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How can we "stimulate" mTOR?

Discussion in 'General Treatment' started by Sushi, Mar 12, 2017.

  1. Murph

    Murph :)

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    here's a study(on rats) that gives some insight on mTor in a potentially very relevant context.

    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173809

    They made rats do resistance exercise, then fed them various things (Edit: whey, carbs and whey, placebo), and later measured various things, including mTor. The best performer of the above group for promoting mTor was the combination of whey powder and carbohydrate. (CP in the graphic. SED is sedentary control rats, WP is whey powder, and PLA is placebo.)
    Screen Shot 2017-03-17 at 7.38.35 PM.png
     
    Last edited: Mar 17, 2017
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  2. adreno

    adreno PR activist

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    Well the only options were whey, whey + carbs and placebo.
     
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  3. Murph

    Murph :)

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    cheers, edited for clarity.
     
  4. adreno

    adreno PR activist

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    My point is that there may well be much more potent mTOR activators that were simply not tested.
     
  5. eljefe19

    eljefe19

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  6. Tunguska

    Tunguska Senior Member

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  7. drob31

    drob31 Senior Member

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    I took Cimentidine for it's h2 blocker qualities to block EBV from binding to h2 receptors on lymphocytes.

    This is an interesting coincidence....
     
  8. adreno

    adreno PR activist

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    It doesn't always seem clear whether a substance inhibits or activates mTOR. NAC has been shown to be an inhibitor, but in this recent study it increased mTOR:

    https://www.ncbi.nlm.nih.gov/pubmed/26433892
     
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  9. Tunguska

    Tunguska Senior Member

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    The other linked studies were on T cells. In liver cells it circumstantially rescues mTor. It's dependent on cell type (and maybe cell health?) and there's still not enough information. I hope you guys have more time to clear it up lol
     
    Last edited: Mar 18, 2017
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  10. adreno

    adreno PR activist

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    So in many cases, whether a substance is an inhibitor or activator depends on cell type? In this case, which types of cell do we need activated, i.e. how to determine whether it's potentially good, bad or indifferent? Confusing stuff.
     
  11. Tunguska

    Tunguska Senior Member

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    A lot of this isn't black and white. But it was clear NAC was cell type specific here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411859/
    "Mitochondrial hyperpolarization" was only expressed in T cells (this is lupus, I don't know if that makes a difference). I didn't understand "mitochondrial hyperpolarization" at all, so have fun with that...

    You posted an article about mTor and viruses and they were doing the same thing to an even more precise degree. They're way ahead of us on the selectivity thing. Some people on the forum clearly think the immune mTor is most important. I see hints both ways.
     
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  12. necessary8

    necessary8

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  13. Hip

    Hip Senior Member

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    I only took these supplements for 3 days in a row, at the daily dose of:

    Leucine 5.2 grams
    Glutamine 5.8 grams

    I did not notice much during that short test, except perhaps being in a more relaxed and good humored mood.
     
  14. Janet Dafoe (Rose49)

    Janet Dafoe (Rose49) Board Member

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    Hi,
    I've read several comments on this thread that seem to indicate confusion, so I'll make a few statements to try to clear up a few things.
    Ron did not get mTOR ideas from Fluge and Mella. He says F and M did not do sequencing. Ron started thinking about mTOR when he discovered through sequencing in the Genome Center that TWO me/cfs patients had mutations in that gene. He realized when he saw that that it could be important because mTOR is a major regulator of things related to nutrition, et al. It's relatively hard to sequence. He plans to look for this in the Severely Ill Patient sample. He has not done anything else with it yet, and it is at present just an idea that needs further exploration. He likes to put ideas on PR so you guys can be thinking about things, but often people generalize and conclude too much from what he says. He is careful with his words. He is also very careful not to recommend any treatments. He is not an M.D. And these things are very preliminary. Please be cautious! I try to tell him or read him people's ideas and things they try. He's very interested in your ideas. There are a lot of smart, well-informed people on here! Someone could summarize this tread with bullet points and I'd print it out for him. Please tag me if you do. Thanks!
     
