Health Rising covered this fascinating gut/immune/metabolic study in an earlier blog. Now Bronc is back with an interview with Dr. Armin Alaedini – the senior author of this study. Note that we just covered a study suggesting that the gut could play a major role in the low serotonin levels, ACE2 dysregulation, and at least some of the autonomic nervous system and immune issues in ME/CFS.
First, Bronc, a patient in the UK, gives us a brief update on the situation with the health service there, and then dives into the Alaedini interview.
Update From the UK
Here in the UK, the Department of Health and Social Care has announced a plan to improve the care provided to people with ME. It includes an acknowledgment that there has been a lack of biomedical research into ME but fails to acknowledge the very negative impact this has had on the lives of people living with the illness. It also fails to point the finger at those responsible for this – the National Institute of Clinical Excellence, and the Medical Research Council amongst others. It’s also one thing to call for more research into ME – as has been done – it’s quite another to provide the substantial sums of funding needed to accomplish that – and that has not happened.
At the same time, the DHSC has issued a consultation asking for views about the plan which includes a section about disability benefits and how the Department of Work and Pensions can improve the service it provides to those people who claim disability benefits. This tragically laughable comment ignores the war the DWP has waged on people claiming disability benefits since 2010. The DWP has consistently failed to acknowledge the debilitating nature of ME and instead focuses on the fluctuating nature of the illness to deny many people with ME disability benefits such as ESA and PIP. To compound matters, the British government recently announced that it wants to make it harder for people to claim disability benefits.
Thankfully, there is plenty of evidence revealing how people with ME suffer from a suppressed immune response, which accounts for many of the debilitating symptoms of the illness.
Suppressed Immune Response Could Account for Many of the Debilitating Symptoms of ME – An Interview with Armin Alaedini
Dr. Alaedini has published 4 studies on gut issues in ME/CFS.
I recently talked with Dr. Armin Alaedini about his recent research into this issue. Dr Alaedini is an assistant professor at Columbia University and principal investigator at the Alaedini Lab. Its research is aimed at identifying ‘novel’ biomarkers, understanding disease mechanisms, and finding therapeutic targets in gastrointestinal and neuropsychiatric diseases.
He is also the chair of the ME/CFS Biospecimen Resource Access Committee at the National Institute of Neurological Disorders and Stroke and a member of the Neurobiology of Pain Study Section at NIH. He’s the senior author of 4 ME/CFS gut studies.
Dr Alaedini took time out of his busy schedule to talk to Bronc from Phoenix Rising about his research into ME, but first, check out what Suzanne Vernon – a co-author of the study – wrote on the Bateman Horne Center website about how the study happened. The genesis of this study, which dates back to 2009 – and the formation of the Solve ME/CFS Biobank – demonstrates why the Biobank and efforts like DecodeME can be so helpful.
Suzanne Vernon on the Genesis of This Study
Intrigued by Alaedini’s work on post-Lyme Disease, in 2009, Suzanne Vernon – one of the study co-authors – asked him to collaborate on an ME/CFS study. Alaedini used some of the samples from that study for the 2023 study.
I met Armin Alaedini in 2008 at a meeting in San Francisco that was about solutions for Lyme and other tick-borne diseases through cutting-edge science. I was fascinated by his presentation on immunological findings in post-treatment Lyme disease and I approached him about collaborating on ME/CFS.
At this time, I had just started as the scientific director at the CFIDS Association, now Solve, and had the idea to set up a biobank of ME/CFS samples as a resource to drive and advance cutting-edge ME/CFS science. One year later, the biobank was jumpstarted because Science magazine published the paper describing an infectious retrovirus in the blood of ME/CFS patients.
Within days of that paper being published, blood banks and pharmaceutical companies were in search of blood samples from ME/CFS patients in order to validate the findings, develop tests and treatments. This motivated a collaboration between Solve and 5 ME/CFS clinical centers to collect blood samples from their well-characterized patient populations for biobanking and distribution to blood banks and pharma. Since that time, those precious blood samples have been used in multiple research studies (including this one).
In one of our first collaborations, Dr. Alaedini and his team at Columbia examined ME/CFS blood samples for signs of inflammation. Not finding evidence of inflammatory markers in ME/CFS, he suspected a defect in specific acute-phase immune responses in ME/CFS or a lack of the instigating microbes at the time of the blood draw.
To test this, he tapped into two different studies that had blood samples. The first were those 2009 blood samples from the SolveCFS BioBank that included 131 ME/CFS samples and 86 healthy control samples. The second were blood samples from a study led by Sanjay Shukla and Dane Cook. This super cool study (“Suppresssed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome“)used an exercise challenge to show that there was an increase in bacterial translocation into the blood and slower clearance from the blood following exercise in ME/CFS patients.
