One of the things I enjoy about the TLC podcast (The TLC Sessions – Living with Long COVID ) from Noreen Jameel and Emily Kate Stephens (besides their English accents) is the short bit in the beginning of their podcasts where they discuss what’s going on with them.
There’s something about hearing about the trials and tribulations (and occasional successes) of people with long COVID (them), or any of these diseases, that is surprisingly relieving and heartening. Color changes in the toes, horrific crashes, hair falling out, heart palpitations, pain everywhere, etc. The need for a “shitometer” to measure how bad it was was reminiscent of the “small old shitty baseline” (SOSB) term coined in ME/CFS years ago.
You could tell that something was up with one of them – she was just a little slower – and it turned out that she had overdone it and was in a great deal of pain. How easy it is to relate to relate to that.
The Klimas Interview
Listen to Geoff’s narration
THE GIST
THE BLOG
How nice that they reached out to Dr. Nancy Klimas – a longtime chronic fatigue syndrome (ME/CFS) doctor and researcher. Dr. Klimas, a clinical immunologist, has been jabbing away at chronic fatigue syndrome (ME/CFS) since it came on the scene decades ago, and the Institute for Neuro-Immune Medicine she runs at Nova Southeastern University in Florida is one of the few large centers dedicated to understanding and treating ME/CFS and other complex, chronic diseases. Besides ME/CFS, Dr. Klimas has done an enormous amount of research on Gulf War Illness (GWI) and is now in the midst of a large long-COVID study. Her computational modeling program that uses supercomputers to understand ME/CFS and find precise treatments for it is, to my knowledge, unique in the country.
Dr. Klimas’s big team
THE GIST
- Check out Geoff’s narration of the GIST below the introduction.
- The Living with Long COVID (TLC) podcasts features two women with long COVID talking about their experiences and talking with researchers and doctors Recentlly they had on Dr. Nancy Klimas – a clinical immunologist and longtime ME/CFS doctor who runs the Institute for Neuroimmune Medicine at NovaSoutheastern University.
- Dr. Klimas is coming at these diseases from a neuroinflammatory perspective. She described the five horsemen of these diseases as immunology, inflammation and neuroinflammation, energy production, oxidative stress, and perfusion (blood flows). Each of these facets of ME/CFS has made big strides recently.
- Jarred Younger thinks that the neuroinflammation will become a done deal over the next year. Evidence of increased oxidative stress has been found in a dazzling array of tissues and compartments including the muscles, the blood, metabolites, red blood cells, plasma, lipids, and lastly, and perhaps most importantly, in Shungu’s series of NIH-funded studies – the brain. Evidence of impaired energy production has been found in T-, B-, and natural killer cells, in numerous metabolomic studies, the muscles, the mitochondria, and during numerous exercise studies. Dramatically reduced blood flows to the brain have been found.
- For Dr. Klimas, it all – the reduced blood flows, the high energy needs, the oxidative stress, and the inflammation – shows up most prominently in the brain and that’s where she focuses much of her treatment focus.
- Dr. Klimas talked about putting the pieces together to make a quilt which she’s been trying to do by using supercomputers to model the system interactions occurring in these diseases. She sees a bunch of highly connected systems (neuroendocrine, immune, and autonomic nervous systems) that are interacting together to hold ME/CFS/FM/GWI and long-COVID patients in their stuck place. Her goal is to bring the systems of people with ME/CFS, long COVID, Gulf War Illness, etc. back into “homeostasis”; i.e. back into their happy place.
- Using computational analyses Klimas’s team developed a new treatment approach – a two-stage effort involving etanercept (neuroinflammation) and mifepristone (reset HPA axis) – that’s being tested in GWI and will be tested in ME/CFS.
- The first major factor she goes after is oxidative stress. She believes high levels of oxidative stress are hampering energy production. You can’t fight the oxidative stress in these diseases simply by giving people handfuls of antioxidants, you have to use right antioxidants, and for Dr. Klimas that means antioxidants that can get across the blood-brain barrier and get at Dr. Klimas’s main target – neuroinflammation; i.e. inflammation in the brain.
- Quercetin and luteolin are two nice options: they’re strong antioxidants and mast cell stabilizers that can get into the brain. NAC is an antioxidant that can get into the brain as well. (Shungu’s ME/CFS study showed that NAC can reduce oxidative stress in the brain.) Dr. Klimas also recommended a supplement called D-Hist, NeuroProtek.
- The talk then turned to a small T-cell exhaustion paper by a T-cell expert named Liisa Selin, in which Dr. Selin and Dr. Klimas found “severe deficiencies” in the ability of T-cells to produce cytokines like IFN-γ and TNFα that play a major role in pathogen suppression. Dr. Klimas noted that the T-cells are probably becoming worn out from being activated at all times and that the T-cells found in ME/CFS are reminiscent of “early aging”. A T-cell of a 40-year-old with ME/CFS might look more like that of a healthy 80-year-old.
- The paper also provided preliminary evidence that a nebulized anti-oxidant, anti-pathogen product called Inspiritol may be able to reduce T-cell exhaustion and improve symptoms in ME/CFS. (A Stanford researcher, interestingly enough, found that oxidative stress – as Dr. Klimas – was exhausting T-cells as well.).
- When asked about low-dose naltrexone, she said, the studies showed that it was “a little bit better” than the FDA-approved drugs for fibromyalgia but was a lot safer, and her clinical experience is that it helps most people. They start at 1.5 mg and then go up to 3 mg and then up to 4.5mg. (It wasn’t mentioned in the podcast, but Jarred Younger appears confident that he’ll be able to get a trial of a potentially more powerful form of LDN called dextronaltrexone going later this year. (see video in blog).
- When asked about amytriptyline, Dr. Klimas called it a “messy, old-fashioned drug with a tremendous history” that’s about 100 years old. At a low dose, “it’s pretty good with pain”, is a “pretty decent antihistamine” and is an anticholinergic that can help with dysautonomia. Using it for too long might increase the risk for dementia or cognitive defects, though, and she’ll use it for a while to get things under control (even up to a few years), but that’s about it.
- When it came to viral reactivation Dr. Klimas reported that HHV-6 is the most common kind of herpesvirus reactivation she sees. Lastly, Dr. Klimas talked about the incredible monoclonal antibody cases series that she, Dr. Pepe, and others wrote up about that demonstrated how they quickly sent three long-term long-COVID patients into remission. She is about to begin a clinical trial.
- A “What’s Up Doc” talk with Dr. Klimas is coming up. Register for Dr. Klimas’s Institute of Neuroimmune Conference on May 10th on the Institute’s Events page. Listen to the Institute of Neuroimmune Medicine’s “Hope and Help for Fatigue and Chronic Illness” podcasts.
ME/CFS still doesn’t get much respect, though. The RECOVER project, for instance, doesn’t appear to have listened to our experts much, and a good deal of long-COVID research has been reinventing a wheel that was formed over the decades in ME/CFS. Research funding is still in the pits. It’s clear that in the medical community’s eyes, long COVID is where the action is. It’s certainly where the money is. ME/CFS is still the odd man out.
I didn’t realize until I listened to the podcast how much I yearn for ME/CFS to achieve the kind of legitimacy it deserves. I fully know how good Nancy Klimas is – she’s been an uncommonly articulate representative of this field for decades – but what surprised me was the feeling of pride that swelled up at how well she represented us in the long-COVID space. One of them called her a “powerhouse’, and she was.
The Talk
Please note that this “overview” contains some information not included in the talk and may not reflect Dr. Klimas’s views.
Dr. Klimas laid out an interesting approach to ME/CFS and long COVID. A clinical immunologist, she first and foremost, is coming at these diseases from a neuroinflammatory perspective. She described the five horsemen of these diseases are the immunology, inflammation and neuroinflammation, energy production, oxidative stress, and perfusion (blood flows).
