Questions About Rapamycin Experience

Hi All. Recently started taking Rapamycin and have some questions that relate to my experience that I hope you can help me with.

  1. On the day I take Rapamycin I get a surge of energy. What is that? What mechanism or process is causing that?

  2. My understanding is that during the 7 day break between doses we are “recovering”. What are we recovering from.

I’d really appreciate any input as the more I can understand what’s going the more I can cooperate with it.

Thanks

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My (not a doctor) understanding is that it’s kind of like burning the garbage that is laying around the house. It puts out usable energy.

Over time use of Rapa can inhibit MTor complex 2. You want to go the other way with 2. If you take a break and wait for complex 1 to reach a small value, then 2 will not be inhibited. The argument is whether you should take a big dose and wait 2 weeks or smaller dose and wait one. Or really small dose daily for a few days followed by a pause. I think all of these methods work. I go by my side effects. Use as much as possible without getting high blood sugar or high lipids. It helps my arthritis.

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Hi - good questions. Unfortuntely I don’t think we have good answers yet.

Some people get a surge of energy when taking rapamycin, but other people find the they are more tired and have less energy when they take rapamycin (you can read about the variety of people’s experiences in our side-effects thread here: Side Effects of Rapamycin (part 2)

Right now - its just a side effect (or perhaps a “Benefit”) that some people experience. I’ve not seen any research on this specific feature / bug of rapamycin. Since we (in the longevity application) are typically dosing once per week, we are more likely to see it than the traditional users of rapamycin (transplant and cancer patients who dose daily). See “Benefits” thread here: Anti-aging Benefits of Rapamycin, Personal Experiences (part 2)

I’ve not heard of the term “recovering” between dosing. But, I suspect that someone might have used that term because rapamycin greatly inhibits protein synthesis, via MTORC1. This is something that in longevity terms, is thought to be a good thing because as you get older your basal rate of mTORC1 activation goes up, and that is basically the growth signal for cells, etc. which as you get older is not something you want turned on all the time because it can eventually lead to cancer, and increased cell turnover, stem cell exhaustion, etc. all of which is more likely to shorten your life. When we are younger mTORC1 is only turned on via nutrients, but otherwise would be at a low level.
But - the benefit of having mTORC1 turned on is that if you’ve worked out, your body recovers by rebuilding and growing muscle, etc., so in that type of scenario having mTORC1 strongly turned on is a good thing. If you’ve taken a high dose of rapamycin and then workout, you are not as likely to get as much benefit that day from the exercise, in terms of muscle growth, etc. So perhaps in that sense the person who communicated the idea of “recovering” from having mTORC1 turned way down, and over the following days (rapamycin has a blood half-life of about 65 hours or so), rapamycin gradually exits your system and mTORC1 returns to the previous un-inhibited levels.

Or perhaps the person using the term “recovering” is just talking about how the blood level of rapamycin peaks quickly (about 2 hours after dosing), and then over the following 6 or 7 days it slowly goes down at the rate of half, every 60 hours. So in that sense your body is “recovering” by returning to the previous low levels (or zeroing out) of blood rapamycin levels, and mTORC1 will again rise to its previous levels.

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This is why I don’t work out (lift weights) on the day I take Rapa and often the day after. Not just because I may not get the full benefit of the exercise as Rapa inhibits mTORC1 but lifting SPIKES mTORC1 so it seems the lifting might inhibit the desired effect of the Rapa.

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