Lipkin's Monster ME/CFS Study: Microbes, Immunity & Big Data
The Microbe Discovery Project outlines an ambitious new study by top researchers that has collected patient samples, but needs desperately funds to complete the work.
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What are the commonly available immune modulators?

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Gingergrrl, Nov 16, 2014.

  1. Gingergrrl

    Gingergrrl Senior Member

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    @SDSue, Can they start you on the pulsing schedule if that is all your body can tolerate or do you need to get to the full 3000 mg? You can answer by PM if not comfortable discussing here.

    Also, is muscle milk non-dairy? My former ND put me on this insanely restrictive diet that I have been doing since June. I used to drink this protein drink called "Orgain" and it saved me but it is a dairy product. I am thinking of going back to it b/c I know I can drink it easily. I am not allergic to dairy (or to anything) and the diet was b/c of high inflammation on the US Biotek food sensitivity test.

    But I don't want to totally derail this thread and keep it on immune modulators!
     
  2. adreno

    adreno PR activist

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    I think both sides to this discussion has merits. I support the right of anyone to experiment with themselves as they see fit. But I also think that it is important to question the "old wisdom" of ME/CFS if we want to move further.
     
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  3. RUkiddingME

    RUkiddingME Senior Member

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    Hi Gingergirl, google LDN and Hashimotos, lots come up. It falls in the immune modulator category. I have been on it for three years and don't plan to stop anytime soon :). Good luck- P.S I will uodate my blog real soon, I just didn't want to jinx my progress- :thumbsup::thumbsup::thumbsup:
     
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  4. Gingergrrl

    Gingergrrl Senior Member

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    @adreno I think every discussion on here has merits and I always try to learn something from it. I support everyone from those who see no doctors, have no tests, take no meds or supplements all the way to the other extreme of trying Rituximab or Ampligen (if they were able to get it of course!) and everyone in the middle.

    My issue is that sometimes I am just wanting to hear the information directly from patients with ME/CFS who have tried the treatments themselves without the conversation being shut down (unless of course it turns inappropriate or disrespectful and then I want the Mods to re-direct it and intervene!) But my issue more so that I reacted to yesterday was being told (in two posts now) that EBV/virus/pathogen does not lead to autonomic problems which they most certainly do. It's like someone invalidating your entire existence and experience of your daily life.

    @RUkiddingME Thanks and I am still looking forward to your blog update but understand the fear of jinxing yourself as we talked about before!...
     
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  5. Butydoc

    Butydoc President

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    Hi Gingergrrl,

    I've been following this thread with interest. I do understand you being upset about a physician who does't believe in the pathogen hypothesis concerning autonomic disfunction or doesn't believe there is good scientific basis for that belief. It appears to me that there is a huge number of hypothesis concerning the cause and treatment of CFS/ME. Obviously, they all can't be correct. I believe there is great benefit to our members when physician researchers join our community and support our cause. When the day is over, it is that group of people along with basic science researchers who will ultimately find the key to unlock the treatment of our disease. My concern is that if we antagonize this volunteer group, they probably will not want to contribute or join our community. Debates on the scientific merit concerning etiology or treatment I believe only strengthens our goal towards learning the cause and treatment of this very difficult to understand disease.

    Best,
    Gary
     
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  6. Ema

    Ema Senior Member

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    This is very true, but only if it does not brush over the importance of patient experiences and clinician expertise in favor of only randomized controlled trials. Clinical judgment has always been a part of the art of medicine until recent years. I don't think turning away from that aspect has improved outcomes. Rather the opposite.

    It's frustrating to have every thread turn into a symposium on dodginess, snake oil and RCTs. Patient experiences are the cornerstone of a successful forum and there is a place for both in "science".
     
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  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Dear Gingergrrl,
    Let me just add two comments.

    Firstly it was absolutely not you who was talking about people being narrow minded. You are always very civil and considerate and I recognise that.

