Kell and Pretorius propose that microclots are plugging up the capillaries – reducing blood flows to the tissues and causing a chronic ischemia-reperfusion injury characterized by inflammation and high amounts of oxidative stress.
Ischemia–reperfusion injury, hypoxia–reperfusion injury, or reoxygenation injury – whatever name you wish to call it – occurs when a low oxygen state in the tissues is followed by a resumption of normal oxygen flows. Oddly enough, it’s during the resumption or reperfusion of oxygen flows that the big problems – high amounts of inflammation and oxidative stress – occur.
In their 56-page page review paper, “The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications“, Pretorius and Kell propose that infections are triggering a chronic state of reperfusion injury in diseases like rheumatoid arthritis, chronic fatigue syndrome (ME/CFS) and long COVID. In fact, while the authors don’t emphasize it, they suggest that all chronic inflammatory diseases may have an infectious origin.
These diseases have three things that stand out for Pretorius and Kell: they cause a wide variety of symptoms, crashes – periods of exacerbated symptoms – are common, they’re all associated with high degrees of fatigue, and they all affect more women than men.
The possibility that blood clots, strangely deformed red blood cells, and possibly other factors, are impairing blood flows to the tissues, leaving behind an on-again, off-again ischemic environment, seems to make sense. Ischemia-reperfusion popped up in Wirth and Scheibenbogen’s hypothesis, and has been proposed to be behind the muscle pain and fatigue in fibromyalgia as well.
A 2006 study, for instance, found that muscle ischemia-induced pain played a key role in FM patients’ activity limitations. Elvin felt that the reduced muscle blood flows following exercise that he found in FM could be explained by deconditioning and sympathetic nervous system issues. A 2015 study found that an ischemia-hyperpnea test effectively diagnosed people with fibromyalgia.
The Lights proposed that vasoconstriction was decreasing blood flows to multiple parts of the body and causing the buildup of metabolites and inflammatory agents in ME/CFS and FM. The Lights believed that the huge buildup of muscle injury-sensing receptors may have been caused by the need to constantly monitor the muscles for signs of ischemia-reperfusion injury.
Iron-Microbial Connection
Kell and Pretorius assert that it’s not uncommon for intracellular pathogens such as Mycobacterium tuberculosis, Helicobacter pylori, herpes viruses, and enteroviruses to lie dormant until they get reactivated by high levels of free iron. Iron is usually tightly sequestered in the cell – leaving free iron levels low. Cell death, however, releases free iron – which can then trigger the pathogen to grow – and also has a nasty characteristic of triggering one of the most potent free radicals of all – the hydroxyl (OH-) radical.
Unusual Microclots Are Key
There’s a problem, though. Viral or bacterial reactivation usually happens in fairly small quantities and doesn’t produce a lot of viral or bacterial products. How to translate, then, a relatively small infectious event into chronic and even disabling illness?
Enter microclots. The authors believe that an abnormal or anomalous clotting process has taken place in long COVID and ME/CFS. The fibrin amyloid or ‘fibrinaloids’ produced in these illnesses causes three problems:
- the production of autoantibodies that end up attacking the body,
- unusually long clot persistence times due to the difficulty breaking them down,
- blockage of the capillaries – last and most importantly, blockage of the capillaries when the strangely formed and hard-to-break down clots get stuck in them. That blockage could result in low oxygen uptake and a hypoxic (low oxygen) condition that results in a chronic ischemia-reperfusion injury as well as reduced energy production by the mitochondria. (The commonly used pulse oximeters would not pick up this condition.)
It wouldn’t take much to block up the very small capillaries.
The capillaries are very small. In fact, most of them are so small (5–10 μm) that red blood cells largely pass through them in single file. The fibrin amyloid microclots that Pretorius’s team has uncovered in ME/CFS (blog coming up) and long COVID are from 5 to 200 μm in diameter – easily large enough to block up the capillaries.
Plus, the fibrin amyloids in microclots are also less deformable – making it more difficult for them to move through the capillaries. (Other kinds of cellular debris such as exosomes could be blocking up the capillaries in ME/CFS and long COVID as well.)
Reaching way back to 1989, they referred to Les Simpson’s paper finding altered red blood cell shapes in ME/CFS, and then reaching forward thirty years later, the San Jose State University team found altered red blood cell deformability. One wonders if a major cause of ME/CFS has been readily visible all this time. Ron Davis and the Open Medicine Foundation are exploring the red blood cell deformability issue further in ME/CFS with UC Davis researchers.
More evidence of coagulation issues exists in fibromyalgia. A 2019 paper found evidence of a prothrombotic or coagulatory state, and two plasma proteomic studies pointed fingers at coagulation and inflammation.
Evidence of ischemia-reperfusion injury
The hydroxyl radical causes most of the damage in ischemia-reperfusion injury. The hydroxyl radical is so unbalanced, though, that it doesn’t last long enough to measure. Therefore, its by-products (malondialdehyde TBARS), nitrotyrosine, 8-isoprostane) are – and all have been found – increased in ME/CFS, and several in fibromyalgia as well.
Platelet hyperactivation
Red blood cells, activated platelets (white with irregular shape), and white blood cells.
An ongoing state of platelet hyperactivation – caused by an ischemic reperfusion injury and/or inflammatory state – is a possible scenario.
In platelet hyperactivation, blood platelets form platelet complexes that drive pathological clotting states and damage the endothelial cells lining the blood vessels. Platelet hyperactivation has been found in long COVID.