It’s interesting, looking at them, to see how our conception of these diseases has changed over time. The immune system has always been a big deal in ME/CFS research, but it’s only been in the past couple of years that it’s become pretty clear that neuroinflammation, problems with energy production, and the blood vessels are alive and kicking in this disease. Slowly but surely we’ve gained ground.
Next, a brief look at where we are with these “five horsemen”.
Neuroinflammation
Jarred Younger believes that over the next year the neuroinflammation finding will be a done deal in ME/CFS.
The small 2014 Watanabe study provided the first direct evidence of neuroinflammation in ME/CFS. Since then, a meta-analysis highlighted the “neuroinflammatory features” found in ME/CFS. Rather remarkably, ME/CFS and Gulf War Illness (GWI) showed up next to neurodegenerative diseases like Parkinson’s, Alzheimer’s, etc. in a review of neuroinflammatory disorders. The authors of the paper did not pull their punches when they remarked on “the unbearable physical and mental fatigue can remain in the ME/CFS patients for decades.”
At least three studies have found neuroinflammation in fibromyalgia and multiple studies have done so in GWI. With new studies coming out over the next year, Jarred Younger believes that neuroinflammation will soon be widely accepted in these diseases.
Given the increasing interest in treating neuroinflammation in neurodegenerative diseases, recognizing that these are neuroinflammatory diseases should open up more treatment options over time. The neuroinflammatory review paper offered up polyphenol curcumin, monosodium luminol (MSL), minocycline, Q10 (CoQ10), Bacopa monnieri, Tai Chi, yoga, and interestingly, sildenafil (Viagra). Viagra, which can improve blood flows to both brains (:)), may be able to reduce neuroinflammation, and has been shown to increase brain oxygenation. Future potential treatment options could include stem cells, nanoparticles, exosomes, and intranasal administration as possible.
High rates of oxidative stress have been found across the body.
Oxidative Stress
High levels of oxidative stress may be the most consistent finding in ME/CFS, but it’s always been considered a kind of side issue. That may be changing with the recognition of how widespread it is and the role that mitochondrial damage could play in enhancing it. Evidence of increased oxidative stress has been found in a dazzling array of tissues and compartments including the muscles, the blood, metabolites, red blood cells, plasma, lipids, and lastly, and perhaps most importantly, in Shungu’s series of NIH-funded studies – the brain.
A major hypothesis paper that linked oxidative stress, inflammation, mitochondrial dysfunction, impaired metabolism, pathogens, and cell death together appeared recently. Noting that impaired hydrogen sulfide metabolism can produce a hypometabolic state similar to that seen in ME/CFS, Bindu Paul, proposed that next-generation hydrogen sulfide-based antioxidants will be much more effective in these diseases. In a 2022 paper, Paul proposed that ergothioneine (ET), a sulfur-derived stress vitamin and antioxidant whose levels decline during aging, might be helpful.
Energy Production
Problems with energy production have been found in many compartments of the body
Impaired energy production, has, not surprisingly, always been a concern in this exertion-challenged disease, but only in the last couple of years have how widespread these problems are become apparent. Evidence of impaired energy production has been found in T-, B-, and natural killer cells, in numerous metabolomic studies, the muscles, the mitochondria, and during numerous exercise studies. Chris Armstrong believes the research findings now clearly indicate that a dirty fuel source – amino acids – are preferentially being used to produce energy in ME/CFS.
Blood Flow Issues
Likewise, while we’ve known for ages of the startlingly low blood volume that can be, it’s only been in the last five years or so and the development of better technology that the Visser/Van Campen/Rowe team has been able to show how dramatically impaired blood flows to the brain are. Evidence of microcirculatory problems has shown up, as well, and of course, long-COVID findings have put a new focus on blood clots and blood vessel functioning.
The Key Factor – the Brain
For Dr. Klimas, it all – the reduced blood flows, the high energy needs, the oxidative stress, and the inflammation – shows up most prominently in the brain. In a recent talk with Health Rising, Dr. Clauw – a fibromyalgia and nociplastic pain specialist – noted that all the symptoms of these diseases are symptoms produced by the brain.
In a big surprise, Dr. Klimas called long COVID “a touch more complicated, maybe, than ME”. Thinking of ME/CFS – the disease triggered by god knows how many different pathogens or other insults – as perhaps a bit less complicated than long COVID was startling (and a bit of good news for ME/CFS sufferers.)
It made sense, though. Compare an Epstein-Barr virus-triggered case of ME/CFS that targets the immune cells with a coronavirus-triggered case of long COVID which targets the ACE-2 receptors on the endothelial cells lining the blood vessels and you can see how complicated long COVID can be. Any blood vessel in the body is a potential target.
Putting the Quilt Together
The computational goal – putting the ME/CFS, long COVID, GWI quilt together.
The huge question, of course, is how to put the genie back in the bottle in these very complex diseases. ME/CFS researchers were probably not surprised at how complex long COVID has turned out to be, but long-COVID researchers have been. Many of them have been working with colleagues in other fields they’ve never had contact with.
Dr. Klimas called it putting the little pieces together to make a quilt – and she, of all researchers, has been most dedicated to trying to put that quilt together and she’s trying to do that in an unusual way – by using supercomputers to model the systems that are interacting with each other.
The goal is to get back to “homeostasis” (your happy place :)) where all the systems are working together to produce health. During an infection, the body moves out of its normal homeostatic equilibrium to fight off the infection. When the infection is cleared, the body should move back into homeostasis but, in these diseases, gets caught in a now stable “sick point”.
The Big Picture
The goal is to move it back to a healthy homeostatic state. The findings in this diseases clearly show, Dr. Klimas believes, the outlines of the sick homeostatic setpoint. All these illnesses, feature highly connected systems (neuroendocrine, immune, and autonomic) that are interacting together to hold ME/CFS/FM/GWI and long-COVID patients in their stuck place.
Dr. Klimas’s group models these interactions, identifies potential targetable points for treatment, and then runs hundreds of thousands of virtual clinical trials using every substance under the sun to find drugs that could impact the system. They’re even able to use 3-dimensional structures to look for drugs that target specific locations on proteins and molecules. Her computational researchers give her the results which typically include a bunch of toxic or very expensive drugs that wouldn’t work, but mixed in that bunch are possibilities that can work – drugs or supplements.
It was Gulf War Illness funding that got Klimas’s team to get to this point. Remarkably one in three Gulf War soldiers came down with GWI, and for a very simple reason: they were slow metabolizers who were unable to detoxify the tremendous levels of toxins (Sarin gas, oil well fires, pesticides) they were exposed to. Interestingly, pathophysiologically, they look very much like people with ME/CFS and long COVID: they exhibit high levels of oxidative stress, inflammation, and problems with energy production; i.e. they had a neuroinflammatory illness – similar to what people with ME/CFS and long COVID have.
Klimas’s team came up with a new treatment approach – a two-stage effort involving etanercept (neuroinflammation) and mifepristone (reset HPA axis) which is in phase I trials. As to the identical ME/CFS trial for which they have funding – which always seems about to begin – it still has not begun and Dr. Klimas said it was getting IRB approval. (Dr. Klimas said that GWI has about 35 clinical trials going (all apparently funded by the Department of Defense).
The RECOVER Initiative
Does the Recover Initiative simply need more time to get its act together? (Image-by-ElisaRiva-from-Pixabay-.gif)
Dr. Klimas did introduce a way for long COVID, ME/CFS, and similar diseases to move quickly: build a clinical trial network across the country like happened with HIV/AIDS. Once that was done, it took a couple of years to come up with the first good treatment and ten years to come up with definitive treatments – and that was in the 90s – and medicine has moved a long way since then.
