Given that a vegan diet doesn’t activate mtor to the same extent as a meat based diet, I’m thinking it may be the case that meat-eaters need higher levels of rapamycin than the vegan. If this is true, then I’m wondering what downward dose adjustments would be appropriate for the vegan to get the same level of anti-aging benefits while avoiding side effects.
I’ve reduced my intake of rapa over the past few months from 6 mg / wk to 3 mg every 9 days on this basis (I’ve had a couple skin infections w/ the higher dose.) I’m wondering if it’s likely to be the vegan diet that makes 6 mg per week excessive for me. Anyone have any thoughts?
Right now there is not much scientific data behind the current dosing or optimal dosing for longevity. The general idea of dosing around 5mg, in one dose weekly comes mostly from data provided in the 2014 Mannick rapalog trial paper.
But this was just focused on immune function in the elderly, not slowing down aging in general. The mouse studies in the ITP program have been successful in lifespan improvement with much higher doses (in a dose dependent manner), but people aren’t mice and we don’t live in pathogen free environments.
But even with the Mannick trial, they didn’t adjust for weight (typically larger people require a higher dose for the same effect), and other variables.
I’m talking with a rapamycin researcher later this week so I’ll see if I can get some insights on the science behind your question…
It could be connected. I’ve been a vegetarian for a few decades. And may be because of that I need a much smaller dose than other people to have the same results. If I accidentally take even 1mg over my regular dose, I would have unpleasant side effects. It never occurred to me that my veggie diet and Rapa dosing could work synergetically.
Thanks for having brought together this valuable site and community! Would love to hear any thoughts on this topic also.
And perhaps also if you, the researcher and/or others have any thoughts on interactions with say a quarterly 5 day water only fast — good to skip rapa that week or instead go for the combined (synergistic?) effect of both on that once a quarter occasion?
If the 0.5 mg / day 5 mg / week, 20 mg / week everolimus study is the basis for rapamycin protocols, shouldn’t the standard rapa dose be 2.5 mg a week? (If one dose of everolimus is equivalent to half a dose rapa).
Perhaps - in theory, but I think Dr. Green and others who first really started human adoption of rapamycin probably looked at the ITP results and decided to increase the dose upwards.
The 2014 Mannick Study didn’t do a 10mg dosing, they did 5 and 20mg. I think generally the doctors like Alan Green are thinking that the 10mg would have been a good dose, so are defaulting on around 6mg rapamycin for people.
Okay, I might be thinking too much like a computer, but if that paper is the basis for 5 mg, it can be 5 mg but then it should be everolimus, not rapamycin. And if it was rapamycin, it should be 2.5 mg not 5 mg if you’re basing the dosage on the paper. It’s totally fine to say the dose is increased because a higher dose is better if there isn’t much more side effects. As any weekly dosing amount is far away from the daily dosing in mice studies.
I think it may be more accurate to say that the paper is likely the basis of the weekly dosing strategy. The actual dosing levels are likely a combination of data from many different papers. But ultimately - this is probably something best answered by Alan Green and others prescribing rapamycin.
Spoke wuth him yesterday morning. Will write up a summary. The rapamycin monkeys are on a lifespan study and we may have good results in a few years, they arre waiting for 90% to die. .
As far as diet… And mTOR, there is a dose dependent blunting, of mTOR 1 and what you eat does not seem to change The blunting.
That seems counterintuitive. So if person A eats nothing but leucine & mtor is thus highly stimulated & person B is a vegan who avoids all mtor stimulating foods & mtor is thus very low, then the same level of rapa would still bring their mtor levels to the same place? Simple logic (which could of course be wrong) would seem to indicate that the mtor adverse vegan would be overdosing & risking repressing mtor2.
Assuming the administrators in the monkey & dog trials know the results so far, I’m wondering if there’s any hint as to how things are going. Perhaps there’s an unwillingness to publicize it, especially for the dog trial, but we could possibly get some hints. One would be how bullish Kaeberlein or his close friends are on rapa. Have they started taking it recently or expanded their dosing???
I’ll see if I can somehow get the audio file provided so you can hear Adam Salmon’s complete response. But in brief, I think what he was saying is that once you start blunting / inhibiting mTOR1 via a dose of rapamycin its not suddenly becoming unblocked by a leucine dose. It largely remains blunted, as do the downstream signalling aspects like IGF-1, GH, etc. Of course, no food (e.g. a 3 day fast) will further blunt mTOR1 signalling, and thus will further upregulate autophagy, etc… but we don’t know the optimal levels of mTOR1 inhibition over time for longevity, don’t know the optimal levels of autophagy, don’t know the responses on a per tissue/organ level… etc. So it quickly becomes obvious that what we don’t know probably overwhelms what we do know, in this area; so overthinking this and trying to optimize it given many unknowns probably isn’t of a lot of value (at least this is the sense I got from the discussion).
Interesting. My real concern is somewhat the opposite in that if you consume no mtor stimulating foods (water fast or strict vegan), that continuing w/ the same dosing would start hitting mtor2 faster.
I guess I’m reviving an old thread here. But I found this searching for what people are doing with their diet around rapa dosing.
The way I understand and I think what @RapAdmin is trying to say is rapamycin is such a powerful mtor1 inhibitor that nothing we will typically do can effect that. It’s like rapamycin is an iron door. High protein or leucine or whatever might be banging on the door but it’s blocked. It doesn’t matter. It can’t get through the iron door no matter how much it tries. The door doesn’t even flex. Since we are intermittent dosing, at some point the rapamycin is wearing off and the door opens… whenever the time comes.