The authors hypothesize that untreated platelet hyperactivation and microclots could lead to 5 scenarios – many of which apparently can overlap:
- Return to health – Patients recover spontaneously, where their fibrinolytic system returns to healthy clotting and lysis cycles.
- Hypercoagulable state forms that triggers more platelet activation and blood vessel damage – Patients do not spontaneously recover, but instead develop a persistent hypercoagulable state with the persistent triggering of hyperactivated platelets and persistent endotheliitis, that may lead to more widespread endothelial damage.
- Microclots trigger immune dysfunction and/or autoimmunity – Microclots trap inflammatory molecules and distort them, causing the production of autoantibodies that may mistakenly attack the body as well.
- An increase in free iron causes past viral/bacterial infections to flare up – Some individuals, who previously might have suffered from EBV, Herpes simplex virus or Lyme disease, might suffer from a flare of those original symptoms, caused by reinfection, or even by the vaccine.
- Spike/COVID-driven ME/CFS – In some individuals, the persistent microclots and widespread endothelial pathology may culminate in eventually COVID triggering ‘spike/COVID-driven ME/CFS’.
The Gist
- Ischemia-reperfusion injury occurs during reductions in blood flow when the blood flow is resumed causing an explosion of oxidative stress and inflammation.
- The authors believe that long COVID, ME/CFS and rheumatoid arthritis are ischemia-reperfusion diseases.
- Unusual microclots found in long COVID and ME/CFS that are of irregular shape and are difficult to break down – which clog the small capillaries that carry blood to the tissues – are a main feature.
- A possible complication of ischemia-reperfusion injury is something called “platelet hyperactivation” which results in hypercoagulation (more clotting), possibly autoimmunity, and an explosion in free iron which, in turn, promotes viral and bacterial reactivation.
- This new focus on reperfusion injury and clotting is leading to a range of new treatment possibilities including anti-clotting drugs and supplements, drugs like fenofibrate, metformin, lactoferrin, biologics, and treatments like apheresis and hyperbaric oxygen therapy.
- This is actually just the tip of the iceberg. Long-COVID patients and their doctors are trying many more things. A future blog will focus on those.
Possible Treatments
The authors start off the treatment section by noting that, as with any complex illness, multiple treatments will probably be needed in ME/CFS and long COVID. Lots of treatments new to the ME/CFS/FM communities are being tried to long COVID, and a future blog is going to address them, but I think this idea – that multiple treatments are going to be needed to really move the needle on these illnesses – is probably spot on. We need assessments of treatment protocols more than anything.
Old School
Potential treatments for long COVID already in common use in chronic fatigue syndrome (ME/CFS).
Low-dose naltrexone, N-acetyl cysteine NAC), curcumin, flavonoids, melatonin – are all well known supplements that have anti-inflammatories/antioxidant properties. Niacin (B3) was also mentioned. Green tea catechins (epigallocatechin-3-gallate, as well. One warning: As mentioned above, vitamin C is to be recommended only if one is sure that free or poorly liganded iron is absent.
Magnesium – Magnesium is, of course, very well known, but the authors provided a new slant on it stating that “‘Magnesium’ was experimentally one of the earliest substances that the authors found to inhibit fibrin amyloid microclotting (then known as dense matted deposit formation). People with low magnesium ion levels were found to be more susceptible to COVID-19, and magnesium supplementation has shown benefits in SARS-CoV-2 therapy, ME/CFS [93,897], and in maintaining endothelial cell function.”
Newer School
New, or less used, treatments in ME/CFS.
Anticoagulants and platelet inhibitors – The authors mentioned heparin (unfractionated heparin (UFH)) and low molecular mass heparin (LMWH), and specifically recommended the LMWH form, but quite a few other possibilities exist. Dr. Holtorf has reportedly been using heparin successfully in some ME/CFS patients for years, though the vast majority of ME/CFS experts have not. With a recent paper from Dr. Pretorius’s group demonstrating the presence of microclots in ME/CFS (blog coming up shortly), anti-clotting treatments are receiving more and more interest.
Thrombolytics (clot-busting supplements): nattokinase, serrapeptase, and lumbrokinase – the authors noted that the fibrin amyloid microclots contain compounds (antiplasmin) that make them difficult to break up via the normal processes.
- Nattokinase – Nattokinase leads the list of fibrinolytic and amyloid-degrading compounds. Found naturally in the Japanese fermented soybean food natto, it may have antiviral, antiplatelet, anti-inflammatory, and anti-hypertensive (high blood pressure) properties. It’s a supplement, that has not, however, been well studied.
- Serrapeptase (serratiopeptidase) – the authors reported that serrapeptase has similar properties as well as having anti-mucus effects. It also has not received much study.
- Lumbrokinase – another fibrinolytic (fibrin-degrading) enzyme, lumbrokinase is apparently under study in long COVID.
Biologics – (Enbrel), and infliximab (Remicade) have been very effective with RA (rheumatoid arthritis) – and with fatigue in RA. RA was mentioned in conjunction with ME/CFS and long COVID several times in this paper. A potential RA / ME/CFS connection is fascinating. Fatigue, exercise intolerance, jacked-up sympathetic nervous systems, and similar metaboreflex problems appear to be present in all three diseases. A hypothesis that inflammatory factors are sensitizing the metabolic receptors in the muscles in RA seems entirely possible in ME/CFS.
