I understand the general consensus around dosing for Rapamycin is 6mg once a week for six weeks followed by a four week break. This is to prevent mTOR2 inhibition.
But I wanted to know what opinions and evidence there are for varying this pattern. For example assuming the six weeks on four weeks off is fixed, what happens if the dose during this time is varied, say taking 20mg once a week, or 8mg ever day for the entire 6 week period.
Could you knock out mTOR2 if you followed the latter reigeime within the 6 week period?
There are different regimes and schedules. Rapamycin directly does not inhibit mTORC2 and even chronic (every day schedule) does not inhibit it in all cells.
In mouse studies rapamycin was administered daily, but does make mouses (pre)diabetic and raises blood lipids. Daily schedule may make organism more susceptible to bacterial infections. In dog study they used two/three or once per week schedule, but dogs metabolize rapamycin much faster than humans. In dog aging project schedule is once weekly. So really taking rapamycing and determining the right schedule is walking a thin line between unwanted side effects and hopefully receiving the benefits. Some people use two weeks in between doses but take larger doses. Some use it daily for a period but stay off for a certain period (two weeks on / two weeks off or similar pattern). It is also highly individual on sideeffets. Blagoskonny also proposes that different schedules would be used in prevention of different conditions, but made no comments on what conditions require different schedules. Higher doses mean more side effects and some on this forum have observed that they get better results in terms of biomarkers with low or median doses. Breaks in schedule as you are proposing are not really common among the community here from what I read. I am currently taking 5 mg weekly for 5 months, will do a complete blood tests in September and at that time I will reconsider my dose. I am playing with idea of taking it for two weeks daily (1mg) and two weeks off as my main benefits I am observing are probably due to inhibition of pro-inflammatory factors in autoimmune conditions (joint pain, skin inflammation, allergies…) and weekly schedule definitely seems to help but want to see if that schedule would give me more benefits as they would be inhibited for a longer period at a time. So as you see schedule and dose seems to be really personal as we really have not enough human data for prevention and longevity.
Hope this helps a bit.
I personally did Levine biomarkers and Aging.AI 3.0 biomarkers. Unfortunately I did not do a comprehensive lipid panel including lipoproteins, which I think could be useful in addition to that. You also need some insight into metabolic health, so sugar, insulin, HbA1c etc. should be useful as well.
Attia proproses this biomarkers to test.
Stating the obvious here, but at this early stage pretty much all recommendations by anyone (even the most expert) are merely opinions. But it’s good to hear many opinions/viewpoints to stimulate our best judgement for our own dosing choices. I just started taking Rapa, but definitely plan on taking prolonged breaks periodically. I’m attracted to the idea of cycling mTOR1, not shutting it down permanently. It seems mTOR1 has important roles to play in staying healthy, so I’m wanting it to be in full force from time to time. Perhaps we evolved with the expectation that mTOR1 would naturally be downcycled periodically and our bodies take advantage of those times for repair/autophagy-type activities. Also, the fact that even 7 days after taking Rapa, there is still potentially significant Rapa still in my bloodstream makes me think occasionally it’d be good to get that down to 0% for awhile.
Well, if you think about it, our ancestors had times of scarcity/famine. They needed to ‘fast’ for days or weeks on end when no food was available. It makes sense that our bodies developed a survival mode that helped us through the famines our ancestors experienced by upregulating autophagy and storing fat.
Also, my friend who is an incredibly intelligent biologist stated that humans may have had genetic traits that allowed us to live a lot longer (among other advantages) in the past. However, many of those traits required a lot more energy to maintain. These ancestors with high energy requirement traits probably got wiped out in one of the many famines in our history as they could not get enough food to keep themselves alive.
Now that we have plentiful calories, we can allow our genetics to re-develop traits that may use a lot of energy but may provide us with helpful advantages. Unfortunately, genetic engineering is frowned upon, and it’s probably too late for anyone who is reading this forum anyways.
tomorrow will be my third weekly dose of R 2, 3 and tomorrow another 3 mg , I’m 77 mostly healthy but arthritis in a couple of the fingers I rely on as well low back and joint pain . I was shocked after the first 2mg how fast that this various pain dissipated , no side effects only positive then week 2 and 3mg I had a headache all that day , I didn’t know what to expect the following day , it turned out to be normal feeling good .
I decided instead of moving up to 4mg stick to 3 again to see what side effects accompany it
Yesterday (day 5) and today I feel the perceived “effects” wearing off , slight joint pain returning , finger soreness ,
So I am really looking forward to 3mg in the morning .
with all the discussion of taking a break after some weeks of R ,
I am wondering do others have experiences like I where the pain and probably inflammation is reduced after R then comes back before the next dose ?
Or do these beneficial things build up and stay with longer time / higher dose ?
at this point the question is for me , and this is not having had blood tests done as of yet …is why would I want to not have a weekly dose ?
Are you on a daily dose or a weekly dose? Not clear to me. In any case, if you have chronic pain/conditions already, maybe a daily dose until stable and improves? I started a daily dose of 1mg for psoriasis and it helped enough over a month’s time so that I am on a weekly dose of 4mg for maintenance or whatever.
Jonas , weekly , I guess technically I have chronic pain but I have lived with it for sometime , its not debilitating , one finger is bent a little etc I still keep active , resistance exercise hiking etc
its good your Ps cleared up and now only the weekly 4 to maintain ?
have you had a blood test ?
Why take a break? I don’t think that’s necessarily “common knowledge.”
I was up to 10mg per week, but my LDL cholesterol had risen sharply when I had my last blood test done, so I lowered it to 7mg per week. I’ll test every 6 months and if lipids are still elevated, will continue dropping dosage. (Everything else in the blood test had improved, though!)
When you say enough, what do you mean? It cleared completely?
I don’t have psoriasis, but my father does. I have just sometimes bad flare-ups of seborrheic dermatitis that is sometimes borderline psoriatic in appearance. I can keep it under control most of the time with little ketoconazole cream and when it is really bad (usually in dry cold weather and surprisingly in summer when I swim in sea a lot) I add a little hydrocortisone cream twice weekly. With rapamycin I have noticed that I almost don’t use either any more. I almost had a period of few weeks without any symptoms… I have researched some and found that IL-6 and IL-17 (and other e.g. IL-17-23 axis) proinflammatory factors play a great role in body’s overactive immune response that causes it. Funny enough, I found similar statements are valid for psoriasis as well. Since rapamycin inhibits proinflammatory factors I was thinking maybe my seborrheic dermatitis is responding to rapamycin, but could not find any pattern. At the beginning I had a terrible flare up, followed by weeks of almost clear skin, now it appeared again, but not really in any serious capacity. So that why I was thinking that I would change my schedule to daily rapamycin, to see if seborrheic dermatitis would respond better. It is really reassuring to read you experience with psoriasis and that after response you are able to maintain it with weekly doses.
Are you using rapamycin externally in the form of lotion or spray? Rapamycin has done wonders for my skin. In addition to clearing up my recurring actinic keratoses, it has cleared up the former rough patch on my scalp and minor seborrhea.
Not yet. I did not find time to do it… have this in the back of my mind. I have seen your photos and your skin really does look amazing after using rapamycin lotion.
After 2 years on 6 mg a week I stopped for 6 weeks. I noticed inflammation coming back, lower sleep quality, and less optimal digestion/ elimination. Those are all things I noticed having improved when taking rapamycin. Everyone’s different and there are probably lifestyle changes I could make to make those changes more persistent. But that was my experience.
