, especially IBS, it can often cause reactions such as nausea, anxiety, and bloating (some practitioners estimate this to occur in about 30% of patients). For this reason it is often recommended to start in small doses (3-5g), sometimes split throughout the day, and gradually increase up to the 30g target over the course of several weeks. Given the list of side effects, including less common but potentially serious ones, it is very much worth running this by your healthcare professional prior to use.
Although there is less research into it than l-glutamine, there is rapidly growing interest into the effects of creatine supplementation on dysfunctions of the epithelial barrier (which would include intestinal permeability aka "leaky gut") [1]. The upshot is that it is an well studied supplement that is very well tolerated by almost everyone.
Zinc carnosine is another one that can be helpful, if tolerated. However it is believed that enteric-coated formulations are required to be effective (which may be hard to find) due to very high absorption rates and susceptibility to stomach acid prior to reaching the intestines [2].
I am also carnivore with NO energy or fatigue issues.
HOWEVER, I am constantly experimenting with foods, isolation, etc. - and I discovered that PLANT-BASED milks or creamers for my coffee give me TERRIBLE CFS.
- Almond Milk
- Cashew Milk
Specifically "big brand" names you find at chain stores. They must be chemically treating these foods with something. I don't trust them.
That is what I was referring to - a period of lethargic, listless, slow physical being. The "zip" is not there. A few days after terminating consumption of plant-based creamer - back to normal.
> This study shows that endoplamic reticulum (ER) stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance. Alleviating ER stress decreases WASF3 and restores mitochondrial function, indicating that WASF3 can impair skeletal muscle bioenergetics and may be targetable for treating fatigue symptoms.
So it's a stress response, not necessarily causal. It's long been suspected that some sort of perennial stress state was involved in this problem (anything from adrenal fatigue to illness genes never turning off). So does this tell us more or is this just another biomarker?
Though I say 'just', finding a biomarker for CFS would still be something people could be tested for, which is way better than where we are now.
There needs to be more research into this horrible disease. There are no yet confirmed biomarkers for it, so doctors dismiss patients as crazy or "making it up." Once there is a biomarker, perhaps like this protein, we can actually start testing treatments to see what works.
The scary thing is that there seems to be a vicious path, of COVID->long COVID->ME/CFS. We're not sure what makes COVID evolve into long COVID, which also means we have no idea how many people who catch COVID eventually wind up with long COVID or ME/CFS. And there is a total media blackout on the topic, seemingly because politicians don't want to admit they fucked up.
Hopefully once there is a way to verifiably test for it, a lot of things will change for the better.
they could do transport chain simulation with blood or muscle samples most likely but it would require expensive equipment so not really feasible if a million people have it
perhaps organic acids testing could show something?
> doctors dismiss patients as crazy or "making it up."
I don't think that's true, at least not in my experience anyway. People (myself included) are too quick to conflate "all in your head" with "making it up".
Things "in your head" can and do have real, physical, life-limiting, effects.
If it turns out that ME/CFS doesn't has a physical marker, then what? There may never be a way to verifiably test for it other than symptomatically. It's no less real for the people living with the effects, but there may be no pill to take, or injection to administer.
Yes but recent studies have shown that it's neither of those, meaning that the symptoms are physiological. Not that I'm dismissing the importance of proper care of people with my psychiatric issues with fatigue or pain, it just doesn't apply to ME/CFS/LC anymore.
> If it turns out that ME/CFS doesn't has a physical marker, then what?
The problem is that ME/CFS is similar in presentation to other conditions such as for example certain kinds of depression. The difference is that exercise is thought to help with those conditions and exacerbates ME/CFS. Thus there are two different groups of people, one who you are helping by encouraging them to exercise and one who you are harming. If you can't tell them apart the system is bound to hurt someone.
PEM (post-exertional malaise) is a core symptom of ME/CFS, but I've never heard of it being a symptom of depression. IME it's more correct to say that depression can be a symptom of ME/CFS - having your life blow up can do that.
First problem, I do not have ME/CFS, let's use the Maes et al (2012) scale. 0-5 scale, 5 being the worst.
"1 means mild exacerbations of fatigue/pain/neurocognitive symptoms following exercise (either cognitive or physical)" Yep, after a longer, harder than normal bike ride I'm quite fatigued, in quite a bit of pain (bad back, knee, shoulder), and can't think particularly well.
"2 means moderate exacerbations of symptoms following exercise; 3 means severe, incapacitating exacerbations lasting less than 24 hours;" Accurately describes what happens when I do HIIT style intervals that exceed my work capacity, or what it's extremely hot outside. Dreadfully exhausted, usually have to nap, or lay on the couch, every muscle hurts, extremely sore, difficult & painful to move for 24-72 hours.
I'm not saying ME/CFS does not exist, this is just a terrible indicator.
The worst part is making it so specific obscures the large body of existing research that would provide tools for treatment protocols here, eg work capacity in athletes.
I'm not saying the existence of a symptom (PEM) is as good as a diagnostic test; rather, in the absence of diagnostic tests, they are "enough" to diagnose CFS. And PEM isn't the only common symptom, there are others, such as a constant lactic acid-like burning sensation in the limbs.
I know you said you don't have CFS, but trust me - the fatigue we suffer after PEM is nothing like "normal" body fatigue after exercise.
I think we'll find a diagnostic test eventually. At least, I hope we do.
"Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems ... Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate‐quality evidence)"
Fairly plausible, mitchondrial biogensis is an adaption to exercise, it may be impaired in ME/CFS patients, but not totally inhibited, and more mitochondria may lessen the severity of the pathogenesis of ME/CFS.
The only way a competent clinician can fail to distinguish CFS from depression is if the patient is outright lying. Most CFS patients for example have exercise intolerance, in which after the patient exercises more than his or her limit (which in severe cases could be walking on level ground for 10 minutes) everything proceeds like it does for a healthy person for 24 hours, then he or she becomes incapacitated for days. Eating lots of carbs, glutamine and creatine will tend to make the period of incapacitation shorter than they would otherwise be at least in non-severe cases of CFS. And this is consistently what happens after every exercise session that goes above the patient's individual exercise threshold. And if the threshold changes, it does so only gradually over a period of months. And if it changes, it changes for reasons other than how diligently or frequently the patient exercises.
My experience (in California) has been that most doctors have been willing to assume I am being truthful, but a significant fraction seem to want to spend their time and energy only on conditions that the patient cannot be deceiving them about.
> The difference is that exercise is thought to help with those conditions and exacerbates ME/CFS
It's proven to be the case. A repeat cardiopulmonary exercise (2-day CPET) is currently the only widely replicated biomarker for ME/CFS. Only ME/CFS shows a reduction in performance and a lowering of ventilatory threshold on the second day. Anyone else (sedentary, cancer, heart or lung disease, MS, depression) will show an improvement. [1]
A study this year showed a striking effect looking at the metabolites in urine after exercising female ME patients vs sedentary healthy controls. The ME patients just did not excrete metabolites as the healthy controls did. [2]
"This indicates that ME/CFS patients have a general metabolic dysregulation that is part of their exercise intolerance and PEM in which altered metabolic excretion is a contributing factor."
There's also a very simple clinical discriminator between ME/CFS and depression. If you ask a depressed person what they would do if they were suddenly cured, their answer will be "Not sure, I don't know, I can't think of anything, nothing really." If you ask someone with ME/CFS the same question, the response would be "Go to the shops, drive my car, walk on the beach, see my friends... etc".
> If it turns out that ME/CFS doesn't has a physical marker, then what? There may never be a way to verifiably test for it other than symptomatically. It's no less real for the people living with the effects, but there may be no pill to take, or injection to administer.
To me, this argument does not make sense. Consider the example of Physics Girl (I linked the video in another comment). The video shows her before COVID, and after COVID. It's obvious that her COVID infection did something to cause her to go from being an amateur astronaut to being bed-bound. There is clearly some kind of imbalance, somewhere. We use biomarkers like CRP levels to determine whether someone has an infection, others for cancer, or any other disease. Why would it be different for this?
If we can identify some kind of biomarker... be it a protein, something in the blood, etc, and link it to COVID, then we can start testing treatments to see how they impact the biomarker.
> Consider the example of Physics Girl (I linked the video in another comment). The video shows her before COVID, and after COVID. It's obvious that her COVID infection did something to cause her to go from being an amateur astronaut to being bed-bound.
I didn't really make an argument to "not make sense". Right now, ME/CFS may just be a collection of symptoms rather than a specific _thing_ that can be tracked, measures and cured. Or it may be a specific infection. We don't know.
Sure, it's compelling. But the plural of anecdote isn't data. It may seem obvious, but so far we haven't found the biomarker yet and must surely keep an open mind that one may not exist.
I'm not saying we should stop looking, but that the thing we're looking for may not appear.
I think a more logical approach (for me) would be to say that there might be multiple biomarkers which could present ME/CFS type symptoms in different ways.
Dr. Bhupesh Prusty has recently given some lectures on his discoveries related to Fibernectin, for example. That could be a massive breakthrough, but we need more studies on it.
One other data point that might interest you: apparently a large percentage of ME/CFS patients are finding relief through valtrex. Apparently there is some relation to the herpes virus, although nobody understands how or why.
> apparently a large percentage of ME/CFS patients are finding relief through valtrex
_Are they though?_ This needs a citation. What constitutes large? A majority? That's unlikely, especially in the UK where medications aren't prescribed unless there's measured clinical value in it. I'm sure some are finding relief, but until we know how many and how much relief it could just be a placebo effect, right?
I hope that anyone affected by ME finds relief, but the discourse online about it always confuses me. There's always a slight undercurrent of "those mean doctors" and a breakthrough _just_ on the horizon:
"That could be a massive breakthrough, but..."
"apparently a large percentage of ME/CFS patients are finding relief..."
"Apparently there is some relation to the herpes virus, although nobody understands how or why."
In reality, nobody actually knows. Some scientists have got some ideas, some of which stand up to some form of scientific scrutiny. But that's basically it.
This study screened for active vs latent on number of viruses in patients vs assumed health controls, bottom chart here is what you would evaluate Valtrex effectiveness against.
I don't see any mention of Valtrex there. The point is, multiple studies have been done for antivirals in ME/CFS, and there is no difference in fatigue between arms.
EBV, HHV6 and HHV6 tend to reactivate during stress, but don't typically cause symptoms. I think what we're seeing in ME/CFS is this reactivation, but it's not necessarily what is causing the problem (if it was, antivirals would help, but they don't).
Great point, agreed, viral re-activation seems suspect on causality.
I was suggesting to crossreference Valtrex effectiveness against the activated virii in the study I linked. If Valtrex is not effective against the reactivated cohorts, we need more falsification around antivirals <-> ME/CFS.
>Viruses can trigger ER [endoplasmic reticulum] stress, perhaps explaining why ME/CFS and related conditions often arise after infection.
Since you mention herpes, I'll bring up what I've read about Epstein-Barr (EBV) (which belongs to the herpes family of viruses). It's estimated that 90% of the global population will contract EBV in their lifetime. In most people, EBV goes dormant for after the initial infection is cleared and more or less stays that way for life. But in some people, for unknown reasons, it can chronically reactivate, triggered by stress, other illnesses, immune dysfunction episodes, etc. Apparently it loves to hang out in the spleen, although I believe it has been found to reside in other organs as well in these cases of chronic reactivation.