The result of this impressive collaborative research study is a compelling explanation for what could be causing PEM.
Check out the earlier study that this one built on.
The Armin Alaedini Interview
- Antigen – any foreign substance that evokes an immune response in the body. Dietary antigen – a food particle that sparks an immune response; bacterial antigen – a bacterial particle that does the same. It’s usually the immune response that does the damage.
- Increased gut permeability – leaky gut; where the barrier between the gut and body breaks down – releasing bacteria and food particles into the bloodstream – causing an immune response.
- Bacterial and dietary translocation – the movement of gut bacteria and food particles through the gut wall into the bloodstream.
- Innate immune responses – the quickest immune response to damage or pathogen entry. Often associated with inflammation.
How did you get involved in the field of ME research?
I have always been interested in the study of complex medical conditions, especially those that are poorly understood and understudied. I became specifically involved in ME research because of my acquaintance with Dr. Suzanne Vernon, who at that time was the chief scientific officer at The Solve ME/CFS Initiative. I was fortunate to have her support for an NIH-funded project, which resulted in our recent publication that demonstrates how microbial translocation links gastrointestinal, immunologic, and metabolic defects in ME/CFS.
2) In the paper you co-authored, “Suppresssed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome“, it notes that the relationship between immunologic, metabolic, and gastrointestinal abnormalities remains unclear.
In your study, you examined two groups of people with ME: one at rest and one undergoing an exercise challenge. They were compared to a group of healthy people. Can you explain what differences you noted between the healthy control group and the people with ME and between the two groups of people with ME? What may have caused this elevated antibody response to microbial agents in people with ME?
I had been particularly intrigued by the fact that gastrointestinal complaints are common in ME/CFS. Data from the patients in our study clearly confirmed this, showing that gastrointestinal symptoms were indeed much more common and more severe in ME/CFS study participants than in the non-ME/CFS controls.
Along with this, we found a specific marker of injury or damage to the intestinal lining, called FABP2, to be higher in the blood of ME/CFS participants than in controls, providing a potential biological link to at least some of the associated gastrointestinal symptoms. Increased intestinal permeability due to damage can lead to greater translocation of dietary and microbial antigens, which are typically constrained within the gut lumen, across the intestinal barrier. This, in turn, may result in an immune response to those translocated dietary and microbial products to counter and remove the potentially inflammatory antigens from systemic circulation.
Indeed, our data pointed to a significant increase in antibody responses to microbial and dietary antigens in ME/CFS patients in comparison to controls. What especially surprised us, however, was the fact that we did not observe an expected rise in the more immediate, or what we call “acute-phase”, innate immune responses. Specifically, we found that despite the increased markers of intestinal damage and higher antibody responses, ME/CFS patients did not exhibit a significant acute-phase immune response to counter-circulating microbial products.
This was suggestive of a suppressed systemic immune response that could possibly explain some of the ME/CFS symptoms.
3) Your study also noted you found an ‘enhanced antibody response to dietary antigens in ME/CFS’. What might be causing this?
The antibody response to dietary antigens is likely part of the same process resulting from a dysfunctional intestinal barrier that results in an enhanced immune response to the contents of the gut lumen. These would include both microbial and dietary antigens that the immune system is generally tolerant to and does not mount a significant antibody response against under normal conditions.
4) People with ME suffer from post-exertional malaise which means that exercise will exacerbate their symptoms. What differences did you note between the healthy participants and people with ME who took the exercise challenge? What might be causing the differences in their response to exercise?
Intense exercise is known to cause increased intestinal permeability. Therefore, a maximal exercise challenge can be a particularly useful tool to better understand the effect of gut barrier function on the dysfunctional immune responses we were seeing in the ME/CFS cohort.
The data from the exercise challenge confirmed our earlier data, suggesting that ME/CFS patients have a dysfunctional immune response, characterized by a suppressed innate/acute-phase response that is ineffective at countering microbial translocation from the intestinal tract into systemic circulation.
At the same time, another part of the immune response, the adaptive immune system, tries to compensate for this dysfunction by producing antibodies against those microbial antigens. However, the antibody response appears to be inadequate, as the ME/CFS patients continued to have increased circulating microbial antigens. We hypothesize that these microbial antigens can trigger downstream inflammatory responses that impact the central nervous system and may contribute to some of the hallmark symptoms of ME/CFS, such as fatigue.
We also compared metabolic responses in response to exercise between ME/CFS and control study participants. Of particular significance, we found a suppression of glucose and citrate metabolic responses in ME/CFS that to some extent correlated with the suppressed innate immune responses in these patients. This dysfunctional metabolic response is not only conceivably capable of contributing to the observed immunosuppression in ME/CFS, but it may also further underlie energy deficits that drive ME/CFS symptomology.
