What an intriguing study this Chilean, Portuguese, Austrian and Canadian study is. The study takes two fascinating factors in ME/CFS – the plasma and the endothelial cells – and ties them together. (The plasma is the liquid portion of our blood through which nutrients, hormones, and proteins travel across the body. It’s a light-yellow color and does not include white or red blood cells or platelets.)
It’s been at least five years since researchers found evidence that something in ME/CFS patients’ plasma was hindering energy production, yet no one has been able to identify this mysterious x-factor. The idea of a mystery factor in the blood might be responsible for well, everything, got more interesting when Goebel last year was able to produce fibromyalgia symptoms in mice by giving them something from the plasma (IgG antibodies) of fibromyalgia patients.
Then there are the endothelial cells. These cells lining the blood vessels are responsible for opening them up to allow for more blood flows and also play a role in inflammation and coagulation, and have received increasing interest in ME/CFS, fibromyalgia, and long COVID. That interest dates back at least to 2000 when disturbed endothelial acetylcholinesterase activity was found.
Three recent studies have found evidence of endothelial cell dysfunction in ME/CFS, and several suggest it is present in FM, and/or long COVID. Bruce Patterson’s long COVID treatment plan, for instance, is focused on preventing immune cells from reacting with the endothelial cells lining the blood vessels.
Getting at the Heart of Post-Infectious Illnesses? Bruce Patterson Talks on Long COVID and ME/CFS/FM
Jeffrey Lubell recently brought another slant to the idea endothelial cell/ blood vessel dysfunction idea when he proposed that leaky blood vessels are literally drowning the tissues near them, causing hypoxia (low oxygen levels) and pain.
Should There be an Increased Focus on Lipedema, the Lymphatic System, and Adipose Tissue Fibrosis in Ehlers-Danlos Syndrome, Fibromyalgia and ME/CFS?
Nitric oxide (NO) – a gas – is the big player here. By releasing NO via the eNOS enyzyme, endothelial cells increase the size of the blood vessels – allowing rich, oxygenated blood to get to the muscles when we exercise, the brain when we think, etc. eNOS production can be enhanced by several different factors, including, interestingly enough, the same G protein-coupled receptors (GPCRs) that some researchers think are getting targeted by autoantibodies in ME/CFS. These GPCRs use substances like histamine, bradykinin, and acetylcholine to promote eNOS production, causing the blood vessels to open.
Nitric oxide does more than open up the blood vessels, however. The authors noted that NO also promotes the production of mitochondria and fatty acid oxidation in the muscles. Given that premenopausal women exhibit higher muscle fatty acid oxidation than men, the authors wondered if problems with NO and associated problems with fatty acid oxidation might help explain why more women than men get ME/CFS. Nitric oxide also protects the endothelial cells from oxidative stress – a known factor in ME/CFS.
The question in the “Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients” study – funded by a 2019 Ramsay Award from the Solve ME Initiative – was whether something in the ME/CFS patients’ plasma was doing a number on the enzyme endothelial nitric oxide synthase (eNOS) that triggers the production of nitric oxide. The international crew of researchers assessed eNOS production in a clever way.
First, they grew or cultured endothelial cells from human umbilical veins and then exposed them to plasma from 11 ME/CFS patients and 12 healthy controls. They measured the cells’ production of eNOS at baseline, and then assessed the ability of the cells to respond to different eNOS boosters.The big question was whether something in the plasma of the ME/CFS patients would inhibit the ability of the endothelial cells to respond to a trigger.
Because the study was most interested in whether autoantibody-associated endothelial dysfunction was occurring, it targeted substances such as histamine, bradykinin and acetylcholine that were likely to be inhibited by GPCR autoantibodies. If GPCR autoantibodies in the ME/CFS patients’ plasma were reducing the production of nitric oxide as suspected, the NO inhibition should show up most readily when they were introduced.
The study, though, found reduced eNOS production across the board: both at baseline and when enhanced with factors like bradykinin, histamine, acetylcholine, and insulin. Whether the endothelial cells were exposed to GPCR-related factors, or insulin, or were not exposed to any factors at all, once the ME/CFS patients’ plasma hit the endothelial cells, their production of nitric oxide tanked. That didn’t mean the GPCR autoantibodies were out as a possible culprit but did suggest something more complex was going on.
Further testing revealed that the signal to produce NO; i.e. eNOS gene expression was, in fact, normal; i.e. the genes designed to produce NO did respond. The fact that eNOS protein levels were normal as well suggested that something “post-translational” found in the plasma was interfering in the step from eNOS to the actual production of NO.
