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Hypothesis piece by Amy Proal, a microbiologist with ME/CFS

Discussion in 'ME/CFS research news' started by Dolphin, Oct 21, 2017.

  1. dannybex

    dannybex Senior Member (Voting Rights)

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    Lastly, and I do mean lastly, Ms. Proal, writes on her latest blog (not sure what happened to 'bacteriality.com' where she interviews patients who yes, avoided both regular light, wore sunglasses inside, and avoided sunlight), that she is "a microbiologist who also suffers from ME/CFS."

    My questions for @Amy Proal are:

    Have you recovered completely or are you still taking antibiotics and benicar, when Marshall himself said that his protocol would cure people in 2-3 years?*

    And if you're not recovered, have you been taking antibiotics and benicar for for 13-14 years?

    If you're not recovered, how did you get a PhD in Microbiology in 2011? If you're not recovered, what would you rate your level of functioning at? 40%, 50%, 90%?

    Thanks in advance.



    *Way back in 2004 Trevor Marshall gave an interview to the one site back then for patients with ME/CFS, ImmuneSupport.com, which was renamed about 10 years ago as 'ProHealth.com', where he claimed he was helping to cure people within a couple years:

    https://www.prohealth.com/library/t...d-fibromyalgia-hopeful-results-emerging-22073

    Some key quotes:

    "The seco-steroid 1,25-D is the active hormone resulting from sunlight on our skin, and the Vitamin D we ingest. Both these sources of 1,25-D have to be attenuated if these bacteria are to be killed." In other words, you have to avoid sunlight.

    "I am a researcher with a PhD, not an MD, and I cannot treat patients directly. I help their physicians understand the disease process, so that those physicians can work with the patients to cure the disease."

    And the biggest lie of all, the one I know so many wish they had never read or fallen for:

    "It seems the protocol is working just as well for these CFS and FM sufferers as it did for the sarcoidosis patients, most of whom have progressed to "cure" over the last two years."
     
  2. Mij

    Mij Senior Member (Voting Rights)

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    I remember when Marshall tried to sue a sick member on a CFS group years ago.
     
  3. dannybex

    dannybex Senior Member (Voting Rights)

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    YES. Me too. I was trying to think of her name and the situation, but all I remember is that he was almost successful...was kind of counting on the fact that his filing was last minute and that she was so sick she wouldn't be able to get to the court, but she did, and stopped him from proceeding.
     
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  4. Mij

    Mij Senior Member (Voting Rights)

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    Last edited: Feb 26, 2019
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  5. Milo

    Milo Senior Member (Voting Rights)

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    Please do tell, why would he sue a patient?
     
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  6. Mij

    Mij Senior Member (Voting Rights)

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    @Milo the court papers were online in Ventura CA, but they've been removed. This dates back to 2004, so I don't remember the exact details. Penny was the administrator for CFSExperimental Yahoo group.

    There is some information here
     
  7. JES

    JES Senior Member (Voting Rights)

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    What happened to Mikovits was a sad story indeed and I agree that she completely lost the plot, but back in the day when the initial discovery was made, I remember that the traffic to PR forums more or less doubled and I started to see signatures left, right and center that said "XMRV positive". These treatments seem to go in trends, before it was Lyme, EBV, XMRV and now many people are more broadly looking at the microbiome. What also seems to be common with all treatment protocols is that there is a real risk of getting worse, which is very unfortunate indeed. I trialed a low-dose antiherpesviral treatment that is available without prescription for HSV infections, but it ended up causing me a serious case of myocarditis and a massive temporary worsening, which took months to recover from. It seems that our bodies cannot tolerate treatments that the average person can, which makes it double more difficult.

    But anyway, for me the topic is not about Marshall Protocol but about the blog post of Amy Proal, which more broadly discusses the microbiome. The idea that the microbiome is involved in ME/CFS symptoms is now pursued by several leading ME/CFS researchers, so I think Amy is on the right track here. I also agree with the following statement in her blog (immune suppressant drugs have not been found helpful in ME/CFS):
    The following statement I also find interesting and it's something that is supported by the findings of Horning et al., i.e. that CFS/ME patients' cytokine profiles are different in the groups of short-term disease (<3 years) and long-term disease (>3 years).
     
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  8. Sisyphus

    Sisyphus Senior Member (Voting Rights)

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    thanks for doing all that. Quacktastic misdirection like this gets me to something that would be anger if I had the energy, but I've given up on replying to it. There was a thread on a certain other board regarding electro-hyperchondia syndrome in which one of the EHS proponents started in on shoving chlorine dioxide into kids with autism. He insisted that "it's not bleach", etc. I decided not to post further in that thread, it seemed futile.
     
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  9. richie

    richie Established Member (Voting Rights)

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  10. Mij

    Mij Senior Member (Voting Rights)

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    Is there evidence of 'damage' from inflammation? Not all inflammation is bad.
     
  11. richie

    richie Established Member (Voting Rights)

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    Good point, and maybe relative to what. IFN gamma can be protective at some stages of MS and against anxiety. There may be a pay off - the damage worthwhile, temporary, manageable etc. and better than the symptoms of the condition.