Our data pointed to defects in specific metabolic responses involved in energy production, as well as in specific acute-phase innate immune responses that are supposed to counter microbial translocation by removing circulating LPS and other microbial components from blood.
But more interestingly, the suppression of these responses (metabolic and immunologic) correlated, suggesting a relationship or interaction between them that gives potential clues regarding causality. There is, in fact, prior data showing that suppressed glucose and citrate metabolic responses have a direct negative impact on innate immune responses.
Interestingly, those same metabolic responses in our study participants also correlated negatively with IL-10, an immunoregulatory cytokine that is known to be expressed in response to microbial products through different signaling pathways and to be particularly important as a key mediator of intestinal immune homeostasis.
We believe that the observed increase in IL-10 levels in ME/CFS during exercise limits the inflammatory reaction triggered by circulating microbial products, while enhancing the antibody-mediated clearance of translocated microbial and dietary antigens, as was clearly seen in our study.
There is also data from previous studies indicating that glucose deprivation can upregulate IL-10 production. So, there seems to be a mechanism here whereby the suppression of metabolic responses involved in energy production not only directly dampens the innate immune cell function, but it also enhances IL-10 production, which further limits the expression of acute-phase immune responses that are meant to counteract microbial translocation.
There is data from other studies indicating that uncontrolled microbial translocation is associated with neuroinflammation and cognitive dysfunction in the context of other conditions. This is important, because brain imaging studies in ME/CFS are in fact suggestive of low-level neuroinflammation and altered brain function in conjunction with impaired cognitive performance and other associated symptoms, including in response to exercise.
5) In your study, you observed an increase in antibody responses to both microbial and dietary antigens, reflecting greater epithelial cell damage, which point to enhanced translocation (movement) of gut luminal antigens across a compromised intestinal barrier in ME/CFS. Did your findings point to a possible treatment for this damage to the intestinal barrier?
Indeed, the data point to a number of potential targets to consider for therapy in the context of ME/CFS. These include reducing or repairing the intestinal damage in order to decrease the microbial translocation; blocking or sequestering the already translocated microbial antigens; reversing the identified defects in the acute-phase immune responses towards the microbial antigens, and targeting the suppressed metabolic pathways.
Indeed, it may include medications directed at the targets I previously mentioned, such as specific immunomodulatory agents, or inhibitors of intestinal barrier dysfunction, or activators that reverse the observed metabolic dysfunction.
As we don’t yet fully understand the cause-and-effect relationship between these potential immune, gut, and metabolic targets, more research is needed to better characterize the interaction between them in order to move this research toward the development of effective therapies.
Dietary approaches can certainly be envisioned to have a role in treatment because diet can impact the specific pathways involved. For example, dietary change alters the gut microbial population, which can lead to positive changes in gut barrier function, or it can lead to the production of certain metabolites by the gut bacteria that potentially counteract energy-producing metabolic dysfunction in the body.
6) What further research is needed to address the issues highlighted in your study?
More research is needed to better understand the relevance and level of contribution of the identified defects in the intestinal barrier, immune response, and metabolic pathways to ME/CFS symptomology, as well as to further characterize the molecular pathways involved, in order to move this research closer to development of effective treatments for ME/CFS.
The article suggested that endotoxemia (the presence of bacterial toxins in the blood) could be causing many symptoms in ME/CFS. If endotoxemia is present in ME/CFS, what would it take to show that?
We already have direct data pointing to low-grade endotoxemia in ME/CFS. In the recent study we published, we not only showed an increased immune response to microbial antigens but also increased levels of LPS in response to exercise in ME/CFS patients compared with healthy controls. Other groups have also shown increased microbial products, like bacterial DNA, in ME/CFS.
Taken together, the data point to low-grade endotoxemia that may explain many of the symptoms associated with ME/CFS, such as fatigue and flu-like symptoms.
The GIST
- Thanks to Bronc from Phoenix RIsing for allowing Health Rising to post his interview with Dr. Armin Alaedini. Dr. Alaedini recently published a remarkable study suggesting that problems in the immune system, the gut, and the metabolism could be “conspiring” together to produce post-exertional malaise in ME/CFS
- Using samples stored in the Solve ME Biobank, some of which dated back to 2009 and the XMRV saga, this study took a deep dive into the immune system, the gut, and the metabolism.
- The results made it clear that exercise was indeed causing ME/CFS patients’ guts to leak – spilling gut bacteria and food contents into the blood. As that happened, one side of the immune system – the antibodies – leapt into action. Another side, though, the early inflammatory immune response did not.