I would be shocked if this were the only virus to do so, but at present it seems to be the most studied, perhaps because EBV is fairly strongly correlated with a bunch of cancers, auto-immune disorders, and chronic conditions (including MS as recently demonstrated in a huge study by the VA, n=10,000,000). Very interesting and important stuff. I look forward to further research into these mysterious long-term effects of viral infection.
>It's obvious that her COVID infection did something to cause her to go from being an amateur astronaut to being bed-bound
We know that infections cause sickness behaviour (fatigue, depression, etc.) due to the effect of the cytokines on the brain. The interesting thing is that the brain itself releases similar cytokines in response to mental stress, and mental stress also activates the glial immune cells in the brain.
Infections also activate the HPA axis (the body's stress system) in the same way as mental stress does. This is to give the immune system energy to fight the infection, and also to prevent a fatal over-reaction by the immune system. Chronic long-term stress can result in a blunted HPA axis response, and this is commonly seen in ME/CFS.
Patients who have been bedbound with ME/CFS report that they were trapped by fear that there was something wrong with their bodies, and they felt fear when going outside or doing anything, and this caused further symptoms. Reducing that fear, and experimenting with activities again in a calm manner seems to be key to recovery. Looking at some of the tweets from physics girl, it looks like she may be stuck in this state.
The name ME comes from the observation in the 1950s that the brain stem was inflamed as shown on CT scans run in the Royal free hospital in London (what is now called St Thomas' hospital). In the 1980s they found numerous immune and metabolic dysfunctions in sufferers as well and the list of physiological things wrong has steady increased since. Yet mostly doctors have treated patients with psychology and tried to force them to exercise despite being intolerant to it and despite thousands of papers showing the biology of the disease. None of what medicine has done can be justified, it ignores all the science and evidence.
Your comment kinda casts doctors as the boogiemen though and I struggle to understand the motive for them to act in this way.
Doctors, generally, want the best outcome for their patients. I find it hard to believe that they're doing something actively harmful that's against accepted best practices, informed by scientific literature, because... they hate their patients?
If there truely were thousands of papers showing a specific biology for the disease that could be targeted and treated why would any doctor ignore that?
Unwillingness to admit they don't know what's happening, memes, resentment of criticism after malpractices.
Any illness with primarily neurological symptoms have a history of medical malpractice and gaslighting.
As early as 1944, an author in the Journal of Nervous and Mental Disease remarked: "The history of prefrontal lobotomy has been brief and stormy. Its course has been dotted with both violent opposition and with slavish, unquestioning acceptance."
The last recorded lobotomy in the United States was performed by Dr. Walter Freeman in 1967 and ended in the death of the person on whom it was performed.
> Unwillingness to admit they don't know what's happening, memes, resentment of criticism after malpractices.
Let's assume that all doctors fit your description. (I don't agree, but let's go with it.)
What's the alternative? I just can't accept that the vast majority of medical professionals are ignoring a potential cure or refusing to accept that one for ME may exist because it might hurt their egos.
Which is how it's managed to persist because no one believes the victims. This is going to have it's me too moment at some point and people are going to be horrified how widespread it really is.
When it was first suggested that doctors/surgeons not washing hands & medical equipment between patients was harming patients, the majority of the medical community was up in arms calling the person who suggested it crazy and taking it as an attack on their professionalism.
Being medical professionals doesn't educate them away from having the same human flaws and cognitive biases that we all are capable of.
It took some 20 years for this to become an accepted truth.
I remember learning about a physician who helped his sister with child birth and she died. He was aware of the washing hands but ignored it. I believe he ended up committing suicide as he wasn’t able to cope with basically killing his sister due to his ignorance.
> "He didn't discover it, he was told by midwives over and over and over until he looked into it. Midwives at the hospital observed that when doctors delivered babies, mothers were at a higher risk. Any housewife knew that food would spoil faster if handled with dirty hands and they always used vinegar solutions to clean their hands, tools, and surfaces. Any housewife would do this and midwives did it because mothers and their babies are more important than pumpkin preserves. Only doctors never washed their grubby hands while it was a deeply ingrained habit in most midwives. Semmelweis listened to women. No wonder they locked him away."
Which is uncited/unsupported, but back in the Black Death time of the 1660s: "The villagers established a system of boundary stones around the village’s periphery, boring holes into the rocks and leaving coins soaked in vinegar – they believed it acted as a disinfectant – in the holes. Merchants from surrounding villages would collect the money and leave bundles of meat, grains and trinkets in return." - https://www.bbc.com/travel/article/20151026-the-sleepy-villa...
And from the same Reddit thread:
> "Oh again with this "before Germ Theory no one knew anything about disease!" bullshit. We always knew dead and dirty things caused disease. Dead animals for artillery ammo, dead animals buried by wells, leaving your swords in latrines. We also knew how copper and silver could help heal and prevent disease."
So, it's not like Semmelweiss proposed Germ Theory, or was the first to observe a connection between death and disease, or between 'disinfectant' of some kind and reduced disease. And https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1299347/ says:
> "(notably Alexander Gordon of Aberdeen) had shown that puerperal fever was contagious some 40 years before Semmelweis. The mortality rate in lying-in hospitals did not fall but rose after Semmelweis' treatise was published, and his ‘much-cited but seldom-read’ thesis is immensely long (over 500 pages) and so badly written that it is almost unreadable. [...] Semmelweis deserves to be remembered for his observation in 1847 that making medical students wash their hands in a disinfectant solution before going from the post-mortem room to the lying-in wards of the Vienna lying-in hospital, led to a fall in mortality due to puerperal fever from a very high level to a moderate level. [...] After his death in 1865, Semmelweis was totally forgotten, not only in Vienna but also in Hungary where he was born and to which he returned in 1850. It was not until the late nineteenth century that the introduction of Listerian antisepsis applied to obstetrics led to a steep fall in deaths from puerperal fever. Only then was Semmelweis' work recalled and his faults forgotten."
Which is fine, he shouldn't be knocked, but how did it take 200 years for humans to decide to use the tools that were already internationally known (vinegar) to a large number of people (housewives, midwives) to avoid some kind of death-related contamination, on childbirth and hospital and post mortem scenarios? And why did it take a guy writing a 500 page near-psychosis rant?
Was that low hanging fruit and if so, how much more of that is still in the world today?
Doctors generally want the best outcome for their patients, but are heavily optimized for what they see most often.
If 90% of your patients come in sneezing and it's a flu for 30 years, then you generally give them advice for handling a flu and it works most of the time. But that also means you have a tenth of the experience handling the edge cases, at best.
Confounding variables make this a lot worse, like people having multiple symptoms, or not telling the doctor things because they felt dismissed before, or that they stopped seeing them because they gave actively harmful advice.
Having a lot of experience with doctors is what has convinced me medical training needs reform. Doctors actively ignore patients telling them objective factual reasons their advice is incorrect or harmful, and treat you as a hypochondriac for arguing.
I have stopped seeing a number of doctors over the years after they looked at my medical history and said "let's try X again", and when asked why, "just to see", when I have already tried X and two or three other medications in the same family as X, in the history (often from their own larger department, not something I provided), in the last 2 years.
I have stopped seeing doctors over me telling them that raising the dose of a medication made me much worse and having them then cut the visit short by leaving the office, saying they were late for something else, and telling me they were writing a script for double the dose as they left (and no, the drug in question did not have strange dose-response relationships like, say, Seroquel).
I have stopped seeing doctors over them insisting I just had a cold when I told them I was too exhausted to reliably walk two blocks to their office without an escort, every day for a week, not sleeping, and unable to keep any food down, without changing their mind, when I turned out to have pneumonia.
"Tried to force them to exercise ... ignores all the science and evidence"
This is a baseless claim, there's a Cochrane review showing exercise is beneficial. Pacing appears to be a common strategy, and it's exercise in of itself.
Doctor isn't writing a prescription for exercise, they're suggesting you work towards performing more of it because the best (limited) clinical evidence we have suggests it helps.
However, if you reach the threshold that triggers post exertional malaise, it can take weeks to get back to your original baseline, if you get back at all. Exercise can be dangerous to ME/CFS sufferers if it isn't carefully moderated.
No, that's not true. The first CT scanner wasn't invented until the 1970s. There was never any inflammation found: Acheson said that it was always "presumed". The name ME was dropped in the 90s because of a lack of inflammation.
>In the 1980s they found numerous immune and metabolic dysfunctions in sufferers as well and the list of physiological things wrong has steady increased since
Meanwhile, it is easy to get Pfizer and Moderna vaccines (mRNA based), and hard to get Novavax (protein based). By hard I mean impossible. mRNA are not well understood, have nasty side effects for some people (including me), and lose their efficacy after a few months, thus the need for boosters. You can verify this with blood tests that show antibody levels. With Novavax, which is based on technology that's been around for 20 years, it appears (based on studies) that it keeps its efficacy for at least a year after multiple doses, and it has minimal side effects (including my own shot).
That said, many governments have relationships with Pfizer and Moderna, and so these vaccines are easily attainable, while no such relationship exists with Novavax, and it is impossible to get it. I say impossible after asking about 50 doctors, contacting pharmacies, and finally contacting Novavax themselves, who told me that it is not possible to get until the new mix comes out.
So why would a vaccine that seems to actually work be unavailable, while ones that do not work are easy to get?
I realize that this is more a commentary on COVID than ME/CFS, but I'm arguing that they are very similar. Just consider Physics Girl, who contracted COVID a year ago, and is now bed bound:
https://www.youtube.com/watch?v=vydgkCCXbTA
Probably GP meant they fucked up by downplaying the danger's of COVID and doing the least possible to keep the hospitals from overflowing. Where, instead, they should have done more to prevent people from getting COVID.
On ME/CFS they failed to fund any research for 70 years, on many occasions saying things that led to patients being abused and not believed by their families or doctors. This led to an attitude in the NIH that it wasn't worth funding research which persists still to this day. There has been no real funding for research out of the NIH since a brief spurt in the 1980s, even now what funding its allocated has mostly ended up on Cancer.
That is all a political failure that has led to no progress on the disease and widespread abuse of patients.
That's not really a failure of politicians, because politicians don't have medical expertise. They rely on the guidance of experts in the medical profession to steer funding. So it was a human failure perhaps, and as all allocation of limited resources has winners and losers. So blame the system, and human biases, but not the government specifically.
Politicians don’t allocate funding into specific diseases. They allocate large blocks to places like the NIH, which then have scientists determine where to allocate funds.
Would it have worked to spend lots of money on this kind of research 50 years ago? Were our tools -- scanners, DNA/RNA chips, etc -- and our knowledge anywhere near good enough to make it likely it would have paid off?
To me it sounds like trying to do rocket research in the hope of reaching the moon back in 1900.
Doing it once the time is ripe is a completely different matter. I hope it is ripe now.
> doctors dismiss patients as crazy or "making it up"
It's very easy to frame what doctors say like this, but in my experience at least that's not really what they're doing. A doctor is a classification machine - they take your symptoms as inputs and output a disease or a syndrome, hopefully with mitigation measures associated with it.