Dr. Klimas didn’t want to comment on how well the RECOVER Initiative is doing, but she did note that it’s essentially duplicating that effort. It’s created dozens of clinical centers, has a clinical trials network, has centralized depositories and databases.
Her message seemed hopeful. Nobody was studying “postviral” illnesses prior to ME/CFS, and building an effort like this from scratch isn’t easy. It takes years to build that kind of infrastructure and find the right teams. Her remarks were reminiscent of what former National Cancer Institute chief Vincent DeVita said about the development of the National Cancer Institute Centers. They were a big mess for a while, but they did work things out over time. Hopefully, the same thing is happening with RECOVER.
There’s no reason it shouldn’t. The RECOVER money pot was so big that over 200 institutions applied to be part of it, and as Suzanne Vernon said years ago, a lot of “really sharp” people are a part of it. ME/CFS, Dr. Klimas still thinks (she’s been saying this for years), should be part of the network.
Still, Dr. Klimas did ask what is the use of basic science if it doesn’t move the needle on treatments, and we’ve seen no evidence yet that the research being done in RECOVER is anything other than very basic.
Treatment
Low-Dose Naltrexone (LDN) – When asked about low-dose naltrexone, she said, the studies showed that it was “a little bit better” than the FDA-approved drugs for fibromyalgia but was a lot safer, and her clinical experience is that it helps most people. They start at 1.5 mg and then go up to 3 mg and then up to 4.5mg.
It wasn’t mentioned in the podcast, but Jarred Younger appears confident that he’ll be able to get a trial of a potentially more powerful form of LDN called dextronaltrexone going later this year.
Amytriptyline – When asked about amytriptyline, Dr. Klimas called it a “messy, old-fashioned drug with a tremendous history” that’s about 100 years old. At a low dose, “it’s pretty good with pain”, is a “pretty decent antihistamine” and is an anticholinergic that can help with dysautonomia. Using it for too long might increase the risk for dementia or cognitive defects, though, and she’ll use it for a while to get things under control (even up to a few years), but that’s about it.
Antioxidants and Mast Cells – Mast cells are major players in these illnesses – and she has one of the mast cell pioneers – Theo Theoharides – on her team. (See mastcellmaster.com.) Mast cell activation syndrome (MCAS) is very, very common in her patients. Given how hard it is to test for it, the best way to diagnose it is to treat it and see if the treatment works. Check out Dr. Theoharides on mast cells below.
Interestingly enough, though, reining in the mast cells is not her first objective. The first of the five horsemen she goes after is oxidative stress. She believes high levels of oxidative stress are hampering energy production. Since the mitochondria are major drivers of oxidative stress, the cells “hunker down” and turn down their energy levels in order to avoid being damaged. .
While too much oxidative stress means our antioxidant systems are getting overwhelmed, Dr. Klimas stated that you can’t fight the oxidative stress in these diseases simply by giving people handfuls of antioxidants. You have to use right antioxidants, though, and for Dr. Klimas that means antioxidants that can get across the blood-brain barrier and get at Dr. Klimas’s main target – neuroinflammation; i.e. inflammation in the brain. Anything that attacks inflammation in the brain will attack inflammation in the body.
Quercetin and luteolin are two nice options: they’re strong antioxidants and mast cell stabilizers that can get into the brain. NAC is an antioxidant that can get into the brain as well. (Shungu’s ME/CFS study showed that NAC can reduce oxidative stress in the brain.) Dr. Klimas also recommended a supplement called D-Hist, NeuroProtek.
T-Cell Exhaustion, Early Aging, the Herpesviruses, and Another Treatment Option
The talk then turned to a small T-cell exhaustion paper by a T-cell expert named Liisa Selin, in which Dr. Selin and Dr. Klimas found “severe deficiencies” in the ability of T-cells to produce cytokines like IFN-γ and TNFα that play a major role in pathogen suppression. Vishnu Shankar at Stanford also recently found evidence of T-cell exhaustion in ME/CFS that he traced to oxidative stress as well. He believes exhausted T-cells may be overstressing the mitochondria causing them to break down and produce more oxidative stress. It feels like we are starting to put the pieces together.
The paper also provided preliminary evidence that a nebulized anti-oxidant, anti-pathogen product called Inspiritol is able to reduce T-cell exhaustion and improve symptoms in ME/CFS.
Dr. Klimas noted that the T-cells are probably becoming worn out from being activated at all times and that the T-cells found in ME/CFS are reminiscent of “early aging”. A T-cell of a 40-year-old with ME/CFS might look more like that of a healthy 80-year-old.
The idea of early aging has cropped up a couple of times in the ME/CFS literature. While the idea that early aging is taking place is rather daunting – if not particularly surprising – it may also provide a window into new treatment options. On one of the Unraveled Patreon podcasts, Dr. Kaufman said he believed that longevity research could be really helpful in ME/CFS, and, Dr. Eleanor Stein will talk about why she believes longevity research will help inform ME/CFS in our upcoming “What’s Up Doc?” series.
Has Liisa Selin found a biomarker of T-cell exhaustion?
With that, Dr. Klimas turned to the Epstein-Barr virus (EBV) reactivation that occurs in long-COVID patients during the initial illness and later, and of course, the EBV reactivation that’s been seen in ME/CFS for decades. Given the overwhelming interest in EBV, it was interesting to hear Dr. Klimas call another herpesvirus – HHV-6 – the most commonly reactivated virus in ME/CFS. A recent paper highlighted HHV-6 activation in both ME/CFS and long COVID. Personally, tests suggested that HHV-6 was much more reactivated in me than EBV.
On Dr. Klimas’s way to stating that a crippled immune system has let the dogs out, so to speak, in ME/CFS, she also referenced John Chia’s enterovirus findings.
Monoclonal Antibodies to the Rescue?
Then it was onto the incredible monoclonal antibody cases series that Dr. Klimas, Dr. Pepe, and others wrote up about how they sent three long-term long-COVID patients into remission in a week. (Dr. Klimas said Dr. Pepe has 15 more patients with similar stories.)
The study used a monoclonal antibody called Regeneron which is no longer effective against the more recent coronavirus variants – and is almost, but not completely, unavailable. Dr. Klimas has funding and was able to get some of the drug. She hopes to start a 20-person trial by May.
Unfortunately, we didn’t get to hear about the possibility of using monoclonal antibodies against EBV or HHV-6 in ME/CFS, but Dr. Klimas said pharmaceutical companies were eagerly awaiting the result of the 20-person trial. Why RECOVER is not doing a spate of experimental trials to assess treatment possibilities like this is beyond me.
- Listen to the podcast.
- A “What’s Up Doc” talk with Dr. Klimas is coming up on Health Rising.
- Register for Dr. Klimas’s Institute of Neuroimmune Conference on May 10th on the Events page.
- Listen to the Institute of Neuroimmune Medicine’s “Hope and Help for Fatigue and Chronic Illness” podcasts.
Upon diagnosis several years ago I attempted contact with Dr Klimas because I found someone with ME/CFS that she had helped.
No response to telephone calls,
No response to mail.
So I wrote a personal letter offering the MRI taken almost immediately after my first debilitating PEM – no response.
I still have the MRI .
Sorry to hear that. I briefly saw Dr. Klimas before the pandemic started and I can tell you that the administration was not a high point at that time :). Maybe you should try again?
Effective administrative help and/or regular contact with a business consultant might help Dr. Klimas organize her goals without spreading herself too thin.
I will refrain from the word I was going to use for Klimas…. and I have no idea why Cort – who generally does good stuff – gives her any profile. She’s been talking a good talk on ME/CFS and its treatment, and trials blah blah blah for a long time with nothing to show for it.