- Plus an anti-inflammatory factor called IL-10 that knocks down the early immune response and interferes with glucose metabolism was elevated in ME/CFS – setting the stage for impaired energy production.
- This study found that while exercise significantly increased the levels of two key energy factors (citrate, glucose) that power the early immune response in the healthy controls, it did not do so in ME/CFS.
- That suggested that the early immune response against the bacterial invaders simply didn’t have the energy to get going in ME/CFS. That lapse in protection allowed toxic bacteria to persist in the bloodstream in people with ME/CFS.
- The findings suggested, then, that a metabolic breakdown that hobbled the early immune response allowed high levels of bacteria to persist in the bloodstream of people with ME/CFS after exercise. That produced a condition called “endotoxemia” whose symptoms (fatigue, cognitive changes, headache, nausea, increases in heart rate, and decreases in blood pressure) bear some similarity to ME/CFS.
- More study needs to be done, but Dr. Alaedini proposed that if his hypothesis is shown to be true immunomodulatory agents, inhibitors of intestinal barrier dysfunction, or drugs that reverse the observed metabolic dysfunction could be helpful.
- Dr. Alaedini is currently attempting to secure funding in three areas: exploring defects in gut barrier function and gut immune response, developing an animal model that mimics the gut-immune-metabolic dysfunction they identified, and exploring the gut-immune-metabolic axis in post-infection syndromes such as long COVID and Lyme disease.
Metabolic defects appear to be contributing to the dysfunction in the immune response to bacterial translocation and endotoxemia through the mechanism we describe in the paper. However, we believe that the root cause of the endotoxemia lies in gastrointestinal dysfunction.
Our data point to multiple potential therapeutic targets for ME/CFS to explore at the levels of metabolic, immune, and gut barrier function. Several previous studies have identified mitochondrial abnormalities in ME/CFS (which may underlie the metabolic dysfunction and energy deficits).
To move forward, we need better-controlled human studies and relevant animal models to replicate prior studies and better understand if and how they might contribute to ME/CFS symptoms. In other words, we need studies directed at delineating the cause-and-effect relationship between the observed metabolic dysfunction on the one hand and the ME/CFS-associated symptomatic response on the other.
These may include characterizing the potential genetic and proteomic underpinnings of the observed metabolic deficits, the integrity of the gut barrier function at the cellular and molecular level, and the mucosal immune response at the cellular and molecular level (both adaptive and innate).
What are your next moves? Have you tried to get a larger study funded, and if so, how did that go? Are you doing any other work on ME/CFS or related diseases?
We are currently seeking more funding for studies in three areas in particular. One is to focus on the gastrointestinal system and specifically on the defects in gut barrier function and gut immune response in ME/CFS through the direct study of the gastrointestinal tract in patients (i.e., going far beyond just blood work). As part of this, we’re also seeking to understand the relevance of food sensitivity/intolerance, given its high prevalence among ME/CFS patients.
Additionally, we would like to develop an animal behavioral model that recapitulates the specific gut-immune-metabolic dysfunction that we’ve identified in ME/CFS patients in our recent study. The development of a relevant animal model of ME/CFS may greatly advance our understanding of ME/CFS and aid in the development of therapeutics.
Finally, we’re interested in exploring how ME/CFS and post-infection syndromes, like those occurring after COVID and Lyme disease, are related by exploring the same gut-immune-metabolic axis in those patients. Ultimately, the mechanisms and the potential diagnostic tools and therapeutics developed for ME/CFS may be relevant and applicable to subsets of patients with various post-infection syndromes as well.
I have had a leaky gut for 20 years and have tried everything to combat my issues with M.E. I found this person online https://drgominak.com/about/ and she said that B Vitamins and D vitamin can help leaky gut. I took the B’s but they kept me up all night so I stopped them. I could not take the D orally because of the leaky gut so I got injections. I have been taking 100,000 IU every two months by injection. The gut is healing and I can get more in now. To my surprise it healed my gum disease and while I was at 10’s for the pockets and had lost 3 teeth and so sensitive all that is gone. I tracked the Vitamin injections with the lab results. I did nothing else during that time so I know it is the injections. Thought you might find that interesting.
Roberta, how long have you been taking the injections?
