I have a question regarding the dosing protocol for Rapamycin.
It is well-established that for longevity purposes, oral Rapamycin is typically taken once a week (e.g., 5-6mg) to allow for a “washout” period, which helps avoid the continuous inhibition of mTORC2 and minimizes side effects.
However, I’ve noticed that most non-oral formulations—such as topical creams for skin or toothpaste for oral health—often recommend daily application.
My specific questions are:
Systemic vs. Local Effect: Is daily use of topical considered safe because the systemic absorption is too low to suppress mTORC2 throughout the rest of the body? Furthermore, even if systemic levels remain low, could chronic mTORC2 inhibition within the local tissue itself lead to negative side effects
I would love to hear from anyone with experience in pharmacology or those who have experimented with different Rapamycin delivery methods.
Great question. Hope someone can provide a good answer. My guess is there is little or no human data on topical Rapamycin.
And be careful with the “well established” statement, as there is no data on Rapamycin in humans for longevity.
I can answer from N=1 personal experience. I am extremely sensitive to rapamycin. I can take 1mg and feel it in multiple ways. (Those who are inclined to argue with me about this, save it; it’s not worth your time or mine.)
I use rapamycin toothpaste (that I make myself, with transcutol). Daily. I don’t feel any rapa effects.
In this study of topical daily application of rapamycin skin cream there was no systemic absorption of the rapamycin (it was not detected in the blood in the subjects in the study). See here: Rapamycin May Slow Skin Aging (Drexel U. Study)
And the results were successful - so I think that is where the daily dosing strategy originated for all topical formulations of rapamycin (creams and toothpastes).