ME/CFS in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms...

[uglevod]

in addition, the way the bacteria stop the VDR from transcription is to produce ever-increasing concentrations of an antagonist, such as Capnine, which ultimately stop 1,25-D from activating the VDR. In this way the bacteria stop the VDR from transcribing most of the antimicrobial peptides.

Yeah and looks like there are even more ways like the data from the following very recent paper:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177120/
Our macrophages are equipped with the ability to detect and kill invading pathogens, and yet, these cells of the innate immune system are still subject to infection by intracellular bacterium. In particular, mycobacterium, the type of intracellular bacteria responsible for diseases such as tuberculosis and leprosy, are very successful at establishing infection within macrophages.
Following infection, virulent mycobacteria persist and grow within the macrophage, suggesting that the intrinsic activation of an innate antimicrobial response is subverted by the intracellular pathogen
Upon infection of monocytes with M. leprae, there was no upregulation of CYP27B1 nor its enzymatic activity converting the inactive prohormone form of vitamin D (25-hydroxyvitamin D) to the bioactive form (1,25α-dihydroxyvitamin D)

 

[Hip]

Someone collected all reports from the forum and for CFS the anecdotal success rate was about 60%. For me its a very high figure so I'am taking my chance.

Would you have a link to that page where all the reports are collected to get a 60% figure? I always like to collect info on the efficacy of the various ME/CFS treatments.

I have considered trying the MP myself; though given that it takes 4 years, I often think: I wish I had started the MP 4 years ago. I did actually try it a long time ago for around 2 months, in the early years of my ME/CFS. The only immunopathology I experienced in those 2 months was a very mild sensitivity to bright sunlight.

I wish you good luck with the MP.

 

[Hip]

Rituximab is an TNF alpha inhibitor(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447167/).

That paper does not say that rituximab is an TNF-alpha inhibitor. Rituximab works by depleting B-cells.

 

[Murph]

The author, Amy Proal, has been making videos to help explain her hypotheses. I watched them and found them quite useful. She has a PhD in microbiolgy and either has or had me/cfs.

This video argues that neuro-inflammation could be caused by dysbiosis, either in the blood or gut (affecting the brain via the vagus)

pro-tip: in YouTube, click on the gear-wheel in the bottom right and increase the speed of the video to make long videos more palatable.

references:
1 Infection of Fungi and Bacteria in Brain Tissue From Elderly Persons and Patients With Alzheimer’s Disease: https://www.frontiersin.org/articles/...
2. Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus: https://www.cell.com/neuron/fulltext/...
3. Microglial control of astrocytes in response to microbial metabolites: https://www.ncbi.nlm.nih.gov/pubmed/2...
4. Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury: https://www.ncbi.nlm.nih.gov/pubmed/1...

This one argues that an infection can affect the immune system in a way that makes subsequent infections have an easier ride. Interesting stuff. She talks in particular about me/cfs at about 8min50s.

If you get an infection that partially disables your immune system, even your existing microbiome could suddenly become a real problem, she argues.

This hypothesis seems quite plausible and would appear to support a far broader set of enquiries and interventions than just the Marshall protocol, (which I don't know too much about but am skeptical of!).

 

[MonkeyMan]

The author, Amy Proal, has been making videos to help explain her hypotheses. I watched them and found them quite useful. She has a PhD in microbiolgy and either has or had me/cfs.

Very interesting -- thank you for posting. To my limited understanding, what she describes is actually bridging the work of Jarred Younger (on neuroinflammation) with the work of Ron Davis and his colleagues (on tryptophan, etc.).

Maybe everything is all starting to come together!

 

[uglevod]

Would you have a link to that page where all the reports are collected to get a 60% figure?

I've looked over and found updated numbers slighly above 60% for CFS. Details sent via PM.
Please note: this % was calculated before Marshall found the link between EMF and chronic inflammation deceases(like CFS) and immune stimulation properties of very low(effectively almost absent) levels of EM radiation(at least below -60 dBm) on Olmesartan.

Further details could be retrieved from his last videos: https://www.youtube.com/user/DrTrevorMarshall/videos
and the paper "Electrosmog and Autoimmune Disease"

 

[Hip]

I've looked over and found updated numbers slighly above 60% for CFS. Details sent via PM.

Thanks for sending me those details. It does indeed report a 60.1% success rate for ME/CFS (out of 183 ME/CFS patients).