25-Jun-08 Test Result 84
06-Aug-09 Test Result 79
24-Oct-14 Test Result 96
04-Oct-17 Test Result 79
04-Mar-20 Test Result 58
17-Aug-20 Test Result 85
06-Oct-20 Injection
12-Nov-20 Test Result 85
06-Jan-21 Test Result 77
29-Jan-21 Test Result 88
02-Feb-21 Injection
09-Feb-21 Injection
16-Feb-21 Injection
12-Mar-21 Test Result 99
23-Mar-21 Injection
06-Apr-21 Injection
20-May-21 Test Result 114
08-Jul-21 Test Result 142
09-Sep-21 Test Result 158
14-Sep-21 Injection
18-Nov-21 Test Result 130
23-Nov-21 Injection
14-Dec-21 Injection
10-Jan-22 Test Result 125
20-Jan-22 Injection
07-Mar-22 Injection
29-Mar-22 Test Result 121
07-Apr-22 Injection
08-Jun-22 Injection
14-Jul-22 Test Result 130
14-Jul-22 Injection
20-Jul-22 Injection
23-Sep-22 Test Result 139
26-Sep-22 Injection
18-Jan-23 Test Result 112
20-Jul-23 Injection
23-Oct-23 Test Result 133
Wow! Great data, thanks! So your first injection was in 2020? This sounds so simple and yet so promising. Thanks very much!
Simple but expensive because the docs won’t give to you and the naturopath’s charge for testing and injections. Funny thing is I didn’t expect real results. I hoped but really didn’t think it would work to the length it did. I thought I might sleep better but to have it heal tissues was very unexpected and very very exciting. Needless to say I am staying the course!
Ah. Right. And insurance doesn’t cover it. Well, we’ll see. It was your comment about your gums that was relevant for me. Yes, I have all the other afflictions, but nobody that I’ve ever seen mentioned, “By the way, it’s curing my terrible gum problem.” Wowee! Proof that it’s doing something good, that will help me no matter what. I’m all over that! Thanks for your response, and blessings on you. Cheers!
Yes it was a wonderful surprise to have the gums healed…I only wish I had known before I lost the 3 teeth! lol Oh well I know now and I have zero sensitivity, no abscesses and no deep pockets. I hope you get the same results! If it is curing the tissues in my gums I assume it is curing the tissues in my stomach so hoping the leaky gut will be gone soon. I am definitely better than before and as you can see I track everything I can. Wishing you all the best in your journey.
What lab tests did you get? Did it correspond to changes in symptoms. Thanks
What symptoms are you asking about. There are so many as you know.
I’m just wondering what the test results refer to. My friend is trying vit b but is having severe headaches. I’m just trying to see if this might benefit her. Thanks
They are vitamin D injections. I got tested and then got injections. It shows that in the list. If you look at my first post on this I could not take the B vitamins cuz they made me stay up so I moved onto Vitamin D and then I got some unexpected and amazing results. 🙂
Ah so the test results refer to vit D levels. Thanks that’s really useful
WHy is it that more studies need to be done? I’ve heard this for 30 yrs already.
Exactly!
It is tiring to hear again and again! Unfortunately, more studies particularly need to be done in ME/CFS because of the size of our studies. We don’t generally get big studies that can stand on their own, and in fact, few studies can stand on their own – they need to be validated by another group.
It’s rare actually to see a study finding simply validated. An attempt at replication usually includes the next two or three logical steps which does move things forward.
Still, it would be great if we could settle on a consensus.
Hi Cort or anyboddy, way to ill and brainfogged. on how many patients was this study done and how many controls please?
is it not time for ME/cfs fr stooltransplants trials? instead of mousemodels, etc Like Kristi wrote, the gut comes every time back and back. Maybe not a total cure but a bit better would be nice instead of laying here in a dark room.
Sorry but this has already been tried. stool transplants do not seem to alleviate symptoms in ME/CFS:
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04227-y
thanks!!!! no more brain, etc..
Thanks for posting the link!
Exactly!
This all sounds plausible.
I just wonder – PEM can be induced by all sorts of stressors: physical exercise, cognitive exercise, mental overload and even orthostatic stress. Do all of these influences lead to intestinal barrier dysfunction? Is there any evidence for this? In the meantime I would not put this hypothesis central stage, just because: only what explains PEM will explain ME/CFS (my personal opinion).
Good question, I’d also like to know this
So far as I know there’s some evidence for exercise. I would be shocked if anyone else had assessed any of the others, though.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684203/
Yes . I believe a stressor is a stressor when it comes to gut cohesion
Thank you! I had no idea that PEM could also be brought on by cognitive exercise and mental overload (though it obviously does). That would explain why I get so fatigued sitting and working on my laptop! Do you have any studies or papers that you can link me to for that?
“One year later, the biobank was jumpstarted because Science magazine published the paper describing an infectious retrovirus in the blood of ME/CFS patients.”
If only we could focus most research on the pathogens that cause this illness and find something that would eradicate the root cause. I appreciate all the research of these dedicated folks, but after 40 years of illness, the things that have helped the most (even if temporary) were things that kill the pathogens. For years we have heard about studies of the effects of ME/CFS (“this is what happens to the body”). I honestly don’t care as much about the effects of the illness (which implies a focus on treating symptoms) as I would like to know the root cause and how to stop whatever pathogen is provoking it (yes, I’m convinced it’s a pathogen above all, and probably one engineered in a lab, which is what has made identifying it so very political/difficult).
