All true, but sometimes you have to get data (however imperfect) from any source available… and its helped get other groups interested in doing real clinical trials of rapamycin, so it helped kick-off the movement.
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People with severe COVID infections simply cannot take the drug continuously. So, apart from the continuous-use subgroup where some data showed statistically significant differences, comparisons between all other groups did not reach statistical significance. This paper essentially says nothing. Of course, if it serves as a catalyst for many subsequent rapamycin trials, then maybe that’s its only value. But people’s attitudes toward different trials are strikingly different: they staunchly defend a positive study, even a survey with serious design flaws, yet they are clearly resistant to that negative RCT I just mentioned. Well, I really do feel this unspoken rule deeply. But maybe it’s because I’m still young; perhaps after being beaten down by society a few more times, I’ll get used to it.
Of course, this survey study is not a Chinese paper. Excluding the possibility of data manipulation by the authors, if another study replicates it, that would prove it is indeed valid. One paper showed that, compared with patients receiving other regimens, those receiving an mTOR inhibitor as part of their immunosuppressive therapy had a lower risk of developing moderate or severe SARS‑CoV‑2 infection (OR = 0.8, 95% CI: 0.21–0.92, P = 0.041). This repeatedly supports that rapamycin can reduce the risk of moderate or severe SARS‑CoV‑2 infection. I just want to say that I am actually very objective.
The trial should at least have included an aerobic test. It is well known endurance adaptations interfere with strength adaptations. I’m not going to get a chatgpt answer but virtually every endurance coach advises to separate strength and endurance work by at least 6 hours.
And body builders are not necessarily the longest lived people unlike some endurance athletes.
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I don’t see what the issue with the study is here, both groups had the same aerobic interference.
Could be that adding rapamycin pushed more towards endurance adaptions, which are actually good for longevity but he didn’t test for that
But then, that would be another study. This study was about strength training adaption with and without rapamycin. They were not interested in aerobic adaptations.
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He had a 6 minute walk test. That’s about as endurance as it gets for sedentary people in their 60s.
That’s an odd thing to say. Why wouldn’t increased frequency increase benefits, up to the point at which it starts causing a significant increase in side effects? In general, for all longevity interventions, you want the highest frequency that doesn’t cause negative effects. Otherwise you’re missing out on valuable opportunities.
For things worth cycling, like rapamycin, it makes sense to allow things to get back to baseline between doses and then take the next one. It’s somewhat similar with exercise. If you train a muscle group with heavy weight lifting, the stimulus for growth is maximized for roughly the first 48 hours after the training and then sharply decreases. 4-7 days after training any stimulus is almost completely gone and you need to train again to get another stimulus. If you wait and train only once every two weeks or once a month you waste a lot of time that you could have been stimulating growth because you’re only getting growth stimulus for a few days once or twice a month. Of course if you train too frequently, like every day, then you’re sending a stimulus when the system is already stimulated and not back to baseline. But it’s clear that the optimal frequency for gaining muscle is to get another stimulus very soon after things are close to back to baseline.
In case of rapamycin, if taking a dose of x mg leads to no significant side effects when taken once a month, and leads to the system going back to baseline long before the next dose, then the optimal frequency is probably considerably lower than once a month. The exception would be if you took such an incredibly massive dose that you still are not back to baseline after close to a month.
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Dr. Christin Glorioso does her typically excellent in-depth review and synopsis, of Stanfield’s study. Do rapamycin and exercise combine to improve function and reduce biological age? Her conclusion below:
RAPA-EX-01 establishes that the pharmacology of weekly rapamycin does not cleanly separate from anything else happening during the week, including exercise. With a 62-hour half-life, drug levels remain meaningful at the next training session, which means the cycling hypothesis as commonly formulated may not be testable at this dose and frequency. The next generation of trials may benefit from larger subject numbers and longer study duration. For people considering rapamycin specifically because they think it will help them get more out of training in their 60s and 70s, the current human evidence does not support that use.
Well designed clinical trials, such as this one, are the most important tests that we can run to move the longevity field forward. This study has added to our knowledge of the benefits of rapamycin.
I have trained for endurance events while on rapamaycin. I have generally stopped 5-8 weeks before the event. It is tricky as training for endurance is mTOR inhibiting. But I do feel a boost after stopping. Last year the “boost” lasted well beyond my training period. I wasn’t training yet my RHR continued to lower for weeks after and finally bottomed at 40 BPM. My 40 RHR stayed at that level until I started Rapamycin again - and I went up to my typical RHR of 50. In addition, I bulked up. My wife commented on why did I look so buff (her words) as I hadn’t hit the gym over the summer. I didn’t feel stronger but I was heavier and had hypertrophy. A lot of room for self-experimentation in my view.
