I just switched to 6mg every other week.
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That would be interesting and an improvement in design if they followed people up so much later. I still don’t think you would detect an effect. I think it’s a stretch to expect to detect some long-term benefits after just 12 weeks of treatment considering that that’s not even 0.25% of the lifespan of humans.
That’s not a bad idea. The problem with that idea is that we also don’t know what the optimal regimen of fasting is for longevity for humans.
I don’t think it was well designed to answer whether rapamycin is beneficial for longevity. I think it was well designed given the funding limitations. However, he didn’t have enough funding to do a study that gives more answers as to whether rapamycin slows down aging or not. For that he would have needed a longer duration study. Also, the training regimen was far from optimal but it would have been more complicated and expensive to have them on a proper resistance training program. The chair stand up test is practical but a poor test if the goal is to test an intervention that gives a strong stimulus for muscle growth and strength. For some of the participants, standing up from a chair may have been hard enough to recruit type II muscle fibers and sent a strong stimulus for muscle mass gains. For others it may have been too easy to send a strong stimulus and for them the exercise was largely endurance exercise.
If we assume for the sake of the argument that enough time to recover is the other half, why would you assume that you need months of recovery between bouts of doses? The mouse lifespan studies certainly don’t have long periods without rapamycin for recovery between doses.
That I agree with, but that does not mean the period between doses needs to be 42 days (which you seem to have settled on) for it to count as fluctuations between anabolic and catabolic. Even with very high doses, levels typically drop below that which inhibits mTOR significantly within a week.
No we don’t. I would argue that weekly is not necessarily too frequent, depending on how many days the catabolism is enhanced. If you consider rodents in calorie restriction studies, they are basically strongly catabolic half of the day between their daily feeding periods and that certainly isn’t too frequent for them.
I think it’s a matter of different time frames. In the short term, rapamycin will likely reduce muscle mass. But over the long term it will have the opposite effect. That effect may not become apparent until after decades of taking it. It’s reducing the mTOR overactivation which is a part of what causes anabolic resistance later in life. If you’re looking at short term effects you’re looking at the wrong things.
If you have been dosing weekly, without any problems, then the most obvoius simple starting point is to double the dose and take that every other week.
I think he is being overly cautious, which makes perfect sense, since someone in his high status position wouldn’t want people copying his recommendations in case he turns out to be wrong.
Interesting. FYI anecdotally your experience is rare however. I’ve seen hundreds of anecdotes on the use of rapamycin and it’s not common for people to notice negative effects on muscle strength or gains. Of course the effect could be common but just too small for people to notice.
I must commend you here by saying that I think your approach here is one of the most reasonable I have seen.
I’m pretty sure chronically activated mTOR does impair their ability to put on muscle, it just takes far longer than 12 weeks for that effect to appear. It’s years if not decades of overactive mTOR that appears to be a part of what ultimately leads to increasing anabolic resistance at old ages. I would be surprised if that would be reversed close to fully by suddenly blocking mTOR over the short term at old ages when much of the damage is already done.
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My comment was specifically about weekly dosing for recovery. I don’t think you need months for recovery.
When looking at my health markers and physical performance over the last 3, 4 years, I think I’ve had enough mtor inhibition. At my age, I’m not sure that much inhibition is worth it yet. So now I’ve decided to try to compress my catabolic phase into 1 continuous block, and do the same with my anabolic phase for simplicity.
I’m also looking at the mannick study where they administered everolimus for only 6 weeks, and the effects on PD1 expression in cells stayed around weeks after administration. The follow-up PROTECT study also somewhat supports that.
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For anyone switching to a 14 day schedule and is also on Repatha, it just occurred to me it might make sense to take them on the same day. AI agrees.
The only negative I could think of with a higher dosing schedule is the potential effect on lipids. If I take them on the same day, my repatha will be strongest to hopefully counteract any potential damage.
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Yes, I agree it’s a long term agent. Short studies don’t tell us much.
I remember when I started taking rapa, read to not expect any benefits to even start until after 3 months. Noticeable benefits start to show at 6 months.
I think it’s a matter of different time frames. In the short term, rapamycin will likely reduce muscle mass. But over the long term it will have the opposite effect. That effect may not become apparent until after decades of taking it. It’s reducing the mTOR overactivation which is a part of what causes anabolic resistance later in life. If you’re looking at short term effects you’re looking at the wrong things.
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Unfortunately nobody has been on it for decades - so there’s no data to measure.
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Ah, transplant patients?
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Yes, some transplant patients could be a little under three decades on it - it was first approved in 1999 - but transplant patients are a bad model to measure anything in healthy population.
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They’re taking much higher doses (in addition to having other health problems), so those taking it for longevity benefits at lower, pulsed doses likely couldn’t extrapolate from that population.
That said, if we start seeing transplant patients with decades of rapamycin use living past 100, we will likely want to start using doses like those transplant patients 
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Welcome back Peter Attia… who is off supposidly rapamycin?
Or, was that just a ploy to not seem so woo-woo to ABC networks to win a healthcare contributor role on the station… which is now a mute point.
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Keep in mind that the Rapa group gained +28% chair stand reps, and the control group gained 46%. So even the 6mg/w Rapa didn’t negate all gains, and they still got a pretty big benefit from training.
Also, keep in mind that the sample size is TINY. Looking at the plot in Figure 2B, there are two placebo group participants who seem to have DOUBLED their performance in 13 weeks. That has a massive effect on the group means. @LukeMV I reckon you and I have been training a while, and I bet you can’t recall the last time when you doubled the number of reps to failure in 13 weeks!