When my wife had long covid for 3 years and doctors couldn't find anything wrong with her a neurologist diagnosed her with a "functional neurological disorder" and suggested psychiatry. My wife felt dismissed and was really mad about it, but the reality is that some sets of symptoms are psychosomatic, and psychiatry can help, so if the neurologist saw 100 people with my wife's symptoms and made the same recommendation to them all, some of them would benefit (as opposed to her making no diagnosis and none of them benefiting)
Sometimes it is exactly what they're doing. 15 years ago, shortly after surgery to remove a tumor from my femur, I ran into a physical therapy assistant whom I'd been working with when my doctors thought my leg pain was a soft tissue problem. He said he'd heard about my surgery and was glad I was doing well, and then as we parted ways he cheerfully commented offhand that when I'd been working with him and his supervisor, "I thought you were making it all up!" (I still feel angry about that occasionally, all these years later.)
Statistically speaking, you were making that all up. Of course in your case it turned out to be serious, but think about how negligible the odds of that are when you're seeing dozens of patients a day during your career.
Opioid addicts frequently make up being in pain in order to obtain prescriptions. That's far less common in physical therapy patients but it does occasionally happen.
It's not negligible, BECAUSE you are seeing dozens of patients a day. When you're a doctor, factoring the odds into your diagnosis will screw up your diagnosis BECAUSE you are exposed to the whole probability spectrum, not a quanta of it.
Using "chance of occurrence" is a major logical fallacy for diagnosis identification and can ruin the whole practice.
Besides the other responses so far, consider this: the consequences of mistakes about this are asymmetrical. A doctor could be exactly correct about the probability of "making it up", but the cost to the patient of a missed diagnosis is not balanced by the benefit of correctly dismissing other cases. A conscientious doctor could try to consciously account for this, but there's no feedback making them get it right (and pressures against, in our current reality).
Also, when a patient succeeds in getting a correct diagnosis after trying multiple doctors, the previous doctors generally will not find out about their mistake, so there's a bias against them actually learning the right probabilities: you can expect them to be overconfident on this score.
I am not buying that psychiatry actually helped. With this type of condition, some people get better over time. So those people would have gotten better anyway without the psychiatry. I also think the medical community should also rethink the notion some symptoms are psychosomatic. Why is that true? Because doctors can't spot the cause, so it must be psychosomatic? Maybe the cause is there but undetectable or not understood yet.
I'm not saying psychiatry helped my wife - it didn't, because she didn't go to a psychiatrist. Eventually she got better, as you say.
I think it's unlikely, however, that symptoms are never psychosomatic. If what we think had no effect on how we feel then the placebo effect wouldn't exist
A a few weeks after I had COVID I started having panic attacks. I went up a couple of flights of stairs at work and felt immensely exhausted - way more than I should have, I use the stairs at work all the time. I started feeling like there might be something wrong with me and that turned into a panic attack. (Later, of course, that turned out to be a symptom of long COVID fatigue.)
I was 32 at the time. Never had a panic attack before. Sometimes felt something was wrong but clear thinking and a few deep breaths and I was okay. Not this time.
In the subsequent couple of months I had a few more random panic attacks - once on a highway; I had to pull over.
So I went and saw a therapist. I don't think they actually helped reduce the attacks - the frequency dropped with time, together with the fatigue. Now, two years later, I only have the mildest of attacks (and I'm at around 60-70% of energy). But they did help me calm down, gave me tools to deal with an attack when it happens and reduced my stress around the entire experience.
It was definitely money well spent, and as much as I can tell from being my own carer, clinically relevant.
I have only anecdotal proof, but I believe there is also a link with caffeine.
After getting COVID, I went from being an avid coffee connoisseur to getting extreme anxiety from a cup (I've never had anxiety either). I switched to decaf for 2 years before finally incrementally building my tolerance back up. Several colleagues and random people I've met have had similar issues. It goes away over time, but is very real.
We're doing anecdotes here, so... I think the post-COVID symptoms made me aware of parts of my body I
had never had to 'deal with' or pay serious attention (I'm not into sports...). Feeling your heart doing weird stuff in normal conditions, isn't surprising to trigger anxiety and panic. The first time I felt like keeling over after some mild-the-month-before bicycle effort, I fell not only the heart symptoms but sudden fear and anxiety that compounded the situation. I called 911 a week later because I felt very strong and unusual heart symptoms, feeling like a heart attack. Nothing on either ecg, doppler, blood analysis, heart mri, effort test, absolutely nothing - the EMT said at first 'so many calls these days, most looking like panic attacks, poor people suffering with no physical traces of a problem'. ER doc was 'we didn't find anything but don't hesitate next time, it wasn't nothing and even if it's "just" a panic attack we can help'. The problem went away after 6 months of doing frequent/daily light cardio activity...
Holy cow. I'm fairly young and also had weird heart issues during COVID too. Felt like I could feel my heart slow down and get out of rythem a few times over maybe a month.
I went to a cardiologist and did a stress test. Nothing showed up and eventually it also went away. Note, I was a little stressed from work, but nothing unreasonable. Home situation wasn't too bad either.
I've suffered from nearly lifelong depression and panic attacks.
however, about ten years ago my general feeling of anxiety suddenly got much worse. I was able to cope with it using all of my usual anxiety coping skills but it seemed kind of off that everything had shifted. I went onto Lexapro, which helped. But then in 2019 or so things really started getting nutty again, where I'd be up all night with panic, often waking me up in the middle of the night, would be up until 5 am, finally fall asleep, then would have another during-sleep panic attack that would last all day.
Turns out I have a node in my thyroid producing thyroid hormone. I now take a very low dose of medication for hyperthyroidism and my panic-esque anxiety levels are kind of lower than they've been for like my entire life (still need the lexapro though, I am sure that my anxiety issues are not strictly the thyroid node).
Basically it sucks to have psychiatric illnesses that are standalone, but also compounded by other non-psychiatric pathologies.
This mirrors my experience very well, except it started about a decade ago for me. Completely out of the blue, I had a panic attack. Haven't ever experienced anxiety or panic before that, and medical investigations found nothing.
Therapy didn't help but sertraline helped me a lot. I still have no idea what the root cause is, and I've never quite been the same since, especially my energy levels.
However, I am at least functional and can hold down a job!
>Because doctors can't spot the cause, so it must be psychosomatic?
No, because the only replicated findings are that stress (and infections) are triggers, believing in a physical cause is a perpetuating factor, and multi-disciplinary rehabilitation leads to improvement in about 2/3rds and recovery in about 1/3rd of patients.
The problem really is the stigma associated with mental illness as opposed to other kinds of illness. There are clearly mechanisms through which psychiatric effects manifest as real physical symptoms. If there's no obvious physiological cause to symptoms, working with it having a psychiatric basis seems perfectly reasonable. That doesn't mean we shouldn't try to understand more about it though.
Person with Schizoaffective Bipolar Disorder here:
You know, doctors told me for years that the pain in my chest and back was all because of my mental illness, even though my brother and mother both needed spinal surgery for Anklysoing Spondylitis by the time they were 60.
They dismissed me till I told them I wanted an MRI of my spine and chest and there it was, Non-radiographic axial spondyloarthritis, the precursor to AS. So not I can treat it so it does not process into AS. They all told me there was " physiological cause to symptoms".
There is a HUGE stigma in medicine against any pain in people with mental illness, it is their best excuse to not even look. That is why there is no progress.
It is amazing how doctors continue to get away with gaslighting their patients because they refuse to believe them/look at family history, even to the point of not even attempting to rule those things out.
Doctors behave as if medical knowledge was exhaustive, and infer that symptoms they don’t understand come from mental illness.
Most diseases have a psychological component, but patients are seldom referred to a psychiatrist for treating their heart ache when they get an infarction.
I just mentioned these findings (and others about autoimmunity against the satellite cells in dorsal root ganglia) to my mum, a doctor specialized in physical therapy and rehab. She went into retirement this year and many patients with ME/CFS.
Her reaction: "So fibromyalgia is real now. I have a hard time believing it… I spent my career fighting it."
The difficulty is most clinical diagnoses (and some with specific criteria) will be a heterogenous group of diseases. Some patients with the label CFS may well have real pathology which can be treated, but some will be mostly psychological in nature, and some will be malingerers. Of course diseases without a proper diagnostic test will attract malingerers and then make people question those with a real diagnosis. Part of the problem of uncertainty in medicine.
Social recognition is better than the gaslighting folks with ME/CFS and other so-called "functional" diseases (with the scare quotes read "we really think you're nuts but won't say it out loud") often have to endure.
No, your wife _was_ dismissed. Not only that, she was misdiagnosed. And she’s part of a huge patient population that gets misdiagnosed routinely. She has every right to be angry. Misdiagnosis is not benign. It sends you down the wrong path and costs you years.
By all accounts, there is no way to test for or to treat CFS. Assuming it is real, and OPs wife did have it, what is to be done? The doctor ruled everything else out, and now there is nothing more they can do.
Say that then. "I don't know what is causing this. I've ruled out everything I can, you may have CFS or psychosomatic symptoms, but I can't test for either. Here are some resources on both. Psychiatry has helped x% of patients with your symptoms, I can't guarantee it will help but here's a referral."
Much better to say "I don't know" than to give a confident diagnosis just because you've run out of things to test for.
There's a HUGE difference between saying "we don't know what's wrong and we're sorry but we can't help with medication, but sometimes there can be mental things that help" and "we've diagnosed you with a mental issue, your body is fine." The latter is way more dismissive and angering, and assumes that we know a lot more than we do about the physical systems in the body.
Neither of us were in the room, but it sounds like the doctors did the former. They diagnosed with FND, a real physical disease (although kind of a catch-all diagnosis with no tests or treatment, like CFS), and recommended that therapy may help.
There is no simple lab test for CFS, and there are no miracle treatments, but it can be diagnosed, and some of the symptoms can be treated.
For diagnosis, there are clear diagnostic criteria, including the presence of post-exertional malaise, which is very easy to recognize simply by talking to the patient. (“I went grocery shopping last week, and I didn’t think I’d overdone it, because I felt okay that afternoon, and I had a full night’s sleep, but I woke up the next day feeling terrible and I could hardly get out of bed all day.”) There is a lab test that can be done for it, but it essentially consists of making the patient “crash” by exercising two days in a row and observing how much worse they are the second day. It’s not recommended for diagnosis because it’s harmful (it can take months to recover from a bad crash) and, again, not necessary.
For treatment, there are a few supplements and prescription drugs that can help each of the symptoms. Many patients experience dysautonomia (it’s in the diagnostic criteria) and there are several treatment options for that (beta blockers, drugs to raise blood pressure, drugs to encourage sodium retention, and others, in addition to non-pharmaceutical options like increasing salt and water intake). The fatigue itself is harder to treat, but a few supplements have been found to help. Cognitive dysfunction is a major problem that is definitely treatable (with ADHD and dementia drugs); that alone is enough reason to get diagnosed and treated.
Doctors literally say "you're making it up." In those exact words. There is no misunderstanding.
My wife had an emergency department refuse to treat her because they disagreed with an unrelated diagnosis that was in her medical record. Until she admitted that she was "making it up" and didn't have it, so they could "correct" the record, they would not treat her. She ended up having to leave and go to another hospital.
> My wife felt dismissed and was really mad about it, but the reality is that some sets of symptoms are psychosomatic, and psychiatry can help,
Depression is a comorbidity of chronic illness. It's hard not to become depressed when dealing with an unexplained illness.
Psychiatric treatment can reduce the contribution of the comorbid depression, which can create a net improvement for these patients.
Too many patients with chronic illness will refuse any psychiatric treatment because they are resistant to the idea, but they end up suffering more than necessary.
