Hip
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I am not sure if there are any European sources, but some sources are detailed at the bottom of this document.
Dr Markov CBIS Theory of ME/CFS - General Discussion
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I am not sure if there are any European sources, but some sources are detailed at the bottom of this document.
Hip
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Some years ago, I was looking at some pharmaceutical liquid products which you instil into your bladder (via a catheter inserted into the urethra) in order to repair the important glycosaminoglycan (GAG) layer in the bladder.
The GAG layer is a mucous membrane component of the bladder that protects the bladder lining from the toxic substances in the urine. If the GAG layer becomes defective and leaky, it can result in toxins in the urine getting re-absorbed into the body.
A damaged GAG layer also results in the toxins in the urine causing irritation to the bladder wall, which may lead to urinary urgency, increased urinary frequency, and bladder pain.
I am wondering whether a damaged GAG layer in the bladder (and possibly the kidneys, though I am not sure if GAG is found in the kidneys) might play a role in Dr Markov's theory of ME/CFS, where toxins from urinary bacteria enter the bloodstream and cause the symptoms of ME/CFS.
The GAG layer becomes defective in conditions such as recurrent urinary tract infections (recurrent cystitis) and interstitial cystitis (bladder pain syndrome).
The diagram below shows inflammation in the bladder where the GAG layer is damaged:
In the early years of my ME/CFS, I used to suffer from lots of recurrent urinary tract infections (recurring every few weeks), and I've long had overactive bladder, predating my ME/CFS (overactive bladder is similar to interstitial cystitis but without the pain).
So I could well have a damaged GAG layer in my bladder, and that's how I became interested in repairing the GAG layer.
The GAG layer consists of the following components: hyaluronic acid, chondroitin sulphate, heparin sulphate and keratin sulphate. The pharmaceutical approach to repairing the GAG layer is simply to instil some of these components into the bladder using a liquid solution, and this approach seems to work well.
So you have products such as Cystistat and Uromac which are sterile solutions of sodium hyaluronate that are instilled into the bladder, to supply the hyaluronic acid needed to build the GAG layer.
And there products such as Gepan and Uracyst which are solutions of sodium chondroitin sulphate, which supply the chondroitin sulphate needed to build the GAG layer.
These are instilled into the bladder once weekly to begin with, and then after a month or so, once the GAG layer is repaired, you just need to instil once a month as a maintenance regimen.
Although Dr Markov believes the bacterial dysbiosis causing ME/CFS is located on the kidney mucous membranes, I wonder whether some of this dysbiosis might also be found in the bladder (especially in patients like me who have recurrent UTI issues). In which case, GAG layer repair might help seal the bladder, and stop bacterial toxins from bladder bacteria leaking into the blood stream.
The GAG layer is a mucous membrane component of the bladder that protects the bladder lining from the toxic substances in the urine. If the GAG layer becomes defective and leaky, it can result in toxins in the urine getting re-absorbed into the body.
A damaged GAG layer also results in the toxins in the urine causing irritation to the bladder wall, which may lead to urinary urgency, increased urinary frequency, and bladder pain.
I am wondering whether a damaged GAG layer in the bladder (and possibly the kidneys, though I am not sure if GAG is found in the kidneys) might play a role in Dr Markov's theory of ME/CFS, where toxins from urinary bacteria enter the bloodstream and cause the symptoms of ME/CFS.
The GAG layer becomes defective in conditions such as recurrent urinary tract infections (recurrent cystitis) and interstitial cystitis (bladder pain syndrome).
The diagram below shows inflammation in the bladder where the GAG layer is damaged:
In the early years of my ME/CFS, I used to suffer from lots of recurrent urinary tract infections (recurring every few weeks), and I've long had overactive bladder, predating my ME/CFS (overactive bladder is similar to interstitial cystitis but without the pain).
So I could well have a damaged GAG layer in my bladder, and that's how I became interested in repairing the GAG layer.
