Dr Markov CBIS Theory of ME/CFS - General Discussion

[Eddy M]

Yes, I think you may be right that urine will always contain a tiny amount of bacteria.

If you look at the instruction sheet for the urine dipslide test which I uploaded above, it shows various pictures of the bacterial growth spot density on the agar. If the spot density is low, it is considered a negative result. If the spot density is above a certain threshold, then it is considered a positive result.

How Dr Markov determines if a specimen is pathologic? Did he compare to a healthy population?
The urine test of Dr Markov has some red flags:
why exiging warm urine? is there any proof.
Were the thresholds for positivity validated by peers?
Is the Toxicon test validated? reproducible by others?
Some other red flags:
Dr Markov has a business and financial incentive from this theory.
If his theory is true it would have been very easy to convince open minded researchers as Ron Davis. Why trying to convice patients?


An example from MS:
Dr Zamboni proposed Chronic cerebrospinal venous insufficiency as a cause of MS. He proved this by demonstrated abnomalities with an echography probe from a constructor that he had a conflict of interest with.
This probe demonstrated a lot of false positives. Treatement for this condition was ineffective. When scientists did good quality research using gold standard angiography they didn't find a difference between sick and healthy.

I hope that i am wrong but it's too good to be true. The papers of Dr Markov have not one or two but a lot of flaws.

We have to be careful from people taking advantage from our desesperation.

 

[Hip]

@Eddy M, you make some good points, some of which have been mentioned earlier in this thread.

Did you see the overview post of Dr Markov's CBIS theory of ME/CFS? That covers some of your questions.

How Dr Markov determines if a specimen is pathologic? Did he compare to a healthy population?

Dr Ogor Markov said the urine is positive for bacteria in over 95% of CBIS ME/CFS patients, but only positive in 7% of healthy adults. I do not know what threshold he is using to signify a positive result in the Diaslide® dipslide urine tests. Diaslide results report bacterial CFU (colony forming units) per ml of urine.

Is the Toxicon test validated? reproducible by others?

I could not find any info online about the Toxicon lab test, other than what Dr Markov told us, which is that it was developed by a group of Ukrainian scientists led by pediatric toxicologist Dr Borys S Sheiman. The Toxicon lab test detects toxic proteomes of bacteria (toxicoproteomics).

I have asked Dr Oleg Markov for more info about Toxicon. We are awaiting his response.



I think Dr Markov's idea that ME/CFS could be caused by high levels of bacterial toxins in the blood is very interesting, and I'd like to see others look into this.

The strange thing is, I could not find one single study looking to see whether ME/CFS patients might have high levels of bacterial toxins in their blood. You would think that this sort of blood testing would have already been covered by many studies performed decades ago. But I could not find any studies.

There was one recent study which looked at blood LPS levels in ME/CFS, and found LPS to be elevated. But LPS is only one of dozens of bacterial toxins. I could not find any ME/CFS study looking for the presence of bacterial toxins in general in the blood of ME/CFS patients. Which seems like an inexplicable omission.

I'd like to see some investigation into whether ME/CFS patients may have bacterial toxins in their blood.

 

[Hipsman]

I believe in order to comply with regulations, Dr Markov has to create an autovaccine from the patient's own bacteria.

Dr. Igor Markov prescribed me already made vaccine as I wrote in my report previously here, so they have at least 1 ready made vaccine...

 

[andyguitar]

The strange thing is, I could not find one single study looking to see whether ME/CFS patients might have high levels of bacterial toxins in their blood

But there is some research into bacteria in the blood of Fibromyalgia patients. Like this:

 

[perrier]

How Dr Markov determines if a specimen is pathologic? Did he compare to a healthy population?
The urine test of Dr Markov has some red flags:
why exiging warm urine? is there any proof.
Were the thresholds for positivity validated by peers?
Is the Toxicon test validated? reproducible by others?
Some other red flags:
Dr Markov has a business and financial incentive from this theory.
If his theory is true it would have been very easy to convince open minded researchers as Ron Davis. Why trying to convice patients?


An example from MS:
Dr Zamboni proposed Chronic cerebrospinal venous insufficiency as a cause of MS. He proved this by demonstrated abnomalities with an echography probe from a constructor that he had a conflict of interest with.
This probe demonstrated a lot of false positives. Treatement for this condition was ineffective. When scientists did good quality research using gold standard angiography they didn't find a difference between sick and healthy.