I turn off when Cort mentions her.
Exactly the same thing happened when I contacted Byron Hyde of the Nightingale Research Foundation. He still has my MRI (he asked me to send it) but I’ve had no response. That was 10 years ago. 🙁
Cort, I feel very overwhelmed but hopeful by reading your newsletter today. I am in the Recover study through Stanford, CA. I stumbled upon the study when researching Stanford Neurologists as the Neurologist I was referred to I had to wait for months to see. I now see that it’s been good that I have been in the Recover study as just yesterday I had a brain MRI and hopefully it will show something and I can start getting more help. I don’t feel I ever had covid, it was the 2 initial vaccines that injured my brain. Reading here what these researchers are finding out as possible treatments gives me hope. I will share all of this with my primary care doctor and neurologist through Davis, yes, I have three top neurologists now through Davis, Stanford and recently a new one at UCSF. I have not been able to get into a long covid study as Davis said my issue wasn’t lung related, Stanford said no because it was a vaccine injury and not long covid. The UCSF Neurologist is going to help refer me to a clinic which can help me with the fatigue issue which none of my doctors have been able to help me with. Thanks for reading my story, it’s been a long 3 year battle now. Your newsletters have really been encouraging to me. I found out about them when I googled CFS after my 2nd vaccine and was so tired all the time. I thought that maybe I had CFS?
Thanks! If you made it to the MRI tier I imagine you’re getting some good workup done. Those neurologists can historically been a tough group – it’s a good sign that yours are being helpful.
As you may know in Deeks, Heinrich and Peluso UCSF has one of the top long COVID research groups in the US.
Good luck!
Thank you Cort for your reply. It’s all such a long waiting game. Hope I do get into the long covid clinic at UCSF as it sounds like the best place I could be!
Yes I too have been following the The TLC Sessions – Living with Long COVID podcast and have found it very good.
Some high quality guests. (Except the rare episode of the pro exercise brigade that weaselled their way in) But interestingly the hosts do often mention their scepticism of a one treatment idea that fits all. Also it’s forgivable because the hosts were new to having a post viral illness. So back then were unaware of the exercise controversies.
They know now though. Plus we have to remember that only about half of Long Covid patients fit the ME/CFS criteria and have PEM. Meaning exercise is a fair subject for them to discuss.
Also the hosts have an open mind, so that’s refreshing in itself.
They are quite clued up, and fast learners, so ask questions that we want to asked. And also they have a lot of respect for ME/CFS researchers.
Of the podcasts out there on Long Covid and ME/CFS. These ladies are smart, funny, and likeable, they have done a fine job, with a mix of personal and professional. It’s been an epic journey listening to their experience with Long Covid which is usually the first 7 minutes of the show. The second part is interviews with clinicians, researchers and patients)
There’s another similar podcast that also offers hope and quality guests and that’s called
‘Long Covid Podcast’
By Jackie Baxter
Latest episode here https://bit.ly/4d85mTA
Both podcasts offer hope, and for anyone with Long Covid or ME/CFS, and with these diseases ‘Hope is mandatory!’
Thanks for the other Long COVID podcast which I was not aware of. TLC is up on the science and very personable as well – nice!
I found this fascinating, thank you Cort. Nancy Klimas is and has been working so hard on ME and related illnesses, I view her as one of my heroes. It was great to catch up with everything. I’ve tried a few of the treatments here without success but will have a go at a few more suggested. It’s been rather disillusioning, expensive and exhausting but hey, never give up hope!
Anyone know if the Regeneron study is recruiting?
I don’t know. I rather think not – I had the feeling that she had enough participants but if you’re in the South Florida area you might want to give her a buzz. You would need to have only been exposed to the earlier variants that Regeneron is effective against.
Has anyone else tried NAC? I was trying it because it is supposed to help respiratory issues. Suddenly I was faced with high blood pressure. No other changes in my routine to blame so went off the NAC, bp is starting to go back to normal (my normal is classically low to excellent, 110/70 or so. Dug down in the online literature about NAC and it can raise bp. 🙁
Can you show a source that indicates NAC raises blood pressure? I have hypertension as well but all the literature I’ve seen on NAC and blood pressure warns that if you are on antihypertensive meds, then be careful of NAC because it also lowers blood pressure. I’ve never seen a warning of the opposite though.
I saw the same info but also a possible contrary effect. Here’s one article intro:
One Type Of Antioxidant May Not Be As Safe As Once Thought
Date:
September 6, 2007
Source:
University of Virginia Health System
Summary:
According to new research an antioxidant commonly used in nutritional and body-building supplements can form a red blood cell-derived molecule that makes blood vessels think they are not getting enough oxygen. This leads to pulmonary arterial hypertension, a serious condition characterized by high blood pressure in the arteries that carry blood to the lungs.
I admit 2007 seems like ancient history, but since I seem to tend to be the opposite in so many medical things, I had to research it. With lungs already an issue, it makes sense.
Yes we are all different and paradoxical effects can be real in certain cases, like how some people are stimulated by valerian root rather than sedated. But I think the risks of NAC for most of us will be vastly outweighed by the benefits. If you use a blood pressure meter and notice an increase after taking NAC, that could be legitimate cause for concern, or if it just doesn’t resonate right with you it’s good to listen to those intuitions. But for most of us I think the stuff is just so helpful in these conditions. Good luck!
I don’t doubt it’s efficacy..sadly and frustratingly did nothing at all either way
Broccoli seed extract and quercetin were amazing at the beginning and still help a bit now
The Institute for Neuro-Immune Medicine has contact information for appointments with doctors on their website. You are more likely to be able to see Dr. Irma Rey or one of their physicians assistants. They may not have been answering phone calls during the Pandemic shut down?
Dr. Klimas is not only the director of a large staff but is a major researcher in more than one disease. They are conducting multiple clinical trials. She also spends a great deal of time in advocacy….attending conferences, sitting on committees. I recently did email her asking for permission to use a clip from one of her videos. Much to my surprise, she answered in the affirmative….she was at a conference at the time.
I really really really appreciate the effort but the treatments mentioned are not gonna move the dial significantly. Most of us have tried them. I hope these super computers come up with something new!
I usually find some small things that I haven’t done. I’ve never done much with mast cells so I am going to try the Neuroprotek and the D-hist and I’ll throw in NAC and see what happens. The etanercept/mifepristone duo is not new but I imagine that most people have not tried it. If you’ve been around though you may have tried lots of this stuff.
Just wondering whether you had tried NAC in the past Cort? Or maybe giving it another go in combination with those other tablets so it’s technically a ‘new’ thing??
Right – trying it again in that combination and seeing what happens. My guess is that things need to be taken together to have the best effect.
Thanks Cort… Yes agree got to tackle this thing from all angles. Really hoping this combo gives some good results for you. You’ve put in so much hard work on behalf of the community you really deserve after all these years x
Hi Cort,
I, too, was excited to read about so many new potential treatments and also to learn about the supplements that can cross the blood-brain barrier! Thank you sooo much for this article and for all that you do for us!
I wanted to share…Like so many of us, I’ve been doing my own research and experimenting on myself for decades. Some of these most commonly recommended supplements have been on various specialists’ lists for years, and I’ve tried as many as I can afford to try.
I have my own regimen now, but am always looking to refine it both for efficacy and cost, and the neuroinflammation element is such a huge new piece of the puzzle! I’m also excited to try Neuroprotek, as it sounds like it’s a unique formulation that allows it to get into the brain where it’s most needed.
To that end, I have a couple things to share, as well as a question. One is about the D-Hist supplement. I’ve looked at it several times in recent years and, unless I’m missing something that makes it truly unique, my feeling is that it’s incredibly over-priced and those ingredients can easily be found elsewhere, and in a selection of doses.