However the difficulty with that 60.1% figure is that "success" is not defined in any precise way. The person on the Marshall Protocol website who analyzed all the reports by patients and calculated the 60.1% figure said:

My method was to bring up a members progress report. I would make note of the major disease listed by the member. I would then page down to the last page of the progress report and find the last, or last meaningful reply and try to determine if the member was reporting improvement in health, a decline in health or worsening of symptoms. Sometimes this was just that the person said they felt better. Sometimes this was looking at the change in toleration numbers.

A patient may say they "feel better", but we don't know whether that means a minor improvement, a major improvement, or a complete cure/remission.

 

[uglevod]

The author, Amy Proal, has been making videos to help explain her hypotheses.

 

[uglevod]

A patient may say they "feel better", but we don't know whether that means a minor improvement, a major improvement, or a complete cure/remission.

True. I'll try to update my own case on this forum from time to time(in MP speed that means about 1 time/year). For now I just bounce between different symptoms of different levels - currently I'am experiencing far less fatigue and can be vertical many hours during the day and stopped constantly thinking of rest, but my brain fog became immense(walking "zombie") which makes any intellectual work hardly possible - maybe I've got hit by so called Stage Five reaction localized in my poor brain(https://mpkb.org/home/mp/stages/stagefive)... But things are definitely moving. For example my psychotic episodes from which I've suffered since childhood(1..2 per day) are now gone.

 

[uglevod]

Statistics on the success percentages are over here:
https://mpkb.org/home/patients/cohort_statistics

Please note, that many from the cohort were originally in advanced sickness state, had a years history of applying palliative(microbiome growing) therapies behind them, etc.

 

[gbells]

I don't think the microbiome hypothesis will be fruitful. The main thing you see is too many firmicutes (baddies like lactobacillus acidophilus) and too few good bacteria (bacteriodes like bifidus). This isn't unique to CFS though.

I like Trevor Marshalls idea about CFS being an intracellular infection however I don't think his approach is effective. I tried it personally for my CFS and found it to be ineffective and contain problems with their nutritional recommendations. Also, there is more to cells than bacteria. What about viruses? I don't think he addresses that and there were some studies that showed that viral inhibitors helped CFS patients at least while they were on them.

 

[uglevod]

I tried it personally for my CFS and found it to be ineffective

@gbells, how long have you been on the protocol?

It becomes worse(high levels of chronic endotoxemia, constant inflammation, etc) before its get better:
http://autoimmunityresearch.org/transcripts/Auto2012_IngeLindseth.pdf

. What about viruses? I don't think he addresses that

Unless it's a HIV all viruses should be addressed by the immune system itself. Like nearly everyone carries EBV(I do), but few got severely sick with it.

 

[gbells]

@gbells, how long have you been on the protocol?

It becomes worse(high levels of chronic endotoxemia, constant inflammation, etc) before its get better:
http://autoimmunityresearch.org/transcripts/Auto2012_IngeLindseth.pdf

An integrative MD had me on it for a few months maybe 9 years ago (6 months?). I was in their study group but the leader Trevor Marshall decided to drop me when I asked too many questions about the rationale behind some questionable nutritional recommendations like a total ban on fish oil. My doctor ended up losing confidence in him and took every patient off his protocol. All said I'm glad that it happened and have no confidence in it.

Unless it's a HIV all viruses should be addressed by the immune system itself. Like nearly everyone carries EBV(I do), but few got severely sick with it.

That's not true. Nagalase testing is used to assess how well your immune system generates antibodies. The more EBV you have in your system the more nagalase it secretes and inhibits immunity via GcMAF. My nagalase was around 3x normal and I took sublingual GcMAF to treat that, causing it to return to normal over six months. Unfortunately, this gave me Systemic Lupus Erythematosis but also gave me a positive Rocky Mountain Fever lab test reading three times which my doctor treated with doxycycline for 2.5 months curing chronic daily headaches. So there was a good outcome.

http://gcmaf.timsmithmd.com/book/book/4/all/

I think the main thing is the viral load and co-infections. Thats why Dr. Lehrner was able to get some CFS patients well using antiviral drugs. http://drmyhill.co.uk/wiki/Valacyclovir_in_the_treatment_of_post_viral_fatigue_syndrome

Unfortunately the drugs don't cure it so I guess the patients regressed and the treatment ended up getting banned.

 

[uglevod]

Ban of fish oil as a TLR4 agonist seems pretty logical.

 

[gbells]

Ban of fish oil as a TLR4 agonist seems pretty logical.

That's wrong. EPA (fish oil) is an antagonist of TLR4 so it decreases inflammation. There is nothing wrong with taking it except that krill oil works better.

