#9

Here is the fundamental trade-off / balance that we are trying to identify the optimal level for: the short-term decrease in mTORC1 / muscle protein synthesis will (in the period immediately following dosing) result in lower levels of muscle growth and regeneration. But, in the long term the periodic inhibition of mTORC1 will increase the lifespan/healthspan of our muscles.

In the short term, in the few hours after (a large) dosing of rapamycin the research suggests a significant decrease in protein synthesis. If you were a younger athlete training for the olympics you obviously don’t want to do this. But at some point in your life if pure performance becomes less important than healthy longevity, it seems a trade-off will need to be made of decreases short-term performance optimization for long-term performance optimization.

And I should mention also, that for most of us who are not elite athletes competing in the Masters series, or exercising 20 or 30 hours a week, this doesn’t really apply. We are not going to notice the minor hit of a once a week or once every two week dose of rapamycin on our muscle growth and regeneration.

So for the extreme athletes the goal, if we are to shift to the longer-term perspective, is to devise a protocol that minimizes the short-term “hit”, while maximizing the long-term benefits. This is our key challenge.

Here is the main study on how rapamycin impacts short-term muscle protein synthesis:

In this study above they dosed a high level of rapamycin and then did exercise during the peak period of blood/sirolimus (peak rapamycin blood levels) which is in the three hours immediately after dosing). It seems that the decrease in protein synthesis is going to map pretty closely to the rapamycin blood levels, which we can see in this graph:


(The above graph is from the paper included in the first post of the Rapamycin Dosing for Longevity thread.)

Here are some of the studies showing the benefits to muscles of rapamycin administration:

Anyway, this is all just food for thought as the extreme exercisers in our community work to optimize their exercise protocol with rapamycin use.

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Dr. Kaeberlein's Optispan Podcast Series - Rapamycin and More
#10

I’m not a runner but I golf often (always walk, for exercise part of it), and it appears (almost certain) that RAPA has negatively affected the endurance (get tired easier) and also lengthen the time of recovery. I remember couple years back (no Rapa yet) I would take a shower when I got home, and that was enough for my recovery, felt really good after shower. Now, my muscles ache even 2-3 days after. I plan on stopping it for couple months to see if the real culprit is RAPA as i do other supplements also.

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#11

Just curious, reading your original post I made some assumptions in my head. How many miles are you running a week? Based on the level your describing yourself, I would imagine you’re running somewhere between 80-100 miles a week pretty regularly? Probably have been for quite some time?

There’s a lot to think about in that scenario with rapamycin. I think what you’ve experienced is what I would have expected. The first week, it might have even felt good as it also reduces inflammation by a lot. But, every time you take it, it makes the workouts following it harder (and I don’t really know how much harder). So you would likely need more recovery before you can go at it again.

Your already running and moving enough that you’re getting most of the benefits that rapamycin would give you long term anyways.

If anything, rapamycin might help reset some other stuff in your body that your running doesn’t normally tax.

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#12

Thanks again for all the comments. I agree one needs to decided what the purpose of taking Rapa is for. In my case, like midage_runner I was interested getting benefits of fasting with out the fasting. I’ve tried fasting in the past and I see a negative effect with performance, especially in during peak training. I feel like I have a few more competitive years of running so that’s what I’m after. Maybe after a few more years I’ll be able to accept that I’m slowing down and then focus on being able to running into late age.

midage_runner - I’m currently not a super high mileage runner. About 70-80 miles per week and yes for over 15 years at that mileage. I completely agree with your assessment and other posts.

Based on this discussion, I will stop taking rapa and see how I feel. Unfortunately, I took another dose this morning! Maybe once I start feeling back to normal I’ll try a very low dose and see what happens.

Thanks again. This is all very interesting.

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#13

Hi Ultrarapa - i have thought too about rapa as now 70 and all good reports especially for older people. I have no real issues and not taken any meds for health conditions. I run about 20 miles a week and do left heavy weights 3 to 4 days a wk. I do about 35 local 5/10k races a year. In 50s was at a pace in high 6min/mile. Then in 60s slower in the 7.5 min/mile pace. Now in 70s and in the 8.5 min/mile pace. In most races placing in the top 3 in my 70 to 74 yr group so happy about that. And thought about dosing at 2 to 4mg of rapa one a week for maybe one month on and then off 2 months and repeat. Until your comment and others I thought this would improve my endurance with getting rid of old mitochondria and replacing with new. But now thinking maybe not use rapa. Please update again in next few months about your further experiences with rapa. Thanks Michael

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#14

Its interesting. Given the data we have on rapamycin slowing muscle aging:

  1. Even with calorie restriction, rapamycin slows muscle aging
  2. Rapamycin and lean muscle - #2 by RapAdmin

It seems there is the real potential to “flatten the curve” in terms of the decreasing mile paces that runners experience as they age. Since you have so many good data points on your times, it would be really interesting to see if regular rapamycin use could hold you at an 8.5 minute mile into your 80s.