The GAG layer consists of the following components: hyaluronic acid, chondroitin sulphate, heparin sulphate and keratin sulphate. The pharmaceutical approach to repairing the GAG layer is simply to instil some of these components into the bladder using a liquid solution, and this approach seems to work well.
So you have products such as Cystistat and Uromac which are sterile solutions of sodium hyaluronate that are instilled into the bladder, to supply the hyaluronic acid needed to build the GAG layer.
And there products such as Gepan and Uracyst which are solutions of sodium chondroitin sulphate, which supply the chondroitin sulphate needed to build the GAG layer.
These are instilled into the bladder once weekly to begin with, and then after a month or so, once the GAG layer is repaired, you just need to instil once a month as a maintenance regimen.
Although Dr Markov believes the bacterial dysbiosis causing ME/CFS is located on the kidney mucous membranes, I wonder whether some of this dysbiosis might also be found in the bladder (especially in patients like me who have recurrent UTI issues). In which case, GAG layer repair might help seal the bladder, and stop bacterial toxins from bladder bacteria leaking into the blood stream.
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Atlas
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I went with Canephron, which can be found on Amazon. It was quite expensive though, keeping in mind 60 tablets last only 10 days because the adult dosage is 2 tablets 3x per day. It is sold by Bionorica which is a German company.
Dilon Ltd from Bulgaria sells it in several of the Amazon stores, including Amazon UK.
I'm not sure about the other brands, but I would probably just go with one of the cranberry-based UTI support supplements from my local pharmacy if I was to choose again. I'm not sure which of those is available in the EU though.
@MartinK are you planning to do Dr. Markov's treatment also?
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Hope the treatment is working for you Atlas. I'm watching this thread with interest.
Sorry if I've missed something on these pages, but if the idea is that the autovaccine will ultimately rid the kidney of the offending bacteria that are secreting the endotoxins, are there any ideas as to how to repair the kidney wall? IIRC leaky gut can occur from viral infections, stress, poor diet etc. I'm currently drinking bone broth to treat any leaky gut I may have and noticed less discomfort. But the kidney is another matter. Just wondering if the kidney would continue to leak after treatment and the current bacteria is eradicated.
Apologies if I'm asking something that's already been answered or is an obvious unknown.
Considering going this route.
P.S. will also be looking at possible biofilm degradation and fibrinolytic options having scanned through this thread. I'm glad I did.
Sorry if I've missed something on these pages, but if the idea is that the autovaccine will ultimately rid the kidney of the offending bacteria that are secreting the endotoxins, are there any ideas as to how to repair the kidney wall? IIRC leaky gut can occur from viral infections, stress, poor diet etc. I'm currently drinking bone broth to treat any leaky gut I may have and noticed less discomfort. But the kidney is another matter. Just wondering if the kidney would continue to leak after treatment and the current bacteria is eradicated.
Apologies if I'm asking something that's already been answered or is an obvious unknown.
Considering going this route.
P.S. will also be looking at possible biofilm degradation and fibrinolytic options having scanned through this thread. I'm glad I did.
Hip
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Dr Markov believes the bacterial dysbiosis is somewhere in the kidneys, but he does not know the precise location. He wants other ME/CFS researchers to investigate this, and determine where the bacteria are situated.
Dr Markov's best guess is that these kidney bacteria might be found on the mucous membranes of the renal pelvis and the calyces, in which case, conceivably there may be a leak in these kidney mucous membranes (a leak analogous to leaky gut), allowing the bacterial toxins to enter the bloodstream.
But the bacteria might not be there, but might be located in some other non-mucous membrane area of the kidneys, and so in that case, the idea of repairing a leaky mucosal surface would not apply.
Unlike the gut, the blood supply of the kidneys is not filtered by the hepatic portal system, so any toxins entering the bloodstream from the kidneys reach the systemic blood circulation in full force.
By contrast, the blood supply to the gut is filtered by the hepatic portal system in the liver, and this removes 99% of bacterial toxins like LPS which leak into the blood.
