Thanks for sharing. This is interesting.
This is not consistent with what others have observed. Some people even notice more energy in the gym when on rapamycin. So I think your case here is an exception. I say that as someone that has read hundreds of anecdotes on rapamycin.
I agree that for you this may be the case given your sensitivity whereby you feel weaker after taking rapamycin. That said, I think for the vast majority of people taking typical longevity doses it’s not true that rapamycin is incompatible with maximum hypertrophy. My reasoning is that it’s very rare to experience weakness in the gym after dosing and almost completely unheard of to notice difficulty gaining muscle mass when on rapamycin. I will say that this caught me by surprise since mTORC1 inhibition should reduce protein synthesis and slow down muscle growth. But for some reason that doesn’t seem to matter much. Maybe other pathways than mTORC1 are more important for muscle growth in response to training, or maybe the rapamycin increases the sensitivity of the muscles to increased mTORC1 (note that chronic mTORC1 activation leads to sarcopenia in rodents IIRC).
I wouldn’t doubt there is a slight decrease in gains, like there is with metformin, but it’s small enough that it wouldn’t matter to anyone who isn’t a professional bodybuilder or strength athlete. Plus a lot can be overcome with anabolics, and we have the ability now to run them quite safely.
But if you read what I said very carefully, you’ll note that when I took a “typical longevity dose,” I didn’t have much trouble. Most here take something like 6mg a week. My experience at 6mg a week was more typical.
I also maintain that my weightlifting regimen is more intense than that of most people in the longevity space. I’m usually training like a bodybuilder and am under the supervision of a rather elite level coach. I’m typically doing resistance training 6-9 hours a week, 5-6 days a week when hypertrophy is the goal. My position is that rapamycin is incompatible with a program that is optimized for maximum possible hypertrophy, not that it is incompatible with a typical recreational weightlifting program. These are very different things.
Very few people taking rapamycin are truly trying to optimize for hypertrophy. Are they eating 5-6 times a day in a caloric surplus and trying to exceed specific leucine thresholds? Most likely not.
You said that after 6 mg you were “weaker the first session of the week, but I did better as the week went on.” I don’t think that’s typical at all, although one could argue that is just a small effect that many people not so serious about training wouldn’t notice or mention. Many people here do take much more than 6 mg every other week. Almost none of them say they notice effects on performance in the gym after dosing. But again, most are not as serious about training as you are.
I bet it is. I would say the same. I’ve been lifting weights since I was young and in my early years hypertrophy was my main goal and I always trained very intensively because that’s what you need to do if you don’t use gear and don’t have very good genes to gain muscle.
True, these are very different things. I would say whether it’s compatible depends. For people training 5 days a week like you it’s hard to space it apart from workouts which may or may not be necessary to maximize gains. I’m not confident it matters, but I wish we had more data here.
I don’t necessarily think rapamycin is detrimental for those eating frequently to maximize muscle gains. I’ve seen studies showing that eating very frequently doesn’t increase anabolism compared to eating fewer times per day, provided the total daily food intake is the same in both cases. In fact, I’ve seen evidence that if you eat a meal and then eat another meal 3 hours later, the mTOR increase in the second meal will be blunted because of the first meal. The increase in mTOR during the first meal desensitizes you to mTOR increase. That’s probably one reason why eating 6 times a day doesn’t result in more muscle gains than eating 3 times a day if you eat the exact same amount daily overall. If it were that easy and mTOR didn’t get desensitized you could just drink leucine all day and make massive gains from having mTOR highly activated all day, but it doesn’t work like that. Rapamycin might actually sensitize you to mTOR resulting in greater increase when the effects of rapamycin wear off. So the rapamycin might slightly reduce anabolism in the first hours and then increase it later resulting in close to net zero effect.
Btw an n=1 on hypertrophy. I’ve been lifting weights very hard for 25+ years and my weight training is optimized for hypertrophy although longevity is my main focus. I have not noticed any effects of rapamycin on my ability to gain mucle. If I increase my calorie intake I will gain as much muscle as before. If a negative effect on hypertrophy is there, it’s much smaller than I can notice. And note that I’m someone that writes down the reps and weights I do each workout and try my best to beat the last workout, so I am a candidate for a person that should notice if there was a difference. I should add that I do avoid taking the rapamycin on workout days.
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Beth
#127
@Olafurpall and @AgentSmith
I’m only asking out of curiosity what two people who are trying to max out hypertrophy are doing….Note, I’m not trying to stoke a protein war 
I personally aim for 1.6grams per kg (I’d aim for 1.2 if I were not vegan). I base this on listening to Stuart Phillips. But, people like Layne Norton will say 1.6-2.0grams. Layne also says you can probably eeeek out some more muscle if you keep going higher and higher, but it’s just that the average person wouldn’t notice.
I also tend to believe Valter Longo that too much protein has the potential to be cancer promoting, but I know that neither Norton nor people like Attia believe that. I have not personally seen those studies but simply trust Longo has.
All that is to say I’m curious how you two look at the topic. (Or anyone else!).
