mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas

[Hip]

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).

 

[pattismith]

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))

It is possible that the herbal supplement Garcinia cambogia may be able to reduce the type 2 diabetes risk that occurs when taking rapamycin on a long term basis.

If you look at the proposed mechanism by which rapamycin causes diabetes (see this post), it is thought to be due to insufficient activation of beta oxidation (fat burning) in the mitochondria. Metformin is thought to mitigate the rapamycin diabetes risk by stimulating and up-regulating beta oxidation.

This article says that Garcinia cambogia stimulates fat burning, and may activate beta oxidation. Garcinia cambogia is often sold as a weight loss supplement; its active ingredient is hydroxycitric acid (HCA), and Garcinia supplements will typically contain 50% HCA.

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

 

[nandixon]

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…

@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.)

 

[pattismith]

@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.)

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:

 

[XenForo]

@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 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.

 

[Jesse2233]

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.

Interesting thought. I have an allergy to amoxicillin

 

[XenForo]

Interesting thought. I have an allergy to amoxicillin

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

 

[pattismith]

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

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

 

[XenForo]

...you had other clinical manifestations?

nope.

 

[Hip]

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.

 

[Hip]

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.

 

[pattismith]

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.

sorry it didn't help you.

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

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/

 

[Hip]

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

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.

 

[XenForo]

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

 

[XenForo]

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.

 

[nandixon]

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.

@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.

 

[pattismith]

Now that I know what it's like to feel normal, I'm going to be so upset when it ends

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

 

[Hip]

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.

 

[Tunguska]

@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.

 

[Hip]

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.

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.