Hi.
I’ve followed the forum here for a long time. Thanks for all the great info.
I decided to give rapamycin a try to increase my immune response to vaccination. I essentially followed the protocol in Mannick et al. I was curious to extend my protocol to see if it would I could potentially increase athletic performance via increased recovery, reduced inflammation, etc.
A bit of background. I’m in my mid 40s and have been an ultrarunner for almost 20 years. I have always been at the top of the field when I race the 100 mile distance. I would consider my self a high end athlete, but not elite on an international level. I feel like my recovery has slowed (yes, aging is the likely culprit) but I can still mostly train like I did 5-10 years ago. I was curious to see if low dose rapamycin could improve my recovery.
My protocol has been 0.1 mg/kg (~6-8mg) once a week for 6 weeks and then 4-5 weeks off. As others have noted, I felt really good for the first few cycles and didn’t have any noticeable side effects (including blood work). The after my last cycle (4th time on) I really noticed that my recover from long runs (20-30 miles in the mountains) takes so much longer than usual. It seems like I have persistent delayed onset muscle soreness for 5-6 days after a hard effort. Even shorter efforts leave me sore. Prior to using rapamycin, I might have DOMS for 2-3 days after a hard effort.
I do other sports as well and lift weights and haven’t noticed an effect (positive or negative).
Are there any other high level ultra or marathon runners here who are experimenting with rapamycin? I would be interested in any data that you have. I wonder if my life style and diet are already optimized and rapamycin is not providing a benefit, but rather is detrimental. Is my dosing or protocol off? Should I not take an off cycle?
Cyclist, I have been taking weekly 4 mg rapamycin+gfj for months (and before that in various other schedules) without side effects. Last month I suddenly got stomatitis so I decided to skip my dose end of February and as you can see I got a very big and sudden boost in performance according to hrv4training, then I decided to take rapamycin again around march 11th and you can see performance decreasing again. So my impression is at least rapamycin doesn’t blunt endurance training effect but it does decrease performance
Rapamycin is a double-edged sword. Though it inhibits sarcopenia “Rapamycin can partially inhibit the rapid activation of protein synthesis by insulin, growth factors, and other growth-promoting agonists”
So yes, I would think rapamycin might hurt recovery time, especially for such extreme activity that you participate in.
I go to the gym several times per week, but I do not do extreme workouts so I don’t experience any subjective difference in recovery time.
The mTOR Pathway in the Control of Protein Synthesis
The integration of rapamycin into a regimen of high levels of exercise is something I think we are still working on and trying to optimize. Please continue to test and share data.
Thanks. I have.
I agree the data are not so clear for high level endurance athletes. I for one felt like it was improving my performance at the beginning of my training cycle (lower volume, higher intensity), but I’m sure it’s having a detrimental effect on long, hard runs.
So many variables though…
hrv4training also does lactate threshold pace estimates. The app is pretty expensive (for an app) but at least for lactate threshold pace estimates you don’t need a subscription either (unlike for FTP estimates)
I’ve posted a few times about my own experience using rapamycin as an endurance athlete.
I think we have to be very careful with it as endurance athletes. I have experienced similar things to you in the past. Long term regular use seems to always catch up to you. For me, my central nervous system would seem to burn out faster and my muscles would start to become more catabolic quicker.
What made me interested in rapamycin was it’s ability to induce autophagy without fasting. I wanted to know what type of stressors this would put on my mitochondria and if could be harnessed in my training regimen. I think it can, but not in the way I originally thought.
I’m starting to test with it again based on things I’ve learned in the past. Don’t have any solid numbers to give you, but I would caution against using it as often as you are, on a higher dose like 6mg a week. I think as time went on, and the cumulative fatigue increased, your muscles would likely become more and more catabolic without the ability to properly recover.
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:
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.
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.
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.
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
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.