The authors stated they were surprised that these biologics have not been trialed in ME/CFS. A small trial is underway. Dr. Klimas’s modeling studies suggested that Enbrel be used first to tamp down neuroinflammation, followed by mifepristone to reset the HPA axis, and a small trial, long delayed by the coronavirus epidemic, is hopefully underway. A recent case series found that a perispinal application of Enbrel produced rather amazing results in a long-COVID patients. On a positive note, the authors reported that as biosimilars begin to come in, the costs of these expensive drugs are expected to fall.
Colchicine – has long been used in various inflammatory diseases. One of Dr. Montoya’s ME/CFS patients apparently did well on it.
Metformin – Metformin is a first-line drug for type II diabetes that was first suggested for fibromyalgia for its mitochondria-enhancing effects. Numerous studies suggest that mitochondrial problems exist in FM, and several animal studies suggest that metformin may, by increasing mitochondrial and antioxidant activity, reduce pain; and one found that FM patients with mitochondrial problems did well on metformin.
A prediabetes connection may also exist in FM and chronic fatigue syndrome as well. Marco’s 2014 blog, “The Energy Disorders: Diabetes, ME/CFS and FM – Can Diabetes Tell Us Anything About Chronic Fatigue Syndrome and Fibromyalgia?” noted that small fiber neuropathy is common in diabetes, that Type II diabetes patients also suffer from fatigue, early onset of muscle pain, reduced oxygen uptake during exercise, exercise intolerance, endothelial cell problems, and delayed recovery.
Different forms of diabetes exist. Could a form of diabetes be present in ME/CFS, fibromyalgia, and long COVID? Peter Attia, MD, believes that our testing procedures are terrible at picking up pre-diabetic conditions and that they are vastly underdiagnosed in the U.S.
Fenofibrate – is usually used to treat abnormal lipid levels, but the authors stated that it appears to be at least somewhat protective against reperfusion injury. It’s been used in diabetes type II, reduces high levels of uric acid, and get this, it may also enhance the proliferation of the peroxisomes that have recently become of such interest in ME/CFS. Vijay reported that he’s been doing well on it.
Ergothioneine – is a new, to me, at least, anti-inflammatory, and antioxidant that has been shown to help prevent ischemia-reperfusion injury. The authors noted that it is not easily obtained in pure form, but its “availability via mushrooms can provide a convenient supply.”
Lactoferrin – since lactoferrin binds iron effectively, if higher amounts of free iron are triggering viral and bacterial reactivation, then lactoferrin could be helpful.
Other, Non-Pharmacological Methods
H.E.L.P.: apheresis – removes factors that impair blood vessel health such as lipoproteins, fibrinogen, and inflammatory factors. It also may improve blood flows in the microcirculation. The authors noted that heparin-mediated LDL precipitation (H.E.L.P.) apheresis may be best for long-COVID patients as it may remove fibrin amyloid microclots with high efficiency”.
Hyperbaric oxygen therapy and 02 nanobubbles – could, by increasing oxygen levels, stop or slow down the reperfusion-ischemia reaction. Several fibromyalgia studies suggest hyperbaric oxygen could be helpful.
Conclusion
Long COVID is opening new treatment options for the ME/CFS and FM communities.
The possibility that unusual, hard to break down, and less deformable microclots are impairing blood flows and causing a chronic ischemia-reperfusion (read free radical rich, inflammatory) state in chronic fatigue syndrome (ME/CFS), long-COVID and fibromyalgia (FM) are spurring interest in many treatments that are mostly new to the ME/CFS and FM communities. This blog touches on a few of them – many more things are being tried in long COVID. A future blog will dig into those.
Yes, i see this, and i also see 3 very specific cases or genetic pheno types that drive these micro clots / hyper coagluation issues within me / cfs. It only takes about 10 mins to look at the genetics and classify them. Once classified the right nutritional supports make a world of difference. I dont have ‘statistically significant’ numbers for each case yet – but am willing to look at anybody’s genetics who sufferes from me / cfs for free and let you know what i see. Coagulation is not the root cause, so although Nattok/Seraptase help, they wont permanently resolve it. It will come back. Getting to the root cause puts an end to it returning.
:). I think a personalized approach is going to be key. No one size fits all approach here unfortunately.
Michael – What sort of genetic data would you need to see to evaluate this?
a txt file from any of the major basic dna kits like 23andme.
This is interesting, Michael. If I am interested, what next?
Thats so interesting, thank you Cort. My son’s Pots and cfs starting to make sense. After pots and cfs diagnosed aged 16 he was found to have hemochromatosis (iron overload). But also severely vitamin c deficient. Vit c supplements seemed to have immediate weird effect (dilated pupils and hypersomnia) ⁰But after abandoning vit c and over a year of giving blood to get his iron down he suddenly completely recovered. Well for 7 months. Then completely crashed again with shingles (herpes zoster). Since then pretty much housebound. Another attempt to get the iron right down but no sign ificant effect on pots or cfs. Nine years of this. We need a breakthrough.
contact me at foodforyourjeans.com or michael.kreder@gmail.com
Michael, how can I contact you directly?
It is so frustrating (and frightening) to wonder if the things I’m doing are making things worse. I have been prescribed iron infusions and taking iron & copper supplements per doctor orders. When I read these articles about too much iron in the cells I worry I’m making things worse.
