Last week a scientist made a questionable claim that “if you hope to keep your muscle when you age you don’t want Rapamycin”. He based this claim on a short and small study of 8 young and healthy people (pubmed: 21430254). In this trial the participants ingested once 10 g of essential amino acids with or without 16 mg of Rapamycin. The purpose was to see how Rapamycin impacted muscle protein synthesis (=muscle building). The result showed that in the Rapamycin group the muscle protein synthesis did not increase. Does this mean that it’s not possible to build muscle on Rapamycin? No. Does this mean that Rapamycin led to an increased risk of muscle breakdown? No.
The first thing that I want to point out is the difference between essential amino acids and Rapamycin. The first triggers anabolic processes in the body. Like muscle building. Rapamycin on the other hand inhibits anabolic processes and stimulates catabolic processes instead. So taking essential amino acids and Rapamycin at the same time is like pushing the brake and gas pedal on a car. Not an optimal situation and this is not aligned with how people take Rapamycin in the longevity field. The two most common ways of taking Rapamycin is also once every week or once every other week (pubmed: 37191826) and not for every meal.
The second thing is the 16 mg dose of Rapamycin. This is almost three times higher than the most common dose regime used in the longevity field which is 6 mg once every week (pubmed: 37191826). Higher doses led to higher inhibition of mTOR. So it’s not possible from the trial data to say that the same effect will apply also to lower doses. Most likely there will be some kind of effect but how big that effect is something we don’t know. The lowering effect of muscle synthesis will most likely also decrease for every day until the next dose is taken.
The third thing to point out is that studies show that despite catabolic processes being stimulated it’s still possible to build muscle. Like one study found it was possible to achieve this on 20% calorie restriction or 5:2 fasting (pubmed: 35084574). It will go slower to build muscle but it’s possible to build. If a person has a personal goal to optimize muscle gains then I would say it’s more preferable to decrease catabolic processes to a certain level.
Last point is that chronic overactivation of anabolic processes has been observed in aged human muscles and this does not lead to more muscle. Instead it seems to lead to muscle breakdown mainly because of the lack of catabolic processes such as cell clearance and autophagy (pubmed: 29089899). There are two upcoming human trials which will see if Rapamycin can slow down muscle breakdown and improve muscle performance in elderly. Some animal studies support this already (pubmed: 31308131, 35440545, 32908143).
So “if you hope to keep your muscle when you age you don’t want Rapamycin” is a questionable claim based on not sufficient of data.
If you find any studies on that please let me know. I think I heard Joan Mannick said something about that also when Peter Attia interview her and Nir Barzilai. Would be interesting to find the studies supporting that
mTOR is not something bad and if a person gets a wound or has been through a surgery then we need the anabolic processes to heal quicker. We know that if a person practices for example CR then the wound healing will go slower. But the thing I wanted to point out was that it’s incorrect to say that muscle protein synthesis will be shut off if a person takes 6 mg once weekly. It’s possible to build muscle on Rapamycin but probably it’s not the best time to try to build muscle on the Rapamycin day. Or what’s your view on the topic?
I had been taking RAPA regularly for over a year (and some other supplement also), and for some reason I started getting noticeably weak, or weaker (Naturally I am pretty strong, but I don’t usually exercise much other than some weights and walk) so about 2 months ago decided to stop RAPA (still do most other stuff). I don’t know if it is good or bad for longevity (stopping RAPA), but I have definitely gained my strength back. The way I usually measure is by doing push-ups, which I can force myself to do 30, but I can easily do 20. Before stopping RAPA the most I could do was down to 17 (from 30) and that’s a big drop. Just yesterday (2 months after stopping Rapa) I tried, and I was able to push myself to do 25 (almost where I was before).
It could actually be just me but have come to the conclusion that if you do not regularly exercise and you do RAPA weekly most likely you will lose strength and that has to come from a weakening of the muscle. Now, I’m contemplating of doing RAPA maybe for two weeks on and 5-6 weeks off and see how it goes. We are different and obviously this is anecdotal and n=1 but thought it is worth sharing. I know we are here because we are all in Fanclub of RAPA and it hard to be objective against something you believe in, or you like, but it would be interesting to know if anyone else has noticed a loss of strength (relatively speaking) while on RAPA.
Whomever did that “study” certainly didn’t do their homework on being able to show anything (except to generate a news blip).
You’d actually need to do an RCT and have individuals do similar workouts (or better yet use individuals as their own controls) and give them some months of standard dose Rapamycin and see the actual outcomes, with them not changing diet, and with have a consistent workout regimen - then same off of the rapamycin, with 1/2 the group starting with placebo and the other 1/2 with rapamycin, then switch.
