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

[uglevod]

I agree with the experts

I'am not sure "expert" is a right word for someone whose knowledge of Vitamin D is bound by a few words like "calcium", "sun", "rickets". I think you will not object the theory that Marshall knows "slightly" more on Vit D metabolism than your quoted "experts".

https://articles.mercola.com/sites/...y-i-dont-recommend-the-marshall-protocol.aspx

Yeah, another well known "expert" .. but in what ... in selling tanning beds?

$2.59 million in refunds for Mercola tanning beds
https://www.consumer.ftc.gov/blog/2017/02/259-million-refunds-mercola-tanning-beds

Hmm, lets see from his own comments:
https://articles.mercola.com/sites/...y-i-dont-recommend-the-marshall-protocol.aspx

Dr. Mercola:
Thanks for posting your comments however you are have a SERIOUS misunderstanding of
my motivation. This has NOTHING to do with revenue streams.
...
What you and many people fail to realize is that I ran this site for the first three years without selling one product. After spending $500,000 of my own money I could not do it any longer so I had to have a revenue stream to keep the site up.

From "spending" 500k to at least $2.59 million in revenue from tanning beds. "Nothing to do with revenue streams", huh?

... "Keep the site up" by generating millions of $ for himself? Oh, what a favour to everyone!

 

[gbells]

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.

I just had a look at this presentation on the MP. It was an 18 question survey of 180 patients who were on it. It is suspicious that there is no link to the actual questions and the presentation only shows two endpoints. Where are the other 16? Most of the gains were achieved at year 2 with a small number at year 3. However the patients reporting improvement dropped 10% from year 3 to 4. Symptom severity among the responders dropped from year 3 to 4 by 65%. Notice that at the end of four years of treatment patients were left with only 65% improvement (35% symptoms). If you translate this into the MyHill severity scare it gives you a score of 30.

https://mpkb.org/home/patients/cohort_statistics


30: Moderate to severe symptoms at rest. Severe symptoms with any exercise.

Given that these patients still have severe symptoms it is clear that the treatment was a failure and didn't cure them.

More likely explanations are that most of the improvement is because the benicar drug is anti-inflammatory (35%) and also from placebo effect (30%)
Toxicol Appl Pharmacol. 2013 Aug 15;271(1):106-13.

 

[uglevod]

A more likely explanation is that most of the improvement is because the benicar drug is anti-inflammatory and also from placebo effect.

Yeah, I personally feel the "anti-inflammatory" + "placebo" effect of Benicar every day.

 

[uglevod]

However the patients reporting improvement dropped 10% from year 3 to 4.

It could be "stage 5" reaction:
https://mpkb.org/home/mp/stages/stagefive
An over-exuberant Stage Five reaction can happen in latter stages of the MP, even in the absence of antibiotics, as the immune system becomes increasingly self-sustaining and uninhibited by bacterial ligands.

The characteristics of patients suffering from an over-exuberant Stage Five are as follows:

• usually (but not always) have been on the MP several years

 

[Hip]

Says who?

If you read the logs of patients who have got better on the MP, several years is the sort of timescale that you often see. One point of comparison is the timescale for Valcyte or Valtrex treatment for ME/CFS, which Dr Lerner's studies indicated takes about 1 or 2 years.

I am also skeptical of the efficacy of the MP for ME/CFS, but I keep an open mind to trying it. I certainly praise Prof Marshall in for highlighting the hypothesis that microorganisms are the likely cause of many chronic diseases.

while having an unlikely mechanism of action

I would say the mechanism of action is appropriate for ME/CFS, if you subscribe to the pathogen theory of ME/CFS.

The MP works by stimulating the release of the antimicrobial compounds cathelicidin and beta-defensins, which have a broad-spectrum action against bacteria, viruses, fungi and protozoa. Beta-defensins have been shown to have antiviral effects for the enteroviruses and herpesviruses associated with ME/CFS.

 

[Murph]

The thing about a protocol that takes years to work is that it

1. Allows people who spruik that protocol to claim that the protocol never really fails, patients are just too impatient.

2. Motivates the people who used it to say it was effective even if it wasn't since they invested so much in it and they're unlikely to enjoy the cognitive dissonance of realising they were duped.

3. Opens up to a range of false positives among people who would have experienced a natural remission in that time period.

I'm especially inclined to be negative about things that demand a patient feel worse before they feel better. That's a high price to pay.

None of these are specific rebuttals of the Marshall protocol. Maybe it's brilliantly effective. But it fits so neatly into a category marked 'suspect' that one can't help but wonder why...

 

[gbells]

Dr. Lehrner's research is fascinating. I'll have to review it in more detail. Patients on anti-virals responded between 6 months to a year.