    The old questions - do some ME patients have an infection and are pro inflammatory cytokines responding? (allowing that if the infection were identified, such might better be re-labelled). Are others autoimmune and better having an immune suppressant?

    Does proinflammatory cytokine equal inflammation?

    Complex areas, of course.
     
    Last edited: Feb 27, 2019
  12. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    When you change your definition to something else.

    Inflammation is originally defined as a group of processes characterised by opening up and leakage of blood vessels. That makes the tissue red - hence inflammation. Inflammation is mediated by chemicals like histamine, prostaglandins, kinins, and cytokines so these are sometimes taken as signs of inflammation.

    However, if you find some chemical signals without any opening up or leakage of blood vessels that is not inflammation in the original sense. It is a bit like saying that because you can hear a cotton-picking work song someone must be picking cotton - not necessarily.

    The term neuroinflammation is almost always confusing and eminent neurologists have said this. Actual inflammation in brains is called encephalitis. There is no encephalitis in ME.
     
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  13. dannybex

    dannybex Senior Member (Voting Rights)

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    I agree the microbiome is an important field of study. My problem is the integrity of the author, who on that very page tells people that "I worked with the Marshall Protocol in the early days", when in fact she's continued to author papers -- including another one on vitamin D -- and several others that were published in 2018. Also she puts in links in some of her replies to their flawed hypothesis that vitamin D deficiency is 'flawed', which is classic MP.

    I'm all for more study on the microbiome. I'll just look for it from those with respectable reputations, tied to legitimate institutions and journals.
     
  14. richie

    richie Established Member (Voting Rights)

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    Hello JE
    I have often wondered myself whether equations of raised proinflammatory cytokines equalling inflammation are valid, so thanks for the cotton picking analogy.

    Given language changes and that inflammation as originally defined very often causes pain and other pathological symptoms, there is an argument for extension of "inflammation" to processes involving classically pro-inflammatory cytokines, which in some cases mediate the symptoms. The trouble is that inconsistency creates confusion and argument as to terminology besides the points a given article might be making, which causes scraps and wastes time. The scientific community would ideally be consistent as to usage and if not, at least each scientist frank as to which definition they are using.



    Knowing sth about language change, I know that's not how people behave.......
     
    Last edited: Feb 27, 2019
  15. Hip

    Hip Senior Member (Voting Rights)

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    In the Marshall Protocol, you are taking the drug Benicar which activates the vitamin D receptor (VDR), so as I understand it, even if your vitamin D levels are low, you will still have VDR activation from Benicar.

    The overall idea of the Marshall Protocol is not to reduce VDR activation, but to increase it. Taking Benicar and avoiding vitamin D is supposed to serve that purpose of increasing VDR activation. Activating the VDR releases the anti-microbial peptides beta-defensins and cathelicidin.

    I am not sure if I understand the mechanics, but Dr Marshall said something about the inactive form of vitamin D (called 25-D) being an antagonist to VDR, whereas the active form (called 1,25-D) is a VDR agonist, and that when too much 25-D binds to the VDR, it inactivates this receptor, and stops 1,25-D from binding to and switching on the VDR.

    So when people say that the Marshall Protocol is wrong because vitamin D is essential, I don't think they've understood that in theory at least the MP aims to increase VDR activation.

    Whether that theory is right is another question, but I don't think we should throw the baby out with the bathwater when it comes to chronic diseases, the vitamin D receptor, and intracellular infections.

    Dr Trevor Marshall developed his protocol originally to treat his sarcoidosis, which is associated with an intracellular L-form infection of the bacterium Propionibacterium acnes. Thus antibiotics make sense in this context.

    Marshall also noticed that his sarcoidosis was made worse after strong sunlight exposure (this was in Australia), and that's where the sunlight and vitamin D avoidance started. In sarcoidosis, vitamin D metabolism is abnormal, because this disease creates high levels of the enzyme which converts vitamin D into its active form. I don't understand the whole story, but possibly his sun avoidance may make sense in the context of sarcoidosis.

    However I don't agree with Trevor Marshall's idea that whole swathes of diseases, including ME/CFS, are caused by intracellular bacterial infection, nor the idea that vitamin D levels are a central factor in these many diseases.


    Don't get me wrong, my view is that many chronic diseases will likely turn out to be caused by chronic infection (in conjunction with other causal factors), but there are more infections to consider than just L-form bacteria.

    In particular, in terms of tissue evidence, ME/CFS is mainly linked to intracellular enterovirus infection; but there's no evidence of an intracellular bacterial infection in ME/CFS, except in the small subset of cases linked to Chlamydia pneumoniae.

    However Trevor Marshall was adamant (I am not sure if he still is), that chronic viral infections were not the cause of ME/CFS, and it was all down to L-form bacteria. I think viruses not intracellular bacteria are likely the key to ME/CFS.

    So if we take away the antibiotics, and take away the sunlight and vitamin D avoidance, it's possible Benicar's activation of the VDR alone may still have some benefit against viral infection.