I hope that i am wrong but it's too good to be true. The papers of Dr Markov have not one or two but a lot of flaws.

We have to be careful from people taking advantage from our desesperation.

If memory serves me correctly, I think Dr Zamboni's wife has MS and he did the treatment on her and she showed improvement. I have not been following this story, so I do not know what the status of her condition is now.

 

[mattie]

If memory serves me correctly, I think Dr Zamboni's wife has MS and he did the treatment on her and she showed improvement. I have not been following this story, so I do not know what the status of her condition is now.

Italian physician Paolo Zamboni has publicly acknowledged that a therapy he developed and dubbed “the liberation treatment” does not cure or mitigate the symptoms of MS. A randomized controlled trial — the gold standard of medical research — he and other Italian researchers conducted concluded the procedure is a “largely ineffective technique” that should not be recommended for MS patients.

 

[Eddy M]

@Eddy M

I think Dr Markov's idea that ME/CFS could be caused by high levels of bacterial toxins in the blood is very interesting, and I'd like to see others look into this.

I agree with that the theory seems interesting. But some skepticism and healthy criticism is good and make things advances. We need to learn from the past and not repete the same errors.
Anoher point that is a red flag is the autors used Fukuda criteria and we all can agree that these criteria made harm and no good.
The other problem is the 6 months - 2 years for improvement:
Is it due to the vaccine?
Is it auto improvement of non CFS patients
If patients began to administer auto vaccines from now the consequences could be bad due to the long time frame to say that the treatment is inefective.

 

[Hipsman]

The other problem is the 6 months - 2 years for improvement:

If I remember correctly, Oleg Markov said on PR that 6 months - 3 years of treatment is for full remission. During my appointment Dr. Igor Markov said that there will be incremental improvements as the treatment continues, so some improvemnts only after first cycle of vaccines (if those vaccines target correct bacteria), but I don't know if that applies to all ME/CFS patients he treats...

 

[Eddy M]

A randomized controlled trial — the gold standard of medical research

https://www.cochrane.org/MR000034/M...d-controlled-trials-and-observational-studies

Our results across all reviews (pooled ROR 1.08) are very similar to results reported by similarly conducted reviews. As such, we have reached similar conclusions; on average, there is little evidence for significant effect estimate differences between observational studies and RCTs, regardless of specific observational study design, heterogeneity, or inclusion of studies of pharmacological interventions. Factors other than study design per se need to be considered when exploring reasons for a lack of agreement between results of RCTs and observational studies. Our results underscore that it is important for review authors to consider not only study design, but the level of heterogeneity in meta-analyses of RCTs or observational studies. A better understanding of how these factors influence study effects might yield estimates reflective of true effectiveness.

RCT are considered gold standard but the evidence is lacking. Observationnal studies have the same power and more researchers are aknowledging it. I hope that it wil be considered for ME research. It economizes time and money and permits to other actors than phamarceutical industries to make research.

 

[Eddy M]

If I remember correctly, Oleg Markov said on PR that 6 months - 3 years of treatment is for full remission. During my appointment Dr. Igor Markov said that there will be incremental improvements as the treatment continues, so some improvemnts only after first cycle of vaccines (if those vaccines target correct bacteria), but I don't know if that applies to all ME/CFS patients he treats...

When did you begin the treatment? Did you feel any result? Are more people trying the treatment.
it would be intersting to have some preleminary results.

 

[Hip]

The other problem is the 6 months - 2 years for improvement:

Indeed, skepticism and criticism is very valuable, as long as the skeptics spend some time to understand the theory and the empirical data, so that their criticism is precisely targeted and scientific. If they just give the theory a cursory glance and then conclude "it will never work", that's not particularly helpful, and is not really conducive to discussion. Skeptics should ideally "get their hands dirty" so to speak, and help point out any points of failure of the theory.


One point of skepticism I have about the Markov CBIS is theory of ME/CFS relates to the fact that antibiotics do not help, and you'd think they would if ME/CFS is due to a kidney dysbiosis infection.

If the bacterial toxins found in ME/CFS patients' blood originate from a kidney dysbiosis infection, why don't strong antibiotics generally improve ME/CFS symptoms, at least temporarily? Dr Markov says antibiotics may make the kidney dysbiosis worse in the long term, and that makes sense, given what we know about intestinal dysbiosis after antibiotics.

However, in the short term, you might expect antibiotics to reduce the populations of kidney bacteria, and thus reduce the amount of toxins these bacteria are releasing. So you would expect ME/CFS symptoms to improve, at least temporarily after antibiotics. But they don't.