Another thing I wanted to mention was in response to you sharing about your current diet. You also mentioned not having looked at mast cell stuff much so far, so I would like to share a little word of caution from my own personal experience.
I have had some pretty amazing results in times past from an anti-inflammatory diet (my own personal version of the autoimmune paleo diet, which is very similar to keto, though more restrictive). I still get a lot of benefit from working with diet but am unable to maintain quite as strict as I would do best with due to brig so low functioning, low income, and also because it has become so complicated trying to manage my body’s contradictory needs.
My point is, though, that this is also how I found out that that I have a histamine intolerance (and very likely also have MCAS). Unknowingly, many of the wonderful nutrient dense anti-inflammatory foods that I was eating in that diet turned out to be high histamine foods and/or histamine liberators.
I accidentally put myself into a state where my “histamine bucket” was full, and I began to develop full body symptoms. This went on for many months and no doctors I saw were able to recognize what was happening. I eliminated one potential allergen after another for months while it got worse and worse. So bad that I was having all kinds of new food reactions, full body itching and hives, rashes, hot red cheeks, stuffy nose, etc etc… all of the symptoms of allergies AND all of my chronic pain and headaches (including pain that’s not ME/CFS/FM related) was waaay worse.
Finally a friend suggested I look into histamine and MCAS. I did a deep dive, went on a low histamine diet, began supplements recommended to stabilize mast cells as well as antihistamines, and amazingly not only did it work for the histamine symptoms, but over time it (in combination with other things) has helped improve my ME/CFS significantly!
So just a word of caution. It might be worth it to do a little preventative look into histaminic foods and make sure you’re not overdiing it.
…
And now my question (for you and really anyone here):
I keep hearing about people using different wearables to help them pace more effectively. I noticed you mentioned it above and specifically mentioned sleep. I’m wondering if you know of other specifics on what’s best to monitor and how, or may have a suggestion on where I can find that info?
I’ve heard other people talk about finding monitoring their heartrate as a means of pacing and preventing crashes super helpful. I wouldn’t even know where to begin!! I would very much appreciate any guidance or resources that you (and/or others here) can provide on this topic!
Thanks so much!
Indeed sadly I seem to be running out of go tos. I find it amazing that klimas hasn’t come out with anything that is sufferers haven’t worked out for ourselves.
I’m not dissing her. I just find it truly startling that research is stalled like this.
Thanks for posting tho Cort. I guess, like you say, newbies will find this stuff helpful and there’s usually always smthg someone hasn’t tried
Bewildered by the etanercept / mifepristone duo which apparently reduces excess cortisol.
My biggest handicap in ME / CFS is cortisol / adrenal insufficiency. To wit: I cannot function before 2 pm no matter what.
Thanks again, Cort for your hard work.
Hi Cort, I love your newsletter and especially the “Gist” bit for those of us who need it!
In your above post, you mention the etanercept/mifepristone duo, but I can’t find any reference to that in your newsletter or Gist. You also say it’s not new, but I’ve never heard of it! Can you please explain a bit about what it is and whether it’s worth trying?
Also, what of Ergothioneine (ET)? I noticed it mentioned in your newsletter, but not the Gist. Worth trying?
Thanks so much for all of your great work, Cort!! It really helps and means a lot!!
Hi Sharon – thanks! You can find more about the drug combo here – https://www.healthrising.org/blog/2019/09/01/klimas-chronic-fatigue-syndrome-guld-war-bacopa-etanercept/
I need to look into it more but I would think its worth trying 🙂
Dr. Klimas has seemed like she’s everywhere doing everything possible for decades. I don’t know how she does it all.
So what is the ordinary person with ME/CFS reaching decades into the past supposed to DO? Who should they SEE? What should they TRY?
And how much effort – out of their tiny daily allotment of energy – SHOULD they expend?
All the stuff presented, no PATH to wellness. Except, if you’re very lucky, through expensive private visits with overworked specialists not covered by Medicare.
Just as much out of reach as ever.
I’m just trying rather fundamental things right now. I’m on a keto-autoimmune diet (no grains, no nuts, basically protein and vegetables and some fruits) and to my surprise it seems to be helping a bit. I’m also having my main meal early – around 5:30, (Intermittent fasting), watching my daytime stress scores on the Oura ring, am doing stretching regularly, and using exercise bands, and doing mild core exercises. Also some brain retraining.
If I could get a handle on sleep that would help immensely = my readiness scores track almost exactly with sleep.
I do believe its helping a bit – which is nice! I’m still hoping I can find the right combination of things that works for me and find a way to wiggle out of this thing. Other people have been able to.
I talked to an ME/CFS expert not so long ago. She’s at retirement age but she’s sticking around because she’s excited at what’s going on.
I haven’t had a carb in ages, take ldn, and do my usual stretching every day. My sleep consists of small stretches stitched together with 3-5 unavoidable naps during the day.
I mind my energy – don’t do things I don’t have to – have an assistant – all the accommodations of 34 years. I’m as good as I’ve been able to cobble together without medical help – and still have a tiny bit of energy left for my writing.
I’d rather be well, as I’m sure you would.
Little bits of ‘better’ are NOT the solution. And WE shouldn’t have to figure it out in such detail – others diseases have specialists and tests and protocols and are managed by the medical personnel in a way that works, through our normal insurance pathways.
I had (unrelated) surgery at Stanford. It was unbelievably draining to go down there from Davis twice for necessary surgery. No way I could do the two-hour-each-way trip for their CFS clinic’s ‘help.’
I want a proper explanation: diagnosis, treatment, cure – not an expensive personal solution which helps a little.
I wish I had confidence this was happening from the Long Covid research. I still see nothing helpful out of the billions spent, not even for the LC folk. Hope I’m still alive if and when something happens.
Didn’t mean to imply they are the solution – just what I am trying to do right now. I agree we need real fixes. I hope RECOVER surprises us!
I look at those monoclonal antibody results in long COVID and I wonder what about EBV or HHV-6….
Didn’t mean to sound snippy – just fractious. It feels like we’re closer (we, by definition) but there are still ‘doctors’ in the UK and Australia (and probably everywhere else, including the US) pretending it’s all in our minds, so it would be nice to have them silenced with a CURE/explanation/treatment – and some researchers are off reinventing the wheel in miniature instead.
Keep at it – we’ll probably hear it here first.
Alicia, I like you’re common sense style.
Its probable going to be a common sense scientist that’ll get this thing solved as well…that just guess
☝️ “my” inserted
Cort ,how the heck does one edit one of these posts?
I make a lot of mistakes😄
If you haven’t already looked into orthostatic intolerance, that is something fairly concrete that can be investigated, and it has decent treatments that can improve symptoms.
Only part of the picture, unfortunately.
(The Bateman Horne Institute has lots of info on this topic for patients and doctors, including lectures and articles. Cort has also written on it in his usual helpful style.)
Apologies if you already have looked into it. I hope I didn’t sound like a “just do yoga” type.
Been there, done that. For the longest time I managed my POTS with extra salt and potassium.
Then had to deal with swollen ankles, etc., couldn’t tolerate diuretics AND they didn’t do anything ( two different ones prescribed by cardiologist), so have ended up cutting out almost all salt instead. Just to keep my ankles sort of normal most of the time. Food is no longer something tasty – I eat to keep going. I figured that one out on my own – it works.
Re the POTS – I dunno. I can’t stand or walk, so I’m already sitting most of the time. It doesn’t seem worse than before.