For myself, I am totally unconcerned that Rapamycin is in any way getting in the way of my training. (That said, I take 2mg/wk, which is a low dose but has been enough to move several biomarkers).
Extremely well said!!
Interestingly, Rapa shortened lifespan in obese diabetic mice. (Sataranatarajan et al 2016)
So there might be something to be said for underlying metabolic health to also play a role.
It should be noted that the pneumonia case was in a patient who had taken one dose of Rapa. I feel that is more likely to just be a coincidence than immunosuppression.
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@relaxedmeatball thank you for the comments and they make a lot of sense. I’ll consider going back to weekly, but in the meantime, I did try my first larger 14 day dose of 14mg.
HOLY MOLY!!! I took it on Thursday night and have felt like the energizer bunny ever since!
I did start an experiment of taking the Synthroid brand of t4 at the same time, and I assumed that was the source of my euphoria, but Claude said nah, it was the rapa (which is unfortunate because that means this is fleeting).
I was so nervous about taking this dose but it turned out to be a very pleasant surprise. I’m used to most people saying how they get tired.
There is still a small chance it was Synthroid… I’ll know soon enough.
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Reading the past 200 comments… I need to caution against fooling ourselves. I’m not saying most commenters are coping. The criticism of the trial design is mostly valid.
But ask yourself: would you be equally critical of the design and consequently the results, if the trial would have been favorable for Rapa? Would the shortcomings be discussed to the same extend?
We are biased in favor of Rapa and similar interventions (Telmisarta, Ezetimib, SGLT2i etc.). Therefore we have to be particularly honest to ourselves.
Saying that - to give the results a more uplifting interpretation:
as discussed here, there is the open question how to bridge the rather large dose in mice and monkeys with the small dose in human volunteers (often 5 mg to 10 mg once a week). What this trial indicates: the typical dose in volunteers can produce a notable side effect seen in mice with much larger intake of Rapa. If we believe, that you can’t get the benefits of Rapa without getting at least some of the side effects - this study could be supportive of the current dose used in anti-aging.
To confirm this, someone would need to dig up a study in mice with a low dose of rapa, that didn’t result in muscle effects (demonstrating, that the trial result indeed mimics are large-dose-equivalent in mice).
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A Scott Carney interview with Brad talking about his study.
Nothing you don’t know in here, but we rarely get to see Brand in these long form conversations. He seems like such a nice human.
I’ll note that he says if we have other studies showing rapa blunts muscle growth than he would think it’s nothing we should use for longevity. I think that overlooks the other potential benefits it has… for example, IF IF IF it can prevent heart failure/cancer/fill-in-the-blank, then having a little less muscle might be an excellent trade off. And on that note, as someone who is newly experimenting with every 14 day dosing, I wish we knew how infrequently we can take it while not sacrificing the other potential health benefits… I realize we may never have these answers.
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Rapamycin’s biggest use case is slowing down cancer progression but we don’t actually know whether low to moderate doses taken once weekly or even less frequently actually do anything in that regard. Worst case, rapamycin only temporarily weakens your immune system and blunts exercise recovery effects without providing any benefit.
With SGLT2i we at least have good reason to believe that it helps with slowing down CKD progression in addition to lowering the risk of heart failure even if we were to completely disregard the ITP study.
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Stanfield’s study has degenerated into clickbait for YouTube influencers.
Someday, we will look back and think how meaningless and inadequate this small, short study was.
On the bright side, it will slow down the number of people jumping on the bandwagon and drying up or raising prices on our Indian sources.
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One thing i still don’t get is the way this study is being portrayed though. Everyone is acting/reacting to it as if RAPA was supposed to help with muscle growth. No body is taking RAPA to grow muscles; there is steroids for that LOL. what is this obsession with longevity and big muscles. If anything, it is almost common knowledge that things that help grow muscle are usually bad for longevity, otherwise we would all be jumping on the roid wagon LOL. Plus, last time I checked not many people in body building crowd are practicing calorie restriction (another longevity intervention). This study means nothing to me, and I think we should stop mentioning it unless something new comes out.
As far as I’m concerned, I’m happy with this study. Basically, It implies (indirectly) that it mimics calorie restriction and that is a good thing for longevity, But If somebody else likes to read it differently go right ahead, do as you please. So to finalize. the study is fine and implicitly showed RAPA is good for longevity, the problem is people have decided to attach their own stories to it. LOL
I haven’t changed my weekly dosing and do not intend to.
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Muscle mass is pretty important for longevity though. So if this study did in fact suggest that rapamycin inhibits muscle growth over the long term (and it did not) that would be a real downside
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Yes, but where do you guys get it that muscles continue (or should continue) to grow as people get older? It is a MUTE point; it is detrimental to growth of something that it is not supposed to grow. I think the only thing that grows as people get old it is ears. So, if someone were to be worried that RAPA won’t let their ears grow then by all mean stop using it LOL.
BTW, not only did this study suggests that RAPA inhibits muscle growth but the mechanism by which RAPA works does in itself inhibit growth, any growth, not just muscle, so yes please don’t go give RAPA to your kids and grandkids LOL. and yes, RAPA does in fact inhibit muscle growth in long term, intermediate term, short term and for as long as one will be using it, but that fact alone has nothing to do with longevity.
Muscle is important for longevity and healthy aging (no brainer there) but maintaining muscle is what it is important, NOT GROWING MUSCLE. Excuse my French but after 25 you’re growing shit, not muscle and not anything else, naturally, and if people decide they want to grow muscle that is all fine, but growing muscle has no relation to longevity.
Again, this study has nothing to do with longevity and everything to do with muscle growth, two very distinct and two very different things. How people mix them up or confuse them, it is totally beyond me.
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