Dr Markov said that antibiotics can make ME/CFS symptoms better in the short term, but generally I don't think that is the case. Plenty of ME/CFS patients have taken antibiotics without noticing any improvements. So antibiotics usually do not help (unless you have bacterial co-infection like Chlamydia pneumoniae).

The exception to this "antibiotics do not help" rule is the long-term heavy-duty antibiotics that Dr Kenny De Meirleir sometimes prescribes his ME/CFS patients, which some patients report have made major improvements (and others report the antibiotics made them permanently much worse — maybe that reflects what Dr Markov is saying about antibiotics making dysbiosis worse in the long term).

But generally speaking, antibiotics do not seem to help ME/CFS.

So how can we explain this in terms of the CBIS theory?



One explanation for the ineffectiveness of antibiotics might be that the kidney bacteria live in biofilms, which antibiotics cannot easily penetrate.

It's known that biofilms play an important role in urinary tract infections, so this explanation would be consistent with what we know about UTIs.

 

[Eddy M]

Indeed, skepticism and criticism is very valuable, as long as the skeptics spend some time to understand the theory and the empirical data, so that their criticism is precisely targeted and scientific. If they just give the theory a cursory glance and then conclude "it will never work", that's not particularly helpful, and is not really conducive to discussion. Skeptics should ideally "get their hands dirty" so to speak, and help point out any points of failure of the theory.


One point of skepticism I have about the Markov CBIS is theory of ME/CFS relates to the fact that antibiotics do not help, and you'd think they would if ME/CFS is due to a kidney dysbiosis infection.

If the bacterial toxins found in ME/CFS patients' blood originate from a kidney dysbiosis infection, why don't strong antibiotics generally improve ME/CFS symptoms, at least temporarily? Dr Markov says antibiotics may make the kidney dysbiosis worse in the long term, and that makes sense, given what we know about intestinal dysbiosis after antibiotics.

However, in the short term, you might expect antibiotics to reduce the populations of kidney bacteria, and thus reduce the amount of toxins these bacteria are releasing. So you would expect ME/CFS symptoms to improve, at least temporarily after antibiotics. But they don't.


Dr Markov said that antibiotics can make ME/CFS symptoms better in the short term, but generally I don't think that is the case. Plenty of ME/CFS patients have taken antibiotics without noticing any improvements. So antibiotics usually do not help (unless you have bacterial co-infection like Chlamydia pneumoniae).

The exception to this "antibiotics do not help" rule is the long-term heavy-duty antibiotics that Dr Kenny De Meirleir sometimes prescribes his ME/CFS patients, which some patients report have made major improvements (and others report the antibiotics made them permanently much worse — maybe that reflects what Dr Markov is saying about antibiotics making dysbiosis worse in the long term).

But generally speaking, antibiotics do not seem to help ME/CFS.

So how can we explain this in terms of the CBIS theory?



One explanation for the ineffectiveness of antibiotics might be that the kidney bacteria live in biofilms, which antibiotics cannot easily penetrate.

It's known that biofilms play an important role in urinary tract infections, so this explanation would be consistent with what we know about UTIs.

The problem is that you can't go to high level discussion about a theory if the foundation is wrong.
I can write a book about how to design a bridge. But if one fundamental formula is wrong, when you will build the bridge it will collapse.

The theory has a fundamental flaw:
In the 85 pages document there is no mention of post-exertionnal malaise.
Just explaining it vaguely in the text and a mention in the Fukuda criteria : "Increasing fatigue up to exhaustion after physical or mental effort lasting more than 24 hours. "
in table 1 page 20 of the clinical caracteristics of patients; NO mention of PEM. (I think that PEM is the cardinal and most debilitating symptoms for the majority, correct me if i'm wrong) This is weird for a study about CFS/ME.
Imagine i publish a study about anemia and not talking about haemoglobin values. Fukuda criteria have very low specificity and very high sensitivity meaning that the false positives are times more than the true positives.
This alone is a major red flag.

What i didn't understood from bacterial dysbiosis. Dysbiosis means that the makeup of bacteria is abnormal, not true infection. if you culture the urine and are positive without urinary symptoms there's a term in medicine: Asymptomatic bacteriura and it's treated by antibiotics in population with risk factors.

I couldn't find data about the difference between healthy and sick.

The toxicological diagnosis could be interesting but i need to read more about it.


ME patients are willing to experiment anything, we need to be careful.