Alicia- I want to second SarahTee’s thoughts about medication for POTS. In addition to Bateman/Horne Center, Dr. Peter Rowe at Johns Hopkins published a paper on many medications that improve orthostatic intolerance…it is about 25 pages with lots of detail. I think because of long covid, my general practitioner is willing to prescribe for my POTS now which he would not have done in 2014. I would understand if you are just warn out at this point or do not have financial resources for more pharmaceuticals. I use a combination of Fludrocortisone and Midodrine…and get some standing time. I must use both. I have considered whether I should try Mestinon.
That’s exactly how I feel about what’s been going on.
A whole lot of small studies
..,20 people…..(LMAO).laugh my arse off
And still after many years of research.
The people that need the most help are being left in the dark.
If Ron Davis’ team thinks we are all stuck in a metabolic trap, And thinks they can reverse it,…then why in sam hell are they wasting fundraised money on silly little studies….GET ON WITH THE METABOLIC TRAP THEORY WORK ALREADY….and start reversing some people and focus on that..SHEEESH! like, am I missing something here or WTF!
And here in Canada the TRUE DOLT govt offered a mere $200 disability increase up from an average of aprox.$750/month.
There’s something seriously wrong with the system that clearly isnt helping people that are in need of help the most.Pure evil intent by the TRUE DOLT govt
Oliver – I always hope that these comments do not discourage others…especially people new to the problems…to not try to stablilize. Starting with Dr. Klimas’s videos to patients and also the lecture to doctors, I started getting a comprehensive care program put together for myself in 2014 that stopped my slide into a severe state. Her recommendations on self measuring lead to a diagnosis and medications that manage POTS and get me some standing time….thank goodness. No I’m not recovered. Dr. Shangru’s work on NAC clearly shows brain inflammation is reduced and thus managed….not solved…but I’ll take managed anyday. LDN had several impacts but most importantly was an improvement in adrenal function. More than anything was to learn to respect energy limits and not cause crash after crash. Many more parts and pieces for an individualized program.
Additionally, Oliver – her supercomputer generated theory of a double attack to first reduce inflammation by 50% and then reboot the HPA axis – you’ve tried this? It has only been in trial for GWS and was successful in mice and partially successful in human trial. She only has just been privately funded to try on ME/CFS…but will she find the subjects? I would like to know if anyone has talked a practitioner into prescribing the two medications without FDA approval which would only come after a successful human trial.
@Janet Mosser- THANK YOU! For all that you said! I wanted to stand up and clap!
You mentioned the difficulty in finding test subjects for clinical trials, which is just one of many barriers that we suffer from because there is such a lack of education and infrastructure needed to support everything that needs to be done to address our disease.
I recently learned about Solve ME’s ‘Solve Together’ patient platform that anyone in the US can join. It is attempting to serve several functions, including being a means of recruitment for clinical trials.
I’ve pasted the link below for you & anyone else who’s interested in signing up. I’ll also paste their own description of the platform, as it’s much more comprehensive than what I’ve stated here.
Thanks again for your comments and sharing!
https://solvecfs.org/research/solve-together/
“solve-me-logo-color
HOME
>
RESEARCH
>
SOLVE TOGETHER
Solve Together
Solve Together is a dynamic, patient-centered platform that integrates multiple data sources designed to speed up the discovery of treatments and cures. We make data on post-infectious diseases accessible to researchers, expediting the identification of diagnostic and therapeutic targets. Patients can create reports for their doctors, sync health-tracking wearables, and discern their distinct symptom and health trends. Solve Together will also enable Solve to connect researchers with individuals interested in participating in clinical research studies.
Any U.S. adult can join Solve Together, whether they have ME/CFS, Long Covid, other post-viral fatigue-related illnesses, or none of these conditions (serving as “Control” participants). Joining is free, voluntary, and participants can opt out anytime.”
It’s not an attack on klimas. And I take the point that her stuff is helpful. But it’s so limited!!! And has not progressed. I think it’s fair to say that.
I figured out most of the treatments on my own and I’m not funded by the Pentagon etc. I just would like to know why these things take so long. Like you say 2014… that’s a decade ago and yet we’re still in the same position.
Don’t you think it would be nice to know why there’s no progression and also, Janet, don’t. You think it’s useful that feedback may filter up to her?
I agree some of her protocols are good. But there’s been no major changes and I’m truly startled by the lack of progress. I just don’t understand it. And I think I’m allowed to express concern at that.
If you look elsewhere on this particular page, I’ve thanked Cort for posting this and klimas for the work she has done.
So I mean,Janet, I’m still entitled to voice my opinion. I’ve earned as have you
I don’t understand why her work has not progressed. She has identified a unique treatment protocol – etanercept plus mifepristone – in GWI that she’s testing out. I agree that it does take so much time to do that (the pandemic didn’t help). She is also finally about to begin a mifepristone+etanercept+hormonal factor in ME/CFS. She said she gets the results of the GWI trial they will all be fed back into the supercomputer and it will learn from them.
With regard to the nutraceuticals she’s testing things that are available and that the modeling says will work. While that’s not groundbreaking for people who have already tried them if the trials are successful they would spread the word and ultimately be helpful .
Im not an immunologist, but don’t the t cells get turned over every so often? If they are worn out, can’t the body just replace them and make new ones?
I don’t know but if they are finding energy problems just about everywhere I wonder where the energy to replace them would come from (???)
Did Dr Klimas mention the doses of quercetin and luteolin she recommends?
No she didn’t.
Cort, you have an uncharacteristic typo – it should be “reining in” (equestrian idiom), not “reigning in”.
(Feel free to delete this comment.)
OMG – thanks!
I am interested in learning if any other ME/CFS patients have had repeated positive ANA tests. A positive ANA test is an indicator that the immune system is activated.
Yes, I have a positive ANA, along with a high Rheumatoid factor.
Yes, I had positive as well but no clear indication of the reason. Since we have to have a sense of humor to survive this, I find it funny that there’s a test but no idea what the results might mean.
Yes, I’ve had repeated positive ANA results for at least 12 years, the specifics of which have changed with each test. The bigger problem for me has been in getting any useful interpretation of this data. It’s clear that I’m making multiple kinds of antibodies, but I can’t get access to a specialist who can tell me what any of it means.
In addition to ME/CFS and MCAS, I also have Hashimoto’s, a diagnosis of FM, and have been told for years that I “might have Lupus… let’s just keep retesting every so often…” (I have other confirmed and suspected commonly co-occurring illnesses, I’m just listing the immune related ones for relevance to this discussion.)
I would also really like to be tested more thoroughly than just the standard panels, ideally for a broader range of antibodies, and would love to have my T cell, B cell, and NK cell functioning evaluated… but have no way access to that.
(I’m in the US, am on Medicaid, and haven’t ever once been able to see a doctor who knows anything about ME/CFS or MCAS, etc despite having been ill for 30 years, am now housebound, have been bedbound in the past, etc.)
cort,
whats the BEST place to GIVE for ME/CFS?
I couldn’t pick one – in equal measure IMHO
Listed alphabetically
If you’re in the UK
We all know that not every treatment works for everybody with ME/CFS. That said, I want to share my remarkable improvement in sleep, I have a Galaxy sports watch and before changing my nightly regimen, I would often have scores as low as 59 and just feel like a zombie the next day. I was drinking a sports drink throughout the night when I woke up with a dry mouth and this was frequently. My ND suggesting switching to Daylyte in plain water. Daylyte is a mixture of hydrating minerals. It is like a miracle. Most of my sleep scores now are in the 80’s and I have even had a 90. The lowest score has been a 73 which is still in the “good” range. I do feel better with more sleep.
I had my worst sleep in memory last night – 43! I’m getting an electrolyte suggested in an Unraveled podcast. It might be Daylyte – I hope it works!
You and me both Cort.