    Secondly, the point I was making about the link between viruses and autonomic dysfunction is that we don't seem to have a mechanism that links the two on the basis of what we know of other diseases. I am not disputing the fact that virus infections often occur at the beginning of ME and that autonomic dysfunction comes with it. In ME everybody agrees on that. But if we want to understand the mechanism of this in terms of specific cells and biochemical processes we do not seem to have a good place to start. It could all be cytokines maybe but then why is there no fever etc.? So I am not in the least doubting that in your case viruses may have upset your immune system. I am just saying that it is very unclear how, and if we do not know how it is I think unclear how we might want to modulate the immune system to put it right. It may well be that some of these drugs do a good job but I think we need to remember we don't really know why - just as Dr Montoya recently suggested his antivirals might not be acting as antivirals.
     
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  8. Gingergrrl

    Gingergrrl Senior Member

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    Dear Gary,
    I am in the car on the way to my echocardiogram so am trying to respond to this from my phone (and I am not driving!)

    I just wanted to explain that I don't feel I was saying anything antagonizing and that is just not my style of communication. I have great respect for Dr. Edwards and my posts for him have been questions in which I did not understand how or why he is dismissing the pathogen theory and the autonomic dysfunction that we experience.

    OMI and INIM and all the top CFS researchers seem to acknowledge and treat this association otherwise I am taking Famvir for nothing and you would not have had such significant improvement from Valcyte that you could ski again!

    My intentions are solely to do things to improve the lives of other PWC's and have been told over and over again how helpful my posts are. I am involved with advocacy and trying to help on every level that I can think of!

    If anything I said in this thread missed the mark or hurt anyone, I sincerely apologize as this was not my intention!
     
    Last edited: Nov 18, 2014
  9. Tired of being sick

    Tired of being sick Senior Member

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    Treating symptoms are just that..........
     
  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Gingergrrl, it seems likely that nobody is hurt but you and I apologise for creating a the misunderstanding responsible.
     
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  11. Butydoc

    Butydoc President

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    Hi Ema,

    I completely agree. It's not an either or, but both. I'm a clinician and consider my experience at least as important as my book learning. Both are certainly necessary in able to practice medicine at its highest level.

    Best,
    Gary
    Hi Gingergrrl,

    I actually am one of those people who do enjoy you post. Out of interest, you mentioned my experience with Valcyte. I presently believe that this drug may be acting as a inhibitor of microglial cells in addition to it's antiviral properties. The same seems to be true with doxycycline. I'm starting to believe that the positive effects i received from these drugs are more from their inhibitory effects rather that their antimicrobial effects. This would be very important to separate which one of these possibilities are correct. Last time I spoke to Dr. Montoya, he also believed this might be true.

    Best,
    Gary
     
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  12. adreno

    adreno PR activist

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    This is very common. People take a drug or supplement, feel better, and conclude it must be because of effect "x", when in fact the real reason they feel better (or worse) is because of effect "y". Meds and supps often have a wide range of effects, many that we often are unaware of. I have made these wrong conclusions myself many times. It's confusing correlation with causation. Researchers do this all the time, too.
     
    Last edited: Nov 18, 2014
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  13. lnester7

    lnester7 Seven

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    @Gingergrrl After a few days in bed due to a equinecea tea (everytime I think something does not agree w me I reaplicate 3 times w no other variables to make sure),

    I everytime (which I rearly do) introduce a new herb or tea I google w the word inmune modulator and Inmunebooster ( 2 searches) and read.
    While you are at it, I learnt also that vassocontrictors help me, vasodilators Make my POTs worse, So I also always introduced teas and foods google vassocontriction+ word, second search Vassodilator+ word. If you wanna try to observe this also. As in the other test, do not mix the two groups while testing.
    Note: Exception of perppermint, I use this dilator for then known dysautonomia intestine cramps !!! I make sure will not be standing and I will be at rest.
    Also coffee, This is a rare one, It makes me feel better.
    Other than that all others have being right.
     