Increased levels of the Thr495 eNOS protein that inactivates eNOS and makes it less likely to interact with calcium suggested that problems with calcium metabolism might be present. That finding indirectly supported Wirth and Scheibenbogen’s novel claim that problems with calcium handling could underlie all of ME/CFS. The authors also suggested that inflammation could be behind the Thr495 eNOS elevations.
The study had a number of limitations. First, it was quite small and needs to be expanded. Second, because it was a laboratory study it may not reflect what’s going on in the body.
- This small study looked at two potentially very important factors in ME/CFS – the endothelial cells in the blood vessels and the potential that a mysterious X-factor in the blood is contributing to ME/CFS.
- The endothelial cells open the blood vessels allowing oxygen and nutrients to flow to the muscles. They also participate in inflammation and mitochondrial energy production.
- Several recent studies and three recent hypotheses have suggested that endothelial cell dysfunction may be happening in ME/CFS. Other studies have suggested the same in FM and long COVID.
- This laboratory study cultured umbilical endothelial cells from healthy people and then exposed them to plasma from people with ME/CFS and healthy controls. It measured the activity of the enzyme (eNOS) that triggers nitric oxide – the main blood vessel vasodilator – at baseline and when eNOS enhancers were added to the plasma.
- The lower eNOS levels at baseline and after enhancement found in the endothelial cells bathed in the plasma from ME/CFS patients suggested that something in the plasma – some mysterious X-factor – was stopping the endothelial cells from dilating properly.
- Because the effect was found across various factors it didn’t appear that the autoantibodies believed to affect the endothelial cells in ME/CFS were solely responsible.
- The fact that eNOS gene expression was normal suggested that the signal to start nitric oxide production did get through – but was inhibited during later stages.
- Increased levels of a protein suggested that problems with calcium metabolism – as Wirth and Scheibenbogen have suggested – may be present.
- Much bigger studies are needed. This unique finding – which linked an x-factor in the blood with endothelial cell dysfunction will hopefully prompt them.
- Large endothelial cell studies seem almost sure to show up in long COVID. The NIH’s decision not to include people with ME/CFS in its long COVID studies will make it more difficult for the kind of definitive studies needed to explore this area to show up but other groups may include both long COVID and ME/CFS patients in their research.
Given this and past study results, it could be affecting the ability to produce energy and move the blood around. Note that we don’t know that a mysterious X-factor exists – there’s simply some evidence that it might. That finding needs to be validated.
Given the recent fibromyalgia plasma study which was able to invoke FM-like symptoms in mice simply by providing them with IgG antibodies from FM patients autoantibodies or other antibodies would seem to be a candidate.
The autoantibodies in question in ME/CFS interact with the same GPCR receptors that help to turn on nitric oxide production. The study, however, found other factors that turn on NO production are also affected – suggesting that the GPCR autoantibodies aren’t the end of the story.
The Endothelial Dysfunction Story in ME/CFS
The idea that something has seriously gone wrong with the blood vessels in ME/CFS has been around at least since 2012 when Newton found evidence of it in both the large and small arteries. With three recently published ME/CFS hypotheses (Fluge et. al.; Wirth and Scheibenbogen; Sfera et. al.), that focus heavily on blood vessel dysfunction that idea has been picking up steam.
Systrom’s invasive exercise studies provided powerful indirect support when they suggested that the blood vessels are leaking either just before they reach the muscles, or after they’ve left the muscles.
A couple of studies have also found direct evidence of endothelial dysfunction, including a recent one that linked disease severity to it. Several more studies have implicated endothelial cell dysfunction in different ways: via miRNA levels, via plasma effect in the lab (this one).
We’ve seen this pattern – in spades – before: studies, most of them small, take stabs at an issue and slowly build up evidence that it’s present – yet with no money to produce definite large studies no conclusions are reached. With three hypotheses showing up in ME/CFS, with this study adding the mysterious X-factor to the equation, and with studies implicating endothelial dysfunction in long COVID as well, this time it feels a bit different.
In a best-case scenario, studies like this would trigger large-scale investigations into both the X-factor and endothelial functioning- and perhaps kill two birds with one stone. The NIH-funded ME/CFS research centers may be our best hope for large, definitive blood vessel studies. Thus far, the centers have been focusing on other matters but the next generation of centers may decide to probe this emerging topic. Let’s hope the NIH really gets with the program – recognizes that ME/CFS’s time has come – and finally supports them with robust levels of funding.