Whenever a new quarter happens(as in spring,summer,fall ,winter) I get all messed up. Last night I had bad nightmares of wolves attacking me and tearing me to shreds.very graphic..woke up screaming
Hi Cort, see my reply to Betty and links below on the supplement probably also containing lithium and boron microdosing. Feel free to delete this comment. Thanks!
How interesting. Is this the one? https://www.amazon.com/Electrolyte-Concentrated-Supplement-Hydration-Electrolytes/dp/B07VLBW3F5?th=1 In that case, looking at the bottle label, it not only contains hydrating minerals, but also a small dose of L-Lysin and is microdosing Lithium (at 1mg/serving) and boron.
Lithium (at high dosage) is not only the leading drug in treating bipolar mood disorder (in the range of 1800 mg for acute control and 900-1200 mg for long-term control https://www.drugs.com/dosage/lithium.html), but microdosing Lithium seems to be an actual thing: https://store.juliarosscures.com/products/lithium-orotate-monolith , low dose lithium in Alzheimer’s https://www.researchgate.net/publication/352286153_Lithium_A_therapeutic_option_in_Alzheimer's_disease_and_its_prodromal_stages, and here’s a guy microdosing both lithium and boron, citing anti-inflammatory action of boron: https://www.linkedin.com/pulse/tale-two-elements-boron-lithium-alan-russell .
I have a bipolar parent, so microdosing might be worth a try alone because of the family connection.
I wish I could order Daylyte in Germany, but alas Amazon does not ship the product from the US.
Because of the small amount of electrolytes contained in the drops, I’d wager the therapeutic effect might not come from electrolyte effects, but from among the ingredients/trace minerals listed in the section below (lithium, boron, sulfate, L-Lysin).
Googled a bit – everyone be safe when using this and be informed about what are safe amounts and risk of toxic overdosing of boron etc.
Found that there’s supplements available for lithium in the sizes of ca. 5 mg and 1mg (1000 mcg), and for boron of around 3 mg (e.g. as tablets that might be halved or cut further).
Cort, I tried Neuroprotek and it didn’t work. This did work, however:
https://www.amazon.com/Ulmubra-Liposomal-Absorption-Flavonoid-Supplement 500mg
and it’s not that expensive. Take two a day. It will take a month to see a difference.
Great article, thank you. What would we do without people like you and Dr Nancy Klimas? God bless all who keep pushing uphill for real progress on ME/CFS and related illness.
The article mentions Quercetin, but it’s important to note that quercetin is not very bioavailable. It can be combined with bromelain and this combo is best taken on an empty stomach apparently. And there are other formulations that are marketed as ‘bioavailable quercertin’. But straight up quercetin may not be getting where it needs to go very easily.
All of the research going on is very exciting, encouraging and heartening! But why is FM so often left out of mix, or tagged on at the end of a sentence? So many studies have found very similar disease process and symptoms. The course of my own disease has affected every facet of my life for over 40 years. Crushing flu-like illness, pain and fatigue now 80% of the time. It takes me 4-5 days to recover from going shopping or to a soccer game. I was so relieved when both providers and the general public started showing less eye-rolling at the diagnosis.
Why are we being minimized so often? Is there an explanation why we have to scan articles for the FM at the end of the sentences or why it’s sometimes referred to and sometimes not?
Good question! Because it hasn’t been associated with Long COVID as much as ME/CFS I tend to focus more on the ME/CFS long COVID overlaps. Sometimes I’m just too tired to dig into another condition. Sometimes, because there’s more focus on immunology in ME/CFS and long COVID than in FM, the overlaps just aren’t there. Also, for whatever reason, the research on FM is not as exciting right now. A ridiculous amount of funding is going to assessing the effects of exercise in FM.
Even though about 40% of long COVID patients appear to have FM, FM seems to have been left behind a bit.
Despite that some of the most interesting blogs over the past year or so in my opinion have been on FM and I have an interview with Daniel Clauw, a leader in the field, coming up and a blog on thyroid issues.
Cort, what’s the basis for Nancy Klimas recommending those supplements? Is there any evidence backing them? Is there evidence that they cross the blood brain barrier?
Or is it yet another speculative roll of the dice? That could waste peoples’ precious money (again)
Matthias- Before making this kind of specious comment about one of our few serious substantial researchers, I would hope you would actually go out and study her team’s work. She has no financial motive in her recommendations such as selling her own supplements and does not make these kind of statements before doing a deep dive into the research of others as well as extensive testing on her patients. In doing the computational computer analysis, that department input research from all over the world in order to generate the computer driven models of possible theories to solve ME/CFS as well as GWS. You should find and listen to some of these presentations….it is seriously interesting. And yet computational scientists still have to bring the ideas to her in order to apply the human brain and knowledge to the problem. It is fascinating to hear her talk about the research like GET and the poor research methodology often leading to years of bad medical advice. She thinks the same thing happened with the Rituxin monoclonal research. Additionally, I watched her as an audience member at a conference, question Dr. Shangru about his ongoing research design, specifically challenging him to identify a way for practitioners to test brain inflammation now without access to his amazing technology. When recommending UBQ, she specially referred to a “kick ass” Japanese study that she thought was very well done. I believe she has funding currently to replicate that study…not positive but I think I saw that. In one presentation she explained as a practitioner, she could not tell a GWS patient’s symptoms from an ME/CFS patient’s symptoms….the clinical presentation looks the same. Taken as a puzzle to solve, she drove a deep, deep testing comparison and eventualy found that the GWS patients have very over active immune response whereas the ME/CFS patient has an almost non-functioning immune system….yet symptoms to a doctor look the same. In her human trials for ME/CFS her team knows that subsets of patients must be used as it will be critical to getting any real information….men vs women, more specifically post-menapausal women vs pre-menapausal women.
Thanks Janet. Maybe I was harsh. But she’s been talking a good talk for a long time, as long as I have had illness (since 1990). And wasn’t she talking of trials about 5 years ago?
I am sure her heart is in the right place, and it does seem like our illness is very complex and defies easy answers.
And I find it interesting that she’s only fairly recently jumped on the brain bandwagon.
Andrew Lloyd is the researcher I respect the most. The guy who said ‘it’s in the brain’ after the Dubbo studies, many years ago, and got widely mocked by many in the patient community.
ME/CFS is described as a multisystem disease. The brain plays a major role, perhaps even a central role. I agree with Loyd. Yet no serious damage is visible with current technology. There is a factor that disrupts the functioning of our brains. Proteins, toxins, inflammatory response? I am following Jarred Younger’s research with great interest, and I hope that his test is positive, then we will at least know that there is an inflammatory response in the brain.
Janet, the comment you attributed to Dr. Klimas that she couldn’t tell GW Syndrome symptoms from ME/CFS symptoms is critically important. Our organization has worked with GW veterans since 1990. The VA and DOD attribute GW Syndrome symptoms to toxic chemical exposures. Why has this never been pursued in ME/CFS research? Today, we live in a soup of toxic chemicals in our air, food and water. Chemical toxins stored in the body can cause immune perturbations that seesaw between an over and underactive immune system. An overactive immune system can cause autoimmune-like symptoms; and an underactive immune system can allow herpes viruses (like HHV6A), EBV and others as well as bacteria, mycoplasma and fungi to activate. The same things that cause relapses in ME/CFS patients are those that can release toxins stored in body fat into blood circulation. Aerobic exercise, sudden weight loss, heat, extreme stress, etc. Without a way to safely remove toxins from the body, this release in the blood stream can cause even more serious symptoms. Finally, the brain is storehouse for toxins because every brain cell has a fatty sheath.
As someone who battles chemical sensitivity and who has to stay away from many of the toxic chemicals in our environment I fully endorse more of this research! My chemical sensitivities came on about 15 years into my ME/CFS/FM saga. The symptoms are different but I think that in my case they must be connected.