  14. xrunner

    xrunner Senior Member

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    Hi @Gingergrrl
    I can only answer question 3 with regard to my own personal experience which may not be applicable to others.
    I grouped them based mainly on the effect they had on my energy levels.

    Worse:
    - Ginseng (any kind)
    - Beta glucans

    Indifferent:
    - Mushrooms: maitake, shiitake, AHCC, MGN3, reishi, cordyceps etc.
    - Proboost
    - Olive leaf extract
    - Vitamin D

    Better:
    - Probiotics
    - GcMaf probiotic
    - Resveratrol
    - Cat's claw

    Apart from for the first two that made me feel awful from the start, I have tried the others for extended periods of time. With the exception of probiotics and the Gcmaf, the effect of the good ones I tried was only temporary so I needed to keep taking them but this may be risky.
    I would agree with Prof. Edwards' point that long-term we don't know the effects these might have on our system and if they have a beneficial effect they might also have other less positive effects.

    In my case for e.g. Cat's claw and Resveratrol gave me a significant improvement in energy levels and sense of well being within days but after two, three years of use I became over sensitised with the first causing inflammation in my tendons and the other starting to make me rather irritable. So I gave up.
     
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  15. lnester7

    lnester7 Seven

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    LDN is not only great Inmune modulator, It rased my NK cells like nothing else did (not until I did the 4.5mg)
     
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  16. Gingergrrl

    Gingergrrl Senior Member

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    @Butydoc

    Dear Gary,

    Thank you for the kind words about my posts and I appreciate it.

    I wanted to ask you a few questions from your experience. You said that Valcyte may be acting as an inhibitor of microglial cells in addition to as an anti-viral and I was wondering if you could explain what that means in the most basic scientific terms?

    Also, does Famvir potentially do that same thing or only Valcyte? I was put on Famvir b/c I am IgM positive for EBV and VZV but the other herpes viruses like HHV-6 only IgG positive and CMV was negative on all counts so told I didn't need Valcyte (from an anti-viral perspective.)

    From a microglial perspective, could Valcyte benefit me in a different way? Also, I know you took Colchicine, too, and do you think it was the combo that helped you vs. the anti viral alone?

    Thanks for any info!
     
  17. Butydoc

    Butydoc President

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    Hi Gingergrrl,

    To my understanding, microglial cells are like macrophages of the central nervous system. There has been several papers concerning over activation of these cells in people with CFS/ME. When activated, they release chemical signals that affect other cells in a pro inflammatory fashion. Some believe this may cause many if not all of the symptoms of CFS/ME. There are several drugs that cause an inhibitory affect on these type of cells. Recently a paper came out of Stanford which demonstrate that Valcyte is a potent inhibitor of microglial cells.

    I don't know any information concerning Famvir.

    I didn't really feel much benefit from colchicine. What I found interesting was the very positive response I had to doxycycline. As it turns out, minocycline is also an inhibitor of microglial cells. Maybe my improvement is from a synergistic reaction to both Valcyte and doxycycline on these microglial cells.

    Best,
    Gary
     
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  18. Gingergrrl

    Gingergrrl Senior Member

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    Gary, did you take the doxycycline for a known bacterial infection or for the microglial effects?

    Thank you for all of the other info as well and I wish I knew if Famvir had the microglial effects too!!!
     
  19. Hip

    Hip Senior Member

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    That's a good set of questions, @Gingergrrl.

    One this site there's a list here of immunomodulators used in ME/CFS (though the weblink for each immunomodulator no longer works).

    Perhaps the immunomodulators that you hear about the most, and the ones which are regularly used by ME/CFS specialists, are: oxymatrine, Nexavir, Imunovir, low-dose naltrexone and Valcyte.