When doctors can't identify or treat the core illness, they can at least address comorbidities and work on increasing quality of life. Psychiatric care is at the top of the list for helping people's quality of life in these situations.
My wife was recently diagnosed with fibromyalgia and the doctor explained it exactly this way. It literally just means "nerve pain". There were no markers for rheumatoid arthritis so they just give it a label that is essentially just a placeholder. They can only treat symptoms anyway so it doesn't matter. I've got narcolepsy which was identified decades ago, but the mechanism was only isolated about 20 years ago and there's no direct treatment. Only ways to reduce symptoms. My condition definitely originates in the brain and can be treated with the same kind of CNS stimulants they give to people with depression or ADHD. So declaring a condition to be "in your head" isn't really synonymous with it being imaginary. For narcolepsy, most patients have a very explicit emotional trigger for symptoms. Emotions trigger neurotransmitters and neurotransmitter failure is the specific mechanism for causing the syndrome. So you can say it is most assuredly "psychosomatic" without that connotating it being some kind of emotional weakness. Your brain is part of your body. It controls thought, perception (including pain), emotion and literally every physical process beyond basic reflexes. Malfunctions in your brain can do all sorts of unpredictable things.
Fibromyalgia is more than just a placeholder, there are specific symptoms associated with it (such as the presence of myalgia in multiple locations on both sides of the body above and below the waist), it's just that it's severely understudied, not much is known about the cause, and it's pretty much diagnosed by exclusion.
Fun fact, the drug Xywav which has been FDA-approved for narcolepsy (and ideopathic hypersomnia) has also been shown in studies to help with fibromyalgia. They even sought FDA approval for that but the FDA rejected it on the grounds that there are too many fibromyalgia patients and therefore the risk of abuse is too high (the drug is related to GHB).
There is no evidence for functional neurological disorder, it is simply a hypothesis. As a diagnostic category it is essentially a "god of the gaps" construct. Remember also that the name is a re-branding of what used to be called conversion disorder (previously known as hysteria), that was found to be an acceptable term to patients.[1]
It's heavily published on and widely accepted as valid by neurologists, but that does not make it true.
The concept with FND is that there is no identifiable structural pathology, but that the neural circuits are dysfunctional, and that this can be fixed with things like cognitive behavioural therapy. This is typically framed to the patient as "the hardware is completely OK, there's just a problem with the software." (As most of this audience would recognise there is very little overlap between how brains work and how computers work.)
However, more advanced imaging techniques, such as 7T MRI are now showing structural abnormalities in these patients, which is a pretty fundamental problem for the above hypothesis. An attempt to rationalise this by FND proponents is made here.[2]
A recent example involves a 10yo child who developed a movement disorder following Covid.[3] Typically these would be diagnosed as functional movement disorder [4][5][6] and psychological therapy advised. However this group showed that in fact it was due to a neuroimmune pathology, with auto-antibodies forming that targeted some portion of the basal ganglia. The patient recovered completely with immunosuppression.
Thank you for this excellent synopsis. One would think rheumatologists would be curious how many people with these symptoms could be helped with immunosuppression. Alas.
Said by no neurologist ever... This reflects a complete lack of understanding of the diagnostic criteria. FND is not just a diagnosis made when it doesn't fit anything else. If you actually understood the diagnosis and still felt like it was BS for some reason, it would be because you would be arguing that patients are intentionally feigning their symptoms rather than "the diagnosis just does not exist at all" or that symptoms can be explained by an immunological or other medical cause. Just ask Dr. Google about the Hoover's sign or tremor entrainment and once you understand them, the corticospinal tract, and the most basic neuroanatomy of movement, and then see how big of an idiot you look like for posting this.
my pet theory is that long covid is associated with an autoimmunity to the ACE hormone. If covid uses the ACE2 receptor to enter your cell, the spike protein must resemble a portion of the ACE hormone, and it's easy for your immune system to "miss" and attack the wrong thing. Once you are "allergic" to your own hormones, you have two problems: 1) chronic immune response and inflammation and 2) lack of effectiveness of ACE due to it being removed or disabled by your immune system
And that's ignoring that there is a mechanism normally preventing this. And what happens when you become allergic to your own hormones is called a cytokine storm ... and it's serious enough that you can say comfortably that no doctor will miss it.
we're not talking about disabling an RAAS pathway though, we're just talking about interfering with it and making it less effective. it's a gradient of many shades
According to medical professionals I trust, Long Covid is likely to be multiple diseases with multiple causes, and any individual can have some of each.
Autoimmune reactions may be the longest covid; cell/organ damage is another; it is also possible that people may have less-than clinically detectable viral activity, or viral activity in some "pocket".
I'm not a medical professional, this is not medical advice.
I understand there is an interesting back-story to this paper that will be published in the Washington Post next week. If the findings are replicated (they look promising) we will owe a debt to the patients involved, as well as the researchers, but in particular to the 38 yo index patient with Li Fraumeni syndrome.
I got long covid in Jan 2022 but after 9 months the neurological symptoms went away. I got sick just this week and the brain fog came back.
Taking probiotics and supplements (omega 3, Multivitamins) and aspirin accelerates the process of getting better for me. I use n-back exercises from Brain Age Concentration Training as measure.
Im confused as to how you reached the conclusion that probiotics and those supplements speeds up the recovery, if your data points are 1) that took 9 months to recover and 2) that only happened in the last week. Is it that this week's brain fog has already gone away and the only difference you can think of is taking those things? In which case it's really nowhere near enough data points to draw conclusions.
Really, even for stuff like people saying "when I get a cold, I always recover faster if <x>" is almost certainly either a placebo effect, or a random opinion that may or may not align with actual medical reality. Because not only does something like "a cold" or "a flu" or "covid" cover many variants rather than being a single identical type of infection, but even if they somehow knew that every time they had been infected by an identical form of a virus there are still so many variables such as how much of the virus initially breached their body, how much sleep they'd had in the lead up to and post- infection, what they'd been eating around the time, etc etc
Which is why we use studies looking at large numbers of people to figure out what does and doesn't help recovery rather than relying on anecdotes.
And in your case it seems like even less data than someone making a judgement based on potentially dozens of colds over their lifetime, it's just one or two data points?
(Although since probiotics and vitamin supplements won't, in typical doses, cause any harm except to your wallet, there's certainly no harm in taking them after a sickness - and even if there isn't a link between them having a physical impact in speeding up recovery, they could still or course work wonders as placebos too!)
Feeling and performing better after taking an aspirin as opposed to days I did not take it. Effects don't last more than a day.
Clinical trials and online polls convinced me to try homemade probiotics and multivitamins. I can link them once I'm not busy. No idea if they had any effect but might as well include.
Interesting, as aspirin is an anti-inflammatory - there's also a super small scale trial that happened in Madrid where a short course of 30mg of predisone had positive impact on those suffering from long-covid.
As a side note there is the following study CFS/me which might be of interest
"We aim to find genetic causes of why people become ill with myalgic encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) with our ground-breaking research. Take part from your home"
Sorry, but they will not find it. At best ME/CFS has a polygenic cause but unless they are also testing for nutrient deficiencies this will come to nothing.
The cure can only come from personalized medicine, looking at the individual, not looking for a common cause.
But surely this is a treasure trove of data? Sure the research is aiming to find some sort of common ground, but it still would be possible to use the raw data later on
There is some research currently on low doses of naloxone as a treatment for long Covid/CFS/ME. Would naloxone have anything to do with this protein, or is it an unrelated approach?
We think it just reduces some of the brain inflammation and thus alleviates some of the symptoms. Its also a treatment sufferers become tolerant to and it stops working. Its also very hard to dose right and requires constant adjustments and its not without side effects that often make it not worthwhile and for some people it never works.
It should be authorised as a treatment for ME/CFS and Long Covid in the short term alongside Ablify as sufferers should get to try these and see if they work but they are both very far from a good treatment and do nothing for the core parts of the condition.
There's no process to "authorize" an existing approved prescription drug as a treatment for ME/CFS and Long COVID. Doctors can already prescribe those drugs off label if they wish (although the patient might have trouble getting insurance coverage for those claims depending on their policy). In order to make them on-label treatments then the drug company or some other party will have to conduct a large-scale clinical trial and go through the FDA regulatory process to prove that it is safe and effective. This is expensive, but drug companies do such studies all the time in order to increase revenue and extend patent protections.
It depends on the country. In the UK for example, medications are indeed licensed to treat certain conditions. Specialist doctors are able to prescribe off-label regardless, but most are reticent to do so.
I could be wrong, but I believe naloxone isn't really orally bioavailable. Most of the very limited research focuses on low dose naltrexone (LDN) instead, naltrexone being another opioid receptor antagonist with paradoxical properties, namely analgesic and anti-inflammatory properties, at low dosages.
There could be a link here, although it is tenuous and purely lay speculation. ER stress is discussed in the article:
>Both S1 and the people with ME/CFS had biochemical signatures of ER stress in their muscles, and treating S1’s cells in a dish with a drug that blocks ER stress lowered WASF3 levels and restored mitochondrial function. On the flipside, using toxins to artificially induce ER stress in cultured cells or in mice caused a rise in WASF3 levels, Hwang says.
LDN has been found to be quite effective in alleviating ER stress specifically in the epithelial barrier in IBD [0], rather than the ER stress - WASF3 levels being investigated in muscle cells in the above article. Certainly worth investigating. And, as noted in the article, the WASF3 angle is merely one potential pathway of the disorder.
>Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers.
There was also a study out of Yale showing effectiveness with a combination of guanfacine and N-acetylcysteine (NAC), an anti-oxidant also used for the treatment of TBI.
All I can say is that having significant gut dysbiosis is enough to have significant fatigue - think for sure, you can end up having fatigue from cell energy production issues, but it's clear to me that there are definitely different causes of CFS.
It's possibly the same thing. Endoplasmic Reticulum Stress, the type of stress which may cause this protein to become elevated, was induced in mice by exposing them to endotoxin, a type of toxin produced in the gut.
Throughout my late teens and early 20’s I suffered from chronic fatigue. Tested positive for mononucleosis three times until later finding these were false positives to Epstein Barr.
Later learning my body was having an autoimmune inflammatory response to viral activity causing debilitating fatigue.
Took variety of treatments including steroids, anti depressants, supplements … and so on.
When I was 22 I met person on the campus of mizzou who simply showed me some meditative stretches and breathing exercises. The idea was to just slow down and focus on improving your bodies own health where it’s at.
This is a oversimplification but the key for me was to stop thinking this was a virus or disorder or in general things were happening to me .. in which I was a passive unfortunate recipient looking for professionals to help.
Instead I decided from now on I would just try and be a healthier person in mind body and spirit where I was at that moment.
The change of mindset to where it is my responsibility to improve my own well being has paid massive dividends. As a middle man I have no real health issues, no chronic fatigue or reoccuranr high white blood cell accounts indicating and over reactive immune system.
My case will lot insipidity apply to all but if I could impart any wisdom would be just take things into your own hands and be an active person working on improving your own condition whatever it may be.
Change the mindset of shoots this sucks and no treatments work … why is this happening to me… to what are things I can do to improve my existence. Am I a nice person. Am I healthy (weight / exercise).. do I like my job and find it is meaningful…
Sorry if sounds dumb and corny but made a world of difference for me.
