Itaconate Shunt Hypothesis Part 2: Interview with Robert Phair and Janet Dafoe

[@heretoday788]

Robert Phair is a true gift to the ME/cfs community. We are always looking for researchers who are willing to help, and he's one of them with equal parts curiosity and compassion. It's great to see his hypotheses continue to evolve with more research.

[@anitahaviland3036]

Fascinating 35 years ago it was all psychosomatic, and many MDs still think so. I've been up and about using acetyl-l cartine and creatine monohydrate. NADH corrects Lymphocyte Dysfunction Syndrome. I am only at 50% unfortunately. How can this help us who have it better live our lives? This looks as if we would do best on a keto diet. Am I wrong? On a keto diet I am warm. Having any sugar immediately makes me cold. Exercise once drained all of my oxygen to the point that my heart had a spasm and I dropped to the floor. Went to ER, my hands were blue/lavender. I didn't do that again. It was a three mile walk.

[@GodsChild145]

@@anitahaviland3036I don’t see how it would even be POSSIBLE for someone with ME/CFS to walk 3 entire miles…. That’s insane!!! It’s no wonder you were in the hospital. Also your hypothesis on the Keto diet and no sugar and it making you warm or cold…. I don’t think food can change your body temperature and I don’t think changing that would make anyone better… now obviously sugar is inflammatory and with this disease or any disease for that matter the body is completely full of INFLAMMATION, so you are supposed to stay away from inflammatory foods and eat a ANTI inflammatory diet aka we should all be including super foods and antioxidants.

[@riceman78]

Rob\David\Janet and the entire OMF team are an absolute godsend - please never give up. 🙏

[@patrickjohnson1309]

How sure are ya,there a god send?? There been working on it for a decade and to no fruition yet!!

[@GodsChild145]

@@patrickjohnson1309personally I think that the CAUSE and also the treatment and CURE was figured out a LONG time ago…. What was it 2009 or 2011 when Scientists Judy Mikovitz was the lead scientist…. Ummm ANYWAYS I FULLY BELIEVE that they have all been THREATENED with their and their families lives on “not finding” the cure and staying far away from whatever it is or scewing their results to mislead because it all leads back to the ones or shall I say what CAUSED IT and they will NEVER allow that truth to come out.

[@wearitlikeadiva]

Every time I get a notification from OMF about ME/CFS I jump on it to see what the brilliant minds have found in research. I am a 22yr warrior of ME/CFS.

[@terriealabama7612]

Me too! 22 years. The only good thing is the great community of people.

[@oshagyro1988]

I'm 35 yr old, but struggiling with ME/CFS for almost 22yr. And still in hope that one day we get a cure.

[@olivertruswell]

Thank you for all your hard work. Whenever you release a video like this I get excited and this one didn't fail to deliver! I know this sounds cheesy but having hope and dreaming of an end to this illness makes it bearable.

[@elizabethstranger3122]

Im a severe ME patient , completely bedbound for over 2 years, and I feel the same! The only things that makes me not want to give up the fight is my love for my family and friends, and having my hope, and these videos give me so much hope. Having hope makes it easier to wait... waiting to one day live a more bearable existence

[@EndersWorlds]

I was so excited to hear how this theory links into bhupesh prushty's work on HHV-6, I was thinking throughout this what about that theory as a starting point. It's incredible we have these three potential start point's that all lead into the itaconate shunt theory. Looking forward to hearing the next one, it sounds like we might have more of an idea next time whether the theory is looking like a definite (ie not hypothesis but leaning more towards a hard fact). So that's very exciting. Thank you so much for doing these videos, we learn so much about it all, and it has helped me understand how all these thing's we keep reading about in various studies link up, or how they fit together in some places. Fingers crossed your research goes well, wishing you all the luck in the universe and sending you all good thoughts.