Yes, politics seem to be driving all of this. I mean really…50 years of nothing, then funding being channeled away from the truth. Its not like out govts havnt done it in the past
Yes, a real tragedy.
These are just the vagaries of science I believe. Pathogens were a big area of focus in ME/CFS at first but interest fizzled over time. At one point I was told the NIH specifically said they would not fund any more pathogen research in ME/CFS.
It wasn’t just ME/CFS – I remember Kristin Loomis of the HHV-6 Foundation bemoaning about ten years ago how difficult it was to get pathogen work funded in this country.
With the emergence of the coronavirus, though, I was told that “pathogens are back!”
Major Epstein-Barr virus findings in multiple sclerosis have also led to more interest in that pathogen. The problem has been the post-infectious aspect – until now no one has been interested in the ability of pathogens to produce long term chronic illnesses like ME/CFS.
The findings here relate to some other recent information presented on Health Rising. The gut definitely plays an important role in these disorders. It may explain why TUDCA contributed to the recovery story in ME/CFS since it detoxes the liver and combats leaky gut syndrome. Also, the disruption of seritonin in long Covid noted by the U. Penn is interesting since seritonin is produced in the gut and impacts the brain and sleep.
Tudca is what cleared all of my food sensitivities. I can now eat everything, yet I still suffer from PEM. From my research, I believe it’s the lack of bile salts and digestive enzymes that lead to the gut problems and food intolerance as a result. Our food is fermenting in the gut without the necessary enzymes. However, I do not believe this is the root cause. My illness started with 6 weeks of really bad headaches after a summer flu. The gut problems appeared two years after that and only after drinking 1l of kefir a day for over a month. I strongly believe the problem starts in the brain. It is what controls everything else after all.
Did you start a super low micro dose of TUDCA and work your way up?
Not really. I took Tudca in an attempt to help my liver after years of experiments with all sorts of medication and supplements. It was about 2-3 weeks into the sumplementation when I realised that i had not had a reaction for a few days. I did not think much of it at the time but got curious when the reactions returned about a week after stopping the supplement. I then restarted it, and in a few days, the reactions were gone again. Tudca turned out to be one of my best discoveries however eliminating the reactions has not cured me nor has it helped the crashes. I don’t think crashes after mental exertion can be explained with a gut permeability or microbial translocation through the gut lining. I am more inclined to believe the theory of the BBB permeability and neuroinflamation being the root cause.
Can you tell us the brand of TUDCA you took/take? I ask because here in Canada none of the supplements are regulated!!!
A company could put dog food in a castle and call it TUDCA and get away with it in Canada.thanks for posting about tudca
I couldn’t agree with you more on your BBB theory. Sounds like you’ve had a similar history as me in terms of being sick for many years and trying all meds and supplements. It’s no wonder studies show stroke patients develop gut permeability following a stroke. Starts in the brain more likely than the gut. Thank you for giving me the final push I needed to give TUDCA a shot. It’s the last and final I’m willing to try. If I can get the same response as you then I’ll take it.
Interesting that TUDCA has been used in Chinese medicine for years. I am going to try it now that you mention it helped you. I went to a TCM Doctor and he gave me some energy herbs and they got me moving after many many years of being stuck on the couch. They did not cure me but gave me the energy to have a better quality of life. I infused them in glycerine to make them palatable.
Here’s the recovery story
https://www.healthrising.org/blog/2023/10/02/efthymios-artificial-intelligence-chronic-fatigue-syndrome-recovery/
For me, my gut and extensive food intolerances have been a central focus for me simply because my reactions to food have been so extreme. Also what happens in my gut appears to significantly affect my brain (Michael VanElzakker PhD). Also my autonomic nervous system (ANS) seems to be involved, as my sympathetic nervous system and immune system, wind each other up and my parasympathetic nervous system, seems to calm my immune system down.
And there’s something else that seemed to going on too. I was caught by something else. My thinking is that it’s along the lines of Robert Naviaux’s cell danger response. I believe my improvement came through spending years and years trying to get all my ducks in a row, consistently enough, to unlock something. And maybe each person has their own, personal combination lock, that needs to be painstakingly figured out and unlocked, if that’s possible.
I still have issues but they’re more manageable. I can make myself worse, if I do too much and am too stressed but if I rest and relax, I can now regain some energy relatively quickly. I’m not perfect, or completely ‘cured’ but I’m a whole lot better than I was and that makes a huge difference.