I wish some runners would test this theory out for a few years to help us understand if the animal research in fact translates to humans.

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#15

Just a quick follow up.
I’ve stopped my Rapa dosing and after a few weeks I have been recovering a lot better after long/hard efforts. I would like to do the experiment and go back on my weekly dosing, but I can’t afford to take another period of reduced recover. I’ll probably go back on once the racing season is over.

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#16

I decided to give rapamycin a try to increase my immune response to vaccination.

High level of exercise achieves both of those goals and much more.
Rapamycin may be redundant for high level athletes and impede performance, IMO.

Strategy of using rapa off season is least likely to hinder performance, I am not sure of any benefits though.

The only real study we had was done on ordinary old folks, not athletes.

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#17

But shouldn’t it be the case that rapamycin slows the decline of muscle / strength / health over time? I’m thinking of all this type of research:

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#18
  1. These are not human studies.
  2. Even if they were, high level athletes have a dramatically different physiology than say, sedentary type 2 diabetics… almost a different species.

Brad Stanfield is starting his rapa human study on muscle growth, hopefully that will shed some light.

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#19

Probably not for fit people. Here is the target population:

image
image792×91 30.4 KB

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#20

Yeah true, but at least a first study on HUMANS regarding MUSCLE growth to give us some clue.
If rapamycin actually shows muscle growth inhibition in non-athletes, then for sure athletes should stay clear. If it shows improvement, still not not sure what it would do for athletes.
So still somewhat helpful.

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#21

Yup, this is more or less the conclusion I’ve come to. I still believe there might be something to it, but I’m waiting on more studies to come out so that I can understand more.

I do think that rapa offers something for athletes. I’m taking it about once a month now at a lower dosage of 4mg. Still hits me pretty hard, I feel fatigued, then I even feel a good rebound from it where I’m super productive for a day.

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#22

I just came back from Flagstaff 7-8K feet. Did a decent bike ride of 2700 ft ascent, 18 miles about 48 hours after taking 5 mg of rapamycin. Holy crap ! My muscles never ached this bad before. I was exhausted and my HRV overnight hit the bottom. I felt worse than after my endurance race few weeks ago. This is a second time something like that has happened. Last time I tried to do intervals within 48 hours of taking rapa, I had nothing in the tank.

I have a hard time timing rapa between my activities. I do majority of my exercise on Friday, Saturday and Sunday. I don’t want to take my rapa too soon after the big efforts because I am concerned it may impair recovery and body adaptions, can’t wait too long because then I end up taking day or two before my hard efforts and I can’t perform.

Tuesday seems to be the best time, so I can recover on Monday and still have enough time to recover from rapa by Friday ! Double recovery. :rofl:

Honestly if it wasn’t for my periodontal disease I would quit it, but I am waiting for my next evaluation to see if my pockets improve.

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#23

I did have really bad peridontal disease and lost a tooth a couple of years ago. However, I have progressed a lot since.

One big thing I found was that sucking melatonin (a 10mg pill will do much that every night I am probably taking an average of a gram now) resulted in my gums not being inflamed. That is not sufficient necessarily for them to grow back, but is something that has an immediate (same day) effect. It is also a same day negative effect as it is not fixing the mitochondria in the gums, but helping them fight infection. Hence if you stop sucking melatonin the inflammation can kick off again.

This was a very visible shift from dark red to pink.

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#24

If I used a 4 week loading cycle for workouts: hard, harder, hardest, easy…I’d over lay Rapa onto the easy week (biggest dose) and maybe the hard week (lower dose). The longer the time between doses, the bigger the rapa dose I can tolerate. I don’t think I have to take Rapa all the time to get a benefit. It’s an idea anyway.

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#25

That sound like a good plan.
I stopped the rapamycin 10 days before the last big race.
It’s probably not a bad idea to adjust the dose and frequency based on current exercise regimen.

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#26

This is what I started doing. I do 4 week cycles. The fourth week is my rest week. I take it towards the beginning of that week and back off total load for the rest of the week.
If I’m running high mileage, and cross training endurance a ton, there’s just no need to take it weekly.

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#27

@midage_runner i agree. Rapamycin is a tool in the toolbag…use it where appropriate for goals and in coordination with other tools. I’m going to start ramping up my training again. I may have to backoff Rapa even more but I hope to ramp up the training load slowly enough that I can handle it.

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#28

What dosage are you guys using? I was using 0.1 mg/kg, but I was thinking about half or a quarter of that once every 3-4 weeks? Not sure it would have much o an effect, but… I’m a bit hesitant to get back on rapa given my training load, but really curious.

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