Right. Iron is a tricky subject. You should know though, that iron supplementation has been very helpful for some people with POTS. We have a POTS recovery story of a young man with seemingly normal iron levels who recovered after iron infusions. I imagine your doctor has a good reason for suggesting them.
https://www.healthrising.org/blog/2016/11/19/iron-man-pots-chronic-fatigue-syndrome-recovery-ferritin/
Due to low ferritin levels I received iron infusions. I think it helped some of my lightheadedness caused by POTS..but I later found that I had iron deposition on my liver and spleen, so wondering if too much iron in my system (perhaps from inflammation or infusions) caused this. Maybe this is contributing to my reactivated EBV..hmm lots to think about
Same here! I got iron infusions from ferritin and iron saturation of 13. I immediately felt better but energy left after few weeks. I have chronic mono and cytomegalovirus, IgM. Then got breast cancer this year and wonder if the iron was bad idea as I read something bout iron and cancer. Dang cog fog
What tool /test is used to classify a persons genetics please. Blood ?
Spit
I am very interested. What Do you mean by looking at the genetics?
I am sick since mononucleosis in 2017.
Michael, will old 23andme data work (V3 chip)?
Hi Michael, Just curious how you could look at genetics for free? I have me/CFS, long Covid. I feel in need of figuring out what could work for me. Thanks
Michael Kreder, I would like to contact you about looking at my genetic data. I had my whole genome done thru Nebula. I have celiac disease and MECFS that got much worse after covd vaccine. None of my doctors will even look at my genetic reports.
Syncope from POTS is an extreme physiological reaction. One would think that these micro clots would be extremely numerous, and very visible. The sympathetic nervous system has an amazing ability to vasoconstrict large blood vessels, when one suddenly stands. The sympathetic nerves can produce more norepinephrine, because the baroreceptors feed back to the nerve that blood pressure upon standing is too low. Or, one can create additional norepinephrine receptors, AND “up regulated “ norepinephrine receptors in the synapse to adjust to low pressure. Seems to me that it would take a pretty big hammer to seriously damage the sympathetic innervation of blood vessels.
Hey Cort, thank you once again. Was there any discussion that the ichemic repurfusion injury was triggering mitochondrial fission as per Prusty’s findings? Do you think thiamine might be helping to prevent this process?
It was a long paper and I didn’t cover all of it (such as MCAS) but I don’t remember anything about Prusty. I have to get caught up on Prusty but they are suggesting that an inflammatory milieu triggered by an ischemia reperfusion injury was present. I imagine inflammation is a part of Prusty’s paradigm???
https://www.youtube.com/watch?v=YH1wn3D9HNg&t=18s
Prusty is towards the end. This was originlly released in German and Ron Davis mentioned him recently too.
The Morley Robbins protocol focuses on the amount of iron circulating and use a mineral wheel to adjust. They also suggest frequent blood donations to get some if the excess iron out.
Curcumin has helped my PEM quite significantly.
Interestingly, my MCHC* labs have been flagged as low for years. The first time they came back low I asked my primary about it and she said it was nothing to worry about. A few years later I am diagnosed with ME/CFS and POTS. Does seem related or am I overthinking?
*MCHC is short for mean corpuscular hemoglobin concentration, and is a measurement of the amount of hemoglobin in your blood
Pretty much all of my 12 or so blood tests have come back with low MCHC, aside from maybe 3. Also asked GP, also said nothing to worry about
That’s so odd as both Me and my MEeps are elevated. Both my MCV and MCH. Plus RDW goes back and forth between low and high.
In his book “From Fatigued to Fantastic” Jacob Teitelbaum M.D. writes “I have found other blood thinners like Coumadin and Nattokinase to be useless for CFS” Here is the link to the page in his book:
https://books.google.co.za/books?id=_Id415UKE0cC&pg=PT146&lpg=PT146&dq=nattokinase+cfs&source=bl&ots=wZQbW7U4LU&sig=ACfU3U17NNrzYfujZBYPSqEuWaYh02zYDA&hl=en&sa=X&ved=2ahUKEwjDmqjIu4n6AhVIe8AKHfTODmMQ6AF6BAgkEAM#v=onepage&q=nattokinase%20cfs&f=false
Well, there’s that! 🙂
Thank you for this detailed explanation and particularly for linking the new findings to other research relevant to ME/CFS, FM etc. As always, your analysis, encyclopedic knowledge, and ability to write in layperson’s terms is astonishing. And so appreciated.
One point worth highlighting in your next blog is that although a significant percentage of pwME were found to have microclots in venous blood, not all peME had this. Once again it points to the need for individualized testing and treatment.
I also wonder if microclots could gradually move out of the circulating blood yet still be clogging up capillaries and tissues.
Good point.. Here’s to identifying subsets and the correct protocols for them. Everything we see in long COVID suggests that will the be case there – and if that’s the case in long COVID its doubly the case in ME/CFS.
Hi Cort! Thank you for this article. I’m wondering since I’ve had elevated ferritin levels if that can have a connection with this hypothesis? Do you know if that is common in me/cfs? I know that inflammation can be a cause for elevated ferritin levels.
One really interesting study that compared common blood tests between people with ME/CFS and healthy controls found that ferritin was higher in the ME/CFS. I don’t know if it was considered “elevated” but it was higher.