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Washington Post article:
A cheap drug used by longevity enthusiasts may have a surprising impact on exercise
Researchers anticipated rapamycin would enhance the effects of working out, while also initiating health improvements of its own, but that wasn’t the case. […]
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Using my own N=1, I am pretty sure Brad got it wrong… or maybe it’s just he looked at the wrong things. Matt Kaeberlein says the problem with research is we are looking only in the light of the street lamp – what we already know… missing so much more outside of our knowledge.
Strength is not merely muscle size… but bones with connective tissue ligaments, and tendons. Without a doubt… my strength has a least doubled… not while on Testosterone… I hit my strength limits on TRT in a year, but once I was on rapamycin… I was able to up the weight load and repetitions, consistently every 3-4 months.
Sadly, I think his study has set rapamycin backwards, was too small of a study size, not long enough time for the study to tell the whole story, and looking at the wrong end points. Thus creating more confusion and requiring more money to correct. Even Matt who was involved seems to hedge the resulting conclusion might not be accurate. Brad tried using his own limited money… sweet… but lacked power. More harm than good.
Actually, I time my rapamycin dose so that I do my evening workout… eat a big steak dinner then take my dose before bed and I don’t excerise the next day. But, I already only exercise every other day. I just synchronize work to hours before my dose.
Hopeful that the University of Arizona’s 12 million 6-year rapamycin human clinical study with 750 participants will provide solid information.
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“Stanfield said. The effects weren’t large, but “the signal was definitely in the wrong direction.”
IMO: Rapamycin helps preserve muscle mass and delays sarcopenia. The study wasn’t large enough or long enough to verify this.
My own experience is that it may blunt exercise results in a small way, like statins.
Until he publishes the final results and we are able to parse the results, we won’t really know how big the effect is.
As I previously posted, as a result of this study, I am going to a once-a-month regimen.
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You’re getting great results but you can’t be held as a model because of your mix of high level testosterone replacement + recently HGH. I should think either of those can counteract the “wrong direction” observed in the rapa subjects. He didn’t get anything wrong. He merely reported on the data collected.
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True Medaura, and I did say and @LukeMV has alluded to the synergy of multiple things that can lead to positive benefits. I did preface that my TRT had been in effect a full year and I had reached my maximum performance - only to find I could go significantly higher in strength once on rapamycin with a steady increase to my now current maximum. I am of the belief that TRT and Rapamycin in tandum is giving a great balance. But, rapamycin increased my strength. Now exploring if I can squeeze a bit more strength using Maraviroc.
Like @desertshores I was indicating the trial wasn’t big enough or long enough. No doubt from Brad’s own statements was due to cost. Which I think skews the results - nice try. But not enough to really tell us much. So often the trials like PEARL using compounded rapamycin - offer hope only to get it wrong in potency or some other limiting issue. See following video it also states how PEARL got it wrong - so much effort and time wasted.
Why I am holding out for the 12 millon dollar 720 person human clincal trial that is already explaining how with these funds and a 6-year process they will get it right. Includes as speaker @mkaeberlein .
Not sure if I have seen this on the rapamycin.news site link:
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I didn’t contribute to fund his research project because I did not think it would give us any more information. I don’t think it has.
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my N=1 study shows that Rapa does blunt exercise for 24 hrs. I take a dose on an empty stomach which seems to increase effects compared to taking dose with food. Seems like taking anabolics like TRT & HGH too close to Rapa dose may blunt the effects of Rapamycin.
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Exactly… my dosing of TRT is 3 days post rapamycin dose. And 4 days before next rapamycin dose. Skip HGH on Rapamycin nights til next night.
Hi All, I skimmed this thread in hopes of a consensus on dosing perhaps changing from 6mg/wkly to 6mg every other week or similar?? Desert changed to monthly…
FWIW I have lost weight and grown alot of muscle on 6-10mg / wkly, but I’m using many strategies; TRT at 1000 free T, HGH secretagogs, etc. kaatsu.com C4 etc
Does 6mg every other week sound like heading in the right direction vs weekly??
tnx curt
It something to do the maths on based upon the concept of the length of the trough.