Large endothelial long-COVID studies seem almost certain to come and they provide a superb opportunity to study long COVID and ME/CFS side by side. Since the NIH has decided that it will not allow people with ME/CFS to participate in its Congressionally funded long COVID research studies, we’ll have to look to other groups to include ME/CFS patients in their long COVID research efforts.
Thank you Cort. As a mecfs and fibromyalgia sufferer I believe there is something to this and I hope research in this area increases.
Thanks Cort, excellent reporting as per usual. A question please? I had a neuroopthalmologist mention Flammer Syndrome as a possibility which is also found in MS. From my understanding, overproduction of endothelin 1 looks to be an issue. Have you come across anything in ME that suggests our blood vessel constriction is the same?
Overproduction of ET-1 has been found in FM twice (https://pubmed.ncbi.nlm.nih.gov/28901422/) but a 2004 study did not find it in ME/CFS.(https://pubmed.ncbi.nlm.nih.gov/14739476/)
Another possibility may relate to autoantibodies against the ET1 receptor – which may increase (or decrease) ET1 effects. These autoantibodies apparently do play a role in ME/CFS:
(and could possibly be related to the “factor X”) 😉
Increasing NO has helped me, through using Kuvan (BH4), Berkeley Life or Humann Nitric Oxide Boosters, or citrulline or ornithine.
which do you think helped the most? Thanks.
That’s interesting. I heard about BH4 for fibromyalgia and CFS. How do you get Kuvan? I thought that was a prescription drug that’s very expensive and I don’t even know if it’s available here in the US. I think you have to be diagnosed with PKU. Please update me if I am wrong about that. But perhaps you are referring to nitric oxide booster suppliments through Berkeley Life and Human that contain citrulline or ornithine. Is that what you mean? If so, may I ask what is your favorite over the counter suppliment for the price and effectiveness to increase energy. Does it help with other symptoms? I tried to look for BH4 suppliments but can’t find any but I am very tired this morning, so I will check again when I feel more alert. I am sorta on a strict budget to be honest. But I would like to try it if it helps with energy. My energy levels are beyond pathetic since the pandemic. It just took me 2 weeks to clean my home. Now I want to sleep for an entire month. Thank you, Lil
My favorite energy supplement is NMN. But Kuvan, which is available from 7 mail order specialty pharmacies in the US, really helps me too. I had high phenylalanine and low tyrosine on a plasma amino acids panel which convinced my insurance to pay for it. I don’t have the main PKU mutations, but I do have fairly common mutations on 2 genes, one involved in producing BH4 and one in recycling it. It’s milder than full blown PKU so I only need 1/5 if the typical Kuvan dose, making it cheaper. And, it went generic recently, so price would be dropping. I know of a couple of researchers who think BH4 is significant.
I so understand .. email if you need a friend.,,I do.
But it’s confusing for me cause people with CFS and Fibromyalgia are suppose to have elevated nitric oxide levels usually and if you have too much of NO, viruses can get turned on such as Herpes HHV6 and Epstein Barr I read. So that would contraindicate using it I would think. It’s complicated, I’m confused by the complex NO/ONOO cycle.
Hi, I hope you don’t mind me asking a question. My husband was diagnosed with ME/CFS two years ago; he has been ill for three years. We are in the UK, he’s 52. He is very weak now. I spend a lot of time researching as it’s so harrowing to watch him suffer so much and for our two children to see him. He had Hodgkins Lymphoma 17 years ago and he then developed RRP – growths on his vocal cords from a virus – he’s had 17 operations to date. Our children are adopted. His mental and physical health is awful now.
I bought the 23andme DNA test, which took a few months to come back. Well, it is very interesting as just found out he has one gene mutation variant for PKU (his father was half-Irish). I have read that you can’t have PKU with just one variant but I have read a couple of studies that say you can have ‘Compound Heterzygous’. Not 100% sure of the meaning, but I think it’s possible you can have PKU with just one variant if this is present? Please excuse my ignorance. Another reason this is interesting is because my husband’s father developed headaches, fatigue and had seizures from 50; then gradually dementia. He was misdiagnosed with Epilepsy for years then changed to TIAs; they never seemed to work out what was wrong. He was in a residential home at 60; couldn’t speak and hardly walk – he died aged 74 in the home.
I have bought a home test for amino acid panel but my husband hasn’t the energy to do it at the moment. My question is, do you think it’s possible this condition could be misdiagnosed as ME/CFS? And, could it be adult-onset? He has had so many horrible illnesses, I can’t believe that they are not somehow all connected with a genetic origin. Here in the UK it’s very difficult to find a doctor who will listen or look at things outside of the box.
