Invest in ME Conference 12: First Class in Every Way
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mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Jesse2233, Apr 6, 2017.

  1. Hip

    Hip Senior Member

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    I am a little more tired than usual on the rapamycin protocol.

    Although I have seem glimmers of improvement: for example, there is small church opposite my house, attended by Asian Christians, and after each service, the young children of the families play in the church front garden, shouting and laughing, and generally being noisy, as excited kids are. Normally this sound drives me crazy, due to my ME/CFS sound sensitivity (hyperacusis).

    But the other day, these kids were playing as usual, but instead of the sound irritating and grating on me as it normally does, I perceived the sound of playing children as joyful and life-affirming, which is unheard of for me. That's probably the way most healthy people will perceive the sound children playing, and it made me realize how terrible a disease ME/CFS is, that turns joyful sounds into a grating cacophony.

    But this was just a one-off, and so far I have not seen much in the way of symptomatic improvement.


    Currently I am taking 0.25 mg of rapamycin daily (but with my CYP3A4 inhibitors, this should be equivalent of around 1.25 mg daily).
     
    Last edited: Oct 20, 2017
  2. pattismith

    pattismith Senior Member

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    I'm thinking about a rapamycin trial too, I'm interested in its ability to regenerate mitochondria and to improve glutamate uptake.

    http://onlinelibrary.wiley.com/doi/10.1111/jnc.13200/full
    from table 1:

    mTORa
    Serine-threonine protein kinase mammalian target of rapamycin, induces EAAT2 over-expression Up-regulation of GLT-1 via mTOR- NF-кB signaling cascade in OGD may promote glutamate uptake in brain ischemia and neurodegenerative diseases
    Wu et al. (2010), Pignataro et al. (2011), and Ji et al. (2013))

    You can also take hydrocitrate tablets (Solgar makes it at less)
     
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  3. nandixon

    nandixon Senior Member

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    @pattismith, That article is saying that activation of the enzyme known as the mammalian target of rapamycin (mTOR) increases GLT-1 and therefore increases glutamate uptake.

    Thus, the drug known as rapamycin (aka sirolimus), which inhibits mTOR, leads to decreased GLT-1 and decreased glutamate uptake.

    So rapamycin/sirolimus apparently does the opposite of the beta-lactam antibiotics, for example, with respect to GLT-1 and glutamate.

    I wouldn't be dissuaded from trying it for that reason, though. I'm still having fairly decent success with it myself. (I'll try to do an update later.)
     
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  4. pattismith

    pattismith Senior Member

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    Thank you very much @nandixon,

    it wasn't really explained in the paper, so I should have dig more.
    I bet I need to think a bit more before trying Sirolimus, as I do worry about this glutamate issue :thumbdown:
     
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  5. XenForo

    XenForo

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    I wonder if people with a penicillin intolerance or a monosodium glutamate intolerance are the ones who respond positively to rapamune. I have an intolerance to most antibiotics.
     
  6. Jesse2233

    Jesse2233 Senior Member

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    Southern California
    Interesting thought. I have an allergy to amoxicillin
     
  7. XenForo

    XenForo

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    Amoxicillin is one of the beta-lactam antibiotics. I get bad diarrhea when i take amoxicillin.
     
  8. pattismith

    pattismith Senior Member

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    it maybe more a microbiota disruption than a real allergy, did you had other clinical manifestations?
     
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  9. XenForo

    XenForo

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    nope.
     
  10. Hip

    Hip Senior Member

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    I've now been 23 days on rapamycin, but no sign of improvements so far. The people who saw major improvements said they these improvements manifested at around the 4 to 6 week stage, so I am starting to suspect that I may be a non-responder to rapamycin. However, I am going to keep taking it until I complete 5 or 6 weeks.
     
    Last edited: Nov 8, 2017
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  11. Hip

    Hip Senior Member

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    I have stopped taking rapamycin after being on it for 4.5 weeks, with no signs of improvement (if anything I was slightly more physically tired on rapamycin).

    But don't let that put off others thinking of trying rapamycin, as most ME/CFS treatments work for some patients but not others, and several people reported significant improvements on rapamycin.
     
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  12. pattismith

    pattismith Senior Member

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    sorry it didn't help you.

