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Might the Marshall Protocol be an effective treatment for EBV ME/CFS, but not other forms of ME/CFS linked to other viruses?

uglevod

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I don't think MP posts come even close to the number of posts about supplementing vitamin D here.
Yep, I realize that the primary focus stays on palliation through various supplements(even those with confirmed Lyme disease complex prefer to palliate). This is the standard medical advice after all - pharma just uses(and will continue to apply) diff. drugs for this purpose like prednisone, MTX, etc - so no surprises here. But this was never a path to cure.

Vit D was named vitamin like when, 60 years ago? but in reality it is a secosteroid hormone:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384440/

The bad news for those who are really sick and keep applying the D hormone therapy on themselves is that their condition almost always directly comes from the pathogens shutting down immune activation properties of this hormone, leaving its steroidal/anti-inflammatory part intact, so temporal correction of low levels of D just brings no more than an extra palliation effect to them(with the eventual relapse).

More and more scientific papers shed the light on the pathways pathogens use to persist within the cells. Here is one of the examples, the latest paper on how M. leprae shuts down D mediated immunity:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177120/
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)
 
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pamojja

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so temporal correction of low levels of D just brings no more than an extra palliation effect to them(with the eventual relapse).
I've now for 10 years corrected my vitamin D levels (~70 ng/ml), 4 years ago had a remission from a 60% walking-disabilty from PAD (already improved greatly the first 3 years), since 2 years ago no real PEM anymore (before constant). How many decades to the eventual relapse? o_O
 

uglevod

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According to Trevor: 10..20 years.

My D25 is 4..10ng. I'am 3 years into MP and my PEM is greatly improved(no crashes - 5..10 minutes of rest now VS 2..4 hours before).
 

uglevod

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I'am puzzled why you've decided to raise D25 that high. Normally, without therapy it almost never overcomes 30..35ng.

There is an U-shaped relationship between D25 and long-term outcome(mortality).
https://www.ncbi.nlm.nih.gov/pubmed/27589046
After adjustment for differences in baseline features and treatment, it was confirmed that extreme values of vitamin D (<10 or >30ng/mL) are independent predictors of mortality

P.S. normalized D25 is 20..30ng in healthy individuals:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074219/
.. median 25(OH)D3 level increased steadily from 43 nmol/l in winter to spring and doubled to 89 nmol/l in summer, with a drop again in autumn ..

89/2.4 = 37ng and it's a summer peak(only 3 months per 12)...
 
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Hip

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Since MP was empirically proven to be the only CFS therapy with positive results so far
You need to perform double-blinded placebo controlled trials in order to prove the efficacy of any treatment. This has certainly not been done with the Marshall Protocol. The only evidence for any efficacy of the MP is anecdotal.

Secondly, many other ME/CFS treatments have shown anecdotal efficacy for ME/CFS.
 

pamojja

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There is an U-shaped relationship between D25 and long-term outcome(mortality).
https://www.ncbi.nlm.nih.gov/pubmed/27589046
Observational studies can't show causation.

But I know they are always used to make it appear to support one's bias. I could do the same:

Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study

Am J Clin Nutr November 2014 ajcn.086413

Background: Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain.

Objectives: We examined the prospective relation between serum 25-hydroxyvitamin D [25(OH)D] concentrations [which comprised 25(OH)D3 and 25(OH)D2] and subsequent mortality by the cause and incident diseases in a prospective population study.

Design: Serum vitamin D concentrations were measured in 14,641 men and women aged 42–82 y in 1997–2000 who were living in Norfolk, United Kingdom, and were followed up to 2012. Participants were categorized into 5 groups according to baseline serum concentrations of total 25(OH)D <30, 30 to <50, 50 to <70, 70 to <90, and ≥90 nmol/L.

Results: The mean serum total 25(OH)D was 56.6 nmol/L, which consisted predominantly of 25(OH)D3 (mean: 56.2 nmol/L; 99% of total). The age-, sex-, and month-adjusted HRs (95% CIs) for all-cause mortality (2776 deaths) for men and women by increasing vitamin D category were 1, 0.84 (0.74, 0.94), 0.72 (0.63, 0.81), 0.71 (0.62, 0.82), and 0.66 (0.55, 0.79) (P-trend < 0.0001). ..
 