Thank you very much…..great to hear these things have made a difference.
“GPCR autoantibodies aren’t the end of the story” oh god. Opened up a can of worms. Waiting for another lengthy comment from Herbert Renz-Polster about a 20k€ per Infusion BC007 that didnt help Cfs cases and only helped some long covid patient. Some of them got even worse as the baseline 2 months later. Plus, their study about using BC007 for GPCR antibodies in heart diseases just casually feel under the rug. Nothing ever published. Despite being done for years. Just hide it to collect more money for other diseases where we can test it again for no avail.
But the article is very nice. Good infos about “something in the blood” where Ron just stoped and throw his hands in the air. Because using a filter system to find what it could be wrong wasnt an option.
I love that long covid brings so much good studies on the way. They coming closer every day. Blood vessel must be a key player. NO production still happens. Because when you use shear forces on your skin. It still gets red. It means they just wont release it on their own anymore. Sadly no one really studies sfn of the vascular system. Only always from the skin. Cfs is probably a case of sfn of the vascular system. Meaning the body isnt able anymore to open or close the blood vessel to the bodies needs aka no desperately NO production. No NO production als stiffens red blood cells. Also a key marker for cfs studies in the recent years.
I suspect your right.
I’ve started using transdermal magnesium ( supported by bit c and potassium). Magnesium helps generate no. My blood pressure drops from high to normal in seconds and stays that way for a few hours then I need to repeat
@badpack I’d love to know what’s your issue with BC007 research?
„GPCR autoantibodies aren’t the end of the story“
Of course that’s true. Much research needs to be done. But as you might know, BC007 doesn’t only eliminate functional auto-antibodies… from what we know yet, it seems this medication also repairs blood cells and microcirculation and works as a strong antiviral. Altogether it’s a promising medication and could be an important piece oft he puzzle and pretty soon available.
„20k€ per Infusion BC007“
Not sure if you know any details about aptamers? It’s a synthetic compound, which is very easy and CHEAP to produce… Furthermore it’s very stable and can be stored at room temperature for years. It will be a very cheap medication, compared to other ones…
„that didnt help Cfs cases and only helped some long covid patient.“
That’s simply not true. They treated only FOUR LCS-patients until today… No persons with ME/CFS has been treated yet without having a covid infection before… One of the LCS patients had ME/CFS as a result of the covid infection and her condition improved in a drastic way, so that they spoke of a „cure….
Look at the statement of berlincures and University of Erlangen:
„In four patients treated with BC 007 under compassionate use conditions at the University of Erlangen with the intention to neutralize these autoantibodies, an enormous remission of LCS could be achieved in a short time, so that one could speak of a cure.“
If you know better than the ppl who worked with this new kind of medication, it would be kind to share your reliable sources with us.
„Some of them got even worse as the baseline 2 months later.“
Again that’s funny cause i just watched a video recently with a PhD from university of Erlangen. He described the experiments with BC007 with these 4 patients… and he gave an update on their health… according to what he said, these persons are still fully healthy, 4-6 months after their treatment with BC007. Also the one who had ME/CFS as a result of covid… who came to the treatment in a wheelchair, not able to follow a conversation, not able to read a book, not able to walk… and now working again, able to hike, able to read books…. According to what he said, she came back to the university in high heels with a smile on her face and expressed her gratitude to the ppl who treated her. How about that?
„Plus, their study about using BC007 for GPCR antibodies in heart diseases just casually feel under the rug. Nothing ever published.“
That’s again simply not true. The studies about BC007 for cardiomyopathy are still going on. You can find the results of their phase I study online. The phase IIa study will be finished end of 2022 and phase IIIa/b study will follow and they plan to finish it end of 2023 / beginning of 2024.
For Long Covid they have a totally different timeline… With an emergency approval after their phase II-study, the medication could be available much more quickly… maybe in 1-2 years, if everything goes on smoothly…
Furthermore the government of the German state Bavaria plans to fund the study for BC007 and ME/CFS. They made their decision just 2 days ago. It just needs to be confirmed when they meet end of march / beginning of april. This would be the first time, that ppl with ME/CFS who never had covid could be treated with BC007.
Maybe the scientists of the University Erlangen, Berlincures and the patients are wrong and you know better. In this case please share your reliable sources with us before you try to bury the hopes of so many ppl. Tks!
Yea, not interested in arguing with you if you dont even know the basics and how much of this aptamere is needed and know that they themself said its 20k per Infusion.