 

[andyguitar]

If the bacterial toxins found in ME/CFS patients' blood originate from a kidney dysbiosis infection, why don't strong antibiotics generally improve ME/CFS symptoms, at least temporarily?

One explanation for the ineffectiveness of antibiotics might be that the kidney bacteria live in biofilms, which antibiotics cannot easily penetrate.

So you have answered your own question @Hip ! There is also the problem of antibiotic resistance and using the right drug for the bacteria.

 

[Eddy M]

One more point: There strong financial incentive from the authors

Just look at this page: https://cbis.vitacell.com.ua/en

Normally scientists don't sell their papers, they publish them in scientific papers and give them for free if you ask them directly. I don't know about ukranian culture.

 

[Hip]

One more point: There strong financial incentive from the authors

Just look at this page: https://cbis.vitacell.com.ua/en

Normally scientists don't sell their papers, they publish them in scientific papers and give them for free if you ask them directly. I don't know about ukranian culture.

You are right, I never noticed that before.

I never read that page properly (I have great trouble reading text, due to a viral brain infection), and I did not notice that Dr Markov is selling his papers. That's not the norm in science.

Scientific journal publishers of course make a fortune selling scientific research — research which is often paid for by the taxpayer, and some consider that to be wrong; but scientists themselves usually do not charge for papers.

When we searched the Internet for reviews and reports about the Markov clinics, some people said they were pleased with the treatment they received at the clinic, but others said the treatment did not work for them, and said that Dr Markov is just interested in money. I don't think it is any secret that Dr Markov would like to cash in on his CBIS theory and autovaccine treatment.


On the other hand, if we compare Dr Markov's prices to that of say the late Dr Paul Cheney, one of the ME/CFS doctors involved in the Lake Tahoe ME/CFS outbreak of 1984, I believe Cheney charged something like $800 per hour of his time, and in my view, Cheney was not one of the most scientifically rigorous ME/CFS doctors; I think he just used to try out various dietary supplements on his ME/CFS patients.

The theory has a fundamental flaw:
In the 85 pages document there is no mention of post-exertionnal malaise.
Just explaining it vaguely in the text and a mention in the Fukuda criteria : "Increasing fatigue up to exhaustion after physical or mental effort lasting more than 24 hours. "
in table 1 page 20 of the clinical caracteristics of patients; NO mention of PEM. (I think that PEM is the cardinal and most debilitating symptoms for the majority, correct me if i'm wrong) This is weird for a study about CFS/ME.
Imagine i publish a study about anemia and not talking about haemoglobin values. Fukuda criteria have very low specificity and very high sensitivity meaning that the false positives are times more than the true positives.
This alone is a major red flag.

Do you mean that Markov's theory has not explained how PEM arises?

Well, lots of different ME/CFS theories have been proposed over the decades, but almost none have offered any explanation for how PEM arises. Or indeed offered much explanation for any of the other symptoms that appear in ME/CFS. I would not discard a theory because it cannot directly explain PEM or other symptoms.

The fact that the authors used the Fukuda ME/CFS criteria rather than the more precise Canadian consensus criteria (CCC) is not ideal, and I agree there is a concern that the patients Dr Markov is treating might not be CCC patients.


I wish we could find some lab test that could measure levels of bacterial toxins in the blood. I don't seem be able to find any such tests which are commercially available. But such a test would help us confirm or refute Dr Markov's theory.

 

[Eddy M]

You are right, I never noticed that before.

I never read that page properly (I have great trouble reading text, due to a viral brain infection), and I did not notice that Dr Markov is selling his papers. That's not the norm in science.

Scientific journal publishers of course make a fortune selling scientific research — research which is often paid for by the taxpayer, and some consider that to be wrong; but scientists themselves usually do not charge for papers.

When we searched the Internet for reviews and reports about the Markov clinics, some people said they were pleased with the treatment they received at the clinic, but others said the treatment did not work for them, and said that Dr Markov is just interested in money. I don't think it is any secret that Dr Markov would like to cash in on his CBIS theory and autovaccine treatment.


On the other hand, if we compare Dr Markov's prices to that of say the late Dr Paul Cheney, one of the ME/CFS doctors involved in the Lake Tahoe ME/CFS outbreak of 1984, I believe Cheney charged something like $800 per hour of his time, and in my view, Cheney was not one of the most scientifically rigorous ME/CFS doctors; I think he just used to try out various dietary supplements on his ME/CFS patients.