[@piper4352]

I appreciate it when Janet is involved in these presentations. She asks the questions which help me understand what these brilliance scientists are explaining. She seems to know when I’m getting lost in his explanations and has Robert expand on his data so I’m able to pick up the thread again. Thank you to both of you, you allow me to regain my hope for the future again.

[@GodsChild145]

Yes without Janet it would be pointless in listening because of the confusion. So THANK YOU JANET ❤

[@timoluetk]

Thank you so so much for your hard work and making it understable for us!

[@bettyjeanpetrinovich7373]

Thank you so much for acknowledging Chris Armstrong. I go back far enough to remember his first presentation, how much sense it made, and how much hope it gave me.

[@gmbowdle]

As someone who suffers from ME/ CFS, the comment about the cat standing in front of the notes, gave me a laugh. In all seriousness, thank you for all the work you are doing on this awful disease.

[@lindabailey1828]

I do not think anyone with CFIDS (like me, 29 years) can understand all of this although I am so grateful for these scientists that dedicate all there time to CFIDS!

[@gloriaharbin1131]

Thank you both for your commitment, devotion, and hard work on solving the science and finding help, for those of us with ME/CFS. Sending love and appreciation.🙏

[@andrewgifford7740]

Thank you to all involved, for your smarts, efforts and science.

[@anonamuss1604]

Thank you so much for this ipdate, you have no idea what these videos mean to me. Every time I start to lose hope I come back here to remind myself that progress is... well.. in progress. Most of ithe content is beyond my fogged brain but I watch it anyway. Each year I think to myself maybe this willl be the year I get my life back but as each year passes, these videos remind me that even though things seem bleak there is light at the end of the tunnel which isn't an oncoming train.

[@riceman78]

I would love to know a bit more about what it will take to prove that this hypothesis and what the timeframe will be for that.

[@patrickjohnson1309]

Me too.

[@Kaylaut]

Me three

[@copperednz]

Incredible work. Yes, this is complex but so exciting! As Janet says, if the hypothesis is confirmed, there could be many diseases that may benefit.

[@2hff728]

So exciting. Thank you Janet and Robert!

[@LifeAtTheCrossroads]

Amazing. I've watched the 1st part of this hypothesis and am just now starting the 2nd part. I'm diagnosed and suffer with CFS, and I am very grateful to you for what you are doing. Thank you.

[@peacekeepermoe]

Thank you for this presentation. Looking forward to part 3 and to hear of any clinical trials if any have started, or some animal studies : )

[@oliviaelliott4623]

I'm long covid since March 2020. This makes sense. Some check-point problem that almost causes a cellular dysfunction. I get fatigued easily and chest pain/lung tightness. I almost feel that I'm not tolerant of histamine anymore.

[@cherylallis2458]

My doc prescribed zyrtec 24 hour to be taken twice a day, rather than once per day as the bottle states. (I take the generic.) I had blood tests showing high eosinophils.

[@craig543]

Such exciting work and just a few days after the German Parliament was talking about ME again. Let's hope some serious European investment is on the cards but thank you for leading the charge.

[@TomSFlint]

Absolutely splendid video. Thank you allnso much for everything.

[@Gusski84]

Thank you Janet/Robert for this hugely informative update and the behind the senses work; all the heavy lifting we suffers don't get to see. Can I add in respect to the timeline question; while a cure would be amazing - and yes wouldn't we all want that to happen - I am curious is a workflow chart with projected dates for experiments/data collection and analyses needed to progress the theory forward? To have a bench mark timescale i.e experiment X & findings end of Q1, and so on, would be so helpful and to know science is happening. Thx again for all your efforts, care, and the fight you put into helping those who can't fight for themselves.

[@christynebliton3139]

This is wonderful work :) How does it relate to post-exertional malaise? Does exertion cause the itaconate shunt to become more extreme through the inf alpha signaling somehow, over 24 hours? Why does it take 5+ days for it to recover back to where you started? Is that something inherent with the innate immune system? I'm in a PEM waiting for it to stop, and as you know, it sucks.

