I am exploring the combination of these three drugs for my once per week mTor1 inhibition. My understanding is they all inhibit mTor1 via different mechanisms. My motivation is to have a more robust inhibition of mTor1 but still pulse it weekly and minimizing any side effects. Just thought I would share here to see if anyone had an interesting reaction or any wisdom to share. Other than monitoring for side effects, I am not sure how to evaluate the success or counterproductive nature of the regiment.
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Rapamycin itself is enough of a powerful m-tor inhibitor, there is zero evidence that adding other two will give you any additional benefit. There is plenty of evidence that they can give you side effects.
Metformin only makes sense if medically indicated - DM2 or PCOS, to mimic some of the benefit just eat low glycemic loads
Meclizine is an anti-cholinergic and those can increase risk of dementia over time, yes it extended life in ITP in mice but not worth the side effects IMO… unless you have chronic vertigo.
Exercise is a selective m-tor inhibition; fasting, calorie restriction and low BCAA protein also suppress(or reduce activation of) M-tor, as well as allegedly EGCG and curcumin.
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Recognizing that we don’t have clear data, do you think 100 mg or so of Meclizine once every week or two is going to approach the dementia risk level? I would think there is a different threat profile with pulsing as opposed to the continuous long term use in the few studies that do exist on anti-cholinergics?
I don’t know. There is a level of risk that compounds with alcohol, 1st generation antihistamines, etc.
Better question is what is the benefit of 100 mg of Meclizine weekly especially when added to rapamycin?
and then does the benefit outweigh the risk ?
I just don’t see much benefit of meclizine on top of rapamycin which has clear benefit in humans and does all the heavy lifting, but I do see some potential risk of meclizine so for me…
benefit < risk
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I agree with the others here, I don’t think Meclizine is worth the risk. I recommend you read the entire Meclizine thread: Meclizine / Dramamine II, Approx 15% Lifespan Increase, Another mTORC1 Inhibitor - #26 by RapAdmin
I don’t take Metformin because of the negative impact on exercise recovery. See this thread: Rapamycin + Metformin - #2 by RapAdmin
and: Metformin and its impact on exercise (on high dose 1700mg, N=46)
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I guess its the expression “the dose makes the poison”. If we believe that that the benefit is dose dependent, then higher doses of rapamycin buys you some additional side effects. My thought is that lower doses of drugs that act on different pathways can have greater mtor1 inhibition than what you could achieve with a high dose rapamycin. Its a made up and untested theory…but just sharing the thoughts in my head to get some feedback on it.
That is true (dose makes the poison), but there are other ways to inhibit mTOR without meclizine or metformin; eg. fasting.
I can see an argument that lower dose meclizine and metformin (in addition to rapamycin) might be a “net positive” for a person who is sensitive to dosing with rapamycin, and doesn’t exercise much (and thus not missing much with the metformin dosing).