    Here is some info on these immunomodulators:

    Oxymatrine
    Oxymatrine is a herbal extract from the plant Sophora flavescens. Oxymatrine is inexpensive, especially if you buy the White Tiger brand. You can also buy Dr Chia's Equilibrant brand of oxymatrine. Dr Chia said he found around 25% of his enterovirus-associated ME/CFS patients had significant improvement on oxymatrine. He has reported cases of bedbound ME/CFS patients going back to work after a couple of months on oxymatrine. However, 50% of patients did not respond at all to oxymatrine, and the remaining 25% only saw some mild improvements.

    Here is some info on Dr Chia's oxymatrine treatment of ME/CFS patients, from a presentation given by Chia in 2010:
    The graph below shows the cytokine changes Chia found in the responders to oxymatrine (top 7 lines) and the non-responders to oxymatrine (bottom 10 lines). Those who got better on oxymatrine showed a shift to the desired Th1 immune response. This shift to Th1 is measured by an increased in the ratio (IL-12 p35 + IL-12 p40) / IL-10, which on the graph is shown on the vertical axis. Those non-responders who did not improve on oxymatrine showed no shift to Th1. This suggests that it is the immunomodulatory effect of oxymatrine, the shift towards a Th1 immune response, that causes the improved symptoms in ME/CFS patients.

    OXYMATRINE CYTOKINES.png

    In the responders, Chia also found a reduction in the amount of enteroviral VP1 protein in the stomach biopsy tissues after oxymatrine treatment, indicating that oxymatrine reduces viral loads. The image below shows the enteroviral VP1 protein (the brown stain) before and after oxymatrine (Equilibrant brand) treatment.

    VP1 Protein before and after oxymatrine.png

    One thing about oxymatrine though is that if you have improved on it, should you then stop taking it, you may quickly (within a few days to a month) fall back to the illness level you had before you started it. Chia has observed this many times.

    Once the benefits of oxymatrine have manifested, Dr Chia says men can stop taking it after 3 to 6 months; but women usually have to continue taking oxymatrine, otherwise they relapse and get worse again. Ref: 1

    Note that Chia has advised against the used of oxymatrine in patients with autoimmune tendencies:

    Around 50% of patients taking oxymatrine will feel worse for a month or two before they get better. The transition to feeling better is often marked by several days of high fever that suddenly appear after around one or two months on oxymatrine. After these few days of fever, that is when you get the improvements, and are thereafter on the home run.

    I have to say, though, that I have not heard many stories on this forum about spectacular successes with oxymatrine. I tried oxymatrine myself, but failed to see either any initial worsening or later improvements in symptoms. But because Chia found oxymatrine only works well for around 25% of patients, 3 out 4 patients trying it will get no benefits, or just mild benefits.


    Nexavir
    Nexavir is a brand name for a porcine liver extract which has anti-inflammatory, immunomodulatory and antiviral properties (it shows in vitro effects again EBV and HHV-6).1, 2 Other brands of the same drug include: 4ME, Kutapressin, Hepapressin and Biopressin.

    Nexavir costs around £120 ($190) per month. Nexavir is given by subcutaneous injection typically once every two days. It is very safe, very well tolerated, and patients usually feel good while taking it.

    Nexavir is employed by several ME/CFS doctors, including Dr Cheney, Dr Enlander and Dr De Meirleir. Nexavir treatment protocols vary, but in one study, ME/CFS patients were given one subcutaneous 2 ml injection of Nexavir for the first 25 days of treatment; then one injection was given every two days for the next 50 days; and thereafter one injection was give three times a week for the next 105 days. This study reported a 42% remission rate in these patients at the end of this course of Nexavir treatment.1 However a 42% remission rate seems high, so I wouldn't trust this study too much.

    Dr De Meirleir reports that around 70% of his ME/CFS patients experience at least a 20 point increase on the Karnofsky scale as a consequence of taking Nexavir.1 Dr Enlander says that Nexavir helps about 30% of his ME/CFS patients, and when combined with other compounds including vitamin B12 and glutathione injections, Dr Enlander reports Nexavir helps 67% of his ME/CFS patients.1

    With Nexavir, I believe people may just take a course of this drug for several months, and then stop. Whereas others may keep taking it.