As a rule of thumb if somebody has been ill for three years or less they generally begin to respond within six months of starting antiviral therapy. Other patients will take longer; at the Clinic they suggest that patients be treated for at least a year before they assess how effective treatment is.

This is not to say that people who have been ill for seven or 10 or 15 years do not respond to this treatment; Dr. Lerner said many long-duration patients do respond to this treatment – but as a group they don’t respond as quickly and, of course, some don’t respond at all. About 25% of his patients were classified as nonresponders.

https://phoenixrising.me/interviews...ntiviral-treatment-study-0510-by-cort-johnson

Motivates the people who used it to say it was effective even if it wasn't since they invested so much in it and they're unlikely to enjoy the cognitive dissonance of realizing they were duped.

Agreed. Again, no evidence here that MP works and the mechanism is unlikely. EBV blocks immunity three ways, one with nagalase plus another with stopping T-cell attachment and finally stimulating Nf-kb. MP isn't targeting any of its effects. Looks like a dead end.

 

[uglevod]

EBV blocks immunity three ways, one with nagalase plus another with stopping T-cell attachment and finally stimulating Nf-kb. MP isn't targeting any of its effects. Looks like a dead end.

EBV primary persists by suppressing VDR:
https://www.ncbi.nlm.nih.gov/pubmed/20593215

I'm especially inclined to be negative about things that demand a patient feel worse before they feel better. That's a high price to pay.

Those with chronic confirmed Lyme are more opened to pay this price since they are already getting reactions from their antibiotics, especially when the D25 level is low enough(that's why all LLMD are always trying to "fix" their D25 "deficiency" as one of the first things).

Olmesartan for them basically makes antibiotics much more intolerable, or brings intolerability back.

 

[gbells]

EBV primary persists by suppressing VDR:
https://www.ncbi.nlm.nih.gov/pubmed/20593215

The article doesn't say that at all.

 

[uglevod]

The article doesn't say that at all.

"We found that EBNA3 blocks the activation of VDR-dependent genes and protects LCLs against vitamin-D3-induced growth arrest and/or apoptosis."

CMV is messing around with VDR too:
https://www.ncbi.nlm.nih.gov/pubmed/27520300

 

[Hip]

That's very interesting that EBV and CMV reduce VDR activation and expression as an immune evasion strategy. That's news to me. I've added those two studies to my list of immune evasion strategies used by ME/CFS viruses.

EBV also does other things for immune evasion purposes though:

EBV makes a "fake" (homologue) version of the human cytokine IL-10 in order to turn down the antiviral immune response. 1

EBV makes a protein called LMP-1 which can induce IL-10, again to turn down antiviral immunity.

EBV inhibits antigen presentation on MHC II, to protect virally-infected cells from immune recognition and attack. 1

EBV utilizes DNA methylation to cloak itself from immune detection. 1

 

[gbells]

This doesn't mean that benicar is an effective way apoptose infected cells. I light avoid and take 5000iu of vit D3 once a week. D3 has a half life of 15 hours. Light avoidance and once a week D3 dosing make sense but I don't see any reason to think that Benicar would accelerate apoptosis. It's just speculation.

 

[uglevod]

I don't see any reason to think that Benicar would accelerate apoptosis. It's just speculation.

If I recall correctly, VDR activation(via the native ligand - D1.25) leads to infected cell apoptosis(among other things).

Believing in whether Olmesartan is a synthetic replacement of a native D1.25 is up to you, here is some data from TM
on this https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360063/

Also, another interesting study on Quercetin as a VDR ligand: http://www.biomolther.org/journal/view.html?uid=614&vmd=Full

They have used more or less the same methods as Marshall.

 

[gbells]

I researched this out. EBV creates proteins which block intrinsic apoptosis by disabling p53 and p73.
https://www.wikiwand.com/en/Apoptosis

For the intrinsic pathway the first thing EBV does it block NF-kB which is pro-inflammatory and causes pain. Next, is p53 which blocks Bax and p73 which blocks Bcl-2.

Now what can we do about it? First the supplement turmeric stops Nf-kB inhibition and induces cathelicidin
through a vitamin D receptor-independent pathway so we use turmeric.

That restores the blocked antibiotic.

https://www.ncbi.nlm.nih.gov/pubmed/22841393

Next we have to generate antibodies to activate the extrinsic pathway to apoptose the cells so the blocked intrinsic system aka D3 and Benecar becomes unnecessary.

 

[uglevod]

First the supplement turmeric stops Nf-kB inhibition and induces cathelicidin through a vitamin D receptor-independent pathway so we use turmeric.

