Of interest, here’s a pro aging pathway that’s very similar to mTOR and is antagonized by rapamycin via autophagy upregulation.
We don’t yet know all of the beneficial pathways of rapamycin.
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I have also started to space out the time between doses more and more - mostly based on the suggestion and hope that with a higher cmax some Rapamycin may cross the BBB.
The past 2 months I took a higher dose once per 3-4 weeks. Having said that: albeit I experienced about the same side-effects taking a higher dose once per 3-4 weeks as I did when I dosed once per week, the intensity of these side-effects has increased. In my case these side-effects are quite apparent and can be bothersome (migraines, sleeping problems, dermal issues, sometimes a mouth ulcer or two).
Besides the question what I find acceptable myself in terms of side-effects, it also brings up the question at what point I may be experiencing toxicities that may in fact be harmful to my health.
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Personally wouldn’t put up with the side effects especially since the high dose/ low dose verdict is still out.
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Nobody can tell me Rapamycin doesn’t give you energy. My husband has been taking 3 mg a week for 15 weeks . In the last 2days he has done so much work around the house it’s unbelievable, first he power washed the pavers around the pool, then sanded them all ( this is a large area) then after hand brushing in the sand he went on to seal it all, with a roller as the seal spray broke. He had moved all the garden furniture into the house to do this, the following day he stripped out the flooring in the 2 car garage and scrubbed the floor which had mold all over it, he dried it off and rolled out a 25 ft roll of floor covering ( I could not help him as it was very heavy) he cut it to size around units and laid it flat using the second roll by rolling it over and over. It might not sound much to you but believe me, we have been married 14 years and he has never worked like this, he is in his late 70s .I’m just sorry I can’t take it due to sugar spikes .
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Which is fine for middle-aged folks but, IMHO, too low for the ancient ones.
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why do you think that?
My reasoning is this: If one is in mid-life, one can be on a moderate dose of Rapamycin (or anything else that one thinks is pro-longevity) and wait for the research to come in future years that may give us a better understanding than we currently have. The younger you are the more time you have to wait for possibly more clarity and adjust your supplement intake accordingly. If, however, one is north of 80, one would be, IMHO, a fool to wait because time is not on your side; to quote MB: “The time is now.” Everybody makes their own decisions. My view is that, when it comes to Rapamycin, the older one is the more one should be willing to gamble with higher doses.
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Sorry, you obviously haven’t been reading the studies. The studies indicate that life extension is dose-dependent, especially in older mammals.
Dr. Mikhail V. Blagosklonny one of the pioneers and leading authority has recommended the highest dose that does not cause unwanted side effects.
At 82 this is the path that I have been following.
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I now think the biggest side effect we need to watch out for is elevated blood sugar levels and diabetic symptoms.
Canker sores, rashes and diarrhea I can live with…
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Sort of…
The biggest side effect that Dudley Lamming who was a postdoc in the Sabatini Lab, has suggested we should be worried about if anyone is using higher than the normal longevity doses (e.g. 6mg/ once per week) is immune supression.
Elevated blood sugars or lipids would take a long time to harm you and are something you’d catch easily with typical blood tests we probably already do. Immune supression is a less detectable risk, that could potentially cause serious problems much more quickly, depending upon the infectious agent (Dudley suggests tracking/measuring Tregs to do this) .
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Yes, very true. There are many things you have to keep your eye out for.
That is almost exactly what I do, not that I have any especial insight as a layperson. I am trying to put on a little muscle as well (I’m 38) and am in general very active and want to dodge the issue of mTOR suppression interfering with workout recovery. I’ve only been taking it for a couple of months and have been gradually building up the dose, up to a peak of 9 mg so far. I think I plan to take it once a month going forward, possibly at slightly higher dosages, but not much higher.
Even with once a month dosing you’re still having a systemic effect for at least a week with the drug’s long half life. Combined with the fact that mice get good, lasting results from intermittent treatment, I think a young person’s best bet is to use infrequent but slightly higher dosing to get a benefit while still being conservatives to avoid potentially unknown deleterious effects. I would think they have the freedom to use this type of less aggressive intervention without being worried about leaving a lot “on the table” since they don’t have much aging related dysfunction to fix to begin with,
I also fast for about 12-24 hours before dosing with rapamycin and then continue the fast for another 36 hours or so, hoping to get a little bit of extra mTOR inhibition without raising the dose.
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I would like to see a rapamycin mice study where the dose doubles every 90 days. (~10 mouse years)
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This may well be true, but I’m not getting a sense of that either in your polling or from the MK study. Are we getting cystitis, pneumonia, cellulitis at a significantly increased incidence? Am I missing it?
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For the average user taking Rapamycin at doses between 3mg to 8mg/ once per week I’ve not seen any issues. So no, you’re not missing anything. I personally believe that at this dosing regimen that for most of us with healthy bodies there isn’t much additional risk.
When I’ve discussed the idea of testing higher doses of rapamycin (not being specific on how high a dose), when I asked Dudley Lamming what things he would watch for or test, this is what he mentioned: Tregs.
But - I’ve not found a way to inexpensively do this blood test. It would be a nice thing to have as an option, I think, if I were to do a regimented approach to testing higher doses.
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If the Mannick paper (which showed mTOR inhibition improves immune function in the elderly) is being used as the framework for rapamycin dosing, it seems we should be using bi-weekly dosing of sirolimus instead of weekly, given that the half-life of sirolimus is roughly double that of everolimus (aka RAD001) used in the Mannick study.
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First of all - please don’t use the description “bi-weekly” , because if you look it up in the dictionary it can mean either twice a week, or once every two weeks, so its a very confusing term. I think what you are meaning by your use here is “once every two weeks” - correct?
The half life of everolimus is about 29 hours, and the half-life of rapamycin is about 65 to 75 hours or so, but I think in both cases thats just a mean, and there is quite a level of variation between people and age and health condition.
Everolimus dose equivalency is something like .6 or .7 to that of 1mg of rapamycin - so you need to take more to get the same equivalent dose.
I think that the doctors who have sort of settled on dosing levels of between 3mg and 6mg or 8mg per week are taking all this information in, and trying to keep it simple for the patients and just specifying once per week to make it easy to remember and follow. Drug adherence is a big problem that doctors face, so they try to make it as simple as possible for patients.
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please don’t use the description “bi-weekly” , because if you look it up in the dictionary it can mean either twice a week, or once every two weeks, so its a very confusing term.
Yes! Can we change the title of this topic to “…weekly vs once every 2 weeks”?
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Biweekly can be confusing, but in general for financial payments (biweekly mortgage payments), biweekly salaries and biweekly Rx’s usually refer to every two weeks. I will edit the topic line 
…oops, I was too slow, thank you!
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Regarding the Everolimus to Sirolimus (aka rapamycin) dose equivalency, on a recent “Longevity by Design” podcast episode, Joan Mannick stated that the dose equivalency of the two is very similar (when accounting for the better exposure/absorption of everolimus compared to rapamycin). So according to Mannick, one does not need to take more everolimus to get the same equivalent effective dose.
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