[@Swirleyful]

Did you watch part 1? It went into PEM a little at the end, I think it links to the production of ammonia in the cycle.

[@christynebliton3139]

@@Swirleyful Thanks. I looked at it again. I was hoping for some king of signaling mechanism triggered by the exertion somehow. If I go a little over my exertion threshold, get my heart rate up a little too long or do too many steps, the PEM can be awful, triggering huge inflammation throughout my body - brain, nerves, muscle, gut, POTS - and intense fatigue and lingering brain symptoms for days. To me it seems like the ammonia idea isn't enough, but he didn't really go into it very much. And how do you explain the delay between too much exertion and huge PEM symptoms. PEM timing of delayed onset and long recovery seem like really important clues for modeling to me. Different symptoms go away at different rates too during the recovery. More clues. I'm looking forward to what he comes up with next.

[@shadowcadence378]

@@christynebliton3139 it seems to me that the symptoms of PEM have a lot in common with other recovery processes in the body - from infections, overtraining, hangovers/intoxication, sleep deprivation, massive trauma, etc. So my guess is that science can already explain how PEM works, just not how we get into that state in the first place from such minimal exertion. And maybe that's why Rob hasn't gone into it. For example, the delayed onset of fatigue and muscle pain is something that occurs with healthy people post-exercise as well, so there's probably already a medical understanding of delayed post-exertional symptoms. In fact I think I've read about it before but I can't remember the details right now. My own theory regarding the long recovery time (purely based on common sense and speculation, take with a grain of salt) is that it has to do with a) getting out of the energy "debt" created by the itaconate shunt and b) detoxing from ammonia and possibly other toxic metabolic byproducts, like lactic acid. I've read about the symptoms of lactic acid poisoning and they match up exactly with my own PEM symptoms - I would love to hear more about this from Rob. It feels like my body goes through various stages of recovery from PEM that surely correspond to different cellular processes that take a lot of time.

[@EndersWorlds]

@@shadowcadence378 ooo I've never thought of that before -that post exercise symtoms in healthy people can be delayed, like the pain in your muscles that you get if you're not very fit and do a lot of exercise for the first time in ages, you get that lactic acid burn-y feeling for a few days, and if I remember correctly (it's been a while as had ME a few years now) when I got that years ago it would kick in the day after and often be worse on day 2 for me before slowly over several days easing off. That's really interesting to remember that! So glad you pointed it out.

[@EndersWorlds]

@@christynebliton3139 after reading the comment by shadow cadence I looked up what they said about healthy people's muscle pain that peaks two 2-3 days after exercise, just like PEM does. I don't know if it's a similar process or not but they're saying that the exercise causes slight damage to the muscle fibers and this then triggers inflammation (cytokines flood the system sending everything that's needed to the sight of the 'injury' to heal it. So the pain is actually to do with the healing response from the body kicking into full gear. I wonder given our bodies definitely seem to feel very inflammation-y during PEM, if this is something similar.... probably not exactly the same, but if our bodies are literally releasing widespread inflammatory cytokines. Exactly why and how on a cellular level, and how that fits into everything else, I don't know though. But I'd love to, I think the OMF are doing a detailed study on PEM if I remember correctly like currently?

[@brobinson8614]

That was good. I clicked on the video playback speed to increase it to 1.25 and found the information was easier to follow as the flow of speech was better.

[@andocobo]

Amazing vid, thanks Janet and Rob! I’m so grateful we get this level of detail from such a knowledgable scientist, I hope this work leads to a treatment soon!

[@riceman78]

This is awesome research. I donate monthly to the OMF. Thanks so much for doing these videos!

[@ryanneilcarr]

Why bother? Not accomplished anything in years. Scammers. Theres no such thing as ME/CFS to start with. Patient is misdiagnosed. CFS isnt a single disease. They say theres a specific disease called ME/CFS. No such thing. 100% dishonest people.