@badpack: Yes at the present time it is of course still expensive to produce in small batches for small studies… but not if it can be produced in large quantities. That’s pretty normal for any kind of new medication, isn’t it? Especially when we talk about a completely new class of drugs…
however, this is currently irrelevant, as it is not available except for studies anyway and these studies are state-funded. Why does the current production price bother you, does not really open up to me… it’s foreseeable that the final production price will be affordable in the future… That’s what matters IMO
and of course you are not interested in arguing cause what you said is simply not true… that’s certainly the easiest way… saying something obviously wrong and then not being interested in “arguing” due to pretended reasons. I already saw that coming.
btw I am also not interested in “arguing”. There’s also the option to discuss it on a factual level instead, which I prefer at all times.
Thank you I hope we can get our hands on a treatment soon….
It has actually been tried in a non Covid ME-CFS Patient but data was not published. The person is from Germany and gave reports about her progress.
Also one of the german LC patients reported relapse in the patient community he is in.
No officia data however.
tks for the feedback. It’s hard to verify information like that… “I heard that a person I don’t know said this and reported that”…
but even if that person had a relapse after several months, it could still be treatable… in this case we’d have to get an IV every few months to live more or less symptom-free… which I personally could live with.
whatsoever… i think it’s best to wait for official information and not rely on “chinese whispers”
Its not that hard if you know one of those persons personally.
For the other one I cant vouch.
I did some research about the LCS patient and i learned that he relapsed 3 after 3 months… i consider this a great success. Of course it must be frustrating for that guy but he should try to relax now and wait for the approval of the drug, that already made him symptom free in the past.
@BC007: Of course that’s a whole different story if you know one of the ME/CFS patients in person. In this case i have to apologize… but there are so many fake stories on the internet, sometimes it’s difficult to distinguish…
Would you mind to share some key data with us? Maybe things like age, how long he/she is sick with ME/CFS, which auto-antibodies have been tested positive? Did BC007 help to a certain degree or no success at all?
It would be great to hear some more details from somebody who really knows something first-hand about these tests.
Many tks in advance. Appreciate it.
I totally agree – studies of small fiber neuropathy of the vascular system would be superb. I wonder if it’s possible to do that?
supposedly, by looking at the back of the eye, some cases of sfn can be suggested
eye doctor explained to me that their machine can check for sfn, but that it did not have the correct algorithms in machine to do it there.
Inflamed endothelium seems to be very much a part of my POTS hypovolemia. I started taking Ivermectin (IVM) this year and within a week my POTS improved at least 50%. Nothing at all had improved my case over the past 30 years. My doc was amazed that I can now shop by foot, without using electric scooters and I no longer need Midodrine 4-10 grams of sodium a day with a gallon of liquid to avoid brain fog. IVM has amazing anti-inflammatory properties. It even resolved my intractable shoulder and ischial bursitis pain which was horrendous. Good stuff. They should research it more thoroughly although I know of at least 75 studies already done into it’s efficacy and safety.
I did not know that IVM is anti-inflammatory. But now I realize that since I started taking it, my knees have been better. Actually, I’ve also not needed the heavy doses of anti-viral herbs that I was dependent on—once every few days is enough to keep me well. I suspect IVM is anti-viral for more than just Covid. A little Covid miracle ; )
Curious to know what dose of Ivermectin helped your Pots?
I take 15mg every 5 days. My POTS and bursitis showed improvement by the second day. It is not an overstatement that it totally gave me my life back.
please, please tell me what dose has been effective for you? I am so sensitive to meds 🙄
A while ago I started feeling better after I started drinking pomegranate juice every day. I later convinced myself it was a coincidence even though the effect was significant and lasted for a long time. I read that pomegranate influences nitric oxide. Might go back to the pomegranate juice or look into other things that increase NO.
Thanks, a nutritious thing to try 🙂
Pomegranate is the only supplement that helps with fatigue for me. I drink a concentrated form by Jarrow mixed with water. Regular pomegranate juice has soooo much sugar. I also have capsules when for when I am on the go. I get the capsules from Puritan’s pride.
Does this mean that cleaning the blood is an option?
It would suggest it’s a possibility.
Niacin — which is required for the krebs cycle — to produce energy — is also required for healthy endothelial function.
Which ties in with Navieax’s (sp) study that found NADPH (from niacin) was the main player in all sorts of metabolic abnormalities, but that of course other vitamins, minerals — and stressors, etc — were involved as well.
Hey Cort and others,
First thanks for another great update. About twenty years ago a doctor in New Zealand was analyzing his CFS patients blood and found they had large misshapen red blood cells. I sent him my blood, and sure enough I had the same thing. This could certainly impair a lot microcirculation functions. Has anyone else heard about this? Dr. Simpson, of who which I referred retired a long time ago. He had no answers.