    Would you explain to me again why mTOR inhibition is supposed to help ME patients, please?:redface:

    it doesn't seem to match with Chris Armstrongs theory, or I am misunderstanding something:

    http://forums.phoenixrising.me/inde...is-armstrongs-presentation-at-stanford.55732/
     
  13. Hip

    Hip Senior Member

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    mTOR inhibition will likely not help ME/CFS, and may make things worse; so rapamycin's benefits for ME/CFS may occur in spite of its mTOR inhibition, not because of it. See @nandixon's earlier post.
     
    Last edited: Nov 8, 2017
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  14. XenForo

    XenForo

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    Friday (in 2 days) will be a full week where I've been working almost full time, and through the weekend too. I've never ever been able to do that and feel like I'm okay. I can keep up with the construction crew, which is pretty weird for me. Of course, I'm not sure if I'll pay dearly for it. In addition to the rapamune, I started taking niadem and nadh, so I don't know what (if anything) is causing the change. I also gave up bicycling, since somehow I no longer seem to have time for it. I'm in mid midlife, so it's weird to have more energy than I did when I was young. I hope I don't crash for a month or two or three. Now that I know what it's like to feel normal, I'm going to be so upset when it ends :(
     
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  15. XenForo

    XenForo

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    I meant to report back that my 1/2 of 1 mg rapamune from Goldpharma seems to work much better than this new 1mg rapamune I bought from buy-pharma.co. The buy-pharma stuff is from singapore, goldpharma was from germany. Both said Pfizer on the packaging. I might try cutting the 1mg tabs in half and see if it makes a difference.
     
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  16. nandixon

    nandixon Senior Member

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    @Hip, @pattismith

    See my later post here. I had to reevaluate the mTOR/mTORC1 situation because of the new T-cell work by Mark Davis and also Maureen Hanson.
     
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  17. pattismith

    pattismith Senior Member

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    I'm sure you won't be upset, because if it happens, you will remember that "normal feeling" and you will know that the recovery is possible and that you will improve again :) :thumbsup:
     
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  18. Hip

    Hip Senior Member

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    After stopping rapamycin 1 week ago, I've had a terrible week of nasty symptoms such as feeling exhausted mentally, increased ME/CFS emotionally sensitivity, and a quite severe and horrible autism-like anxiety. I tend to get lots of comorbid neuropsychological symptoms with my ME/CFS anyway, but this last week they all hit with vengeance.

    These horrible symptoms started to manifest around 3 days after stopping rapamycin, which is consistent with this drug's half-life of 2.5 days.

    Because I had just started taking a new herb, I initially blamed my horrible symptoms on that; but then it occurred to me that it might be due to suddenly stopping rapamycin without tapering down the dose. Sure enough, when I took a dose of rapamycin yesterday, within a few hours, the horrible symptoms subsided considerably, and today I am back to normal. I now plan to taper off rapamycin slowly over a week or two.


    So for anyone experimenting with rapamycin, you might want to consider tapering off gradually, rather than stopping abruptly. In particular, it may be bad idea to take rapamycin until your packet of tablets completely finishes, because then you will have no more rapamycin left in case you do experience these negative symptoms on discontinuation. Better to keep a few tablets in reserve just in case.
     
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  19. Tunguska

    Tunguska Senior Member

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    @Hip Thank you for describing your experience. I had a 50/50 bet I would react like that and couldn't afford to.

    I can't recall if this was discussed already, but in this context it's worth bringing up this study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559110/
    It's a landmark study on the detailed mechanism of NAC benefits in SLE patients. What's striking is the mechanism proposed is so generic it could easily extend to other diseases.

    You can get a ton of ideas from it (I don't have time/energy), but the bottom line is, you can infer it might be worth trying high dose NAC in conjunction with rapamycin therapy.

    Coincidentally, one of the rapamycin responders told me they took high dose NAC daily. (unintuitively, even whey powder could potentially be a substitute)

    I would extend to say perhaps it would also help during rapamycin withdrawal. Furthermore, if the kynurenine pathway were really involved, then your high dose magnesium might be indicated to provide symptom relief as well as a preventative measure against bad reactions to NAC itself.

    Speedy recovery to you.
     
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  20. Hip

    Hip Senior Member

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    That's interesting. I know some ME/CFS patients have found that N-acetyl-cysteine helps reduce the "wired but tired" over-stimulatory symptoms of ME/CFS.
     

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