[@riceman78]

@@ryanneilcarr You are an idiot

[@maxyazhbin826]

high ammonia can be fixed with l-arginine alpha ketoglutarate and the functional medicine practicioners have know that for decades. Functional medicine practioners have known for decades that various amino acids to help the various intermediates in the krebs cycle. Would be interesting if they measured the ANA's before any treatment for ME/CFS just to see if the high interferion alpha could just be lupus. I saw succinate to fumurate conversion was decreased, functional medicine would suggest succinate to increase, yet Ron found succinate

[@Kaylaut]

Thank you. This fills me with hope, and it was satisfying to listen to. I am sure I will listen to it several times.

[@Swirleyful]

Thank you so much for this amazing research. Can't wait for it to get to the next steps already! But like many, I wonder if we have latent viruses, could they take hold during immune suppression? Or could they come right back afterwards and switch the switch back on?! I also wondered if there is any connecting between the bit about mRNA signaling being part of the feedback loop and those who developed a form of long covid or an MECFS relapse from the c shots. Maybe I'm reaching a bit with that speculation! These are all my brain fogged jumbled thoughts.

[@GodsChild145]

Myself and several others I have talked to shots have been the CAUSE of our ME/CFS

[@Truerealism747]

@@GodsChild145 these latest ones or any others I haven't of course had these latest ones but I had CFS then fybromyalgia started 6 months after tetanus

[@missy0610]

I suffer from Post vac Syndrome (thats what its called in Germany) and I am very sure that the Spike Protein from the vaccine can cause the exact same damage as the Spike Protein from the Virus.

[@KittenCasserole]

Fantastic presentation, thanks so much for sharing 🙏🏻

[@thebowserful]

Great video! Would it possible not put the subtitles as always on? I find it very distracting and it hide’s information. There’s a closed caption option in KZbin.

[@kristinae.7084]

So.. . should those of us with ME/CFS consider supplementing with GABA or glutamate/glutamine? Has anyone tried it? Thank you both so much for all the work you do on our behalf!

[@priyaluce]

NOT glutamate. it causes brain to overfire and creates neuronal cell death., See dr Cheney's work. This is why so many PwME are on benzos. Our GAD enzymes are not working so glutamate cannot be turned into GABA, which we are more likely to be low in.

[@Boojerella]

Great question… although glutamate and glutamine can be stimulatory, GABA would get my vote

[@dprice81]

I'm someone who never remembers dreaming. I've gotten sleep tested and they didn't find anything abnormal. I've had IBS and non remembering of dreaming but haven't been really fatigued post exercise until past few years. But I used to have trouble recovering from exercise but I was running a lot and couldn't be considered seriously fatigued the way I am now. Bacteria in the microbiome are supposed to be making gaba. So if microbiome is off, then many metabolites produced by the bacteria are gonna be lower. Gaba is one of those, riboflavin, B12, folate. If not absorbing vitamin d from sun properly, could have low vitamin d status and can therefore produce less vitamin b5. When I take Gaba, I don't really like the effects of it during the day. I can take a little bit before bed and I can remember more pieces of dreams, but I'm not noticing any boost in energy. If I take too much gaba, I feel too drowsy the next day. I've heard higher amounts can bring deeper rem sleep, which you'd think could maybe would feel restful but I already feel super drowsy next day before I get anywhere near that amount. So unless I can just take small amounts and let my body get used to it, maybe I can take more but so far I just noticed remembering dreams taking a small amount but no noticeable increase in energy unfortunately.

[@ProfessorBeautiful]

32:25 Good questions, Janet! & it would not be possible if "dynamite plots" were used; they would obscure the individual data pointsl So kudos from this statistician for that.

[@kimkorsuize]

Thank you guys for this video and hard work ❤

[@Klem19]

This is wonderful thank you Dr. Phair for your beautiful mind and hard work. I have a question. If the positive feedback loop is broken, what happens to ME/CFS patients when another bad infection comes along will they get stuck in this trap again? Thank you.