According to his site high ferritin levels can signal iron overload which I would think would make sense with this hypothesis.
https://www.doctorshealthpress.com/general-health-articles/high-ferritin-levels-causes-tests-treatments/
le Dr Salmanov, grand médecin russe du 20ème siècle, spécialiste des capillaires, pensait que la plupart des maladies se développent car il y a fermeture progressive des capillaires pour plusieurs raisons ; virus, bactéries, métaux lourds, toxines, dysbiose…. Pour les ouvrir, il a créer les bains à base d’essence de thérébentine extrait d’arbre de Mélèze de Sibérie. J’ ai testé quelques fois et c’est vrai que ça donne de l’énergie pendant quelques heures mais le protocole est contraignant et il faut une baignoire.
Il faut faire très attention quand on ouvre les capillaires, surtout pour ce qui ont la SAMA (syndrome activation mastocytes), quand ils sont restés longtemps fermés, la désagrégation des caillots du sérum, les globules rouges et blancs…emprisonnés dans les capillaires fermés libèrent plusieurs acides aminés dont l’effet concerne les allergies. Pour éviter l’exès d’histamine, il faut, pendant l’ouverture des capillaires, PENSER AU DRAINAGE RENAL.
Selon certains médecins spécialistes d’EM/SFC, les reins ne sont pas au top, ce qui empêcherait l’évacuation des toxines… C’est un cercle vicieux.
Et c’est là que , à mon avis, le traitement par apherèse peut être très intéressant. Est-ce logique?
An a proximate translation of Claudine’s comment, should you wish to respond:
“Dr. Salmanov, a great 20th century Russian physician, specialist in capillaries, believed that most diseases develop because capillaries gradually close for several reasons; viruses, bacteria, heavy metals, toxins, dysbiosis…. To open them, he created baths based on essence of turpentine extracted from the Siberian Larch tree. I tested a few times and it’s true that it gives energy for a few hours but the protocol is restrictive and you need a bathtub.
“You have to be very careful when you open the capillaries, especially for those who have SAMA (mast cell activation syndrome), when they have remained closed for a long time, the disintegration of serum clots, the red and white blood cells… trapped in the closed capillaries release several amino acids whose effect relates to allergies. To avoid the excess of histamine, it is necessary, during the opening of the capillaries, to think of the renal damage.
“According to some ME/CFS specialists, the kidneys are not at their best, which would prevent the evacuation of toxins… It’s a vicious circle.
“And this is where, in my opinion, apheresis treatment can be very interesting. Does it make sense?”
Interesting article. Well I finally had the opportunity to try hyperbaric treatments, 40 treatments for 90 minutes at 2 ATA (atmospheric pressure) for fibromyalgia and CFS. Unfortunately it didn’t work. Actually it gave me cataracts. It’s been a nightmare. 4 eye surgeries so far and looks like I may need 2 more. Yes these treatments have been known to help others but just warning you about the potential side effects no one shared with me.
I am having a disagreement with my PCP right now about free floating iron. I had a high TIBC reading but have normal iron. I have been taking an iron supplement for iron deficiency anemia from last years blood test. I had gastric bypass in 2004. My argument was that I have a normal iron but high TIBC because it is not being used or bound. I can also see this causing the microclots? What do you think?
I have had these same iron results on and off for 15 years. High free iron. Sometimes it’s normal range though…
it is all good and well that they find things in long covid that they have found in small studys (eventually) in ME or FM. But we still need the big money long covid has. Otherwise we still are stuck for i do not know how long, when we get the money. Long covid has 1.9 billion. what do we have and where are we going with it and when? not that i am not glad they see overlaps, etc but we need also 1.9 billon to move fast and get regourus research in ME and FM.
A titre d’information, j’ai commandé le remède PADMA BASIC. c’est un mélange de 20 plantes . C’est un complexe utilisé en cas de troubles circulatoires. action tonifiante sur la circulation et améliore la tolérance à l effort, anti bactérien et analgésique, anti-inflammatoires, antioxydants et chélateurs des métaux, améliore la fibrinolyse…
J’espère que ça va m’aider, car j’en ai marre de tester des remèdes qui ne fonctionne pas.
Je rêve d’un traitement miracle comme nous tous ici.
Translation:
“For information, I ordered the padma basic remedy. it is a mixture of 20 plants. It is a complex used in case of circulatory disorders. toning action on circulation and improves resistance to effort, antibacterial and analgesic, anti-inflammatory, antioxidant and metal chelators, improves fibrinolysis…
I hope it will help me, because I’m tired of testing remedies that don’t work.
I dream of a miracle treatment like all of us here.’
Reply – it certainly seems worth a shot Claudine – Good luck!
Cela semble certainement valoir la peine d’être essayé. Bonne chance, Claudine
This article ties together symptoms and some successful treatments I have used. I have excess iron in my blood and have taken Immunopro a whey based supplement that has lactoferrin for years without knowing why it helped so much. Unfortunately, the thick blood problems make iron reduction blood draws (my blood clots in the tube) impossible. I am taking Lumbrokinase in hopes that this will thin my blood and maybe I can have iron reduction blood draws. (Early on I was on a heparinoid from Germany which was available on orphan drug status). Cort, as far as I am concerned, this article brings together all the symptoms I have had. Infections, viral reactivations except for one important symptom set. Did this research include anything on mast cells? Thank you!
Yes – here’s what they said about mast cell activation:
“Another mechanism mediating hyperinflammation is mast cell activation [621]. It occurs during acute COVID [622–624], and the symptoms [625] of those with known mast cell activation syndrome significantly mirror those of individuals with Long COVID [626,627]. The elevation of IL-6 levels, as well as proteases such as carboxypeptidase A3 and tryptase, is a hallmark of this and these are also observed in PASC patients [628].