I think net result is always negative for curcumin - in other words its anti inflammatory effects always dominate or it will not be extensively used for palliation when treating, for example lyme:

https://www.ncbi.nlm.nih.gov/pubmed/24669820

^ one of the possible palliation pathways

https://www.ncbi.nlm.nih.gov/pubmed/22841393

"Recent in vitro studies suggested that curcumin and polyunsaturated fatty acids (PUFAs) also bind to VDR with low affinity."

I think both curcumin and PUFA are VDR antagonists(as opposed to Benicar) - no one showed me the signs of immune activation(blood tests, etc) with tumeric.

P.S. PUFA is well known crap:
http://www.functionalps.com/blog/2011/09/22/polyunsaturated-fats-suppress-the-immune-system/

 

[gbells]

ugle you have it completely backward due to MP misinformation. Curcumin and fish oil are agonists not antagonists and stimulate the VDR. This has been pointed out before. As for Curcumin decreasing NF-kB inflammation, you WANT it to do that since EBV wants to upregulate NF-kB (inflammation) to disable the intrinsic apoptosis mechanisms.

One important mechanism of cell survival is activation of transcription of different anti-apoptotic proteins by TNFs via nuclear factors of the kappa light polypeptide in B-cells ( NF-kB ) signaling cascade [1].

http://pathwaymaps.com/maps/721

MP is presenting a completely wrong model, which is what the experts said about it. Pretty much the only thing it gets right is to avoid light and daily dosing of Vit D3. It is a dead end. This explains the high failure rate.

 

[uglevod]

which is what the experts said about it

This "experts" know very little to be a valuable information points.

BTW, Olm drops NF-kB too.

Curcumin and fish oil are agonists not antagonists

Fish oil is a very common immunosuppressant drug:

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137309
Supplementation of overweight/obese pregnant women with dietary ω-3 FAs for >25 weeks reduced inflammation in maternal adipose and the placental tissue. TLR4 appears as a central target of the anti-inflammatory effects at the cellular level.

Package of D3+curcumin+fish oil is from a supplements list useful in treating all kinds of chronic inflammation manifestations. Also people take them together with abx to drop bacteria die off symptoms a bit(by suppressing TLR receptors I guess).

This explains the high failure rate.

Failer rate is less than 50% VS 100% failer(unless temporary remission) rate of all other therapies...

 

[gbells]

Fish oil is a very common immunosuppressant drug:

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137309
Supplementation of overweight/obese pregnant women with dietary ω-3 FAs for >25 weeks reduced inflammation in maternal adipose and the placental tissue. TLR4 appears as a central target of the anti-inflammatory effects at the cellular level.

Being anti-inflammatory is not equal to being immunosuppressive. Your own study cited above proves my point that EPA aka ω-3 aka omega 3 is not immunosuppressive.

Diets that are rich in ω-6 fatty acids produce eicosanoids, whereas a diet with a more balanced intake of ω-6 and ω-3 fatty acids makes less inflammatory and less immunosuppressive eicosanoids [7].

Failer rate is less than 50% VS 100% failer(unless temporary remission) rate of all other therapies...

Oh no, that's just the symptom improvement rate, not the cure rate. That doesn't mean they are cured at all. That just means they felt better. This includes anti-inflammatory effects of benecar, light avoidance, placebo effect, whatever.

MP is junk science.

 

[uglevod]

What I personally see is a bunch of people taking O3, curcumin, vit C, vit E, etc for years, going into eventual relapse, start taking more powerful anti inflammatory drugs(like steroids), finally get a diagnosis(lyme disease is very common) and starting some sort of anti bacteria protocol.

I've analyzed hundreds of patient stories on the MP forum and the above(^) pattern(including treating the disease with high dose abx pre MP) is very common from their histories(which many do post).

When I arrived to MP one of the symptoms was photosensitivity and https://mpkb.org/home/lifestyle/light/photosensitivity which is now at 50+ position in google search results was at around 5 position 2+ years ago and gave a sane explanation with additional links. Today I have less sensitivity from the lights.

 

[uglevod]

This includes anti-inflammatory effects of benecar

I personally communicate every day with a person who is using Benicar to treat his 12y chronic lyme when all other therapies failed for him. He got a major die-off reactions(intolerable herx) from only 10*4 Olm, even before adding antibiotics and ER several times(prednisone shots) from adding antibiotics(septic shock). So much for the anti-inflammatory effects of Benicar, yeah. Oops, sure, that must be a placebo effect. Yeah and the almost double number of his leukocytes(along with other blood pro inflammatory markers) several days after starting Olm is a placebo effect too.

Note to others: if are are feeling brave enough and decide to make a trial of MP(https://mpkb.org/home/starting/therapeutic_probe) never start Olm with the dose less than 160mg. < 160mg(like 80mg) is usually enough to kick start the immune system(especially if you are already very symptomatic), but almost never enough for herx shock palliation.