[@emilier4314]

Thank you for your work. Merci de france

[@ProfessorBeautiful]

This is quite wonderful and illuminating! May I beg you to give links to the diagrams here and in Part 1, in the Description? Hard to read with these old eyes!

[@joannecarver6693]

Could it be a possibility that the ME/CFS controls that have the same lower levels of Interferon-alpha as healthy controls are alternatively being driven by Interferon-beta or Interferon-gamma in a similar fashion? Different interferons are produced in response to different viruses or bacteria, for example, IFN-gamma is produced in the response to Borrelia Burgdorferi (Lyme bacteria).

[@andocobo]

Good point, that seems like a possible explanation

[@Boojerella]

I’ve heard the same in response to Candida, lower levels of interferon, alpha in chronic fatigue, patients due to a Candida, also common in Long Covid

[@eddie8489]

Can someone elaborate on how this explains the ME/CFS that occurs in EDS patients without having an infection as a trigger? Such as in the case of Whitney’s. Was his triggered by an infection? I’ve read that he as EDS, which can cause extremely loose vessels that don’t allow blood to circulate properly. This alone is enough to cause issues like PEM. So why are we ignoring EDS as a possible etiology of the ME/CFS?

[@robinwinifred]

Thank you ❤

[@Boojerella]

This sounds like Robert Naviaux's Cell Danger Response - with the neighbouring cells being triggered for defense. Has this been researched or compared?

[@nickdriver8337]

Is a Part 3 coming? Been over 18 months now, has this been abandoned?

[@janetkeating4641]

What is the mechanism that keeps it on? Is it that the innate immune system is stuck on on it's own, or is it that the acquired immune system isn't coming on to take over to turn it off? Even if drugs could inhibit the feedback loop, if the virus (or whatever agent) isn't cleared, wouldn't it restart? Thank you for your work. This is so on target.

[@shadowcadence378]

my understanding: innate immune system is stuck on its own, but we don't know why yet. there are a number of pathways that are meant to turn off the feedback loop. we don't know which one is broken or why, but it's probably a genetic mutation. it is not caused by an active virus.

[@EndersWorlds]

@@shadowcadence378 I don't think we know yet if it's an active virus, that's being revisited as an idea now because they originally only looked in the blood. An autopsy study recently found HHV-6 in the brain of every one of the ME patients and none of the healthy controls, and there's beginning to be some evidence building of the possibility of a HHV-6 possibly being involved, they just don't know yet if it's a cause of ME or simply another effect. But there's growing evidence in other fields too that viruses can hide away inside places we didn't realise they were, and that this leads to not being able to find it in the blood (which is why previous research kept saying there's no virus), but still causing issues and potentially activating the innate immune system. That's what bhupesh prushty's work that Robert phair mentioned in the video is about. So there could be a link....this itaconate shunt theory could be being triggered by the virus, but also could, as you mention be being just simply not shut off again for some genetic reason.

[@janetkeating4641]

@@EndersWorlds Fantastic answers, thank you both. If you don't mind, what are your favorite sources for following work on this? It sounds like you've dug deep.

[@EndersWorlds]

@@janetkeating4641 Hey, thanks. My sources are usually the research itself, the ME association uk do a fantastic thing for following the latest research - every Friday they do a research roundup, its all the research that's been released that week for ME, and now also long covid, some of it is obviously pretty lame, but the small number of good quality bio-medical studies that come up are worth a read over. I also follow the open medicine foundation on social media, they usually let us know when a new study has been released by them so we can take a look. Then there's health rising which does a blog and he talks alot about different research and stuff that various ME researcher's are working on, so I keep half an eye out for stuff I might have missed elsewhere from him. Between all of that you often end up hearing other people mentioned or other research mentioned, and that's how I first heard about bhupesh prushty's work on herpes viruses, which is mentioned in this video, alot of ME researchers mention about each others work, and that helps point me to yet more good stuff. Some of these people do you tube video presentations too, and I follow all the different charities on you tube for that reason, every now and again they'll post a video of some researcher talking about his or her latest theories and work. I love this stuff, it keeps me sane and focussed on feeling hopeful, rather than disappearing into despair at ME life.