Importantly for the present focus, mast cells are also activated during (and exacerbate) ischaemia–reperfusion injury [629–634], and the inhibition of mast cell degranulation [634] might consequently be of benefit in Long COVID. Indeed, these findings are consistent with the known beneficial effects of antihistamines in PASC [80] “
Cada vez son más los estudios que hablan de que estamos ante una enfermedad en la que en muchos de los pacientes, están implicados los vasos sanguíneos.
El tratamiento básico estaría formado por
Antioxidantes
Antiinflamatorios
Quelantes del hierro
Fibrinoliticos y/o agentes anticoagulantes adecuados y seguros.
El fibrinógeno puede coagularse en amiloide que es relativamente resistente a la fibrinolisis, estos micro coágulos de fibrina amiloide pueden atrapar proteínas y producir auto anticuerpos.
Por eso creo que B007 funcionó en pacientes porque además recibieron posiblemente terapia anticoagulante triple que eliminó los micro coágulos y BC007 los auto anticuerpos.
Por eso tal vez Abbilify funcionó en algunos porque actúa en la neuroinflamacion y en la inflación sistémica.
Por eso tal vez pentoxifilina funcionó en algunos por su efecto sobre el eritrocitos y su capacidad de reparación del endotelio al inhibir la adhesión de los leucocitos al endotelio vascular y también al reducir la agregación plaquetaria y el fibrinógeno.
Hay un artículo bastante interesante con su Protocolo y todo sobre la relación de los coágulos persistentes, hipo perfusión en pacientes con fatiga crónica. El autor un tal Gustavo Aguirre Chang.
También Bruce Patterson habla de esto. dice que la disfunción de las células endoteliales es el principio y el fin de Long covid, SFC/EM.
Habla De dos grupos de pacientes
Uno.. Con niveles de O2 en sangre venosa más altos de lo esperado, eso implica que la sangre es desviada antes de llegar al músculo y por lo tanto la mitocondria no recibe el combustible.
Otro.. Niveles normales de O2 venoso pero con una cantidad de sangre que llega al corazón baja (precarga) aquí el corazón es incapaz de bombear suficiente sangre al músculo. Yo creo que aquí estaría el grupo de pacientes con POTS.
Systrom y la hipo perfusión cerebral….
Tal vez los vasos sanguíneos sean el todo
O una parte del puzzle pero que están implicados en estas enfermedades parece bastante claro.
Nota…Estoy casi seguro que los pacientes que se recuperaron del covid largo en Alemania usando B007 estuvieron al mismo tiempo antiagregados y anticoagulados (aspirina, clopidogrel, HBPM)
Translation:
“More and more studies are talking about a disease in which in many of the patients, blood vessels are involved.
The basic treatment would consist of
Antioxidants
Antiinflammatory
Iron chelators
Adequate and safe fibrinolitics and/or anticoagulant agents.
Fibrinogen can coagulate into amyloid which is relatively resistant to fibrinolysis, these amyloid fibrin micro clots can trap proteins and produce autoantibodies.
That’s why I think B007 worked in patients because they also received possibly triple anticoagulant therapy that eliminated the micro clots and BC007 the autoantibodies.
That’s why perhaps Abbilify worked in some because it acts on neuroinflammation and systemic inflation.
That is why perhaps pentoxifylline worked in some because of its effect on erythrocytes and its ability to repair the endothelium by inhibiting the adhesion of leukocytes to the vascular endothelium and also by reducing platelet aggregation and fibrinogen.
There is a rather interesting article with your Protocol and all about the relationship of persistent clots, hypo perfusion in patients with chronic fatigue. The author a certain Gustavo Aguirre Chang.
Bruce Patterson also talks about this. says that endothelial cell dysfunction is the beginning and end of Long covid, CFS/ME.
Talk About Two Groups of Patients
One.. With higher than expected levels of O2 in venous blood, that implies that the blood is diverted before reaching the muscle and therefore the mitochondria do not receive the fuel.
Other.. Normal levels of venous O2 but with an amount of blood reaching the heart low (preload) here the heart is unable to pump enough blood to the muscle. I think here would be the group of patients with POTS.
Systrom and hypo cerebral perfusion….
Maybe the blood vessels are the whole
Or a part of the puzzle but that they are involved in these diseases seems quite clear.
Note… I am almost certain that patients who recovered from long covid in Germany using B007 were at the same time antiaggregates and anticoagulated (aspirin, clopidogrel, LMWH) “
I have fibromyalgia and for me I don’t really feel that this study or it’s finding are applicable to me.
I have symmetrical tender points all over my body and I am not in constant pain. But I have to be careful about sitting on my tender points and physical activity because my muscles get sore very easily. I have done hyperbaric oxygen therapy and it made no difference whatsoever. I would like to see more research done into the underactive immune system that FM patient seem to have.
What are the set of tests one should request to confirm or eliminate what is causing fatigue, PEM, and inflammation in one’s body based on this research? I’m guessing checking iron levels, RBC shape, anything else ?
And women more than men .. iron related as well? Women are told we need more iron ti replace it during child bearing years.
I am very curious about this, too. Women and iron component. Thank you for raising this question.
A bery bery old school treatment: aspirin
Antiinflammatory, anti-coahulants, increases CO2, inactivates the enzyme that forms prostaglandins, even used against cancer, etc, etc. Ticks all of the boxes, of issues found in ME/CFS and FMS and and and
Cheap too.