Complications of Epstein Barr have not been ruled out as a cause for CFS. But the problem is that nearly everyone has been exposed so it's hard to find counterexamples (or the lack of counterexamples)
For anyone generally curious about the ME/CFS patient experience and state of medicine, there are a couple good articles in The Atlantic[0][1].
For those interested in latest research, Dr. Bhupesh Prusty presented[2] a very plausible hypothesis with detailed evidence[3] of virus-triggered autoimmunity causing mitochondrial dysfunction in endothelial cells (vascular system).
And there's a promising treatment for Long COVID with a study[4] claiming improvement in many symptoms, and describing the targeted mechanism of disease pathology (also vascular system). Needs trials and replication, or until then doctors willing to risk off-label treatment.
A warning about Long COVID research: Any long-term trials that don't have a control group are virtually useless. When large Long COVID patient groups are studied without any treatment, the number of people reporting Long COVID symptoms declines over the course of the study.
The takeaway is that for many (but not all!) Long COVID symptoms naturally get better over time. This is a huge problem for Long COVID treatment studies that don't include a control group because there's no way to tell if the treatment made the patients better any faster than they would have normally healed.
Yes, that's why I said "needs trials and replication". That small clinical study is useless for insurance companies and standard medical practice today. But it is very useful to point the way toward promising areas of further research, and for any pioneering risk-takers who might be willing to try.
That is, after all, how we learned that stomach ulcers are not psychosomatic (caused by "stress"), but rather by the bacterium H. Pylori. A doctor infected himself, got ulcers, and cured himself with antibiotics!
I have a post-viral syndrome case of chronic fatigue. I've not been diagnosed with CFS formally, but I match many of the symptoms required, including orthostatic intolerance.
It is an extremely complicated condition. I personally have had a pet theory that disturbed barrier function is involved somehow, and seeing this article is extremely confirming for me, since it mentions that as a potential factor. In fact, one study on just the metabolites of people with CFS vs healthy people found that a Vitamin E derivative -- one often a part of healthy cell barrier function -- was significantly lacking in CFS people compared to the normal population, and was a strong marker. However, this seems to have been largely brushed over in later literature, with more popular things like fatty acid processing and such being mentioned.
What has worked for me:
-- Ketogenic diet (avoiding lactic acid production) -- greatly dampened PEMS.
-- Blood glutamate scavengers + Niacinamide + Ribose (1g): Provides NAD + a cofactor needed to transform glutamate in the blood into something else. For some reason, this really seems to help with CFS patients. Helps with resting fatigue. The cheap and accessible BGS I use are NAC, pyruvate, and (sometimes) malic/citric acid. Malic is better as it is right before oxaloacetate, a BGS, in the Krebs cycle, and it turns into Citrate. Citrate IIRC raises the levels of one of the enzymes that eliminates lactic acid. Your blood cells can only use glycogen, so there will always be some level of lactic acid production to be suppressed.
-- Reduced glutamate + free glutamate intake: Lower-glutamate proteins (tuna, etc), no hydrolyzed soy protein, yeast extract, etc.
-- Gotu Kola (biases the glutamate<->GABA conversion towards glutmate->GABA as I understand, a double-bonus), various anti-inflammatories (Quercetin+non-citrus C, liposomal Turmeric+curcuminoids (!! Important, piperine inhibits both Pgp and glucoronidation, which increases absolutely everything in absorption. Liposomal is better), and boswellia for LOX-5 inhibition. Looking to move to a stronger Boswellia extract (5-Loxin) as it's lighter weight.
These changes, while I still have energy issues, have made it safe enough for me to be able to backpack outdoors for extended periods of time. My longest so far has been a 2 month trip (with 1-2 nights indoors).
Hope this helps anyone who struggles with this and is looking to experiment. I wish I was back to 100%, but being able to be out in nature after being mostly bedbound is...well, my heart is much more full when I am. <3 :')
I would love to know if these results apply to fibromyalgia as well, as CFS/ME-like fatigue can be present with fibromyalgia. For example, in my case, the only reason I wasn't given a concurrent CFS/ME diagnosis with my fibro is because I couldn't point to a viral infection that triggered the fatigue.
My working theory is that viruses like COVID trigger autoimmune reactions because of ACE2 binding which causes immune cells to attack the thyroid and cause hypothyroidism leading to fatigue.
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[ 4.9 ms ] story [ 198 ms ] threadI can personally attest to this. I was an extremely energetic person (shooting straight out of bed in the morning, never requiring daytime naps or rests) until one specific week in April of 1996 when I had what I thought was a mild flu. The post-flu fatigue never really went away. I became acclamatised to it over the years and rarely notice it now (except times like this when I'm reminded that I'm significantly less energetic than the average person). I hope they find a treatment (if not a cure) for this soon. As I understand, some suffers are not as lucky as I am.
I recently had a minor cold that caused some sort of heart inflammation and could have exacerbated/triggered a latent heart rhythm issue. About 1-3 times a minute while resting, my pulse wouldn’t follow the normal rhythm (PVCs — could feel it too while pressing finger into the neck, without EKG).
It made me feel less energetic long after the inflammation subsided. I couldn’t identity anything specifically “wrong”. After having a cardiac ablation, I feel a lot better.
If you do, find a electrophysiologist, not a regular cardiologist. Asking the latter is like asking a plumber to find an electrical issue in your house.
Vitamin D only really has dramatic effects in people who are severely deficient. Despite all of the influencers and podcasts claiming it's a miracle supplement and that we're all deficient, actual Vitamin D studies don't show much or any benefit outside of people who are significantly deficient.
But yes, if your Vitamin D is actually low then getting it into the normal range could have some dramatic effects.
Some doctors will prescribe short courses of Vitamin D as an almost-placebo when they can't find anything else wrong. It works quite well as a placebo for many people because podcast health influencers have been talking about it so much lately.
Fat-soluble vitamins (A/D/E/K) can accumulate in your tissues over time if you keep taking too much.
Water-soluble vitamins (such as C) are much easier for your body to filter and flush via urine. You could still overdose in the short-term, but a chronic accumulation is unlikely.
Not going to go into detail but there are several recent studies showing that daily intake of up to 50k IU is safe. The concerns over hypercalcemia, etc. were tied to much larger doses per day.
https://pubmed.ncbi.nlm.nih.gov/28012936/
https://pubmed.ncbi.nlm.nih.gov/30611908/
https://www.newyorker.com/magazine/2003/07/07/a-sudden-illne...
Also, Dianna Cowern, "Physics Girl" has been dealing with long COVID and CFS/ME for about a year now. Horrible.
https://twitter.com/thephysicsgirl?lang=en
S. pyogenes has been implicated in other autoimmune disorders like psoriasis [2], which we know can be triggered by strep bacteria. In psoriasis, we have some evidence that it may set off a kind of bogus vicious cycle where a type of T-cell called a tissue-resident memory T-cell is "programmed" by an initial bacterial infection, but gets into a confused state where inflammation keeps going even long after the bacteria are physically gone. With other disorders, PANDAS [3], the cross-reactivity causes strep affect the brain and cause neuropsychiatric symptoms.
In some cases, strep bacteria are thought to linger in the body even long after a symptomatic infection, hiding in biofilm or in reservoirs like the tonsils, occasionally re-emerging to cause an immune response, similar to the Epstein-Barr virus. I would not be surprised if strep turns out to be the ultimate cause of some illnesses like ME.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684244/
[2] https://pubmed.ncbi.nlm.nih.gov/19781993/
[3] https://www.nimh.nih.gov/health/publications/pandas
I've been tested and evaluated for lots of things. Fortunately, not a dire progressive disease like multiple sclerosis or Parkinson's.
Unfortunately, I have not been able to substantially improve energy level in a sustained way. There are times when I can gain momentum for about three weeks but then there's a collapse. If I push it, I've had vital signs go awry and it's enough to scare the emergency medical personnel who are called when I pass out... and then a few hours later, nothing worse than severe fatigue.
I wonder how far away we might be to sorting it all out, things you shouldn't be doing after a viral infection, or environmental factors that we will discover, or if we will be able to understand this at all without a more fundamental rework of medical understanding.
It is an interesting finding since some treatments for ER stress exist and are worth testing. It's also somewhat linked to the Itaconate shunt theory that Robert Phair at Stanford has been investigating for the past year.
How would you look for DNA alteration, generally?
However, this is likely to be a fool's errand in this case, because this kind of sequencing normally assumes that we can take a sample of many cells from the body, and that all those cells have the exact same DNA changes. If you have a mutation that is induced in a parent or the single-figure-cell stage of embryo development then that will be true, but for DNA modification by a virus in an adult it will not be. Each cell will have a different insertion. Now, there are some techniques that can sequence the DNA from a single cell, but they don't give quite as good quality data, and because you'd be wanting to sample a good number of cells to see what the distribution of insertions is, it will likely also be very expensive.
It totally could be. Viral persistence is a strong suspect. HIV hides in "sanctuary" tissues. Other viruses and bacteria probably can evade the immune system in certain types of tissue.
* Virus' have a high failure rate - many infected cells never go on to multiply.
* However, those infected cells may also not still perform correctly.
* If you have a good chunk of your cells in your body no longer performing their function, yet not dying and making way for replacements either, everything isn't going to work as well.
That would explain why it is a wide range of viruses that can all cause fatigue symptoms, and also why parasitic and bacterial infections rarely cause the same.
Technical term: Virus-induced senescence
In this hypothesis, what would be a solution?
Best I can think of is Chemo-therapy, to kill of the bad cells. But that feels incredibly heavy handed, as well as liable to do more damage.
And time.
Prolonged fasting is known to clear away senescent cells. So that is the intervention which seems most promising here. Intermittent fasting can help the gut by giving it time to rest between meals, and it can improve insulin sensitivity because the body spends more time in a low insulin state. Maybe there are longer chains of mechanism there, but at first glance, they don't seem quite as relevant.
* person gets infected
* enyzmes needed to fight infection are used more
* these enzymes need cofactors like manganese, zinc and iron
* Patient becomes depleted in Manganese, zinc and iron.
* since these cofactors are needed to control oxidative stress in the mitochondria there is more oxidative stress in the mitochondria
* fatigue
https://onlinelibrary.wiley.com/doi/10.1016/j.cdtm.2020.11.0...
https://www.science.org/content/article/protein-disrupts-cel...
[0] In Dutch: https://nos.nl/artikel/2486149-experimenteel-kankermedicijn-...
https://www.mdpi.com/ijms/ijms-22-11714/article_deploy/html/...
Iron deficiency has been a common feature of LC for a while:
https://timesofindia.indiatimes.com/life-style/health-fitnes...
I'm esp. interested in any interaction with food. Because I get depression 4 days after I ate a food. I don't have any other symptoms than low energy and a sense of impending doom. Symptoms stay for 3 days then go away. Started collecting the info in my github. I'm very interested if anyone has more ideas.
I seem to be okay with fermented thyme.
Pepper is no good, swollen eyes, but chilly seems to be okay. Those are never consumed in big quantities, I could test with chilly capsules though and maybe I will.
Diet consists of Lamb, once a day, then some yoghurt or kefir in the evening. Some koffee and milk as well.
Haven't collected everything yet, maybe you find something that helps - or can add some. Trying to get diagnosis for leaky gut, it's a drag to get an appointment. https://github.com/cutestuff/FoodDepressionConundrum
This is what some biologics do.
I have spoke to people who had improvement after doing an antihistamine protocol. In the long covid/cfs space.