[@leemorgan8865]

I wonder if this links in with the trpm3 calcium ion channel research from griffith university? Thanks to the OMF team for their herculean efforts in producing champagne research on shandy funding.

[@Heriboux2]

I've got one question: In case of ME/CFS with high level of HHV-4 (Epstein Barr Virus), I suppose it's not safe to stop even for one day the Immune system process, even else in a sterile place?

[@reece-700]

There's mention in this talk of the "Initial infection", but what if that infection is an ongoing one, like with Epstein Barr virus being constantly produced in the bone marrow, and being re-activated in times of stress/illness? Wouldn't you then have to create an immune therapy that is able to suppress the EBV reactivation?

[@brobinson8614]

If it is EBV driven, it be more likely an anti viral for EBV. Which I think actually is in development There’s a vaccine also being developed, but 1/5 ME/CFS patients struggle with vaccinations

[@khowsare1]

@@brobinson8614 Hopefully the EBV antiviral will be available soon

[@folaraj6343]

Thank you ❤

[@ceceliablair9177]

Since bacteria can start up the pathway too, could this whole mechanism apply as well to Chronic Lyme Disease?

[@maxyazhbin826]

when i had lyme, the doxycline failed and so did buhner's protocol, but osha root cured it

[@Truerealism747]

Yes listed in Dr TS book

[@cherylallis2458]

This theory would explsin why I have not caught a cold or flu since I got ME/CFS in 2006. I didn't get covid, either, even though I have not been vaccinated and 3 members of my household got it. I stepped in to help them as much ss I could with my limited energy- I was around them daily, wore no mask, etc. Didn't get sick at all. If his theory is right, with my innate immune system stuck in the "on" position, the virus could not get enough energy from me to survive. I did take extra vitamin C, D, quercitin, and zinc as well. Maybe that helped, too. Who knows?

[@missy0610]

You talk about interrupting the positive feedback loop through certain drugs and it then not switching back on after you stop taking those drugs. So thats basically like an immune system reset right? Is this what is happening when we see Long Covid patients get better after a Covid vaccine or another infection? Or Post Vaccine Longhaulers getting better after a Covid infection? Because I always wondered what causes this healing, this might explain it.

[@baileystruss7319]

Thank you so much. So what happens if the stimulus is not a virus or bacteria but other stress? Many of us started that way. Mine started during a severe frozen shoulder.

[@kinnearxx]

several studies have shown now that psychological and physiological stress reactivates latent viruses in the body. To my great surprise, recent testing has shown that pregnancy reactivated EBV for me. and I have no viral symptoms so I wouldnt have known without the testing. I had EBV twelve years ago and it was an extremely mild infection. important to also note that sometimes viral persistance can only be shown in biopsies as it is not found in the blood.

[@nitelite78]

32:26 Is there not the possibility that those two high controls for interferon alpha have some kind of infection or pre-infection that has triggered the innate immune system? In which case they would look similar to MECFS patients.

[@stevethorne4978]

How old is this information? Doing some Google search shows this has been tried but wears off in a few months. Thank you

[@susanphoenix74]

Thank you ❤

[@patrickjohnson1309]

When's the next talk due?? Hopefully not another super slow 5 months!!

[@EndersWorlds]

Alas, science takes a lot of time! Funding issues mostly, science is expensive, and funding is very limited, means you can only use so much équiptment at once, so much lab space, and so many scientists working on the problem. Add into the mix that ME is not an attractive area for people to go into researching, which means fewer researchers available to work on projects and it all adds up to slow science. We just have to wait whilst they beaver away at it. And these guys are working hard, must be very hard to find the time to do a talk for all of us, they're busy doing a thousand jobs at once.

