Rapamycin as a performance enhancing drug

I expect that within a few years all of the athletes in the Senior Games will be taking Rapamycin. Rapamycin has uses as a weight loss supplement, immune suppressant, and possible longevity drug, but its role in enhancing strength and endurance is the most surprising. My guess is that the ideal dose and dose interval for muscle growth is different than the dosing regimen for longevity, which may be different from the ideal dose for weight loss, etc.

My own experience with Rapamycin was surprising. I have been a patient of Alan Green for several years on a 6 mg weekly dose. Once I began taking Rapamycin my performance in the gym improved. Unfortunately, I failed to notice that my prescriptions were expiring in late 2021. I was not taking Rapamycin for more than a month while I arranged a conference call with Dr. Green, and during this time my performance in the gym suffered. Insult was added to injury when I became ill with what was possibly Covid in late December of 2021. I began taking Rapamycin again in January of 2022 at a slightly higher dose of 8 mg weekly, but my workouts still suffered.

I use the barbell squat as the best indicator of overall strength. My squat had progressed to 185 lbs for 3 sets of 5 back in Nov. 2021. After my illness and a 3 week layoff from the gym my squat fell to 135 lbs. I expected to recover strength once I resumed my workout routine, but this failed to occur. My squat remained stuck at 175 lbs or less for months. Wtf? Was it long Covid? I felt fine. Was I failing to eat enough? I tried a see food diet and even ate iced cream and junk food for a couple of weeks in an effort to get more calories, but my bathroom scale and the weight on the barbell remained the same or went down. Was I getting enough Rapamycin? I increased my weekly dosage to 10 mg. and then 11 mg, but my body weight dropped and the squat remained stuck.

Three weeks ago I finally reduced the Rapamycin dosage to 5 mg. per week. Boom! The sguat is now 190 lbs, and I have gained 7 lbsof body weight; however, my wild guess is that I am no longer getting the optimal longevity dose.

We really do not understand the relationship between anabolism and longevity. Human growth hormone does not seem to do much for longevity, testosterone replacement is an open question, and 17 alpha estradiol is beneficial. I have a bit of concern that if the performance enhancing benefits of rapamycin become known Rapamycin use will be restricted.

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That’s very interesting. I have to say that I feel my most energetic at 6 mg/ week like you. Is it all just individual responses? Is that a sweet spot?
BTW, have you ever checked your lipids on rapamycin? You had a very good initial response and I’m wondering if you had a corresponding increase in lipids or glucose levels.

My fasting glucose did not change while on the 6 mg dose, but HGA1C and fasting insulin came up slightly. These values were still considered very good from an insulin sensitivity standpoint, but my lipids were out of whack. APOB was quite elevated the last time I checked it, so Dr. Green prescribed rosuvastatin. I am going to wait a couple of weeks at the 5 mg dose level while eating a healthier diet and taking the statin, and then get another blood draw.

I’m trying to see if lipid elevation is associated with better rapamycin response due to better delivery into the cells since rapamycin is hydrophobic.
If that’s the case, will we get less of a response if we use statins ?
This kind of response correlation is suspected in other meds.

There are a lot of moving parts involved. Rapamycin reduces inflammation dramatically. When I was taking 8 to 10 mg per week I barely got sore at all, but now that the dose is at 5 mg per week the soreness is back, but so is the muscle growth. As far as lipid particles are concerned–if my large lipid particle numbers go up on Rapamycin that is bad if those lipid particles are entering the artery walls and turning into plaque. I can only measure what is in the bloodstream and that is not really what I want to know. Finding the best dose for muscle growth takes a few weeks. Finding the best dose for atherosclerosis risk would take at least 5 years I’d guess. Finding the best dose for longevity may take decades.

I see your point. Rapamycin doesn’t dissolve well in water so I’m wondering if the lipid elevation helps move the drug into the cells. Sounds like you had a good response at least in terms of an anti- inflammatory response.

I’m an endurance athlete but also dropped from 8mg to 6mg recently as I felt the higher dose was making me ‘training resistant’. Having exchanged emails with Matt K I suspect I had become mildly anaemic. I seem to be going better in the last week or so but don’t have enough data to be sure yet.

The only strength exercise I do is a single set of press ups twice a week. I’ve gone from 30 repetitions to 40+ with a 15kg back pack. If my hamstring ever heals I will reintroduce kettlebell swings.

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I see your point also. Dr. Green intended that I take the statin every other day and then recheck the lipid panel. Perhaps I would be better off to skip the statin for 3 days starting before the rapamycin dosage day and then take the stain for the remaining four days of the week. This would allow the little lipid particles to distribute the Rapamycin while still keeping APOB in check. I am assuming for now that elevated APOB is a concern so I am going to keep to a strict diet and statin therapy for now. I shall also keep the Rapamycin dosage at 5 mg weekly to keep the lipid levels reasonable and to try to get my deadlift over 300 lbs. Once I am strong enough I may increase the rapa dosage to try to get a better longevity benefit.

@Ray

Have you ever checked any actual inflammation markers?

Re plaque and “what I want to know”, have you ever had a CT cardio scan?

By inflammatory makers, do you mean C Reactive protein? Anything else? I have not checked recently, but I can add tests to the list for my upcoming blood draw. I have never had a CT cardio scan, but it is a good idea. Of course it will show the integral of damage over my lifetime ( area under the curve) rather than the derivative (rate of change of damage associated with rapamycin if any). Even so it would be good to know if I have severe warning signs of atherosclerotic disease even if a perfect CAC store does not really mean no risk of heart attack.

At minimum yes, hsCRP, IL-6 and TNF-Alpha if you want to spend the $.

CT cardio truly shows past history and risk level, everyone should get one as baseline before any intervention, especially forum members here dosing Rapamycin.

A CCAC score of zero TODAY would mean very low near term risk. But if you’re doing major metabolic interventions and “possibly” increasing risk, then you’d want to monitor over time.

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