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  15. Janet Dafoe (Rose49)

    Janet Dafoe (Rose49) Board Member

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    This is what Dr. Jay Goldstein used to do. @Ben Howell
     
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  16. adreno

    adreno PR activist

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    @Rose49

    My impression is that only a handful of people here are experimenting with this. After about a month of focusing on those of my supplements that stimulate Akt/mTOR and removing those that inhibit it, I can almost definitely say that it helps. I am able to get away with more (everyday) activity without crashing.

    It could be confirmation bias, but there does seem to be pattern indicating that mTOR is involved. For example, I could never understand why for example Carnitine works well for me, while Q10 and PQQ does not. But in the light of their effects on mTOR it makes sense.
     
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  17. A.B.

    A.B. Senior Member

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    It might just be confirmation bias but there seem to be quite a few people who used mTOR inhibiting drugs around the time they got sick. I was taking isotretinoin for acne which works by inhibiting mTOR.

    If one reads what mTOR does, it sounds like its job responsibilities would include inducing a Dauer like state in the cell when environmental conditions are unfavorable. A mTOR inhibiting drug might just be one of the factors that can push people over the edge into illness.

    Some (many?) anti cancer drugs work by inhibiting mTOR (because it's upregulated in cancer cells that are growing out of control). My local ME/CFS clinic's main function is to actually treat cancer but they became interested in ME/CFS because apparently patients sometimes develop persistent fatigue and other symptoms after chemotherapy and its a problem.
     
    Last edited: Mar 20, 2017
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  18. antherder

    antherder a.k.a. Princess Dauer, Nematode Nation

    Apologies if this is a really stupid question...

    What might that mean then in terms of the people who have had ME for years, but then later develop cancer - would you expect their ME symptoms to improve when their tumors are actively growing?
     
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  19. A.B.

    A.B. Senior Member

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    No. My understanding is that it's only the tumor cells that switch into high growth metabolism, where ME/CFS seems to involve changes in the whole body. In general adding another disease on top of ME/CFS should worsen overall health.

    It doesn't seem inconceivable that some tumors could improve some symptoms though, if they produce hormones.
     
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  20. necessary8

    necessary8

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    Any reason why you stopped?
    I plan on doing the same, but with BCAAs and Glutamine. Will report back when I do it.

    Janet, let me explain. This actually came about before Ron spoke of mTOR. In the thread about Fluge & Mella research, @nandixon crafted a hypothesis about the PI3K/Akt/mTORC1 pathway being inhibited. He came to this idea by extrapolating from the F&M study (mTORC1 is upstream of the PDKs that F&M found upregulated). He expanded his theory then, to impaired S1P signaling and low ceramides, which he says is consistent with Naviaux's study.
    Here is the first post of his hypothesis: http://forums.phoenixrising.me/inde...-encephalopathy-cfs.48446/page-12#post-800136
    If you follow his posts in that thread you will get the full hypothesis.
    @nandixon, if you want to summarise your theory for Ron to read, this is your chance. You'll be better for the job than me.

    From this people started experimenting with things that might activate mTORC1, like the Leucine & Glutamine thing Hip did.
    And that's where the question about mTOR came from, I believe. And when Ron answered that he thinks mTOR might indeed play a role, that further encouraged us to explore this option. And then in the thread about that Q&A, someone found a paper stating that all antibiotics perscribed for acne work by inhibiting mTORC1 - http://forums.phoenixrising.me/inde...to-2-21-17-research-update.49749/#post-820778
    And then a lot of people came out and said they've been taking antibiotics for acne right before their illness started. Myself included.

    So that was a third argument for trying to activate mTORC1. And so here is a thread about how to do it, about BCAAs, cimentidine, florinef, and all the rest of it. Someone wanted to try ketamine, but I don't know if they did already. And so far, quite some people are saying that taking BCAAs or whey protein isolate made their PEM go away.
     
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