Conversely, omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, exert anti-inflammatory actions through the attenuation of the activation of the TLR4 signaling pathway by either lipopolysaccharides or saturated fatty acids.
Nutrients. 2018 Apr; 10(4): 432.

 

[ljimbo423]

EPA (fish oil) is an antagonist of TLR4 so it decreases inflammation.

I did a search on fish oil as an TLR4 agonist and found only references to it being an antagonist also.

I couldn't find anything on it being an agonist. I take 4 - 4.5 grams a day of EPA/DHA from fish oil and have for months.

I feel a noticeable reduction in inflammation from it. With no adverse effects, only benefits.

 

[nandixon]

I feel a noticeable reduction in inflammation from it. With no adverse effects, only benefits.

I wish I could say that. It seems to end up being a bit of a trade-off, because while fish oil (DHA and/or EPA) does indeed inhibit TLR4 it also suppresses the HPA axis, and a majority of ME/CFS patients already appear to have a hypoactive HPA axis (despite normal cortisol levels). So fish oil is seemingly not good from the latter standpoint.

I don't tolerate any form of fish oil or combination of DHA and EPA, as it makes my fatigue much worse.

I'm guessing that perhaps one reason why some patients tolerate it and others do not may have to do with their relative levels of inflammation versus HPA axis activity, but there are other possible reasons for this intolerance as well.

 

[Hip]

An integrative MD had me on it for a few months maybe 9 years ago (6 months?).

To be fair, you'd need be on it for around 4 years in order for it work. I also tried the MP for a few months (2 or 3 maybe) many years back, but gave it up also (for no particular reason).

I started to get some of the immunopathology (sensitivity to bright light in my case) during those few months, which I think is a very interesting phenomenon it its own right, as people without ME/CFS (or the other chronic diseases that the MP treats) do not get this immunopathology at all, when they take the MP drug Benicar for blood pressure purposes. So experiencing the immunopathology is almost some sort of diagnostic sign.

I've sometimes thought of trying the MP again, but the fact that it takes such a long time to work (if it does work) is disheartening.

One idea I had was trying Benicar intranasally: Benicar has poor blood-brain barrier penetration, but ME/CFS likely involves viral brain infection, so you really want to get this drug into the brain. Maybe that's why the MP is so slow, because of the poor BBB penetration.

 

[gbells]

To be fair, you'd need be on it for around 4 years in order for it work. I also tried the MP for a few months (2 or 3 maybe) many years back, but gave it up also (for no particular reason).

Says who? Dr. Hothead Marshall (laugh). Where is his 5 year blinded CFS patient outcome research justifying this? It's nonexistent. Where are the studies showing all these CFS cures? (crickets)

The expert concensus of the serious healthcare community is that the Marshall Protocol is your typical snake oil peddler with no real data applying a panacea to a large group of diseases (Sarcoidosis, CFS, etc) while having an unlikely mechanism of action and inadequate research support for his claims. Here's an official list of the diseases it claims effectiveness on:

• Sarcoidosis
• Chronic Fatigue Syndrome
• Fibromyalgia
• Chronic Lyme Disease
• Rheumatoid Arthritis
• Multiple Chemical Sensitivity (MCS)
• Myasthenia gravis
• Psoriasis
• Osteoarthritis
• Hashimoto’s Thyroiditis
• Uveitis
• Cardiac Arrhythmia

http://bacteriality.com/about-the-mp/

Its founder Trevor Marshall is a professor of electrical engineering, not healthcare, and the entire theory is based on computer modeling not real patients.

1. http://www.cureality.com/blog/post/2008/03/31/the-marshall-protocol-and-other-fairy-tales.html
   
2. https://sciencebasedmedicine.org/the-marshal-protocol/
   
3. https://phylogenomics.blogspot.com/2010/08/overselling-microbiome-award-2-marshall.html
4. https://articles.mercola.com/sites/...y-i-dont-recommend-the-marshall-protocol.aspx
   
5. https://rationalwiki.org/wiki/Marshall_Protocol

I agree with the experts who say its just a waste of money and a source of false hope for the desperately ill.

 

[uglevod]

EPA (fish oil) is an antagonist of TLR4 so it decreases inflammation.

Oops, i mean antagonist of course(damn brain fog). So its kinda contradicted to MP - lower levels of D25 increase the expression of TLRs receptors and the protocol requires D25 to be less than 12ng/ml, while antagonists block TLR4, decreasing inflammation generated via LPS(endotoxin)->TLR4 stimulation.

Says who? Dr. Hothead Marshall (laugh).

He is much more emotionally stable now. Did you look up his latest videos?