Yes I’m in NZ and that Dr Les Simpson was very strong on his findings that we had misshappen blood cells. He talked about sticky blood. It was way back 1984. It is reported in the Irish Times,Mar 6 1997.He got involved as a professor at Otago University around in the time when lots of people got ME/CFS called the Tapanui Flu, as Tapanui was where they all got it. A bit like the Tahoe group. It was later felt that they all had got a gut infection, perhaps giardia. I think that others have talked about mis-shappen blood.
Yes, this begs a (seemingly) simple enough experiment: using enough transfused blood to completely exchange old blood for new, test whether people with CFS/ME show significant improvements across different metrics. Perhaps several key questions could be answered quite cheaply.
Apheresis, BC007 and something else all, if I have them right – it’s a little confusing, do something like this by filtering some components of the blood out.
About 10 years ago I was the victim of a stabbing and lost about as much blood as I could lose and still live. There was no permanent damage and I was up and about in a few days (although with a limp for a while). A friend invited me to go for a walk and when he suggested the distance I said there was no way I could possibly walk that far he suggested we start out and see how far we get. Well we ended up going even further than he suggested and I felt no fatigue after. If I remember correctly the elevated energy level last for a week or two and then I gradually returned to my regular low ME/CFS level. I think it was the transfusions that were responsible for the big increase in my energy but when I told my doctor of course he said it was just a happy to be alive feeling. I’m sure it wasn’t.
A happy to be alive feeling! Oh my god – you get stabbed and you feel better as you’re recovering from an almost deadly stab wound – and he thinks it’s a happy to be alive feeling. Now, how logical is that? I imagine the normal response is to a) be depleted – you could have died b) and freaked out because you were STABBED…
i think rbc’s live for 5 to 7 days
When I was diagnosed in 1984, I was put on an experimental non-anti-coagulant form of heparin obtained from Germany under an orphan drug application. I was also put on transfer factor shots (which are no longer available in the U.S.) Among my early symptoms were horrendous headaches. A shot of heparin would knock them out. I have always been convinced that my original doctor who was doing research with a doctor of immunology from our local university knew a lot more about what this is than he was saying. I believe that my case and many others were a combination of exposure to HHV6A and in my case a pesticide treatment for fleas in our home.
Currently I take low-dose aspirin and Nexavir (a derivative of pig liver) that is available in cream form directly from the manufacturer. Nexavir is listed as an immune modulator on the HHV6 Foundation website.
Dr. Holtorf apparently still uses heparin in some patients.
Wow, Nexavir! I have been trying to figure out where to obtain this drug. Would you be able to share where you get it from? I was under the impression it was no longer available.
Moshe, you can order Nexavir cream without a prescription directly from the manufacturer. The injectable form requires an RX. Contact them at NEXCO%nexco-pharma.com I use the cream. It was recommended for me by the late Dr. Paul Cheney.
Sorry for the typo. The email to order Nexavir is NEXCO@nexco-pharma.com
Thank you, Betty!!
What were you diagnosed with?
CEBV Syndrome wasn’t coined until 1985, “CFS” in 1988.
Erik, you are correct. My original diagnosis was immune deficiency and chronic encephalopathy. I was one of a number of patients who had immune parameters almost as bad as HIV, but were HIV negative. Evidently the CDC monitored a number of patients with this kind of immune profile.
Oh wow! I haven’t heard anyone talking about Nexavir in so long.
I just want to add to the discussion that I have needed massive amounts of calcium ever since getting ME/CFS. If I hadn’t figured that out I would have slept very little and lost many teeth!
what do you take to keep calcium levels up, if okay to ask?
I took arginine once, which increases NO in the body. I could immediately feel an increase in energy, but it also made my orthostatic intolerance worse as it relaxes the blood vessels. Is there any work around for this? I’m guessing increasing NO through supplements might help those who don’t have much POTS/OI.
Arginine is tricky with HSV-1 and HSV-2, as it will increase the viral load of those two herpes and lead to outbreaks.
I tried arginine many years ago and felt better for the first few weeks before my fatigue worsened. I have high antibody counts to HSV-1, CMV, EBV, and HHV-6, so supplementing with arginine is probably a bad idea. The herpes viruses need arginine to replicate.
Oh! Didn’t know that.. Thanks for the warning!
Look up research on Bartonella infection; it infects endothelial cells and blood vessels. There’s a big clue there!