I also realize some just enjoy the taste of meat and don’t like veggies, so they might eat a lot more protein that is not related to muscle gains. I’m only asking about muscle here.
The cornestone of hypertrophy for me personally has always been heavy weight training. By that I mean I train intensively doing sets of somewhere around 6-12 reps to failure or no more than one rep shy of failure always trying my best to increase the weight or reps if possible from workout to workout. What I eat has always been secondary in importance with the exception that I need to eat more calories to gain weight and less to lose it. The macronutrients are of much less importance.
When younger I used to eat 2 or even 2.5 g of protein per kg. Many years ago I reduced it to around 1 g/kg for longevity purposes. I never noticed it being harder to gain muscle on the lower amount of protein. Maybe it would make more of a difference if I were older, I don’t know, but I think the effect of higher protein on hypertrophy has been exaggerated greatly. The weight training intensity on the other hand has a very noticeable effect on any gains. If I exercise with less weight or don’t go close to failure I will notice much less muscle gain. In my case the intensity also matters much more than the volume of training. By volume I mean many sets of each exercise I do each workout or each week.
Many people train 5-6 days a week and do up to ten sets per muscle group each workout. I have gotten my best results doing just two full body workouts a week consisting of two heavy sets for each muscle group. That way I’m training each muscle group twice weekly. I’m a bit of an outlier here though. Most people need a bit more volume than that to get better results. They will do better doing maybe 3-4 sets for each muscle group.
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Beth
#129
Thank you, that is all helpful and interesting.
And to your point, I should note my 1.6 is also based on me being much older than you are (59). I have heard quantity is not nearly as important for you youngins! I am my happiest on days I don’t hit my number because there are so many beans a girl can eat
I do two workouts with my PT where he hits everything. He is even able to bring me to swearing at him with only body weight by asking me to do some voodoo stuff. We are continuing to increase my weights, too, which is exciting (new PR last week, baby! ) Then I do one pilates session… it does work my muscles but not to the same degree.
Btw, just a fun fact, and sorta off topic, but just yesterday I discovered with him that I now find it hard to blow up a balloon!!! He asked if I could and if I wanted an easy balloon, I said don’t be ridiculous and hand me the big girl balloon! Ha, joke was on me! He had me do that and exhale while not letting any air out in order to get my ribs down, but holy moly, who knew blowing up a balloon can become hard… I used to blow up rafts!!!
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Yes, there is some logic and evidence behind quantity being more important for older people. A main one being that people just get less sensitive to anabolic and catabolic stimuli as they get older such that a young person will get a stronger mTOR activation in response to protein than an old person.
On the balloons. Blowing up balloons is probably good exercise as one gets older. It can help strengthen the breathing muscles.
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Yes, exactly, that is part of what I’m saying. I don’t think most people are either taking enough to see an effect or they aren’t in tune enough with their performance to notice the effect. I will notice one rep or half a rep or a change in reps in reserve. I keep as many variables constant as I possibly can: tempo, rest between sets, etc. A recreational lifter who exercises for health isn’t likely to notice a difference.
Right. Easier when I’m doing a 4 day split, no real issue with a 3 day split, but when I do 6-day PPL, it is harder.
I am open to this thought. I did not run the experiments in an extreme bulk with asany meals as I’m eating now.
This is where I defer to the collective experience of coaches who have tried different approaches and tend to come back to multiple meals a day. I trust them more than studies because studies are often executed under different conditions or with the wrong population. When studies that last a few weeks conflict with years of trial of error by elite practitioners, I discount the studies.
On a practical note, it’s hard for me to consume and digest nearly 4000 kcal in just 3 meals. Maybe others can manage it but it’s easier for me to break it up.
I’ve thought about that, even commented on it on the forum, but do we have evidence that it’s true? I’m open to the hypothesis and am curious about it.
What is your maximum serum level when you train? That is a key part of my thesis.
Let me ask your opinion on what I could do with a 6 day split given that, in my n=1, I am convinced I notice a difference and am unwilling to sacrifice performance. 6 days is typical but not the only split in the rotation - everything is periodized - but I’m running it now. I don’t want to blunt MPS from my last workout, so I want to wait at least 24 hours post-training to dose. I am still thinking about whether a micro dose at the 36 hour mark would do anything worthwhile. Maybe 3mg.
Ah, you have revealed perhaps part of why you see no interference!
Yes, I think you are an outlier in terms of volume. Personally, I recover better from PPL than full body, and can do more intense workouts if I don’t do full body. Upper/Lower is in the middle.
When I listen to elite coaches converse, they often dialogue about the variability that they encounter across their client bases. It is enormous. Another reason why I am skeptical of studies.
Don’t do what I’m doing. I am temporarily on 4g/kg for a few weeks. The problem is that if someone is in a surplus, and they want calories to be readily available for energy, then they want quite a few carbs and to keep fat pretty low. This assumes good insulin sensitivity. Push carbs too high for too long, and one will lose insulin sensitivity. This places a cap on carbs. That means some excess calories must come from protein. Though it converts by gluconeogenesis, the process is slow and doesn’t spike glucose.
You, however, are not bulking.