[@FionaEm]

When Robert says that cells adjacent to innate immune cells stay permanently switched on after infection, does that also happen after exertion? In other words, does it only happen at ME/CFS onset, or repeatedly throughout the illness, causing PEM? I'm presuming the latter, because not every case of ME begins with infection, but every patient has PEM.

[@shadowcadence378]

I would really like Rob to talk about cases that were not triggered by a virus - it's a major plot hole in the hypothesis. However, the stuff talked about in this video is not the direct cause of PEM. PEM would be a result of the reduced ATP production of cells and reliance on ammonia-producing sources of fuel. That is explained in the previous video. He hasn't talked about this, but I am wondering if overexertion *might sometimes cause more cells to have the itaconate shunt switch on* and thus causes permanent deterioration after exertion (something I've experienced many many times).

[@Boojerella]

The cells and staying permanently switched on concept.. that absolutely feels like Cell Danger Response. From Robert Naviaux research. I’d love to know if CDR is ever mentioned.

[@michaelkreder2736]

I appreciate the diagrams and illustrations, but for something as simple as TLR4 - where LPS enters the immune system to upregulate NFKB and TNFA, and then IL-6 - why wouldn't he spend time on the VERY WELL KNOWN blockers of TLR4 to stop LPS into the immune system - so folks can at least partially help themselves from chronic immune activation from gut dysboisis - with too much gram negative bacteria that produce LPS. I can only think of 2 reasons.

[@patrickjohnson1309]

Hurry up and get the third talk out! Omf just keep slothing along!!

[@itsstrawman]

This is great work. Sorry for the oversimplification and if I’ve misunderstood but if interferons are produced in response to the presence of cytokines, is an option to treat cytokine levels with anti inflammatories / immunosuppressants in the hope that interferon production/regulation normalises?

[@shadowcadence378]

my understanding is the interferon production is initially stimulated by an infected cell but consequently uninfected ("bystander") cells produce their own interferon signalling loop independently, and in CFS patients this loop is not stopping even after all the original infected cells that triggered the whole scenario are dead. so I don't think that would work

[@areanaangel8964]

Could explain why some people feel "better" after a subsequent viral infection like a cold for a short period of time. Their overactive cells got infect then died from new infection (but new neighboring cells then got turned on, repeating the cycle@@shadowcadence378

[@bscheur7412]

It sounds to me like a viral “reservoir” could be the “river polluting the ocean”!

[@rhyothemisprinceps1617]

I wonder where the reservoir/s is/are? If lungs or intestines - these sites can be tested. I guess bone marrow & liver could be tested, though procedures would be more invasive.

[@patrickjohnson1309]

Is that horizon getting closer or what??

[@khowsare1]

A question: are there metabolic disorders that create ammonia that we already know about and have a treatment for?

[@rhyothemisprinceps1617]

yes, searching YT on hyperammonemia will find medical education videos on the topic - e.g., kzbin.info/www/bejne/m3PJi5-NbadrrbM I think older ppl can be affected by lower levels of ammonia (below the threshold for hyperammonemia), for example my father had multiple system atrophy & was fine cognitively most of the time but occasionally had bouts of confusion that I think were caused by ammonia from UTIs. There are a few papers in PubMed on ammonia & Alzheimer's.

[@pja8901]

Would Tofacitinib be a JAK inhibitor that would work in this hypothesis?

[@ash0787]

so the level of the measured thing is low in blood would that be relative to a severe infection producing flu like symptoms or sepsis ? or is it just because that molecule does not easily get to the blood under any circumstance ? if theres a company specialized in producing the test then do they already know this information about the range of measurements ? is it not possible that the antiviral state could be active in some cells all over the body ?