So any toxins leaking into the blood from the kidneys will be 100 times more toxic than the same toxin leaking into the blood from the gut.
BrightCandle
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LPS is extremely neuro toxic and even in tiny quantities its dangerous. The sort of quantities that a human can survive on are not easy to detect in the blood because currently there are no known methods for amplifying it, you cant grow it like you could bacteria or viruses.
We do have some reasonably evidence that LPS is present, the microclots seen in ME/CFS patients blood correspond and look the same as a healthy controls blood that has had a tiny amount of LPS added to it and this is distinct and different from the microclotting seen in diabetes and Long Covid.
But there is no known way yet to test for LPS in the blood, if there were the entire theory chain would be trivial.
Hip
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There actually are now blood tests for LPS available (there never used to be); one recent study found that blood LPS was high in some ME/CFS patients; but as you say, there are no tests for all the various other toxins that bacteria make.
That is, apart from the unique Toxicon blood test developed by Ukrainian toxicologist Dr Borys S Sheiman.
Using that Toxicon test available in the Ukraine, Dr Markov observed that the most common bacterial toxin in ME/CFS patients' blood is a toxin made by Enterococcus faecalis. 50% of ME/CFS patients had this toxin in their blood.
I could not find much info on the toxins Enterococcus makes, except for a toxin known as Enterococcus cytolysin. This particular cytolysin is not that well studied, but one paper says Enterococcus cytolysin is:
So if this cytolysin toxin is damaging this immune cells, it could help explain why ME/CFS patients are unable to clear their low-level viral infections.
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Thanks for the clarification Hip. I was looking today at an 'Antibiotics for CFS' table put together by Ken Lassesen where he lists the different antibiotics types versus the genuses of bacteria they're effective against. Seems the Quinolone family is effective against Enterococcus (although also effective against Lactobacillus, which is low in pwMECFS). I wonder if Quinolone antibiotics could be used as an adjuvant treatment to the autovaccines.
Or perhaps a first port of call to try and clear the kidneys (and anywhere else) of the Enterococcus bacteria before Dr Markus's treatment.
Or perhaps a first port of call to try and clear the kidneys (and anywhere else) of the Enterococcus bacteria before Dr Markus's treatment.
Atlas
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From what I understand from the research I have done, if there is a leaky kidney mucosa then that is most likely caused by the bacteria themselves. So completely clearing up the bacteria that are disrupting the mucosal barrier should allow the body to heal itself. (If that is indeed a mechanism by which toxins are leaking — there are other potential ways such as through the absorbent surfaces of the renal tubules)
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Hip
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Dr Markov said that antibiotics do not appear to clear these kidney dysbioses. This may be because antibiotics often prompt bacteria to increase biofilm production, as a defence against antibiotic attack. So you may actually make things worse, because it's probably a biofilm community in the kidneys which is secreting these toxins.
In fact, Dr Markov finds that his ME/CFS patients have usually had a childhood history of long repeated courses of antibiotics, which may have set the scene for getting ME/CFS later in life, perhaps by creating a biofilm community at an early age. This was my case: I had many courses of antibiotics as a child, due to chronic tonsillitis.
And one study has corroborated Dr Markov's findings: this study found ME/CFS patients and IBS patients tend to have a childhood history of lots of antibiotics.
Atlas
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What's curious is that even for some antibiotics which disrupt biofilms in one species, they can enhance biofilms in another species.
For example macrolide antibiotics can be effective against Gram-negative biofilms, but they enhance biofilm formation in Gram-positive bacteria.
So if there is an unholy alliance between E. Coli (Gram-negative) and Enterococcus (Gram-positive), which is what Dr. Markov often finds, it's going to be difficult to make a dent in it.
(Even if it can be cleared with some potent antibiotic combination, that will also disrupt any healthy microbiota, and it is likely that the biofilm colonies can simply be reseeded from spots that were missed or through gut translocation.)