- Gastroparesis
- Thiol intolerance (impaired sulfur metabolism) - could try molybdenum and maybe Boron supplementation (ask doctor if ok)
- High gut permeability („leaky gut“) -> undigested proteins enter blood stream -> autoimmunity (eg via viral mimicry; all kinds of viruses can do that, but COVID and EBV come to mind). Water fasting could help, maybe digestive enzymes
- Mechnical interaction, eg dysbiosis -> bloating -> cervical spine misalignment -> more bloating due to vagal nerve pinching (try massaging back of the neck vigorously to see if depression disappears for a while)
- Auto-brewery syndrome
All of those can be downstream issues of systemic issues, like hypothyroidism (which has been shown to be caused by microbiome metabolites; I wouldn’t just down the next best yogurt though, but look at studies around Bifidobacterium Longum, which looks promising; probably others too).
Although there is less research into it than l-glutamine, there is rapidly growing interest into the effects of creatine supplementation on dysfunctions of the epithelial barrier (which would include intestinal permeability aka "leaky gut") [1]. The upshot is that it is an well studied supplement that is very well tolerated by almost everyone.
Zinc carnosine is another one that can be helpful, if tolerated. However it is believed that enteric-coated formulations are required to be effective (which may be hard to find) due to very high absorption rates and susceptibility to stomach acid prior to reaching the intestines [2].
[0] https://www.mayoclinic.org/drugs-supplements/glutamine-oral-...
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145094/
[2] https://www.sciencedirect.com/science/article/pii/S221074012...
HOWEVER, I am constantly experimenting with foods, isolation, etc. - and I discovered that PLANT-BASED milks or creamers for my coffee give me TERRIBLE CFS. - Almond Milk - Cashew Milk
Specifically "big brand" names you find at chain stores. They must be chemically treating these foods with something. I don't trust them.
Back to cow's milk for me.
So it's a stress response, not necessarily causal. It's long been suspected that some sort of perennial stress state was involved in this problem (anything from adrenal fatigue to illness genes never turning off). So does this tell us more or is this just another biomarker?
Though I say 'just', finding a biomarker for CFS would still be something people could be tested for, which is way better than where we are now.
The scary thing is that there seems to be a vicious path, of COVID->long COVID->ME/CFS. We're not sure what makes COVID evolve into long COVID, which also means we have no idea how many people who catch COVID eventually wind up with long COVID or ME/CFS. And there is a total media blackout on the topic, seemingly because politicians don't want to admit they fucked up.
Hopefully once there is a way to verifiably test for it, a lot of things will change for the better.
perhaps organic acids testing could show something?
I don't think that's true, at least not in my experience anyway. People (myself included) are too quick to conflate "all in your head" with "making it up".
Things "in your head" can and do have real, physical, life-limiting, effects.
If it turns out that ME/CFS doesn't has a physical marker, then what? There may never be a way to verifiably test for it other than symptomatically. It's no less real for the people living with the effects, but there may be no pill to take, or injection to administer.
The problem is that ME/CFS is similar in presentation to other conditions such as for example certain kinds of depression. The difference is that exercise is thought to help with those conditions and exacerbates ME/CFS. Thus there are two different groups of people, one who you are helping by encouraging them to exercise and one who you are harming. If you can't tell them apart the system is bound to hurt someone.
Hence it is important to make a distinction between the two, so you give proper treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988339/
First problem, I do not have ME/CFS, let's use the Maes et al (2012) scale. 0-5 scale, 5 being the worst.
"1 means mild exacerbations of fatigue/pain/neurocognitive symptoms following exercise (either cognitive or physical)" Yep, after a longer, harder than normal bike ride I'm quite fatigued, in quite a bit of pain (bad back, knee, shoulder), and can't think particularly well.
"2 means moderate exacerbations of symptoms following exercise; 3 means severe, incapacitating exacerbations lasting less than 24 hours;" Accurately describes what happens when I do HIIT style intervals that exceed my work capacity, or what it's extremely hot outside. Dreadfully exhausted, usually have to nap, or lay on the couch, every muscle hurts, extremely sore, difficult & painful to move for 24-72 hours.
I'm not saying ME/CFS does not exist, this is just a terrible indicator.
The worst part is making it so specific obscures the large body of existing research that would provide tools for treatment protocols here, eg work capacity in athletes.
I know you said you don't have CFS, but trust me - the fatigue we suffer after PEM is nothing like "normal" body fatigue after exercise.
I think we'll find a diagnostic test eventually. At least, I hope we do.
Cochrane systemic review, "exercise therapy for chronic fatigue syndrome", 8 studies, 1518 participants
"Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems ... Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate‐quality evidence)"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419524/
Fairly plausible, mitchondrial biogensis is an adaption to exercise, it may be impaired in ME/CFS patients, but not totally inhibited, and more mitochondria may lessen the severity of the pathogenesis of ME/CFS.
My experience (in California) has been that most doctors have been willing to assume I am being truthful, but a significant fraction seem to want to spend their time and energy only on conditions that the patient cannot be deceiving them about.
It's proven to be the case. A repeat cardiopulmonary exercise (2-day CPET) is currently the only widely replicated biomarker for ME/CFS. Only ME/CFS shows a reduction in performance and a lowering of ventilatory threshold on the second day. Anyone else (sedentary, cancer, heart or lung disease, MS, depression) will show an improvement. [1]
A study this year showed a striking effect looking at the metabolites in urine after exercising female ME patients vs sedentary healthy controls. The ME patients just did not excrete metabolites as the healthy controls did. [2]
"This indicates that ME/CFS patients have a general metabolic dysregulation that is part of their exercise intolerance and PEM in which altered metabolic excretion is a contributing factor."
There's also a very simple clinical discriminator between ME/CFS and depression. If you ask a depressed person what they would do if they were suddenly cured, their answer will be "Not sure, I don't know, I can't think of anything, nothing really." If you ask someone with ME/CFS the same question, the response would be "Go to the shops, drive my car, walk on the beach, see my friends... etc".
[1] https://www.mdpi.com/2227-9032/8/3/192
[2] https://www.mdpi.com/1422-0067/24/4/3685
To me, this argument does not make sense. Consider the example of Physics Girl (I linked the video in another comment). The video shows her before COVID, and after COVID. It's obvious that her COVID infection did something to cause her to go from being an amateur astronaut to being bed-bound. There is clearly some kind of imbalance, somewhere. We use biomarkers like CRP levels to determine whether someone has an infection, others for cancer, or any other disease. Why would it be different for this?
If we can identify some kind of biomarker... be it a protein, something in the blood, etc, and link it to COVID, then we can start testing treatments to see how they impact the biomarker.
I didn't really make an argument to "not make sense". Right now, ME/CFS may just be a collection of symptoms rather than a specific _thing_ that can be tracked, measures and cured. Or it may be a specific infection. We don't know.
Sure, it's compelling. But the plural of anecdote isn't data. It may seem obvious, but so far we haven't found the biomarker yet and must surely keep an open mind that one may not exist.
I'm not saying we should stop looking, but that the thing we're looking for may not appear.
I think a more logical approach (for me) would be to say that there might be multiple biomarkers which could present ME/CFS type symptoms in different ways.
Dr. Bhupesh Prusty has recently given some lectures on his discoveries related to Fibernectin, for example. That could be a massive breakthrough, but we need more studies on it.
One other data point that might interest you: apparently a large percentage of ME/CFS patients are finding relief through valtrex. Apparently there is some relation to the herpes virus, although nobody understands how or why.
_Are they though?_ This needs a citation. What constitutes large? A majority? That's unlikely, especially in the UK where medications aren't prescribed unless there's measured clinical value in it. I'm sure some are finding relief, but until we know how many and how much relief it could just be a placebo effect, right?
I hope that anyone affected by ME finds relief, but the discourse online about it always confuses me. There's always a slight undercurrent of "those mean doctors" and a breakthrough _just_ on the horizon:
"That could be a massive breakthrough, but..."
"apparently a large percentage of ME/CFS patients are finding relief..."
"Apparently there is some relation to the herpes virus, although nobody understands how or why."
In reality, nobody actually knows. Some scientists have got some ideas, some of which stand up to some form of scientific scrutiny. But that's basically it.
It's also why I opened my initial post with "There needs to be more research into this horrible disease."
https://iv.iiarjournals.org/content/invivo/21/5/707.full.pdf
Other trials into antivirals have been negative.
This study screened for active vs latent on number of viruses in patients vs assumed health controls, bottom chart here is what you would evaluate Valtrex effectiveness against.
https://translational-medicine.biomedcentral.com/articles/10...
EBV, HHV6 and HHV6 tend to reactivate during stress, but don't typically cause symptoms. I think what we're seeing in ME/CFS is this reactivation, but it's not necessarily what is causing the problem (if it was, antivirals would help, but they don't).
I was suggesting to crossreference Valtrex effectiveness against the activated virii in the study I linked. If Valtrex is not effective against the reactivated cohorts, we need more falsification around antivirals <-> ME/CFS.
From the article:
>Viruses can trigger ER [endoplasmic reticulum] stress, perhaps explaining why ME/CFS and related conditions often arise after infection.
Since you mention herpes, I'll bring up what I've read about Epstein-Barr (EBV) (which belongs to the herpes family of viruses). It's estimated that 90% of the global population will contract EBV in their lifetime. In most people, EBV goes dormant for after the initial infection is cleared and more or less stays that way for life. But in some people, for unknown reasons, it can chronically reactivate, triggered by stress, other illnesses, immune dysfunction episodes, etc. Apparently it loves to hang out in the spleen, although I believe it has been found to reside in other organs as well in these cases of chronic reactivation.
I would be shocked if this were the only virus to do so, but at present it seems to be the most studied, perhaps because EBV is fairly strongly correlated with a bunch of cancers, auto-immune disorders, and chronic conditions (including MS as recently demonstrated in a huge study by the VA, n=10,000,000). Very interesting and important stuff. I look forward to further research into these mysterious long-term effects of viral infection.
We know that infections cause sickness behaviour (fatigue, depression, etc.) due to the effect of the cytokines on the brain. The interesting thing is that the brain itself releases similar cytokines in response to mental stress, and mental stress also activates the glial immune cells in the brain.
Infections also activate the HPA axis (the body's stress system) in the same way as mental stress does. This is to give the immune system energy to fight the infection, and also to prevent a fatal over-reaction by the immune system. Chronic long-term stress can result in a blunted HPA axis response, and this is commonly seen in ME/CFS.
Patients who have been bedbound with ME/CFS report that they were trapped by fear that there was something wrong with their bodies, and they felt fear when going outside or doing anything, and this caused further symptoms. Reducing that fear, and experimenting with activities again in a calm manner seems to be key to recovery. Looking at some of the tweets from physics girl, it looks like she may be stuck in this state.
Doctors, generally, want the best outcome for their patients. I find it hard to believe that they're doing something actively harmful that's against accepted best practices, informed by scientific literature, because... they hate their patients?
If there truely were thousands of papers showing a specific biology for the disease that could be targeted and treated why would any doctor ignore that?
Any illness with primarily neurological symptoms have a history of medical malpractice and gaslighting.
As early as 1944, an author in the Journal of Nervous and Mental Disease remarked: "The history of prefrontal lobotomy has been brief and stormy. Its course has been dotted with both violent opposition and with slavish, unquestioning acceptance."