Yah, we often forget about Bartonella! Thanks.
I’m 73 and have had fibromyalgia for at least thirty-five years. In May I had hip replacement surgery. During the surgery my blood pressure dropped to 50/30, and I was given adrenaline to increase it. After the surgery the doctor said I had very little bleeding during the operation. I wonder if other FM patients have had a similar experience.
HI Karen, some passed this on for you.
For Karen, the 74 year old, having blood pressure dropped during hip replacement, comment on last x-faxtor study bij Cort.
Please try to get your blood volume checked. Has to be chromium 51 or Daxor. Testing hematocrit is useless. Try this simple test:
Put one hand on your ear, loosely, elbow pointing forward (above the heart), the other hand relaxed pointing to the floor. Do that for one minute, then put both hands on your legs and count how many seconds it takes to get them to the same colour. Doesn’t have to be precise in seconds, but it might help you convince your doctor to get you tested. In healthy people it takes only 10 seconds. The doctor can be the, hopefully, healthy control.
My hands need 90 seconds.
Please try, I wish Karen the best(test).
This New York Times article on exercise intolerance in Long Covid patients seems relevant to Cort’s post.
The parallels between ME/CFS and Long Covid are disturbing and not getting enough attention by the research community.
Great article! Thanks for linking to that. Everyone who goes to that article (and especially comments on it) helps our cause by supporting the NYT in producing more articles like that.
I agree Betty. Maybe NOW, with the increase in Patients with Long Covid complaining we ME/CFS patients with stop being told, ” There is nothing we can do about it”, “live with it”.
Cort, I’m also curious as to why pheresis hasn’t been tried to test the blood theory. If ME/CFS people feel better for several days afterwards, isn’t that indicative of something going on in the blood? Women who develop postpartum myasthenia gravis improve with pheresis, sometimes dramatically, by removing the AChR antibodies via pheresis. Seems like it’s worth trying.
Before I got sick several decades ago, I regularly gave blood as an O neg donor. I tried plasma donation once but didn’t like the hassle of the two-hour sessions. But if I knew doing pheresis every week or two would give me back my energy and reduce the pain, I’d go for it.
1. I hv been on Warafin a blood thinner
For an unrelated heart value surgery
And on EFA’s
My platelets are also borderline low
My Fibro (had it and CFS for 30+ years) has been much improved since being on blood thinner FWIW
As a coincidence I have had a recent flare up of a new painful foot syndrome feeling very cold and painful. Ruled out arthritis and raynaunds and Natro and I finally decided it was a type of neuropathy (non diabetic) and I said it seems to have something to do with my blood vessels
My core body temp had also dropped from 36.7 ave to 35.8
I tried ALA 600 mg 2x a day
And went back on a very small dose of special T4/T3 thyroid (even though my thyroid numbers are normal)
After 2 weeks of intense suffer
Brgh… 35.8C is cold.
Dose thyroid to your temps and pulse, to your symptoms
read Broda Barnes, Kenneth Blanchard, Ray Peat etc
Why keep suffering?
Suffering my syndrome disappeared
And my core temp went back up to normal
I can now walk without throbbing pain and feet are no longer ice cold.
Crazy illness we hv thx for reading
Btw I also suffer from severe complex migraines hemipalegic recently diagnosed and wonder if many of my CFS friends slso hv chronic migraine conditions TGE overlap is very very obvious too me especially how sodium and magnesium help migraine sufferers so much and how recent research shows migraines affect the sodium potassium gate channels and the msg calcium one as well TGE research says during a migraine the potassium floods TGE brain causing either hyper excitability of neutrons or depression. My potassium is always borderline high and sodium always borderline low regardless how much salt water I drink or limit potassium intake Finslly when I get high BP it actually goes down when treated with salt (opposite of norm) Dr Bell found this as well Namaste
This study appears to provide evidence of high oxidative and nitrosative stress (ONS). If BH4 is oxidized by ME/CFS plasma and uncouples from eNOS it wouldn’t be surprising that eNOS activity is inhibited in ME/CFS plasma.
The potential causes of high ONS are too many and varied to list, and with Martin Pall’s NO ONOO theory you don’t even need an ongoing source of ONS, just an initial hit and run that starts a vicious cycle.
It seems like a portion of every group of people who experience a significant illness (including covid) or chemical exposure (including chemo, pyridostigmine bromide) go onto develop long-term debilitating fatigue of varying degrees. If high ONS is the thread that unites all of these different conditions, perhaps our individual genetic polymorphisms / weak points then determine illness severity, ranging from barely affected to severely ill.
