Rapamycin, metabolism, muscle growth and interactions with other things affecting metabolism

About to start Rapamycin at 30 and wondering about effects on metabolic rate and muscle growth.
I’d assume that the mechanism to regenerate muscle fiber is in some way affected by Rapamcyins effect on the immune system, but I saw some posts here of people with positive experiences as well, how is your experience? Do you still feel motivated to work out or do you feel a hit in things like muscle progression?

I’m going to the gym 5 times / week with controlled macros. Took metformin in the past which absolutely has an impact on muscle growth, so want to make sure.

Then with Rapamycin slowing down metabolism, I am wondering how that interacts with other things that also slow down metabolism, for example blood pressure medicine like Guanfacine or Clonidine.

I’m on Guanfacine for ADHD and it has a pretty big effect on my metabolism. I can’t eat as much anymore without gaining weight, and now my calories are like 1800 for a 181cm 69kg 30years old dude.
My heart rate also drops under 40 bpm regularly when I sleep.

How is Rapamycin going to play into this?

I take Guanfacine. I haven’t noticed any changes to my metabolism. I eat as much as I want and worry about losing weight rather than gaining. It does seem to lower blood pressure. That was great when my blood pressure was too high, but sometimes lately it has been too low.

On the muscle growth issue, the research suggests that in the 2 to 4 hours immediately after taking rapamycin, during maximum mTor inhibition, there is going to be a reduction in your body’s ability to grow muscle. But in practical use, this has no significant impact on people. Most people take rapamycin in the morning (on a weekly, or every two-week dosing period), and on that day do their exercise in the afternoon or evening.

It isn’t like metformin, in terms of impact on muscle growth and regeneration. I have noticed no impact at all of the rapamycin. I workout or exercise 3 to 5 times a week and the rapamycin has had no noticeable negative impact. Frequently people report back that they lose weight more easily while on rapamycin, and especially visceral fat.

As you can see in the graph below, rapamycin has a very sharp peak and then drops off quickly in terms of blood levels.

This is a good video where well-known geoscientist Brian Kennedy talks about the subtleties of MTOR inhibition and muscle growth, and longevity:

I’ve not noticed any impact on metabolism or heart rate. Perhaps others can chime in on that.

There have been some long discussions regarding muscle growth and rapamycin in the past - here are links to them, you may want to review them:

Rapamycin and Exercise / Muscle Growth

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What dosage are you on? I’m on 4mg and it’s a night and day difference for me. I noticed it especially in bodyfat

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My n=1 after 8 months at 6 to 12mg/wk.

Body weight: 78 to 72kg
Pull ups: 6 to 17 reps

My intuition is that rapamycin sensitizes the muscles to MTOR.

I doubt you’ll notice anything at 30 y/o though

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My n=1 trying to work out within 2 hrs of taking 6mg Rapa was barely achieving 50% of what I normally do.
Suggest you only take it on a day when you don’t go to the gym.

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I am on four MG also. With things like push-ups, stairs, pull ups, etc. anytime I have started my improvements in said category have been wildly significant. Of course that was before I discovered things like rapamycin. I think rapamycin is great but the placebo effect is real.

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I had my first test with 1mg Rapamycin. Only took 1mg of Guanfacine to make sure it’s not interacting

Can’t tell if it was the Rapa for the first time, an interaction or something else (stimulant?), but I felt really damn strange the entire day. Very loopy, light headed, uncomfortable and twitchy.

I couldn’t measure my blood pressure at work but could swear my BP crashed down which would explain the symptoms. Also had to run nonstop to the toilet for peeing. (I often reduce Guanfacine from 4mg to 1mg for nights out because 4mg doesn’t play nice with alcohol at all, so it’s not that)

Obviously just a n=1 for a single day but wanted to report anyway. My next dosage will be in 7 days, will report if it repeats, this time work BP values.

For taking Rapa on gym days, I’m a morning dude. Would taking Rapa in the evening mess with muscle regeneration during down time, or mess with sleep stages?

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Yes, the feelings are weird. I’ve been on it about 6 weeks now and have felt everything from euphoria to nausea to high energy. I am OK with the first and last ones… :slight_smile:

If your blood pressure is crashing, I would blame Guanfacine.

Ah so that’s somewhat common? I see!

I’ve been on Guanfacine for years. My BP has already long stabilized on it so fluctuations like this are still abnormal

I don’t know how common it is, but I experience them. The nausea seems to be around when I exercise outside (hiking or cycling) after just having taken my dose of Rapa (within 2 days).

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I have been on it for years also. But it does lower blood pressure. It was fine when my blood pressure was high. But now that my blood pressure is at a healthy level I am worried that it is causing it to drop to unhealthily low levels.

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Hitting my third week and wanted to report back

No side effects currently but I notice I get lightheaded much much faster. When I go to the gym, a few (~8) heavy reps get me to the point where I feel if I do more I might pass out

When I sleep it happens very often that mild pressure onto my arm (like having it under my pillow) cuts off blood flow, and I wake up without any sensation or feeling of my arm

I’d say Rapamycin in combination with Guanfacine had definitely some effect on my body

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Is this only on the day you take rapamycin, or every day of the week after taking rapamycin?

Every day of the week after taking rapamycin. My inkling is that it lowered my blood pressure further, so oxygen circulation is affected, but I can only measure my blood pressure again after the next weekend. Will report back

Would love to hear about people doing regular cardio excerises, like running or cycling for longer periods of time. Have you noticed any change?

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Investing in a good blood pressure monitor would be a good idea. We are on the same dosage of both drugs and I do not have any of these side effects. But I also do not have low blood pressure. I try to watch that as carefully as I used to monitor high blood pressure. I sleep in my side, exercise, etc. and don’t have these symptoms. I would raise this with the doctor that prescribes your Guanfacine.

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The first two days after taking Rapa, I feel nauseous if I exercise.

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I spend quite a bit of time both measuring things and taking notes about my health as well as putting together a document with all the measurements and a number of spreadsheets with summaries. One thing I regret is not measuring enough to start out with. Hence whereas I know some aspects of health have changed I cannot quantify this.

As far as blood pressure goes I keep a sphygmomanometer by the side of my bed and measure the blood pressure after I have gone to bed (waiting a bit for it to settle down) and when I wake up (again if I have got out of bed I wait a bit before measuring it). I now have records back to 2016 for this.

The thing to remember about the cardiovascular system is that it takes a while for it to adjust the dynamic equilibrium when external factors change. Hence when you stand up or sit down (or start running) it does not get into a stable state for a number of heart beats. Hence it is worth waiting until it calms down before taking a measurement.

My view is that if I don’t know what my key metrics are when I am well then I have no baseline to measure against if I am ill (or indeed to assess whether or not things have improved).

You can also get heart monitors like the Polar H10 which when combined with Elite HRV software (smartphone) give a good tool for measuring HRV. That takes about 3 minutes in the morning, but it gives an indication as to whether you have parasympathetic or sympathetic nervous systems dominating or in balance. I don’t know how reliable this is, but clearly when I feel better actually I have the right balance between para and symp systems. It gives an objective value to something which is otherwise subjective.

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Me neither but it gives me a vo2max number which is really really close to my calculated vo2max from my cycling power numbers and for my GF from her running data best times…