The last recorded lobotomy in the United States was performed by Dr. Walter Freeman in 1967 and ended in the death of the person on whom it was performed.
https://en.m.wikipedia.org/wiki/Lobotomy
Let's assume that all doctors fit your description. (I don't agree, but let's go with it.)
What's the alternative? I just can't accept that the vast majority of medical professionals are ignoring a potential cure or refusing to accept that one for ME may exist because it might hurt their egos.
Being medical professionals doesn't educate them away from having the same human flaws and cognitive biases that we all are capable of.
edit: I'd forgotten his name, it was Ignaz Semmelweis - see for example https://globalhandwashing.org/about-handwashing/history-of-h... or https://www.npr.org/sections/health-shots/2015/01/12/3756639...
I remember learning about a physician who helped his sister with child birth and she died. He was aware of the washing hands but ignored it. I believe he ended up committing suicide as he wasn’t able to cope with basically killing his sister due to his ignorance.
> "He didn't discover it, he was told by midwives over and over and over until he looked into it. Midwives at the hospital observed that when doctors delivered babies, mothers were at a higher risk. Any housewife knew that food would spoil faster if handled with dirty hands and they always used vinegar solutions to clean their hands, tools, and surfaces. Any housewife would do this and midwives did it because mothers and their babies are more important than pumpkin preserves. Only doctors never washed their grubby hands while it was a deeply ingrained habit in most midwives. Semmelweis listened to women. No wonder they locked him away."
Which is uncited/unsupported, but back in the Black Death time of the 1660s: "The villagers established a system of boundary stones around the village’s periphery, boring holes into the rocks and leaving coins soaked in vinegar – they believed it acted as a disinfectant – in the holes. Merchants from surrounding villages would collect the money and leave bundles of meat, grains and trinkets in return." - https://www.bbc.com/travel/article/20151026-the-sleepy-villa...
And from the same Reddit thread:
> "Oh again with this "before Germ Theory no one knew anything about disease!" bullshit. We always knew dead and dirty things caused disease. Dead animals for artillery ammo, dead animals buried by wells, leaving your swords in latrines. We also knew how copper and silver could help heal and prevent disease."
So, it's not like Semmelweiss proposed Germ Theory, or was the first to observe a connection between death and disease, or between 'disinfectant' of some kind and reduced disease. And https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1299347/ says:
> "(notably Alexander Gordon of Aberdeen) had shown that puerperal fever was contagious some 40 years before Semmelweis. The mortality rate in lying-in hospitals did not fall but rose after Semmelweis' treatise was published, and his ‘much-cited but seldom-read’ thesis is immensely long (over 500 pages) and so badly written that it is almost unreadable. [...] Semmelweis deserves to be remembered for his observation in 1847 that making medical students wash their hands in a disinfectant solution before going from the post-mortem room to the lying-in wards of the Vienna lying-in hospital, led to a fall in mortality due to puerperal fever from a very high level to a moderate level. [...] After his death in 1865, Semmelweis was totally forgotten, not only in Vienna but also in Hungary where he was born and to which he returned in 1850. It was not until the late nineteenth century that the introduction of Listerian antisepsis applied to obstetrics led to a steep fall in deaths from puerperal fever. Only then was Semmelweis' work recalled and his faults forgotten."
Which is fine, he shouldn't be knocked, but how did it take 200 years for humans to decide to use the tools that were already internationally known (vinegar) to a large number of people (housewives, midwives) to avoid some kind of death-related contamination, on childbirth and hospital and post mortem scenarios? And why did it take a guy writing a 500 page near-psychosis rant?
Was that low hanging fruit and if so, how much more of that is still in the world today?
If 90% of your patients come in sneezing and it's a flu for 30 years, then you generally give them advice for handling a flu and it works most of the time. But that also means you have a tenth of the experience handling the edge cases, at best.
Confounding variables make this a lot worse, like people having multiple symptoms, or not telling the doctor things because they felt dismissed before, or that they stopped seeing them because they gave actively harmful advice.
Having a lot of experience with doctors is what has convinced me medical training needs reform. Doctors actively ignore patients telling them objective factual reasons their advice is incorrect or harmful, and treat you as a hypochondriac for arguing.
I have stopped seeing a number of doctors over the years after they looked at my medical history and said "let's try X again", and when asked why, "just to see", when I have already tried X and two or three other medications in the same family as X, in the history (often from their own larger department, not something I provided), in the last 2 years.
I have stopped seeing doctors over me telling them that raising the dose of a medication made me much worse and having them then cut the visit short by leaving the office, saying they were late for something else, and telling me they were writing a script for double the dose as they left (and no, the drug in question did not have strange dose-response relationships like, say, Seroquel).
I have stopped seeing doctors over them insisting I just had a cold when I told them I was too exhausted to reliably walk two blocks to their office without an escort, every day for a week, not sleeping, and unable to keep any food down, without changing their mind, when I turned out to have pneumonia.
None of them were trying to be harmful.
This is a baseless claim, there's a Cochrane review showing exercise is beneficial. Pacing appears to be a common strategy, and it's exercise in of itself.
>In the 1980s they found numerous immune and metabolic dysfunctions in sufferers as well and the list of physiological things wrong has steady increased since
None replicated as yet.
??? The Royal Free is in Hampstead, and still exists. St Thomas’ is on the south bank of the Thames at Westminster bridge.
How did politicians fuck up?
Another: 19 September 2022, US President Biden declares COVID to be "over" https://www.youtube.com/watch?v=tHT1enFH2sI
Meanwhile, it is easy to get Pfizer and Moderna vaccines (mRNA based), and hard to get Novavax (protein based). By hard I mean impossible. mRNA are not well understood, have nasty side effects for some people (including me), and lose their efficacy after a few months, thus the need for boosters. You can verify this with blood tests that show antibody levels. With Novavax, which is based on technology that's been around for 20 years, it appears (based on studies) that it keeps its efficacy for at least a year after multiple doses, and it has minimal side effects (including my own shot).
That said, many governments have relationships with Pfizer and Moderna, and so these vaccines are easily attainable, while no such relationship exists with Novavax, and it is impossible to get it. I say impossible after asking about 50 doctors, contacting pharmacies, and finally contacting Novavax themselves, who told me that it is not possible to get until the new mix comes out.
So why would a vaccine that seems to actually work be unavailable, while ones that do not work are easy to get?
I realize that this is more a commentary on COVID than ME/CFS, but I'm arguing that they are very similar. Just consider Physics Girl, who contracted COVID a year ago, and is now bed bound: https://www.youtube.com/watch?v=vydgkCCXbTA
That is all a political failure that has led to no progress on the disease and widespread abuse of patients.
https://www.ninds.nih.gov/about-ninds/who-we-are/advisory-co...
To me it sounds like trying to do rocket research in the hope of reaching the moon back in 1900.
Doing it once the time is ripe is a completely different matter. I hope it is ripe now.
Yes, but what part of “a gentleman’s hands are always clean” do you not understand?
It's very easy to frame what doctors say like this, but in my experience at least that's not really what they're doing. A doctor is a classification machine - they take your symptoms as inputs and output a disease or a syndrome, hopefully with mitigation measures associated with it.
When my wife had long covid for 3 years and doctors couldn't find anything wrong with her a neurologist diagnosed her with a "functional neurological disorder" and suggested psychiatry. My wife felt dismissed and was really mad about it, but the reality is that some sets of symptoms are psychosomatic, and psychiatry can help, so if the neurologist saw 100 people with my wife's symptoms and made the same recommendation to them all, some of them would benefit (as opposed to her making no diagnosis and none of them benefiting)
https://my.clevelandclinic.org/health/diseases/9833-munchaus...
Using "chance of occurrence" is a major logical fallacy for diagnosis identification and can ruin the whole practice.
Also, when a patient succeeds in getting a correct diagnosis after trying multiple doctors, the previous doctors generally will not find out about their mistake, so there's a bias against them actually learning the right probabilities: you can expect them to be overconfident on this score.
I think it's unlikely, however, that symptoms are never psychosomatic. If what we think had no effect on how we feel then the placebo effect wouldn't exist
Being told you're crazy is a net nocebo.
I was 32 at the time. Never had a panic attack before. Sometimes felt something was wrong but clear thinking and a few deep breaths and I was okay. Not this time.
In the subsequent couple of months I had a few more random panic attacks - once on a highway; I had to pull over.
So I went and saw a therapist. I don't think they actually helped reduce the attacks - the frequency dropped with time, together with the fatigue. Now, two years later, I only have the mildest of attacks (and I'm at around 60-70% of energy). But they did help me calm down, gave me tools to deal with an attack when it happens and reduced my stress around the entire experience.
It was definitely money well spent, and as much as I can tell from being my own carer, clinically relevant.
After getting COVID, I went from being an avid coffee connoisseur to getting extreme anxiety from a cup (I've never had anxiety either). I switched to decaf for 2 years before finally incrementally building my tolerance back up. Several colleagues and random people I've met have had similar issues. It goes away over time, but is very real.
I went to a cardiologist and did a stress test. Nothing showed up and eventually it also went away. Note, I was a little stressed from work, but nothing unreasonable. Home situation wasn't too bad either.
however, about ten years ago my general feeling of anxiety suddenly got much worse. I was able to cope with it using all of my usual anxiety coping skills but it seemed kind of off that everything had shifted. I went onto Lexapro, which helped. But then in 2019 or so things really started getting nutty again, where I'd be up all night with panic, often waking me up in the middle of the night, would be up until 5 am, finally fall asleep, then would have another during-sleep panic attack that would last all day.
Turns out I have a node in my thyroid producing thyroid hormone. I now take a very low dose of medication for hyperthyroidism and my panic-esque anxiety levels are kind of lower than they've been for like my entire life (still need the lexapro though, I am sure that my anxiety issues are not strictly the thyroid node).
Basically it sucks to have psychiatric illnesses that are standalone, but also compounded by other non-psychiatric pathologies.
We really need proper diagnostics for this condition, so that people can be diagnosed and not dismissed or even denied benefits and support.
Therapy didn't help but sertraline helped me a lot. I still have no idea what the root cause is, and I've never quite been the same since, especially my energy levels.
However, I am at least functional and can hold down a job!
No, because the only replicated findings are that stress (and infections) are triggers, believing in a physical cause is a perpetuating factor, and multi-disciplinary rehabilitation leads to improvement in about 2/3rds and recovery in about 1/3rd of patients.
You know, doctors told me for years that the pain in my chest and back was all because of my mental illness, even though my brother and mother both needed spinal surgery for Anklysoing Spondylitis by the time they were 60.
They dismissed me till I told them I wanted an MRI of my spine and chest and there it was, Non-radiographic axial spondyloarthritis, the precursor to AS. So not I can treat it so it does not process into AS. They all told me there was " physiological cause to symptoms".
There is a HUGE stigma in medicine against any pain in people with mental illness, it is their best excuse to not even look. That is why there is no progress.
Most diseases have a psychological component, but patients are seldom referred to a psychiatrist for treating their heart ache when they get an infarction.
I just mentioned these findings (and others about autoimmunity against the satellite cells in dorsal root ganglia) to my mum, a doctor specialized in physical therapy and rehab. She went into retirement this year and many patients with ME/CFS.
Her reaction: "So fibromyalgia is real now. I have a hard time believing it… I spent my career fighting it."
That being said, when in doubt, I thin that doctors should trust patients (defendants are presumed innocent, patients should be presumed to be sick).
Stiffing the ill to spite possible asshats is a bad societal bargain.