@MeMeMe
Although it's possible that using antibiotics as an adjuvant could speed up treatment I would also consider it risky because of the potential damage to the gut microbiome and because we may not know for sure which biofilm bacteria are going to be enhanced.
It is such gut domination events which could lead to the colonization of the kidneys by antibiotic-resistant bacteria in the first place.
(These gut domination events can also be caused by viruses or high physiological stress, which could explain the various triggers for ME/CFS, if indeed this theory turns out to be true for a subset of pwME)
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Hip
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Also, I don't know too much about it, but I read that bacteria commonly live in multispecies biofilms (aka polymicrobial biofilms), where several different bacteria co-inhabit in the same biofilm.
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Interesting. Was thinking about experimenting with antibiotics but this has definitely given me pause for thought. I guess Markov's approach is far more precise then in theory. Instead of hitting the system with antibiotics at entry in the hope you flush out an undesirable strain, you're sampling the specific bacteria at exit and then reintroducing it. Certainly feels intuitive.
I do wonder though if getting a gut biome reading could offer some clues as to what might be in the kidney. If the gut is showing above average for Enterococcus then perhaps that suggests the same for the kidney. It's my understanding that Lactobacillus is the only other type of bacteria that Quinolones are effective against. Seems like antibiotics can be relatively selective because of the known resistance levels of certain genuses of bacteria. Although obviously not as targeted as taking your own bacteria and exposing your immune system to it should be.
I do wonder though if getting a gut biome reading could offer some clues as to what might be in the kidney. If the gut is showing above average for Enterococcus then perhaps that suggests the same for the kidney. It's my understanding that Lactobacillus is the only other type of bacteria that Quinolones are effective against. Seems like antibiotics can be relatively selective because of the known resistance levels of certain genuses of bacteria. Although obviously not as targeted as taking your own bacteria and exposing your immune system to it should be.
Hip
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An expert on bacteria we spoke to said that you can get dysbiosis in various areas of the body, but the dominant species in these dysbioses will usually be different in each area. So any dysbiosic bacteria in the gut will not necessarily reflect the dysbiosic bacteria present in the kidneys or nasopharynx.
Earlier in this thread a US company which uses genetic methods to identify bacteria in the urine was discussed.
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Damn it, if only it were that simple! That's very interesting and good to know.
Although I see that on average Enterococcus tends to be overpopulated in the gut of pwME, albeit along with Enterobacter and Streptococcus. I think a gut biome test is in order.
Anyway, I'll leave this now as I'm conscious I'm taking this off the topic of Markov's treatment.
Although I see that on average Enterococcus tends to be overpopulated in the gut of pwME, albeit along with Enterobacter and Streptococcus. I think a gut biome test is in order.
Anyway, I'll leave this now as I'm conscious I'm taking this off the topic of Markov's treatment.
Hip
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@MeMeMe, if you want to make some headway into Dr Markov's treatment, without getting into all the complexity and expense of becoming a remote patient of the Markov Clinic and getting his autovaccines shipped to you, one thing you can consider is using the mucosal vaccines that Dr Markov prescribes. These are detailed in the last section of this document ("Additional Supplements and Medications").
Along with his custom autovaccines, Dr Markov prescribed me the IRS-19 nasal spray mucosal vaccine. This is quite inexpensive, and can be bought prescription-free for $18 here (though shipping is $20).
IRS-19 vaccine stimulates immune response against a range of bacteria, including Enterococcus, Klebsiella pneumoniae, Streptococcus and Staphylococcus.
This spray is intended for the nose, but recently I had the idea of instilling this spray liquid into the urethra. I actually tried this, and it was well tolerated, with no discomfort or irritation.
My reasoning is that IRS-19 might actually be more effective in the urethral mucous membranes, as the urethra is part of the urinary tract — the same urinary tract where the kidney dysbiosis is located.
Mucosal immune responses tend to more localised (unlike the systemic immunity you get from injected vaccines, which cover the whole body), so my thoughts are that if you use the IRS-19 vaccine to stimulate the urinary tract mucosa (on which the dysbiosis is located), you may get better and faster results.