    Some viruses have been shown to block or down-regulate the VDR, for immune evasion purposes. EBV blocks the VDR to prevent apoptosis, and CMV down-regulates the VDR.

    The defensins that are released by VDR activation are shown to have antiviral effects: they are antiviral for HSV and CMV, and antiviral for CVB.

    Thus a blocked VDR may turn out to play a role in maintaining chronic viral infection or long-term viral latency, and activating the VDR may thus have antiviral benefits.
     
    Last edited: Feb 28, 2019
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  16. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    The sad thing about all this field now is that I cannot really perceive that anyone knows what they are doing much. The contrast with the intelligent debate in the 1980s and 1990s is stark. Everyone now studies the same thing, whether mirobiome or 'neuroinflammation' in the context of ideas from the 1960s that died long ago. There are no respectable journals now and what were once respectable institutions have been hired out for cash.

    Nevertheless, there are always near-impossible obstacles in science and somebody has always overcome them so I am not necessarily pessimistic. At least a lot more people are looking at ME.
     
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  17. dannybex

    dannybex Senior Member (Voting Rights)

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    Unfortunately -- or fortunately -- there are no studies that back up either claim. Except for a few authored by Marshall, Proal, or the RN on his team, Meg Mangin. And all of them published in questionable journals.
     
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  18. Hip

    Hip Senior Member (Voting Rights)

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    Yes, I believe the effect of angiotensin receptor blockers (ARBs) like Benicar on the VDR has not been demonstrated empirically, but only in silico studies involving computer modeling of the molecular interactions of ARB drugs and the vitamin D receptor, done by Marshall and colleagues. I don't know anything about such molecular modeling, and how reliable it is.



    It's interesting that ARB drugs (which are just regular blood pressure drugs) have very weird Herx-like effects when given to patients with certain chronic diseases, including sarcoidosis and ME/CFS.

    Medicine already knew about the weird effects of ARBs in patients with certain chronic diseases (I can't find a reference to this ARB phenomenon at the moment).

    It's the strange reaction to ARBs in patients with chronic diseases that Marshall became fascinated with, and I believe this led to his investigation of the VDR in sarcoidosis. I think eventually he then came up with this idea of the intracellular bacteria linked to sarcoidosis turning off the VDR for immune evasion purposes, and Benicar switching it back on again, thus leading to a sudden immune response against these bacteria.

    Marshall called these weird effects the "immunopathology" symptoms of the Marshall Protocol (like exacerbation of existing symptoms, fever, pain, body aches, light sensitivity requiring dark glasses); but these effects are not specific to the Marshall Protocol; as I understand it, they are what ARBs cause in patients with chronic diseases.
     
    Last edited: Feb 28, 2019
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  19. Amy Proal

    Amy Proal Established Member

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    I have to say, I did not expect to post on this board in good faith...and then be practically criminalized with claims that are untrue and unfair.

    There is no "conspiracy" here as implied. If you look at my latest paper on ME/CFS my affiliation is clearly listed as Autoimmunity Research Foundation, and my co-author as Trevor Marshall. Not only do I not "hide" this information...I'm very, very proud of it.

    You can also google statements taken out of context from websites created 10 years ago. But I'll say the following. The Marshall Protocol is a reasonable treatment still used by many patients with success. I still work with four medical groups that use the treatment today. It is however true that some medium/severe ME/CFS cases experience too much of a herxheimer reaction for such patients to reasonably remain on the therapy.

    I personally used the Marshall Protocol to help my ME/CFS. I was able to move from bedridden to a place where I can now work.

    If you want to learn more about how the Protocol and ME/CFS I suggest you read the peer-reviewed journal article we published on that exact topic (it's attached to this post): "Immunostimulation in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis." The paper explains the actual molecular biology behind the treatment, and then provides case histories of ME/CFS patients who used the treatment. We made sure to include case histories from patients who benefitted from the treatment as well as case histories from those that did not.

    So I encourage you to get your information from that article. Because, if you wanted, you could take any treatment (let's say LDN), come to this site, google comments, and only post statements from patients that had trouble tolerating LDN. You could make LDN look like a horror story. You could do the same thing for antivirals like Valtrex or Valcyte etc etc. But the truth is that with nearly ALL potential treatments, some patients benefit and others don't (we are living in an era of personalized medicine).

    So I'm very sorry to hear of patients that did not do well on the Marshall Protocol...but that in no way means it's OK to treat me with such cruelty or to somehow dismiss all the hard work and related research I've done over the course of many years.

    And one more thing: dannybex: since you seem to be so confident in all of your negative claims, can you explain to me exactly how the journal we published that article on Marshall Protocol + ME/CFS is a "questionable journal." It's actually a very good, reliable journal:

    https://link.springer.com/journal/12026

    So again, please explain exactly why, according to you, the Springer journal Immunologic Research is questionable. Thanks.
     

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    Last edited: Mar 5, 2019
  20. Amy Proal

    Amy Proal Established Member

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