This MPS stuff doesn’t relate to long term outcomes or even what happens as MTORC1 is no longer inhibited and a likely brisk rebound occurs.
What a waste of time not designing a “study” to show anything at all, and then thinking you’ve demonstrated something.
That hasn’t been my N-1 experience as a menopausal female. I’ve been on rapa 15 months now and and have built muscle and bone mass during that time at least according to my smart scale and mirror.
My muscle mass is up 5 pounds, bone increased by .4 pounds while weight is virtually the same at 102 pre rapa and 100 currently. I don’t think he’s accurate in his claims. Fwiw I can provide screenshots of my smart scale readouts for comparison if anyone is interested.
Yes sir. Prior to rapa I only basically did sprints and walks in my weighted vest. After about 6 months of being on rapa I felt good enough to start some weight lifting. I’m very much a rookie but it’s still helping. It seems pretty important to me for aging well. Frailty is one of my biggest concerns tbh.
In my way of thinking I suspected that RAPA without exercise is probably not a winning combination. So, If you going to do RAPA you need to exercise regularly, and based of your experience that seems true. Even though that is n=1 plus you are e female, but It would be interesting if male members in these boards felt same results, getting more muscle/stronger while on RAPA and exercising?
I’m starting to believe that if you are going to do RAPA you must exercise. Obviously, exercise is good Rapa or not, but if on Rapa it almost seems like a must to me.
That seems reasonable to me. I’m just doing what I can now to set myself up to be in a better position in old age since I previously failed to do so. I suppose it’s better later than never and thankfully it seems to be working.
I take 10 mg sirolimus once a week combined with cr. I have been doing so for 5 years. I do 4 sets of pushups with the last set to failure daily. There is no negative impact for me on a number of push-ups due to rapa except of on the second day after taking rapa, it is a bit harder to exercise and I’m only able to do 5% fewer before the failure. Otherwise, the number of push-ups remains steady with some slight upward trend.
I have been on rapamycin for 2 1/2 years and I have added muscle mass.
Whether or not you take rapamycin you will lose muscle mass if you don’t exercise.
I’ve complained many times before about the idea that you can somehow bank up fitness for old age. I assume this is the viewpoint the original post is coming from, and there’s not really much evidence to support it.
If, instead, we take the minimal evidence backed claim that one should maintain full physical function throughout life then the complaint here becomes a non-issue for those of us who are in good health. We can simply keep track of our fitness, and if we start losing strength (which is a slow process, and anecdotally uncommon) then adjust dosage or discontinue.
People who already suffer from frailty or for whatever other reason need to gain strength quickly might have a more difficult decision.
I’m 165 lbs, I do 8 mg every 8 days. This basically has me ~40 hrs or so over a level of 3, and the other 6 days in recovery.
I can let you know what I recommend for my patients - again, only theory, no proof - but safety is important. I don’t like to see more the 30-35% of the time that the level is >3. So I have some folks who want a high level, theoretically for neurocognitive decline - some of them get a level at 20-24 hrs, then a repeat in 48 hours so I can assess half life and then we can do the math. I have some on dosing that has a level ~9-10 at 24 hrs, then a metabolic half life of 40 hrs for example - so there will be ~4 days or so with a level >3, in this example, so I’d not want them dosing more often than every 12 days if that is what the math worked out to.
@SNK Thanks for sharing! One potential thing is that you may push things to much when you take Rapamycin if you already are taking lots of other things. Here is an interesting timeclip from the researcher Brian Kennedy on the topic.
So I think it’s important to find different ways to measure if things are going in the wrong direction. Max push ups is one way but it’s also good to have other measurements. On below page you can see some measurements I use and I felt progress on Rapamycin. One thing I have recently added is bar hanging also as one measurement.
@DrFraser It was a randomized trial and a wash out period of 2-4 weeks between each arm. It’s a interesting data point but I feel as you that they could have improved the trial much more in different ways.
@blsm Thanks for sharing. Please share your measurements
@JKPrime I also practice CR combined with Rapamycin. But I would classify it as mild CR. How big CR are you practicing?
@desertshores How do you measure that you have added muscle mass? Dexa scan or in some other way?
@Lost Well said about the thing that if things are going in the wrong direction then adjusments needs to be done in for example dose or time interval or even to stop taking it.
@DrFraser Very interesting dose regime to use 8 days interval! That way the dosing weekday differs from one week to another. There is something I like with this. I need to think a bit on it.