The enteric coat produces an allergic reaction in me. Plain old school Bayer type – now we are cooking.
It needs to be used with caution in asthmatics.
I’m asthmathic. I have no problems with it.
The enteric coat is what can provoke allergic reactions.
Pure aspirin doesn’t
And caution with stomach ulcers, acid relux, hiatus hernia. Not advised
One learns how to read and discern how studies are carried out.
No stomach problems here. No hiatial hernia. No acid reflux.
Many others like me.
In fact, many many many. People that have had stents placed are given daily aspirin. You don’t hear about these effects on the stomach in this comunity…
Somehow aspirin has been made into the devil, while NSAIDs like tylenol, which are highly damaging to the liver, are not. Go figure…
I take mine dissolved in water, filtering the fillers out, after a meal.
There are many myths in modern pharmacology. Aspirin is one. Serotonin is another. I hope one day ‘central sensitization’ follows suit.
As always very helpful overview. Thank you, Cort!
I had ME/CFS dxed in 2015, and the disease since pneumonia/mold exposure a couple of years prior. I spent everything addressing gut, heavy metals, infections, spinal cord and structural pathologies, hormonal, MCAS, angioedema, IBS, sleep apnea, TMJ, orthostatic intolerance, mitochondrial, spinal fluid leaks patch. Addressing spinal structural issues was huge. but introducing supplements for blood health into the mix over a year ago reduced PEM significantly if not completely sometimes. I regret not knowing to look into hypercoagulation 10 years ago! Actually, in my case it even turned out that I have a rare underlying thrombophilia that is known to get worse with infections, traumas, and hypoxia among other things.
Unfortunately, my clots got much more visible, not micro, after the SARS2 viral illness. Dr. Paterson Long Haul Cytokine Panel identified endothelial damage markers.
There is a lot to blood homeostasis, like Calcium (during thrombotic events to the SARS 2 toxins, I developed 9 cavities within one months – my ortho confirmed that the body likely was managing coagulation by needing to get calcium somewhere rather quickly).
Vitamin E (see brothers Drs. Shute research) and melatonin (Doris Loh research) were and continue to be the main additions in the past year for me. Both are in large doses (grams).
I copied the notes below from someone who spent a lot more time than I did studying the vitamins:
Vitamin E for circulatory diseases?
“This therapy helps reduce the arterial blockage,” Williams, Nutrition and Diet Therapy, Seventh Edition (Mosby, 1993, p 186), a standard dietetics work. Medical doctors Wilfrid and Evan Shute of London, Ontario successfully treated well over 30,000 cardiovascular disease patients with up to 3200 IU of vitamin E daily. For that achievement, they were ostracized from their medical society. Here are the
principles of the therapy:
1) Vitamin E has an oxygen-sparing effect on the heart, enabling the heart to do more work on less oxygen. The benefit for recovering heart attack patients is considerable. 1200 to 2000 IU daily relieves angina.
2) Vitamin E moderately prolongs prothrombin clotting time, and has a limited Coumadin/warfarin effect. This is the reason behind the Shutes’ using vitamin E for thrombophlebitis and related conditions. Their dose? About 1000 to 2000 IU daily.
3) Vitamin E dilates and promotes collateral circulation and benefits diabetes patients or anyone threatened with gangrene. Dose: Tailored to patient; about 800 IU or more.
4) Vitamin E strengthens and regulates heartbeat like digitalis (foxglove) and its derivatives at a dose adjusted between 800 to 3000 IU daily.
5) Vitamin E reduces scarring when frequently applied topically to burns or sites of lacerations or surgical incisions along with a daily oral dose of 800 IU.
6) Vitamin E helps gradually break down clots at a maintained dose of between 800 IU and 3,000 IU.
7) Vitamin E in doses of up to 56,000 IU per day fail to harm adult humans. Gradual dosage increase is advised, and patients with congestive heart failure, rheumatic hearts or high blood pressure need careful medical supervision.
I do lumbrokinase here and there. I avoid legumes and soy products so no natto or serrapeptase due to my individual tolerance issues.
Yes to mild HBOT therapy, too. Also B vitamins. Phosphatidylcholine and NAC for liver health. Yes to vitamin C, too.
I still don’t know the iron issue well but need to really dive in. Iron is so helpful but as you described, sometimes it is dangerous. Actually, I was told to avoid it as it was a mitochondrial toxin.
Be careful with Vitamin E:
“Vitamin E in doses of up to 56,000 IU per day fail to harm adult humans”- This seems not to be true:
In a study men taking more than 200 (two hundred!) IU Vitamin E had a higher risk for prostata carcinoma
Frank
Hi and thank you so much for this great article on the research. You clarified so many points. I am learning so much all the time (great thing about being bedbound 23 hours a day this summer, plenty of time to read).
I have a question about immunomodulating medications. I am self trialing clofazimine on the advice of a group who says it can “reverse” LC. As far as I know I am the first person with ME to try it. Have you ever heard ANYTHING about clofazimine for ME?
Yes, this is a very ill-advised and high-risk trial. But after thirty-six years of ME, well..
It seems like Taxifolin / Dihydroquercetin would help with ischemia-reperfusion injury:
https://pubmed.ncbi.nlm.nih.gov/16283433/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360081/
It’s basically a more powerful form of quercetin.