Here is a table showing the immune interconnections between various mucosa. You can see that application of a topical mucosal vaccine on the nasal mucosa can stimulate reasonable immunity in the reproductive tract (unfortunately the table does not detail the urinary tract mucosa).
Note that in this table, "blood" means the systemic immune response (which uses IgG/IgM antibodies, rather than the IgA antibodies secreted on the mucosal membranes).
Source: here.
Source: here.
Along with his custom autovaccines, Dr Markov prescribed me the IRS-19 nasal spray mucosal vaccine. This is quite inexpensive, and can be bought prescription-free for $18 here (though shipping is $20).
IRS-19 vaccine stimulates immune response against a range of bacteria, including Enterococcus, Klebsiella pneumoniae, Streptococcus and Staphylococcus.
This spray is intended for the nose, but recently I had the idea of instilling this spray liquid into the urethra. I actually tried this, and it was well tolerated, with no discomfort or irritation.
My reasoning is that IRS-19 might actually be more effective in the urethral mucous membranes, as the urethra is part of the urinary tract — the same urinary tract where the kidney dysbiosis is located.
Mucosal immune responses tend to more localised (unlike the systemic immunity you get from injected vaccines, which cover the whole body), so my thoughts are that if you use the IRS-19 vaccine to stimulate the urinary tract mucosa (on which the dysbiosis is located), you may get better and faster results.
Here is a table showing the immune interconnections between various mucosa. You can see that application of a topical mucosal vaccine on the nasal mucosa can stimulate reasonable immunity in the reproductive tract (unfortunately the table does not detail the urinary tract mucosa).
Note that in this table, "blood" means the systemic immune response (which uses IgG/IgM antibodies, rather than the IgA antibodies secreted on the mucosal membranes).
Source: here.
Source: here.
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That’s a great suggestion as a first approach. I think I’ll buy the nasal spray and see how I get on.
seems reasonable that administering via the urethra would be effective if going via the nose works. Perhaps the nasopharynx plays a role though. I only recently learned about this being an important immune system nexus. I guess in principe the nose could be “closer” to the kidney from an immune system perspective than the urethra is? But I see your logic in that the kidney and urethra share the same continuous mucosal membrane.
Have you seen any results from these treatments so far?
I’m trying not to get my hopes up as I’ve had short term relief in the past but I took high dose thiamine (800mg over the course of the day) and Miyarisan (discovered via you actually in the recent pomegranate supplement post) yesterday and had a VERY good day. Limited symptoms and uncharacteristically positive mood. Going to repeat today and see what happens. At one point after taking 200mg twice not long apart I genuinely felt like I had processes starting back up in my body. Hard to explain. Almost buzzing or recharging. It felt like I had added something I’d been missing, possibly long before getting ME about 7 months ago. Maybe it was a one-off.
I’m straying off topic again. By the way, thank you for everything you do here. You’re a real asset and massively appreciated. Your sharp critical thinking and willingness to experiment is needed here.
seems reasonable that administering via the urethra would be effective if going via the nose works. Perhaps the nasopharynx plays a role though. I only recently learned about this being an important immune system nexus. I guess in principe the nose could be “closer” to the kidney from an immune system perspective than the urethra is? But I see your logic in that the kidney and urethra share the same continuous mucosal membrane.
Have you seen any results from these treatments so far?
I’m trying not to get my hopes up as I’ve had short term relief in the past but I took high dose thiamine (800mg over the course of the day) and Miyarisan (discovered via you actually in the recent pomegranate supplement post) yesterday and had a VERY good day. Limited symptoms and uncharacteristically positive mood. Going to repeat today and see what happens. At one point after taking 200mg twice not long apart I genuinely felt like I had processes starting back up in my body. Hard to explain. Almost buzzing or recharging. It felt like I had added something I’d been missing, possibly long before getting ME about 7 months ago. Maybe it was a one-off.