By all accounts, there is no way to test for or to treat CFS. Assuming it is real, and OPs wife did have it, what is to be done? The doctor ruled everything else out, and now there is nothing more they can do.
Much better to say "I don't know" than to give a confident diagnosis just because you've run out of things to test for.
For diagnosis, there are clear diagnostic criteria, including the presence of post-exertional malaise, which is very easy to recognize simply by talking to the patient. (“I went grocery shopping last week, and I didn’t think I’d overdone it, because I felt okay that afternoon, and I had a full night’s sleep, but I woke up the next day feeling terrible and I could hardly get out of bed all day.”) There is a lab test that can be done for it, but it essentially consists of making the patient “crash” by exercising two days in a row and observing how much worse they are the second day. It’s not recommended for diagnosis because it’s harmful (it can take months to recover from a bad crash) and, again, not necessary.
For treatment, there are a few supplements and prescription drugs that can help each of the symptoms. Many patients experience dysautonomia (it’s in the diagnostic criteria) and there are several treatment options for that (beta blockers, drugs to raise blood pressure, drugs to encourage sodium retention, and others, in addition to non-pharmaceutical options like increasing salt and water intake). The fatigue itself is harder to treat, but a few supplements have been found to help. Cognitive dysfunction is a major problem that is definitely treatable (with ADHD and dementia drugs); that alone is enough reason to get diagnosed and treated.
My wife had an emergency department refuse to treat her because they disagreed with an unrelated diagnosis that was in her medical record. Until she admitted that she was "making it up" and didn't have it, so they could "correct" the record, they would not treat her. She ended up having to leave and go to another hospital.
Depression is a comorbidity of chronic illness. It's hard not to become depressed when dealing with an unexplained illness.
Psychiatric treatment can reduce the contribution of the comorbid depression, which can create a net improvement for these patients.
Too many patients with chronic illness will refuse any psychiatric treatment because they are resistant to the idea, but they end up suffering more than necessary.
When doctors can't identify or treat the core illness, they can at least address comorbidities and work on increasing quality of life. Psychiatric care is at the top of the list for helping people's quality of life in these situations.
Fun fact, the drug Xywav which has been FDA-approved for narcolepsy (and ideopathic hypersomnia) has also been shown in studies to help with fibromyalgia. They even sought FDA approval for that but the FDA rejected it on the grounds that there are too many fibromyalgia patients and therefore the risk of abuse is too high (the drug is related to GHB).
It's heavily published on and widely accepted as valid by neurologists, but that does not make it true.
The concept with FND is that there is no identifiable structural pathology, but that the neural circuits are dysfunctional, and that this can be fixed with things like cognitive behavioural therapy. This is typically framed to the patient as "the hardware is completely OK, there's just a problem with the software." (As most of this audience would recognise there is very little overlap between how brains work and how computers work.)
However, more advanced imaging techniques, such as 7T MRI are now showing structural abnormalities in these patients, which is a pretty fundamental problem for the above hypothesis. An attempt to rationalise this by FND proponents is made here.[2]
A recent example involves a 10yo child who developed a movement disorder following Covid.[3] Typically these would be diagnosed as functional movement disorder [4][5][6] and psychological therapy advised. However this group showed that in fact it was due to a neuroimmune pathology, with auto-antibodies forming that targeted some portion of the basal ganglia. The patient recovered completely with immunosuppression.
[1] https://www.bmj.com/content/325/7378/1449
[2] https://neurosymptoms.org/en/faq-2/can-people-with-fnd-have-...
[3] https://link.springer.com/article/10.1007/s00415-023-11853-5
[4] https://movementdisorders.onlinelibrary.wiley.com/doi/10.100...
[5] https://cp.neurology.org/content/11/5/e686
[6] https://adc.bmj.com/content/106/5/420
And that's ignoring that there is a mechanism normally preventing this. And what happens when you become allergic to your own hormones is called a cytokine storm ... and it's serious enough that you can say comfortably that no doctor will miss it.
Autoimmune reactions may be the longest covid; cell/organ damage is another; it is also possible that people may have less-than clinically detectable viral activity, or viral activity in some "pocket".
I'm not a medical professional, this is not medical advice.
https://www.nih.gov/news-events/nih-research-matters/blood-t...
Taking probiotics and supplements (omega 3, Multivitamins) and aspirin accelerates the process of getting better for me. I use n-back exercises from Brain Age Concentration Training as measure.
Really, even for stuff like people saying "when I get a cold, I always recover faster if <x>" is almost certainly either a placebo effect, or a random opinion that may or may not align with actual medical reality. Because not only does something like "a cold" or "a flu" or "covid" cover many variants rather than being a single identical type of infection, but even if they somehow knew that every time they had been infected by an identical form of a virus there are still so many variables such as how much of the virus initially breached their body, how much sleep they'd had in the lead up to and post- infection, what they'd been eating around the time, etc etc
Which is why we use studies looking at large numbers of people to figure out what does and doesn't help recovery rather than relying on anecdotes.
And in your case it seems like even less data than someone making a judgement based on potentially dozens of colds over their lifetime, it's just one or two data points?
(Although since probiotics and vitamin supplements won't, in typical doses, cause any harm except to your wallet, there's certainly no harm in taking them after a sickness - and even if there isn't a link between them having a physical impact in speeding up recovery, they could still or course work wonders as placebos too!)
Clinical trials and online polls convinced me to try homemade probiotics and multivitamins. I can link them once I'm not busy. No idea if they had any effect but might as well include.
"We aim to find genetic causes of why people become ill with myalgic encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) with our ground-breaking research. Take part from your home"
https://www.decodeme.org.uk/
The cure can only come from personalized medicine, looking at the individual, not looking for a common cause.
https://www.microbe.tv/twiv/twiv-1034/
https://www.science.org/doi/10.1126/scitranslmed.abq1533
It should be authorised as a treatment for ME/CFS and Long Covid in the short term alongside Ablify as sufferers should get to try these and see if they work but they are both very far from a good treatment and do nothing for the core parts of the condition.
There could be a link here, although it is tenuous and purely lay speculation. ER stress is discussed in the article:
>Both S1 and the people with ME/CFS had biochemical signatures of ER stress in their muscles, and treating S1’s cells in a dish with a drug that blocks ER stress lowered WASF3 levels and restored mitochondrial function. On the flipside, using toxins to artificially induce ER stress in cultured cells or in mice caused a rise in WASF3 levels, Hwang says.
LDN has been found to be quite effective in alleviating ER stress specifically in the epithelial barrier in IBD [0], rather than the ER stress - WASF3 levels being investigated in muscle cells in the above article. Certainly worth investigating. And, as noted in the article, the WASF3 angle is merely one potential pathway of the disorder.
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845217/
>Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers.
https://medicine.yale.edu/news-article/potential-new-treatme...
https://www.s4me.info/threads/wasf3-disrupts-mitochondrial-r...
So gut dysbiosis may trigger this very mechanism.
Later learning my body was having an autoimmune inflammatory response to viral activity causing debilitating fatigue.
Took variety of treatments including steroids, anti depressants, supplements … and so on.
When I was 22 I met person on the campus of mizzou who simply showed me some meditative stretches and breathing exercises. The idea was to just slow down and focus on improving your bodies own health where it’s at.
This is a oversimplification but the key for me was to stop thinking this was a virus or disorder or in general things were happening to me .. in which I was a passive unfortunate recipient looking for professionals to help.
Instead I decided from now on I would just try and be a healthier person in mind body and spirit where I was at that moment.
The change of mindset to where it is my responsibility to improve my own well being has paid massive dividends. As a middle man I have no real health issues, no chronic fatigue or reoccuranr high white blood cell accounts indicating and over reactive immune system.
My case will lot insipidity apply to all but if I could impart any wisdom would be just take things into your own hands and be an active person working on improving your own condition whatever it may be.
Change the mindset of shoots this sucks and no treatments work … why is this happening to me… to what are things I can do to improve my existence. Am I a nice person. Am I healthy (weight / exercise).. do I like my job and find it is meaningful…
Sorry if sounds dumb and corny but made a world of difference for me.
For those interested in latest research, Dr. Bhupesh Prusty presented[2] a very plausible hypothesis with detailed evidence[3] of virus-triggered autoimmunity causing mitochondrial dysfunction in endothelial cells (vascular system).
And there's a promising treatment for Long COVID with a study[4] claiming improvement in many symptoms, and describing the targeted mechanism of disease pathology (also vascular system). Needs trials and replication, or until then doctors willing to risk off-label treatment.
[0] https://web.archive.org/web/20230728074923/https://www.theat...
[1] https://web.archive.org/web/20230731145624/https://www.theat...
[2] https://www.youtube.com/watch?v=sBmtnMenHgw
[3] https://www.medrxiv.org/content/10.1101/2023.06.23.23291827v...
[4] https://www.researchsquare.com/article/rs-2697680/v1
The takeaway is that for many (but not all!) Long COVID symptoms naturally get better over time. This is a huge problem for Long COVID treatment studies that don't include a control group because there's no way to tell if the treatment made the patients better any faster than they would have normally healed.
That is, after all, how we learned that stomach ulcers are not psychosomatic (caused by "stress"), but rather by the bacterium H. Pylori. A doctor infected himself, got ulcers, and cured himself with antibiotics!
It is an extremely complicated condition. I personally have had a pet theory that disturbed barrier function is involved somehow, and seeing this article is extremely confirming for me, since it mentions that as a potential factor. In fact, one study on just the metabolites of people with CFS vs healthy people found that a Vitamin E derivative -- one often a part of healthy cell barrier function -- was significantly lacking in CFS people compared to the normal population, and was a strong marker. However, this seems to have been largely brushed over in later literature, with more popular things like fatty acid processing and such being mentioned.
What has worked for me: -- Ketogenic diet (avoiding lactic acid production) -- greatly dampened PEMS. -- Blood glutamate scavengers + Niacinamide + Ribose (1g): Provides NAD + a cofactor needed to transform glutamate in the blood into something else. For some reason, this really seems to help with CFS patients. Helps with resting fatigue. The cheap and accessible BGS I use are NAC, pyruvate, and (sometimes) malic/citric acid. Malic is better as it is right before oxaloacetate, a BGS, in the Krebs cycle, and it turns into Citrate. Citrate IIRC raises the levels of one of the enzymes that eliminates lactic acid. Your blood cells can only use glycogen, so there will always be some level of lactic acid production to be suppressed. -- Reduced glutamate + free glutamate intake: Lower-glutamate proteins (tuna, etc), no hydrolyzed soy protein, yeast extract, etc. -- Gotu Kola (biases the glutamate<->GABA conversion towards glutmate->GABA as I understand, a double-bonus), various anti-inflammatories (Quercetin+non-citrus C, liposomal Turmeric+curcuminoids (!! Important, piperine inhibits both Pgp and glucoronidation, which increases absolutely everything in absorption. Liposomal is better), and boswellia for LOX-5 inhibition. Looking to move to a stronger Boswellia extract (5-Loxin) as it's lighter weight.
These changes, while I still have energy issues, have made it safe enough for me to be able to backpack outdoors for extended periods of time. My longest so far has been a 2 month trip (with 1-2 nights indoors).
Hope this helps anyone who struggles with this and is looking to experiment. I wish I was back to 100%, but being able to be out in nature after being mostly bedbound is...well, my heart is much more full when I am. <3 :')