Hi, Tracey Anne, like you I also believe Robert Naviaux’s research on the cell danger response could help address many different chronic “incurable” diseases. I would recommend anyone with a chronic disease to read his research at the links below:
https://www.sciencedirect.com/science/article/pii/S1567724918301053
https://www.sciencedirect.com/science/article/pii/S1567724913002390
https://www.sciencedirect.com/science/article/pii/S1567724918301053?via%3Dihub
“Metabolic features and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment” – Below is an excerpt from this link:
“When the methods of systems biology are applied across several different chronic disorders, their similarities are brought into focus and a common root emerges. This shared root is the failure to heal completely (Fig. 1, Fig. 2). Once the pathogenic trigger has been treated or removed, chronic disease persists because healing is incomplete. Abnormal persistence of a normal phase of healing cannot be cured using pathogenesis-based treatments.
Each chronic illness can be reframed as the result of the abnormal persistence of a normal phase of the healing cycle (Table 1). If healing can be rebooted or unblocked after it has been derailed, cures of disorders once thought incurable may one day be possible.
Table 1. Provisional classification of chronic diseases caused by incomplete healing and persistence of the cell danger response—the pluricausal diseases.
CDR Phase 1 Disorders— Inflammation CDR Phase 2 Disorders— Proliferation CDR Phase 3 Disorders— Differentiation Hypometabolic Survival States (HSS) and Post-infection Disorders
Implications for ME/CFS and long-COVID
Hypometabolic survival states (HSS), like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), are offshoots of Phase 3A. A mitochondrial hyperfusion loop can occur in Phases 3A-C.
Conceptualizing myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and related multisystem chronic fatigue syndromes like long-COVID as hypometabolic survival states (HSS, Table 1) has important implications for treatment. A highly evolved hypometabolic state like hibernation, brumation, estivation, torpor, diapause, or dauer (Gorr, 2017) may be at the root of ME/CFS (Naviaux et al., 2016) and long-COVID.
While it is a well-known axiom in medicine that no treatment works well for every patient, if the common denominator in ME/CFS, long-COVID, and some of the pluricausal diseases listed in Table 1, is proven to be blocks to the healing cycle caused by hypersensitivity to ATP signaling (Fig. 9), expanded research and testing of ATP signaling modifiers like pannexin channel blockers (Mousseau et al., 2018), antipurinergic signaling therapies (Vultaggio-Poma et al., 2022), and other salugenesis-directed interventions may one day lead to new ways of thinking about the origin and treatment of complex chronic illness.
Can new antipurinergic drugs and pannexin 1 channel inhibitors reduce the most disabling symptoms of ASD, ALS, chronic pain, PTSD, Long-COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and post-Lyme syndrome?”
Thank you very much for the gist! So, another study to show a different reaction of the body to exercise – I like these the best, like Maureen Hanson’s urine metabolomics study 🙂 Maybe it would be great, maybe after NIH study publishes, to do a kind of review blog that gives an overview of what kinds of differences in the reaction to exercise/exertion various studies have found so far? I like these best because they show that exertion intolerance is REAL and physiological! It might be a great thing to hand to doctors. If you ever plan to do a blog like that, drop me an email and I”ll try and send you the list of such studies I’ve bookmarked as “PEM studies” in my browser. It might also be a nice tag to add to your blogs to search for this kind of studies, just not sure what the best tag for this might be!
Hi JR,
I think that is a great idea for an article. In the UK where I live the Department of Work and Pensions, which has responsibility for administering disability benefits uses the fluctuating nature of our illness to deny many people benefits such as ESA and PIP.
The so called health professionals who work for the DWP have no understanding of how exercise intolerant PwME are. The more evidence the ME community can gather on this issue the better to show to them that many PwME are physically unable to work; its not a lifestyle choice as the reactionary MSM would have the public believe.
The medical assessors who work for the DWP are breaking the hypocratic oath of do no harm when they deny disability benefits. Hundreds of people have killed themselves after being left destitute after having their benefits removed due to punitive sanctions.
Very sorry about this, crossing my fingers for progress in the UK, wish me luck for my next application in Germany. Yeah, uninformed assessors with outdated views a usual risk here too.
But I am think it’s also a question of how standardised assessment criteria/questions are written – assessors follow these – in my case I can already see from the criteria how they are likely to conflict with/not capture 2 main features of ME/CFS (namely PEM and total exertion/energy limit per day), because they ask “can the patient do xyz – yes/no”: So if technically I could (and sometimes do) brush my teeth while overexerting, but practically cannot/should not because I’d crash or have no energy left by the end of the day and continuously deteriorate), I can see the criteria will have a hard time reflecting this – either the patient will need to say “no” for everything they can only do with overexertion (which is both uncomfortable and may lead to credibility problems because many patients are forced to constantly overexert due to being without help), or if they are unlucky the assessor will put a “yes”. Assessors might also be annoyed by a situation that does not clearly fit criteria.