I’m straying off topic again. By the way, thank you for everything you do here. You’re a real asset and massively appreciated. Your sharp critical thinking and willingness to experiment is needed here.
splusholia
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If anybody finds a way to try the recommended nasal sprays by Dr Markov's without using crypto currency please let me know! I don’t have the brain power to understand how to set that up (or even understand what it is).
MartinK
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@Atlas hey, I just bought Canephron here in Czech. Yeah!
And yes, I want to add dr. Markov treatment to my protocol. This is very hopeful as I have had a lot of antibiotics in the past and a lot of problems with nasal infections.
I do now also protocol for endothelial dysfunction and Ivermectin as a prophylactic treatment.
I'm finally stable enough!
Dr. Markov wrote this to me:
Preliminary conclusion: "Nephrodysbacteriosis. Chronic Bacterial Intoxication Syndrome (CBIS) with excessive fatigue, weakness, rapid physical exhaustion with a pronounced decrease in tolerance to physical and sports activities, severely limited physical capabilities ("bedridden"), pronounced fibromyalgia (severe muscle fatigue and pain after each movement - walking, sitting, exercises), decrease in life motivations, interest to surroundings, apathy, initial manifestations of cognitive dysfunctions, rapid mental exhaustion with unstable mood, impatience, weakening of self-control; sensation of a strong burning in the muscles; intermittent pain in the joints, in the spine and pelvic pain; thermodependence: intolerance to heat especially in hot weather and after exposure to the sun, which markedly aggravate fatigue and general malaise, as well as cold, which brings relief; a feeling of "hot flashes" and a feeling of heat in the body; orthostatic vulnerability and instability in an upright position; sleep disturbance (insomnia and sleep that does not refresh); a significant decrease in the previous level (before this disease) of professional, educational, social and personal activity; blurred vision; increased hair loss; leukopenia (3.77x109/l). Chronic staphylococcal infection of the nasopharynx: chronic rhinosinusitis with prolonged runny nose and nasal congestion (within several years before the onset of ME/CFS), chronic pharyngitis with frequent sore throat when swallowing; secondary bacterial-associated allergy with cofactor allergens (plant pollen). Secondary bacterial toxicoderma with symptoms of atopic dermatitis and eczema."
And yes, I want to add dr. Markov treatment to my protocol. This is very hopeful as I have had a lot of antibiotics in the past and a lot of problems with nasal infections.
I do now also protocol for endothelial dysfunction and Ivermectin as a prophylactic treatment.
I'm finally stable enough!
Dr. Markov wrote this to me:
Preliminary conclusion: "Nephrodysbacteriosis. Chronic Bacterial Intoxication Syndrome (CBIS) with excessive fatigue, weakness, rapid physical exhaustion with a pronounced decrease in tolerance to physical and sports activities, severely limited physical capabilities ("bedridden"), pronounced fibromyalgia (severe muscle fatigue and pain after each movement - walking, sitting, exercises), decrease in life motivations, interest to surroundings, apathy, initial manifestations of cognitive dysfunctions, rapid mental exhaustion with unstable mood, impatience, weakening of self-control; sensation of a strong burning in the muscles; intermittent pain in the joints, in the spine and pelvic pain; thermodependence: intolerance to heat especially in hot weather and after exposure to the sun, which markedly aggravate fatigue and general malaise, as well as cold, which brings relief; a feeling of "hot flashes" and a feeling of heat in the body; orthostatic vulnerability and instability in an upright position; sleep disturbance (insomnia and sleep that does not refresh); a significant decrease in the previous level (before this disease) of professional, educational, social and personal activity; blurred vision; increased hair loss; leukopenia (3.77x109/l). Chronic staphylococcal infection of the nasopharynx: chronic rhinosinusitis with prolonged runny nose and nasal congestion (within several years before the onset of ME/CFS), chronic pharyngitis with frequent sore throat when swallowing; secondary bacterial-associated allergy with cofactor allergens (plant pollen). Secondary bacterial toxicoderma with symptoms of atopic dermatitis and eczema."