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uglevod

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You need to perform double-blinded placebo controlled trials in order to prove the efficacy of any treatment. This has certainly not been done with the Marshall Protocol. The only evidence for any efficacy of the MP is anecdotal.
Never was a Stop Factor for any protocol/supplement. :)

Positive effect of D3 supplement on health(not symptoms of illness) is purely anecdotal too, but it's not what is stopping people from trying to correct their D25 "deficiency" and for the doctors to recommend D3 therapy.

Double-blinded trial for MP will never happen and the host of reasons is pretty obvious.

This is how medicine works these days - without future profit for their own pockets no med group would dig any resources into any treatment/placebo controlled trials.
 
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pamojja

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56.2 / 2.4 = 23.4ng - seems normal to me. Or what was the point of above quote?
No point, just as your observational data. But if you look closely again, the higher the levels the lower the risk, the higest serum levels had lowest mortality risk.

Conclusions: Plasma 25(OH)D concentrations predict subsequent lower 13-y
  • total mortality and incident cardiovascular disease,
  • respiratory disease, and
  • fractures but not total incident cancers.
For mortality, lowest risks were in subjects with concentrations >90 nmol/L, and there was no evidence of increased mortality at high concentrations, suggesting that a moderate increase in population mean concentrations may have potential health benefit, but <1% of the population had concentrations >120 nmol/L.
>50 ng/ml
 

uglevod

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BTW, those with 50ng could be the healthiest subgroup out of the whole group.
Of course the mortality will be the lowest. High D25 = Low inflammation(primary source of mortality).
 
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uglevod

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And I bet those with naturally highest D25 do not carry any parasite infections, like lyme, babesia or toxo, since D25 is always, in 100% of all times, downregulated during this chronic infections for a robust Th1 response/resistance.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256336/
Similarly, host defense against Toxoplasma gondii (T. gondii) relies on a Th1 cytokine profile response dominated by IFNγ and IL-2 production.130 The potential downregulation of this response by vitamin D can prove problematic in toxoplasmosis. Treatment with vitamin D dose-dependently inhibits both in vivo and in vitro growth of T. gondii, possibly by limiting tachyzoite proliferation within the parasitophorous vacuole because of activity at a cellular level.131 However, no difference occurred in the total number of infected cells regardless of the presence of vitamin D, perhaps refuting a role in cell invasion. Interestingly, vitamin D may be linked to increased mortality in mice infected with toxoplasmosis, presumably because of its downregulation of the Th1 cytokine response.132 This finding suggests a delicate balance in overall immune response against this organism, and further studies would need to be done to establish the role of vitamin D among other variables in determining outcomes.

And when you add to the above the ability of certain intraphagocytic microbiota to block VDR, the overall picture suddenly becomes much more complex. The above "Treatment with vitamin D dose-dependently inhibits both in vivo and in vitro growth of T. gondii" stops to work as intended.
 
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pamojja

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So much speculations... but to answer your open question:

I'am puzzled why you've decided to raise D25 that high.
4 years ago had a remission from a 60% walking-disabilty from PAD (already improved greatly the first 3 years), since 2 years ago no real PEM anymore (before constant).
Remission of diseases considered non-reversible by conventional medicine do take extraordinary efforts. Therapeutic levels of vitamin D and sun are part of that. As well as of most other essential nutrients.

These were my results (intake in mcg Vitamin D/day, whole body sun-exposure in hours/year, 25(OH)D serum levels; averaged, sunexposures before '17 are rough estimates, added total testosterone serum levels because of their high correlation):

Code:
year:  mcg  -  hrs  - ng/ml -  TT

2009:   50  -       -       -
2010:  160  -   60  -   63  -  399
2011:  140  -   60  -   43  -  220
2012:  300  -   60  -   62  -  262
2013:  200  -  220  -   84  -  320
2014:  190  -  220  -   50  -  340
2015:  210  -  220  -   78  -  351
2016:  170  -  240  -   72  -  468
2017:  220  -  340  -  101  -  631
2018:  170  -  340  -   93  -  681
2019:  170  -  330  -   85  -  368
Incidentally, remission of PEM occured with a highest ever serum level of 135 ng/ml in 2017. One possible explanation for this, and also the rather remarkable jump in testosterone, could be a VDR defect.
"The low plasma vitamin D3 levels have been a global problem for last quarter century. However, one aspect that is often ignored is the inability of the VDR to execute the beneficial functions in the presence of genetic alterations in VDR. Even with the optimum level of vitamin D3 an individual may still get little or no vitamin D-related benefits due to polymorphic VDR expression."