I still really like Ron Davis and Robert Phair’s metabolic trap theory. Something must make a percentage of people get “stuck” following a bodily assault.
What if this X factor
(which has been sighted in POTS and FMS too, and perhaps more – I can-t remember)
Is something that is right there
staring back at the faces of the researchers
Without them taking notice
Because it is not something they have traditionally thought could be problematic
NEFAs have been measured high
No one is thinking/writing about that
(being an issue, x factor or not)…
This report on relief of MCAS symptoms in long Covid may have relevance to ME/CFS treatment.
HI Betty, the link to the report you posted isn’t taking me to a report? Do you know the title and author or where it might be online? Thank you
On the subject of mast cells and histamine:
“Vitamin D contributes to mast cell stabilization”
Conclusions: The data demonstrate that VitD is required to maintain the stability of mast cells. The deficiency of VitD results in mast cell activation.”
“Vitamin D supplements really do reduce risk of autoimmune disease”
Have you reqd the studies coming out on vitamin D deff an corelation with severe infections of covid / covid fatalities?
There is vast literature on vitamin D and the myriad effects on health a defficiency has. Also on what good levels are, i.e. the range is set too low.
Also, Betty – have you tried eating liver weekly or more as needed, instead of the gel?
Try this link:
I googled the url string in Betty’s last comment and came up with this – which may be the article Treesha was asking about:
“Case Report: Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection”
I may have to check this out. I know that even just a quarter tab of Gravol (the antihistamine in question if I’m not mistaken) really helps me sleep. I don’t want to take it often as it can affect memory, but if I get even a slightly positive response it might be worth it.
Dr Kevin Lee highlighted this article by Wirth, Scheibenbogen and Paul on Twitter.
It’s called ‘An attempt to explain the neurological symptoms of Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome’. Published on 22nd November 2021.
There is accumulating evidence of endothelial dysfunction, muscle and cerebral hypoperfusion in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). In this paper we deduce the pathomechanisms resulting in central nervous pathology and the myriad of neurocognitive symptoms.’
Not everyone suffers from the fact that the blood ‘vessels are too narrow for the muscles’. Many suffer the opposite, a lack of vasoconstriction in legs that give a low blood pressure (pots). One should also have a hypothesis that something is missing, not just blocking in serum.
Yes, indeed – some people with too lax blood vessels – which would cause the same problem.
Nice idea – something is missing. Let’s hope it’s not that – that would be harder to find I would think.
Interesting, although far from fully developed, new research on Transforming Growth Factor B, circadian rhythms, and ME/CFS:
I’m wondering if the above research can somehow be reconciled with Prof. Martin Pall’s theory – the nitric oxide hypothesis – that postulates that we have too high levels of nitric oxide, leading to the generation of peroxynitrite, causing oxidative stress. https://me-pedia.org/wiki/Nitric_oxide_hypothesis
I was wondering the same thing, George! I left a similar comment below – there were multiple studies in 2003/4 showing excess NO.
Any news on Bupesh Prusthy’s “something in the blood” research? I think he claimed to have identified what that something is a while ago, but haven’t heard anything since… Soooo frustrating when years and years go by and findings like this isn’t followed up on..!
Things take a long time in the poorly funded ME/CFS world. Let’s hope that long COVID excites interest in ME/CFS and improves funding as well and researchers can explore these exciting possibilities more quickly.
When I saw these new studies that perhaps we have reduced production of NO, I was confused because I thought I remembered earlier studies showing too MUCH NO in ME/CFS patients. I looked back through my notes, and there were numerous studies in 2003-04 time period (and perhaps others), showing that people with ME/CFS had EXCESS NO.
Have you had a chance yet to look into these discrepancies? I know these latest studies were in vitro and of small scale, but I found it odd that the results were opposite of earlier studies …. though perhaps I just don’t understand all the details of how these systems work.
Thanks once again for working so hard and doing such a great job at translating complex research into understandable articles for all of us!
Can you provide the references for the studies showing elevated NO in ME patients? I’m only aware of one study that measured NO directly, and it was not a very powerful study.
It’s possible that while eNOS derived NO from epithelial cells is low, iNOS derived NO could be elevated in other cells/tissues.
I independently came to the conclusion that vasoconstriction was playing a large part in my symptoms.
I checked my saliva levels of N.O. and found they were consistently depleted.
This would conform to Martin Pall’s theory of Enos uncoupling.
I wondered if eNos independent ways of increasing N.O. would get round this and sent Martin an email asking for his opinion.
Unfortunately, he hasn’t so far replied.