I recall that mTOR rebound was a known danger in cancer patients. When Blagosklonny pointed it out I changed from a regimen that achieved wash out between cycles, to a regimen that maintains a small amount between cycles.
After a rather high rapa dose on week one, I take a modest dose of 4mg the 2nd week. Whether that is sufficient to prevent rebound, I dont know, but it seems the best course of action til I know more.
Yes grams. Sorry for the confusion.
Could it be you’ll get funky results if your already doing something with the mtor? I believe ginger and melatonin have an affect on mtor, and im taking a large stack which could also be doing something with mtor and/or increasing the bioavailability of rapa. Either way, I might sit this one out and until there is more info
Any thoughts on this? i’m not scientifically literate enough to understand how bad this could be for intermittent use.
Mikhail V. Blagosklonny, MD, PhD
3h
If you take a single dose of rapamycin which inhibit mTOR in first few days, mTOR activity may rebound ABOVE base line later. Its bad This is important and not known to most (or anyone) of us.
So the appropriate dose would be 0.5 mg a day like in the Mannick study then?
I think the focus, instead of if Rapa results in a rebound, should be is the rebound a bad thing? I’m not convinced of that. I’m certainly not going to worry about it or change my protocols based on it.
0.5 mg a day showed slightly better improvement for immunosenescence in the Mannick study than weekly 5 mg dosing, of course not as good as the higher doses. The rebound might negate some of the effect by activating mTOR, doing the opposite that we want?
MB wirites: You want to inhibit mTOR with rapamycin, not to induce it.
If you take rapamycin EVERY day (like transplant patients), then everything is good
https://x.com/blagosklonny/status/1710641951655997446?s=46&t=ujBXvjsf5sfNM8J1qi8RfQ
Wish he suggested the dose. 0.5 or 1 mg?
the rebound is above baseline. I guess the questions are by how much and does it negate rapamycin use or increase overall mtor with rapamycin used intermittently.
The goal is not to induce, per MB. It means it’s a bad thing. He calls the opposite (inhibition) a good thing. Do we know ifMB is taking it every day?
I guess it comes down to what the purpose/benefit of taking Rapamycin is? If Rapa extends life by intermittently causing senolysis and autophagy then a rebound anabolic phase is not necessarily bad. Maybe it’s good.
Maybe i have a rebound effect but i dont see it as a bad thing. Ive taken rapamycin weekly for a year now suddenly stopped for 3 weeks and increased my amino acids + protein BY ALOT compared to when i was taking rapamycin , and I’ve have seen a sudden growth in muscle mass while hitting the gym. The growth is insane. Already see muscle growth within 3 weeks. I’ll continue taking rapamycin, just taking longer breaks in between of dosing as I’m trying to gain muscle and lose some fat. I think its important to have mtor inhibit at times and activated at other times. balance of both.
If one take a large dose biweekly, then taking a much lower dose the following week, lsay like 5 mg, then we could have a potential strategy to reduce the rebound effect? Otherwise, I stick to a low dose every day or 5-6 mg dose weekly.
But this, low dose strategy, is in conflict with the theory (or fact) that, to be able to penetrate different tissues, we need different doses. Some tissues and organs need a high dose. And a high dose seems to increase the risk of a powerful rebound effect.
I guess it comes down to each person has to take a leep of faith. i think I take a felarge doses and I then stick to some low dosing regiment.
And yet…the mice had extended LS (in the Intervention studies).
Were the mice dosed daily or weekly?
I believe it was dosed daily.
They were dosed daily.
wow, I wondered why my infections seemingly took place towards the end of the week when the rapa would have been the least in my body
Here are two post that describes my view on the topic