Source: Vitamin D Receptor (VDR) Gene Polymorphism: Implications on Non-Bone Diseases
 

uglevod

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Incidentally, remission of PEM occured with a highest ever serum level of 135 ng/ml in 2017. One possible explanation for this, and also the rather remarkable jump in testosterone, could be a VDR defect.
Another possible explanation is the hyporesponsiveness to the bacteria patterns(including toxins) through TLR receptors suppression.

Regarding your testosterone: https://www.ncbi.nlm.nih.gov/pubmed/29183872

And as I see you was not checking the active metabolite(D1.25) together with D25(inactive precursor). Many times during infection disease and corresponding chronic inflammation D1.25 goes as high as 80..100 while D25 stays very low, like at 10ng. For the complete picture D1.25 should always be checked together with D25 - what if ones kidneys lost control over D125 production(due to the extra-renal production in activated macrophages).
 

uglevod

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Induced hypo-responsiveness to borrelia(Lyme) through D3 supplementation:

Vitamin D3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes.
https://www.ncbi.nlm.nih.gov/pubmed/20435648

Recognition of Borrelia burgdorferi, the Lyme disease spirochete, by TLR7 and TLR9 induces a type I IFN response by human immune cells.
https://www.ncbi.nlm.nih.gov/pubmed/19794067
 

uglevod

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Induced hypo-responsiveness(https://www.sciencedirect.com/science/article/pii/S141386701500224X) to...

TLR4: (Gram-negative bacteria): Pseudomonas aeruginosa, RSV, MMTV, Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Trypanosoma cruzi, Plasmodium falciprum, Toxoplasma gondii, Leishmania major, Entamoeba histolytica, Filarial nematode, Acanthocheilonema Viteae, Taenia crassiceps

TLR2: (Gram-positive bacteria): Streptococcus B, Staphylococcus aureus, Trepanema maltophilum, Wolbachia, Borrelia burgdorferi, Staphylococcus epidermidis, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Measles, Herpes, Saccharomyces cerevisiae, Candida albicans, Trypanosoma cruzi, Plasmodium falciprum, Toxoplasma gondii, Leishmania donovani, Leishmania major, Leishmana sp., Leishmania mexicana, Entamoeba histolytica, Ascaris lumbricoides, Schistosoma mansoni, Schistosoma japonicum, Taenia solium

.... through D3 supplementation:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074219/
Elevated vitamin D3 level in vivo is associated with down-regulation of cytokine response through diminished surface expression of pattern recognition receptors.

1569366817562.png
 

pamojja

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Another possible explanation is the hyporesponsiveness to the bacteria patterns(including toxins) through TLR receptors suppression.
My goodness, you make everything fit your speculations.. But fine with me, if it drove a non-reversible disease into remission and a goverment certified disabilty got revoked. I'm healthy again. :p
 
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uglevod

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279842/
A major problem with the in vivo use of 1,25(OH)2D3 is the fact that the doses needed to see non-classical effect such as the immune effects are high, resulting in severe hypercalcaemia and accelerated bone remodeling. Due to the flexible structure of 1,25(OH)2D3, however, chemists have succeeded in synthesising analogues of the molecule, some of which share the mother molecules’ effects on the immune system, but not its effects on calcium or bone metabolism (3536).
...
In the third experiment, where the mice got vitamin D3 (1000 IU) for one week, the effect on the inhibition of T. gondii tachyzoites and NO production was less than in the first experiment which vitamin D3 was used only once. These results indicated that the injection of vitamin D3 every day for one week might have more suppressive effect on the immune system.