I’m usually assuming that toxins are one possible trigger for ME/CFS, triggering an immune reaction and thereby some central ME/CFS disease process like the broad range of other known (and possibly immune related) ME/CFS triggers (like infection, operation, stress etc.), and that the symptom of chemical sensitivites which I have too could be present with ME/CFS regardless of initial trigger. The point you’re making about release of toxins from tissue is an interesting new angle!
Side note: I have gait disorder with ME/CFS, which a neurologist not well informed on ME/CFS clinical criteria was quick to categorise as “psychogenic” (because it fit none of the few other neurological gait disorder categories). then I googled gait disorder and found that the category of “psychogenic gait disorder” was coined…(drum roll)…based on the symptoms of soldiers after the first World War! Meaning it was solely attributed to psychological trauma, but fighting in World War I meant exposure to a whole range of factors (extreme mental (and physical) stress, ravaging flu, chemical exposure) all known to also cause ME/CFS.
She’s been doing the modeling for a decade. That’s why we’re asking ” why so slow”. We’re not on this planet forever. Just like thexrest of us, I’m watching the last bit of my youth go by. It’s ok to flag issues you know.its not a direct criticism of the person.
It would be nice to know why things are going so slowly. Most of us have got to the same point as klimas on our own.
I fi d that very disconcerting. Where are the experts making leaps. If Nancy has a super computer, what’s it saying.
She looks like a really nice lady from the interviews I’ve seen. Sometimes tho , asking a question that perhaps may percolate back can relight a fire in someone.
We need help! Fast!
I looked at her research underway. She’s doing a lot of work in GWI – because she has funding for it. I think it’s more the inability to get funding that’s holding her and others up with ME/CFS. She talks about that in the What’s Up Doc session I had with her.
She got Department of Defense funding to build the supercomputer modeling and then has applied it as she can to ME/CFS. The DOD also paid for the etanercept-mifepristone trial – which is over. She said they are funding 25 clinical trials for GWI.
She had to go to private funders to get the small ME/CFS trial going – and it hasn’t started. The NIH will still, I believe, not allow researchers to apply to get funding for clinical trials in ME/CFS via the ME/CFS SEP.
We really, really need to get this post-infectious disease Center going at the NIH. We’re still up against such a wall there.
Mast cell stabilisation and antiinflammatories in general really
One of the three botanicals Dr Younger has found promising is Curcumin but he says it is dose dependent. I wonder if we gradually increased our dosages of curcumin we would get better results??
Il y a un an j’ai pris un traitement de cortisone pendant 8 semaines suite à une double opération de la cataracte. Depuis mon état s’est amélioré. Est ce que la cortisone aurait réduit l’inflammation du cerveau ? Je me pose la question. Bon courage à tous.
Betty Mekdeci-Dr. Klimas uses GWI research/clinical practice to help inform ME/CFS practice/research. The DOD has been generous in funding GWS research which is why her team and others are currently in human trials on GWS. Both Ron Davis and Nancy Klimas have always been most interested on finding something that can substantially change lives of patients….Ron Davis because of his son Whitney Defoe and Nancy Klimas because she continued to see patients. So I think that is why they both seem to have ME/CFS theories along the same line that are fully developed to take to human trials…and both of them continue to be turned down in their grant applications. Both theories propose there is a trigger event and then a multi-system failure where some people get stuck in an unhealthy state. The work of Robert Phair, PH.D. (at Ron Davis’s lab) has lead to looking at the Itaconate Pathway. When humans get “sick”, the Itaconate Pathway is turned on. Most bodies switch this off and return to a healthy state. Davis/Phair know current medications that have the potential of assisting the body to turn that pathway off and return to a healthy state. Which trigger caused this to happen is not their immediate question. Dr. Klimas’s theory for which grants have been written, is based on the HPA axis being stuck in an unhealthy condition and too heavy a load of inflammation. Dr. Gordon Broderick followed by Travis Craddock created the computational biology division which has generated thousands of ideas or models…the HPA axis model was her first choice to put into human trial. They successfully created mice with GWS and successfully, in trial, corrected the condition in mice. They are now in human trials for GWS but she was only able to recruit half the subjects for which there was funding…it will make this a smaller trial.
The Pandemic stopped ongoing human trials and that funding had time limits which the Pandemic also messed up. They have not been successful in creating mice with ME/CFS so must depend on getting grant money based on computer modeling to go into human trials without animal model proof.
va.gov/RAC-GWVI/meeting/jan2014/presentation1NancyKlimas.pdf is a power point presentation showing the comparisons…not up to date
youtube.com/watch?v=hxBlaA3YVXU is a Ron Davis/Janet Defoe
I am loving the narration now available, it helps a ton since reading is so difficult for me (demands so much energy). Thank you Geoff!
I think it is crucial that in progressed ME/CFS brain inflammation and herpes viruses are the main focus now. So good to hear that some of the clinicians /researchers other than Maria Ariza, Bhupesh Prusty, and Jacqueline Cliff and Eliana Lacerda who are directly researching the hypothesis of HHV-6b smoldering brain inflammation have decided to put these observations and questions in the middle of their work.
Regarding the T-cells we urgently need virologists and everyone capable of doing this to research the question whether it is smoldering herpes virus reactivation (a concept that is explained in Maria Ariza’s “The Herpes Viruses [in ME/CFS] Are Back!”) that wreaks havoc on them! Jacquline Cliff and Eliana Lacerda are doing this but we need more researchers to go into this. Because it seems such a low hanging fruit. From my understanding this could be done nowadays at any lab with a specialty in infectiology/virology.
I was also extremely glad to hear Akiko Iwasaki saying at the Unite To Fight conference yesterday to do just the same in her research into long covid and post-covid syndrome. In her research cluster they also follow other routes but herpes reactivation and brain inflammation are one of about five key questions for them too.
Regarding the definition of long covid with exercise intolerance as the core problem of the illness, sometimes referred to as post-covid syndrome I understood in Charité’s Prof. Scheibenbogen’s talk that this looks excactly the same as mild ME/CFS. I found this extremely interesting because it leads to my understanding that there is no new syndrome here. But there is just ME/CFS. And the biggest group of those who develop ME/CFS after Covid are only mildly afflicted. That many recover fully from a mild level of ME/CFS with pacing and that with better information more people could be prevented to cross the edges to more debiltating levels of ME/CFS.
One of the most important things that is needed to be done is that the mild level of ME/CFS is described and understood better and clear diagnostic criteria are developed. They canadian consensus criteria are extremely good in my opinion to correctly diagnose ME/CFS. However, they do so only from an advanced progress of the illness. This is unacceptable because patients who are mildy affected with ME/CFS and where the trigger is unknown or different from the most known triggers like covid, EBV or vaccines will go on on odyssees from doctor to doctor and in online searches without results and won’t find help because the doctors and the information online can’t provide them with an understanding of the mild expression of symptoms of ME/CFS.
I have posted this link before but I think it is sound to provide it again because this group of clinicians and patient-clinicians from a Melbourne institute for GP medicine are the only ones who have a clear idea of how mild ME/CFS looks like and how to diagnose it!
https://www.youtube.com/watch?v=EUIdbbwcnAE&t=3278s
Dr Klimas is a advocate of CFS from the 1980’s not the atypical polio history 1934 pandemic through to the ME 1969 WHO classification. When is the ME history going to take credence over the fatigue symptom model? Until Dr Klimas and others look at the ME history nothing will be forth coming because the cause of atypical polio has been denied even though it was part of the UK Royal Free Hospital 1955 outbreak. Dr Byron Hyde avoided the connection whilst in Australia when questioned (Alison Hunter Memorial Fund) but stressed the importance in his ME London Conference speech 2006. How long does this pretense have to continue at the expense of the world population?