Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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How can we "stimulate" mTOR?

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

  1. eljefe19

    eljefe19

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    On Aminos, looks like Essential Amino Acids activate both mTOR and AMPK, but it appears that mTOR comes out on top? Not sure, but that would fit with people's anecdotal reports of Aminos being helpful.

    https://www.ncbi.nlm.nih.gov/pubmed/27869123
     
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  2. Murph

    Murph :)

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    I really totally honestly have no idea. I'd probably steer away from it without getting advice from someone far more knowledgeable!! how was the ketamine anyway??
     
    Last edited: Mar 21, 2017
  3. eljefe19

    eljefe19

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    @Murph Ketamine was nice. I enjoyed both some palliative relief of ME/CFS symptoms (pain and fatigue) but I also got some great mood boosting effects as well. Also music is enhanced on it. Are you considering a trial?

    More info on mTOR/AMPK;

    http://www.nature.com/nm/journal/v16/n9/full/nm.2207.html
    This paper shows that the medication T3 inhibits AMPK in the hypothalamus, however it increases AMPK in muscles.

    This paper shows the relationship between mTOR/AMPK especially in the presence of Leucine.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132561/
     
    Last edited: Mar 20, 2017
  4. eljefe19

    eljefe19

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    Found something interesting on NAC. Here's a study on NAC's effect in starvation conditions (I seem to remember Dr. Chris Armstrong said ME/CFS looks like a combination of Sepsis and Starvation).


    https://www.ncbi.nlm.nih.gov/pubmed/23000343
     
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  5. Murph

    Murph :)

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    I'm trying to stay out of the k-hole! ;)

    I've also just found this paper which, (admittedly with a small sample size (10 subjects 7 controls) and in vitro) finds that ampk production is inhibited, not exaggerated, in me/cfs patients compared to controls.

    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122982

    so that throws a spanner in any ampk theory! My only comment is that the study looks to have very limited statistical power: It measured 3 time points after stimulation and found a significant difference at only one of them.
     
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  6. eljefe19

    eljefe19

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    Ha I didn't experience the K hole no matter how high I pushed the dosing, which for me, I did pretty conservatively. Tried to keep it to 33-50mg bumps every few hours. @Murph

    One thing I'm trying is a product called Myo-X on Amazon. It's advertised to increase circulating Follistatin and inhibit Myostatin, which should in turn disinhibit mTORC1. I'll report back on that.
     
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  7. nandixon

    nandixon Senior Member

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    The references I see indicate palmitoylethanolamide (PEA) should inhibit mTORC1 and therefore be bad.

    I tried PEA a couple years ago (to inhibit microglia activation), and indeed it was very bad. I normally don't have significant brain fog but the PEA I took actually caused that. It was very insidious too. Probably one of the top 5 worst supplements I've ever taken.
     
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  8. eljefe19

    eljefe19

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    Alright then, thanks, I'll hold off on that one.
    @nandixon Are you still interested in BDNF? I have a new source of 7,8-DHF, also I found Magnesium L-Threonate which increases brain Mg levels, increasing BDNF and synaptic plasticity.
     
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  9. eljefe19

    eljefe19

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    @nandixon @Murph So what if Chris Armstrong is right and ME/CFS mirrors starvation. Well, starvation is supposed to activate AMPK and inhibit mTOR. So, if our bodies' are stuck in starvation mode, and something like NAC can prevent the changes to AMPK and mTOR, perhaps that's why NAC has been shown in vivo to ameliorate ME/CFS symptoms. The authors of that study implied it was due to raised levels of GSH in the brain, but who knows?

    Also Leucine directly inactivates AMPK.
     
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  10. eljefe19

    eljefe19

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  11. Alvin2

    Alvin2 Senior Member

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  12. Tunguska

    Tunguska Senior Member

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    mTor and AMPK work in cycles over 24h with food and activity. It blunts mTor because the cells treat mTor as a major energy consumer (no matter the therapeutic effect you get from it). The best thing you get from AMPK is mitochondrial biogenesis. Thyroid is a major regulator, but AMPK and NO also synergize and trigger it in response to exercise (NO associates with both mTor and AMPK). The other major benefit is AMPK is a determinant of circadian rythm especially in skeletal cells. AMPK is probably a source of symptom relief from other supplements. The problem is activating it at inappropriate times (timing is everything) or too much with respect to mTor over 24h period, which you will very easily overdo. Sorry all I can write.
     
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  13. Tunguska

    Tunguska Senior Member

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    I think this is intuitive if you feed amino acids alone. It mimics how protein feeding induces insulin and glucagon together, and the fact protein processing is not free. If you fed carbs with them I would expect AMPK to go down (well, I imagine you knew that).

    Edit: It's fair to question [how much] that's exploitable for therapeutic purposes. For most people it wouldn't be worth it, but this is CFS/ME... I would frame it as: is it a net benefit or loss versus trying to amplify the mTor/AMPK cycle? In part depends on which downstream signals from AMPK survive. Too much to read. [Sorry for all the edits. This is why I shouldn't post on the internet on days like this.]
     
    Last edited: Mar 21, 2017
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  14. eljefe19

    eljefe19

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    Lol no worries man I appreciate the post.
    I appreciate any discussion on the topic, no matter how brainfogged.
     
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  15. eljefe19

    eljefe19

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    @Tunguska Here's an idea for you bro. I highly recommend anyone interested in mTOR take a look at this;

    There is a product on Amazon called Myo-X Myostatin Inhibitor. The company claims huge reductions in circulating Myostatin and similar increases in circulating Follistatin. Haven't been able to verify these claims yet. If you google 'MyoT12' you can find at least one study that claims it increases muscle hypertrophy, without specifics on the MOA. I'll find it and edit.

    Have you been following the Activin B/Follistatin discussion? If the mechanism claims about MYO-X are true, this product could have massive benefit on mTOR signaling.

    First of all, Myostatin inhibits Akt/mTOR (Reference). On top of that, Follistatin activates Akt/mTOR independently of Myostatin (Reference). So, in theory you would be getting a 2 + 2 = 5 benefit from this combination of actions.

    I'm going to take my first dose tonight. I'll report back.
     
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  16. anne_likes_red

    anne_likes_red Senior Member

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    Don't want to derail but have to mention cold induced thermogenesis is supposed to inhibit myostatin via an increase in irisin.
    As far as I know that's one way people - me included - have had an increase in muscle with cold exposure and no to little exercise.
    Anne.
     
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  17. eljefe19

    eljefe19

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    Yeah but I hate cold showers....
     
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  18. anne_likes_red

    anne_likes_red Senior Member

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    Me too! ...Actually have never come across anyone who does.;)
     
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  19. eljefe19

    eljefe19

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    Any ideas how we could implement the idea in a less intense way? Lol
     
  20. anne_likes_red

    anne_likes_red Senior Member

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    ...Well 15 mins of shivering = the same amount of irisin as an hour of intense exercise. :ill: So not great options either way for pwME. :( Some people find wearing an ice vest tolerable.
    Very slow, adaptive thermogenesis is possibly best. I did something like this - starting bathing a bit less than my skin temperature, and working down gradually. Enough shivering to stimulate adaptation, but not too much so as to crash. (Even with best intentions I still crashed in the early days.)
    There was supposed to be an irisin drug in development but it wasn't successful. Probably best to stick with your original plan!
     

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