So if patient organisations really want to effect change, I’d think they also need to analyse where assessment criteria collide with ME/CFS and propose/lobby for alternative wording or ME/CFS specific interpretation guidelines. And changing generalised criteria meant to apply to all diseases to reflect…
I agree with what you say about people’s experience/symptoms of ME clashing with inflexible criteria/questions. I also agree that the national ME charities should be working on this with the DWP here in the UK. I’m not aware that they are though.
Unfortunately, for people with ME their problems with disability benefits also stem from a reactionary political ideology which prevails across the actions of the DWP bureaucracy from the highest ranking managers down to the so called health professionals who administer the assessments for ESA/PIP.
People with ME, and other disabled people claiming benefits, as highlighted by a UN report into the UK in 2018 are seen as malingerers who don’t deserve financial support from the state. As the UN report notes disabled people in the UK have suffered systematic discrimination when it comes to claiming disability benefits. The more science we have to challenge the scientifically inaccurate beliefs of the DWP regarding ME the better.
I agree it’s both rules and mindsets. Best wishes for y’all!!
… the features of one disease (ME/CFS) will be challenging but necessary.
They are my favorite studies as well! I cannot promise a blog right now but I will send you my email 🙂
The article was very informative although I had to skim read due to brain fog. However, I was saddened to see the recommendation for species other than humans being used for further research. Surely there are enough willing volunteers with these post disease illnesses that we don’t need to torture other species? And how about using cell cultures, genetics, etc rather than another living being with its own right to a decent life?
I particularly hate how reference to ‘animal’ studies is usually with no acknowledgement of ethical concerns. I try to read lots of medical books, articles etc but often have to give up because it’s so painful reading about the way humans use other species for our own ends. We are not more important than other species, in fact we are the most dangerous species on planet earth
Hi Jay,
I couldn’t agree more with your statement that we are ‘the most dangerous species on earth’. I am totally against testing on animals and not just for ethical reasons.
I keep thinking that for those of us who are functional but constantly exhausted right now, a quality of life improvement could be achieved via a blood exchange from a healthy donor. I had to have a blood transfusion after a surgery a few years ago because I lost so much blood and I felt amazing for weeks after getting another persons blood.
I realize all this long-term research is necessary but I cannot find anyone who is willing to try the blood exchange on me as a test for immediate quality of life improvement. I realize there is no money to be made from blood exchanges for big pharma and no doctor is willing to take the risk. It is very frustrating, it seems like such a simple option for those of us who just want to be able to exercise without crashing.
‘Hi Lee,
I have heard of a process call apheresis (blood washing)… blood is drawn out , put through a specific cleaning process and straight back in. Takes several hours but apparently seems to have good potential in some areas of illness. Google away, see what you find
Hi Linda, I have read about asphersis and I think it sounds good but it is expensive and I feel like the blood exchange (same as a blood transfusion), if done over a regular period of time would achieve the same results with almost no cost and very little risk. Again, I believe it will not be tried or studied because no one can make any money from it which is very frustrating. 🙂
Hi Lee, Last year I interviewed Professor Carmen Scheibenbogen from the Charite University Hospital Berlin. Her team in collaboration with several other universities in Germany are conducting clinical trials into several potential treatments for ME. One of these includes removing auto anti bodies from the blood using a machine which filters this stuff from it. In a small proof of concept trial the team had impressive results with this therapy and some patients saw great improvements hence the move to the next stage which is the current clinical trial which I believe is due to report results in 2024.
Hi Linda, I have read about asphersis and I think it sounds good but it is expensive and I feel like the blood exchange (same as a blood transfusion), if done over a regular period of time would achieve the same results with almost no cost and very little risk. Again, I believe it will not be tried or studied because no one can make any money from it which is very frustrating. 🙂
Makes total sense to me and I’m quite sure this process was part of my 20 years of Fibromyalgia and CFS. I had an h.Pylori infection which may have caused all the gut damage in the first place, and food intolerances. Once I treated the bacteria and then strictly cut out gluten, grains, dairy and high lectin foods, I rapidly improved. No doubt leaky gut and leaky brain were causing systemic inflammation, fatigue and rapidly fluctuating moods. I’ve been free from those symptoms for 12 months now. The educational resources of Dr. Datis Kharrazian were invaluable in explaining how it all comes together.
I also have the poor conversion of glucose into energy. A low and slow carb diet helps a lot.
I thought any blood level of Vitamin D above 125 is Toxic?
That’s an odd question from a doctor? 125 what? 125 grams might well be (lol) but 125 i.u. is laughably small.