[@brobinson8614]

Surely some people with ME/CFS somewhere have tried these drugs, maybe for a different reason. And if so how did they go? Wouldn’t we have heard it was successful? Or maybe they just assumed the drug helped them for what their doctor “thought” was wrong, and not for ME/CFS itself

[@brobinson8614]

So I'm back a year later and it turns out 2 people did take these JAK STAT inhibitor drugs. and recovered

[@calebpoirier751]

nutshell: potential drugs will bind to interferon alpha as an antibody (already exists) or block the JAK-STAT pathway. Not currently implemented because of concern about side effects. see minute 43:40

[@ChrisKadaver]

This is interesting. Just 6 months before I came down with ME I tried LCHF diet for maybe 2 months. But I felt quite bad on it so I stopped. I have no idea if it had anything to do with me getting ME though.

[@brobinson8614]

From my reading over the years it seems any ‘major’ stress on the body that’s prolonged (I think more than a week or 2) can trigger ME/CFS

[@ChrisKadaver]

@@brobinson8614 I had other triggers as well though. Like a wisdom tooth extraction surgery. That was the main trigger. But I also was in a really destructive relationship at the time and a way too high stress level on the job I had back then. When I first started losing a lot of hair though, I remenber It hought it had to do with the LCHF diet 6 months earlier. But it didn't take long after the hair loss that I came down with ME. I also figured out later that our water well contained too high amounts of uranium which also are seen in ME patients. So it was probably the "perfect storm".

[@brobinson8614]

@@ChrisKadaver Yes and stress increases hormonal activity that interacts with cytokine communication. Thats can in turn cause immune errors that can make the immune system mistakenly attack a protein with a similar antigen to the foreign pathogen its fighting. And thats the start of auto immunity. Although ME/CFS isn't proven to be an autoimmune disease yet. But Swedish researchers found autoantibodies in a subgroup of ME/CFS patients that targeted the beta2 adrenergic, the muscarinic M2 autoantibodies. Those antibodies already exist for switching on and off, but apparently are more abundant in this subgroup of ME/CFS. Theres also been found in long covid the same auto antibodies, plus several others some that even target cytokines themselves. Which would cause havoc. Those other autoantibodies found in Long Covid have never been looked for in ME/CFS so could be present and could fit the other subgroups of ME/CFS Question. when your exertion threshold drops during PEM does it eventually return to your previous baseline or does it return but a little worse than previously?

[@EndersWorlds]

@@ChrisKadaver this sounds like me, I had multiple physical and emotional stressors in the couple of years leading up to getting ME, working crazy long hours, work stress, money stress, losing weight, doing quite a large amount of exercise (I imagine this on it's own would've been fine but in concert with everything else perhaps added to the mix , I'm always suprised by just how many people with ME talk about how they were really fit right before they got sick and had been doing some kind of training or intense exercise or something), anyway it's like they combined to just mess me up totally, I did get a bout of really bad flu, but that was at least 4 months before I started with ME symptoms so I don't think it was the root cause, though maybe me returning to high working pace quite quickly might've been a factor.

[@baileystruss7319]

Can there be any presentation given showing any link with the metabolic trap hypothesis? I cannot seem to find any common ground in the two.

[@annalocher3114]

he talks about that in the end of the first video. interferon alpha would also turn on the the metabolic trap

[@patrickjohnson1309]

Where are ya?? Get part 3 out!!

[@mariuszara7236]

Ce qualche possibilità di trattamento?

[@keith48993]

Clint Ober - Earthing :)

[@areanaangel8964]

Even the name... Attackanate Shunt.. I dont thats not the spelling but thats what I hear

[@Werter666]

Was this research a dead end?

[@HarmlessHobby]

Bump

[@patrickjohnson1309]

Where's this part 3?? How long do we have to wait??

[@patrickjohnson1309]

Hurry up!!

[@patrickjohnson1309]

Where's this 3rd talk????

[@patrickjohnson1309]

Where's part 3??

[@motherf6969]

In 30 years maybe we will know more

[@beandavidson8482]

#helpmechangethefuture CDC case# 1232781-B4W6H4 B12 education for health care professionals is needed.