Rapamycin and Metformin - exercise effects

I started taking Rapamycin and Metformin at roughly the same time. Like many of us longevity nuts I am an exercise fiend. I had concerns about Metformin because of the studies that suggest a negative effect on exercise. Two weeks in I am happy to report that if anything, my VO2 and performance has increased. I have set two personal bests on the Peloton. I was flying around the tennis court last night and got the comment “you haven’t moved like this in a while”. I also upped my weight on a difficult (for me) 50lb dumbbells for 50 reps - bench, whereas I was stuck at 44lbs for a while. So…. Perhaps it is the synergistic effect of Rapamycin and Metformin together? I do feel my arthritic joints are a bit less inflamed. Time will tell if the trend continues, but figured I would share for others who had similar concerns.

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Impressive! From my research I believe the potential impact of Metformin on hypertrophy is minimal and there is little or no impact on strength.
BTW, are you saying you are doing 50 reps of presses with 50lb dumbbells in ONE SET or 50 reps total over multiple sets?

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So not to turn this into a workout thread but I do this


workout a couple times a month. Been at it for a while. I enjoy high reps. So 50 reps per set, then sets of 35, 21, 14, 10.

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Wild. I may throw that into my routine once a week. I usually stay in the 8 - 12 rep range to focus on hypertrophy. I’m in my mid 60’s so Sarcopenia is my concern.

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Thank you for the interesting report. How are you dosing the Rapamycin and Metformin: How much do you take and how often?

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500mg Metformin at night with dinner. 2Mg of Rapamycin week 1, 3Mg of Rapamycin week 2

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I think it’s important we remain objective when reporting benefits else we risk undermining the credibility of the community. You definitely won’t see any aerobic improvements after 2 weeks (especially not at 2/3mg).

As a reference I’ve been on rapamycin for 11 weeks (now at 10mg/week) and have been training (cycling) 6/7 hours per week. My power in my weekly 20 minute test HAS improved but I couldn’t confidently say that was the treatment and not the increased training volume.

Also the research on metformin reducing adaptation from aerobic training is pretty robust.

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Regarding strength exercises, I like Kettlebell swings and press ups as they cover all the major muscle groups in just two exercises and don’t carry the same injury risk as their equivalent barbell exercises (bench press and deadlift).

See Pavel’s ‘Quick and the Dead’

@Maveric78 I agree on objectivity. Which is why I included actual performance data and not just anecdotes. The point of my post wasn’t the performance improvement. It was more that I haven’t yet experience performance degradation. Again, I also clearly pointed out the duration of the medication, which is admittedly short. Don’t you think folks should share their experiences? And, we should encourage them to? Versus jumping on them if some arbitrary criteria isn’t met? I will happily go away and keep things to myself, but then why is there a forum @RapAdmin?

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We encourage people here to share their personal experiences and share research. I think both are very helpful. We’re still early on the research related to rapamycin and even metformin with regard to aging - so I think the more data points we have the more we all benefit. Thanks for sharing @Danlalane

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I’m just suggesting we hold ourselves to a higher standard here and be cautious with the hyperbole. If you visit other forums you will find people extolling the benefits of NMN and various other supplements which the research consistently fails to support. The placebo effect is real and can be incredibly powerful but with patient data collection we can begin to tease out ‘real’ change.

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Fair enough. Right now - most of what we have with rapamycin is anecdotal in nature, while most of the studies are only in mouse models. Ultimately, well-designed clinical studies are the gold standard we are looking for, but those take a long time.

But until we get there, we have to look at what is happening in people and take it as a given that those results are likely biased, incomplete and possibly inaccurate in some key aspect. The recent posting about NMN is a good example - it sounded good, but then Matt Kaeberlein pointed out that the control mice did not live long, so the “longevity benefit” is likely an illusion. Anyone who has been following the longevity supplements and drug market for more than 5 or 10 years knows that you have to be skeptical and cautious because most things don’t pan out over the longer term.

But, in the mean time, many of us feel the need to do something… with the incomplete, imperfect data that we have.

My personal experience with Rapamycin convinces me that the muscle gains are real:
I am not a gym rat by any means, but I have been going on an average of 3 times per week for the last 14 years.