Also, aparently, Dihydroquercetin is not the same as Quercetin Dihydrate.
Cort, thanks for the great summary of a very long article! I do think the authors have identified an important piece of the puzzle.
As far as nattokinase etc, @organichemusic who is a pharmacist with long Covid, has conducted surveys on Twitter and found that these enzymes generally tend to help people feel better and reduce symptoms.
Was there any mention of how PEM would be caused? I’m also unclear on how microclots etc would explain why my PEM and ME/CFS is milder in the summer than the winter.
For me, the easiest and fastest answer as to why the PEM in you is milder in summer than in winter is because possibly due to the increase in temperatures, with the heat, there is greater vascular dilation and therefore blood circulation improves.
Il serait intéressant de savoir si les personnes en dyalise sont protégés du long covid..Même si la dialyse, ce n’est pas pareil que l’aphérèse , le sang est quand même ” nettoyer” 3 fois par semaine .
Translation:
“It would be interesting to know if people in dialysis are protected from the long covid. Even if dialysis is not the same as apheresis, the blood is still “cleansed” 3 times a week.”
Apo-lactoferrin really helped me in the past (I took it on and off for a couple yrs) but I had to stop taking it. I was diagnosed with an autoimmune disease and was worried that it started to trigger issues because of it ramping up the immune system.
Anyway, I really miss it. I would take it at night and my glands would sometimes swell a bit in my neck but in the morning I felt great. A very noticeable improvement. Would the theory of it reducing free iron therefore reducing infections make sense with it acting that quickly?
I also tried to look into the way lactoferrin affects platelets and coagulation directly but I got too confused 😕
Weird I had the shingles and totally crashed as well. Is there a connection?
How much curcumin? I just started taking it.
Hi!!! I’d like to participate but i live in Brazil….., isn’t possible, is it?
Excited to share our webinar: “COVID-induced Coagulopathy (CAC): The clot thickens…or not?” Dr Mark Walsh, Prof Resia Pretorius, Prof Doug Kell CBE. Moderated by Dr Asad Khan.
Prof Resia Pretorius posted this YouTube video on Twitter. I have watched it. Lots of the content went over my head but I understood some of it. Very complex area and understandably difficult to find the right balance, as a clinician working with patients. I thought Dr Asad Khan asked some very good questions and raised important issues.
https://www.youtube.com/watch?v=yyf7xunWydM
I am considering doing a broader informal study to compare the genetics across healthy controls and me / cfs folks. I have a small sample of 26, with all the same root issue, and of course most have additional things going on as well. I have been in contact with Cort, Ken Lassesen (CFS Remission site), and two other well known researchers (one on genetics, the other well published on mitochondrial disorders). I intend to write an article/blog and get it published. I also intend to publish a formal paper that one MD has agreed to co author with me. One intent of the article/blog is to share enough to get enough participants interested (me / cfs, and controls). I would like to get to 100 controls, 100 me / cfs folks. I dont have all the details worked out yet. The intention is to track the progress of these folks over time after published research is shared showing what helps what; that is consistent with their genetic weaknesses and bio markers – hopefully to show how they can improve if self elected to do so. I am considering group zooms on a weekly basis divided into groups with similar pathway issues. With a sample size of a 100 – i am hoping some of the formal funded research groups will take notice. My history: 2 TBI’s, CFS x2, mold, solvents, heavy metals, candida, sibo, 11 parasites, CCI, vagal nerve dysfunction, post viral malaise, reactive hypoglycemia – I have a personal experience here as well. Please contact me if you want to participate in something like this. You can find me on FB as well. The commonalities across : CFS, folks who dont recover from TBI’s quickly, and post viral malaise is astonishing. I intend to studies even if only informally across all 3 groups.
EDS patients please note the contra-indication for Vitamin C because of the “iron overload” issues. If you have recently learned you may have EDS, look into the info out there on iron overload (mainly from hemochromatosis web sites or the Iron Disorders Institute) and they will explain more about how/when to take Vitamin C so as not to exacerbate the problem.
Lee Simpson was the hematologist (from New Zealand or Australia) who found that CFS patients around the world have a signature distribution of red blood cell shapes (cups, plates, bowls, etc). Acute and chronic CFS each had their unique distribution. Down’s Syndrome also had a unique distribution.
Yes, RBC’s have to squish to get through capillaries, and sometimes backing up, causing pain when tissues were deprived of oxygen, etc. His treatment is B12 shots for acute, and oil of evening primrose for chronic. There’s something in OEP that affects the cell membrane of RBC’s when being formed, to make them more flexible. I thinks there is a prescription drug that does the same thing.
He tested my blood back in the early 90’s when he spoke in RI. I started taking high doses 3900mg/day of oil of evening primrose. It takes about 8 weeks for RBC’s to be replaced in your blood. Within the 8 weeks, I legs felt better. I could actually stand for 5 minutes without my legs throbbing and feeling like lead weights. At high altitudes in the Rockies, I actually breathed better than my healthy friends who were there to ski. I could not.
For the last 20 years I have taking 1300mg of OEP. It’s helped to minimize the Reynauds in my fingers, and I can survive some standing.
Otherwise, my energy level and health are continually declining for the last 32 years of CFS. This site gives me hope.
Thank you for sharing. In terms of Ergothioneine (via mushrooms), I read that while this may protect cells, it can also feed preexisting diseased cells (eg cancer, Crohns, etc). Wondering if this is more preventative than curative?