Do you mean that Markov's theory has not explained how PEM arises?

Well, lots of different ME/CFS theories have been proposed over the decades, but almost none have offered any explanation for how PEM arises. Or indeed offered much explanation for any of the other symptoms that appear in ME/CFS. I would not discard a theory because it cannot directly explain PEM or other symptoms.

The fact that the authors used the Fukuda ME/CFS criteria rather than the more precise Canadian consensus criteria (CCC) is not ideal, and I agree there is a concern that the patients Dr Markov is treating might not be CCC patients.


I wish we could find some lab test that could measure levels of bacterial toxins in the blood. I don't seem be able to find any such tests which are commercially available. But such a test would help us confirm or refute Dr Markov's theory.

Don't forget that Dr Markov is ukrainian. Minimum wage there is 220 USD. 300 USD could be compared to 2000 USD in the USA.

I didn't mean that he didn't explain PEM but it wasn't a criteria for him and wasn't mentionned in the summary table of the symptoms and signs.

I am just saying that selection of patients wasn't rigourous. This implies a lot of things:
What is the proportion of CFS/ME patients? 1%, 2%, 10%, 50%?
The ones who didn't recover maybe had CFS/ME
Mistakes were made in the past and had devastating consequences (ex: PACE trial).

The idea of toxins could be interesting.

 

[andyguitar]

Normally scientists don't sell their papers, they publish them in scientific papers and give them for free if you ask them directly. I don't know about ukranian culture.

I never read that page properly (I have great trouble reading text, due to a viral brain infection), and I did not notice that Dr Markov is selling his papers. That's not the norm in science.

The 85 page document is free. The things he is charging for appear to be guides on how to diagnose and treat. Not scientific papers.

 

[Eddy M]

The 85 page document is free. The things he is charging for appear to be guides on how to diagnose and treat. Not scientific papers.

Citing from the text:
''All clinical paths of removing the mask from CFS and of diagnostical transformation of CFS into CBIS is described consequentially and argumentally in the cycle of 9 reports/articles on clinical diagnosis, on bacteriological and toxicological diagnosis and treatment of CBIS. Below you find the first part of whole study “chronic bacterial intoxication syndrome under the mask of CFS/ME”, namely Reports 1.-6. “Clinical diagnosis”. The second part of the study (Reports 7-9.) will contain data on bacteriological diagnosis (Report 7), toxicological diagnosis (Reports 8) and treatment of CBIS (Report 9). It’s ready for publication and now some data are being translated in English. ''

From the site:

Seems that one part is free. The other is behind a paywall. He is charging for scientific papers as i understood.

 

[andyguitar]

"Clinical algorithm for diagnostics and treatment of cfs/me (CBIS)" and the other dont sound like papers to me. The $60 includes a questionaire for diagnosis. So it sounds more like a guide to diagnosis and treatment. As he is running a private health clinic then I would expect a fee for this. It would'nt be free in the UK.

 

[Hip]

The 85 page document is free. The things he is charging for appear to be guides on how to diagnose and treat. Not scientific papers.

The 85 page document is free, that contains Reports 1 to 6, and can be downloaded here.

I believe from what @Eddy M found, Dr Markov is currently charging $60 for Reports 7 to 9, but as you say, that $60 also includes a diagnostic questionnaire, to help establish if you have CBIS.

So that $60 cost is not just for reports, but for a questionnaire-based diagnosis as well.



In the above link, it says Reports 7 to 9 will be published at some point:

The second part of the study (Reports 7-9.) will contain data on bacteriological diagnosis (Report 7), toxicological diagnosis (Reports 8) and treatment of CBIS (Report 9). It’s ready for publication and now some data are being translated in English.

Dr Oleg Markov emailed me Report 8 for free.

Don't forget that Dr Markov is ukrainian. Minimum wage there is 220 USD. 300 USD could be compared to 2000 USD in the USA.

The purchasing power of a dollar is more in the Ukraine, but not that much more, as far as I can see.

The Big Mac Economic Index, which gives the dollar price of a Big Mac hamburger in different countries, is a common way to gauge the purchasing power of one dollar in each country.

Using that index, we can work out that having $100 in the Ukraine would have the equivalent buying power of having around $257 in the US.


Dr Markov's total treatment costs are about $1500, which covers appointments, consultations and the preparation autovaccines to cover 2-3 years therapy. That sounds reasonable, but to someone in the Ukraine it would be the equivalent of paying nearly $4000 in the US.