My retirement started in 2006 and I am now almost 81 years old. When I was younger I belonged to an amateur track club and jogged regularly from the age of 31 and also played tennis into my late 50s. My longevity journey started in 1965 when my first daughter was born with the likes of Adelle Davis and Linus Pauling. Unfortunately, many of the things they were promoting for better health and immunity didn’t really pan out. The first life extension supplement I took was melatonin. I began taking melatonin in the early '80s because it was known to reset the sleep cycle clock and I was doing a lot of long-distance traveling for the company I worked for. Melatonin was later touted as a wonder supplement and life extender by William Regelson, M.D., a Professor of Medicine at the Medical College of Virginia, Virginia Commonwealth University, in his book “MELATONIN MIRACLE: Nature’s Age-Reversing, Sex-Enhancing, Disease-Fighting Hormone” in 1995.

Exercise and melatonin were my mainstays up until 2012. In 2012 I also added atorvastatin, (a low dose to keep my lipid panel in the range I was shooting for at the time.) In 2016 I added metformin. In 2016 I also added lithium orotate. In November 2021 I started taking Rapamycin, which I import from India. I started out with 5mg /weekly and have steadily increased the maximum dose to 20mg taken with grapefruit juice hours before, with, and immediately after.
So far I have suffered only minor adverse side effects at the 20mg dose. This consists of flatulence and loose stools for the first few days after a 20mg dose.
At the gym my max load has steadily increased on the machines I use for my workouts. I do 3 sets of 5 to 12 reps on each of the machines I use. I use progressive loading, which for me has always seemed to increase max load and muscle mass.

IMHO: Since I have been taking increasingly larger Rapamycin doses for 5 months while increasing max load and muscle mass: I truly believe that this is not a placebo effect.
I have not noticed any effect on my sleep time one way or another.
(I attribute any incoherence, spelling errors, to the fact that I am up past my regular bedtime.)

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To be clear, you say you have experienced these benefits at 2 weeks? That is interesting, and I wonder if it may be because of your fitness level before starting the rapamycin therapy, or maybe because you are younger? What is your age? I ask because at 61, I have had a very different experience. It is very interesting to learn how people respond differently to these protocols, which is why I think it’s important to mention other factors such as exercise, or a sedentary lifestyle, any issues such as arthritis, etc., as you did.Thanks for sharing your experience.

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As I state in my profile I am 47, so still young-ish for Rapamycin. And by exercise fiend I mean very regularly. Cardio days 3-4 days a week, weights 3-4 days a week. I have been trying multiple micro workouts in a day and really enjoying. For example, this morning I did a 20 minute Peloton ride, this afternoon I jumped rope for 20 minutes, after work I went for a 3 mile walk with a 20lb weight vest, this evening I played 90 minutes of doubles tennis. Yesterday I did interval run in the morning on the treadmill for 27 mins, lifted weights for 25 minutes, then 3 mile weighted vest walk. So…. You are correct in saying I have been steadily working on improved fitness and had I not taken Metformin&Rapamycin I would have improved anyway. I just feared that I would be held back, and doesn’t seem that is the case. Starting my third week and still going strong. I don’t think folks need to go off Metformin on nights before exercise if taking Rapamycin too, at least that is my opinion now. Time and longer exposure may change my opinion based on performance.

What brand of sirolimus are you ordering from India…ie what Indian generic drug company…?

I am using Zydus Rapamycin and Glycomet Metformin.

I use Rapacan/Biocon because the seller I used accepted PayPal which gave me a little more confidence that I would actually receive the product. When I learned how to make direct payments to Indian banks I used another seller that was cheaper.
I have been happy with the product and don’t plan to change brands.

Biocon has a full suite of generic immunosuppressants that include:
Tacrolimus
Sirolimus
Everolimus
Pimecrolimus
Mycophenolate Mofetil (MMF)
Mycophenolate Sodium (MPS)

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Hi to all…great info…I’m glad to see more information about sirolimus from Indian generic companies. As long as they can be trusted to deliver, it provides great options for people who can’t get their US MD to write a rapamycin/sirolimus Rx for them.
I personally am taking the Dr.Reedy brand of sirolimus…but I get my Rx filled at my local Rite Aid pharmacy…12 of the 2 mg tablets each month for a $20 copay

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My own experience (which is subjective and possibly wrong) is that Rapamycin is advantageous for older lifters. I perform a simple barbell training program at least 3 times a week, and I ride a bicycle whenever the weather permits.
I have noticed a slight decrease in my strength training progress when on Metformin alone, but a significant improvement when taking Rapamycin alone or with Metformin. I do not know whether Rapa improves muscle growth directly (which seems unlikely since mTOR is suppressed), or if Rapa simply improves exercise tolerance and recovery. I have discovered that I can train every day on Rapa if I want to. Off Rapa I am far too fatigued to train every day. My age is 59. I think if the gym rats discover Rapamycin the demand for the drug may suddenly increase.

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