    Dr Cheney believes that Nexavir will stop working if you don't take regular breaks from it. Indeed, Dr Cheney and Dr Klimas believe this is the case with many immunomodulators: they say that you need to take immunomodulators on a start-stop basis to maintain their efficacy, and to avoid developing a tolerance them. (Though this would not apply to oxymatrine, which once it works, should not be stopped, otherwise you will get worse again).

    I myself took a 4 month course of Nexavir (the 4ME version). I found I made significant improvements in my ME/CFS around the time I took this drug and in the year that followed, and these improvements have persisted. However, since I also started regularly taking several new helpful supplements that year (like selenium and N-acetyl-glucosamine, which I believe may be a microglial activation inhibitor), I cannot be sure that it was Nexavir that caused this improvement. The only way to know would be to take another course of Nexavir, and see if I get further improvements. This is something I plan to do.


    Imunovir
    Imunovir (inosine pranobex) is an immunomodulatory and antiviral drug used by ME/CFS specialists such as Dr Cheney, Dr Klimas and Dr De Meirleir. Dr Chia often uses Imunovir in conjunction with oxymatrine.

    Imunovir is a combination of three components: inosine, acetamidobenzoic acid, and dimethylaminoisopropanol. (These components are chemically bonded together as a molecular complex). However, Dr De Meirleir and Dr Cheney feel that taking inosine alone instead of Imunovir provides equally good results. Inosine is an inexpensive dietary supplement available without prescription, so this makes it cheaper and easier to take inosine rather than the drug Imunovir.

    Dr Cheney’s "pulsing" protocol for Imunovir / inosine:
    Though even with pulsing, some patients report that the effects of Imunovir / inosine diminish with long-term use.


    Low-Dose Naltrexone
    The low-dose naltrexone (LDN) protocol involves taking small doses (around 3 or 4 mg) of naltrexone at bedtime. Because such low doses are used, this protocol works out pretty cheap.

    LDN is thought to have an anti-inflammatory effect in the brain (by reducing microglial activation). LDN is used off-label to treat autoimmune diseases (LDN is believed to reduce B cells), so may be particularly helpful to ME/CFS patients with autoimmune conditions or tendencies. LDN acts on opioid growth factor (OGF) and on the receptor for OGF.

    Some ME/CFS patients initially feel a lot worse when starting LDN, and they have to greatly lower their dose (to 0.25 mg or even less), and then slowly titrate the dose up over many months. There are plenty of accounts of ME/CFS patients doing well on LDN.

    I tried LDN, but found no noticeable improvements or worsening in my symptoms.

    Note that LDN may not work unless you also take vitamin D3.


    Valcyte
    Valcyte (valganciclovir) is a powerful antiviral and immunomodulatory drug that is effective against many herpes family viruses: EBV, HHV-6, CMV, VZV, HSV-1 and HSV-2. When trialling Valcyte for ME/CFS, Prof Montoya found that many of his patients shifted their immune response towards the Th1 mode, indicating that as well as being an antiviral, Valcyte also has an immunomodulatory propeties. Montoya said he is not presently able to determine whether the benefits of Valcyte for ME/CFS arises from its immunomodulation and/or its antiviral effects.

    Valcyte is pretty expensive, though some members of this forum have found good prices for Valcyte from online pharmacies.

    Valcyte is not generally a well tolerated drug, and ME/CFS patients often report feeling bad while taking it. Valcyte can also have some serious side effects, and patients taking Valcyte must be regularly monitored in case these side effects start emerging.
     
    Last edited: Jul 20, 2017
  20. daisybell

    daisybell Senior Member

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    LDN has been great for me... I've been on it for about 2 months, and have gone from being symptomatic walking across the room to walking for 40 minutes today with no PEM. I take it early in the morning - around 6am, and then go back to bed for a couple of hours. The initial side effects have all gone.
    I only wish I had started it earlier!
     
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