#10

I commented in the earlier exercise thread that I saw a worsening of my “gas tank” on Monday evening jiu jitsu classes following my Sunday-morning rapamycin. For the last couple of months, I’ve switched from 6mg weekly to 10mg + grapefruit once every two weeks. Notably, the Monday classes following the rapamycin continue to be low-energy, while the Monday classes on non-rapa weeks are normal. This is now enough for me to be near certain that for my body and training regimen, at least, rapamycin does cause fatigue for 48 to 72 hours.

Brazilian jiu jitsu is a mix of endurance, strength and muscle endurance, with a heavy emphasis on muscle endurance. I’m currently doing 5 days of BJJ per week, but try to keep sparring sessions with partners who can push me to max HR down to 3 a week. I also do 3 days of supplemental weights (deadlifts, farmers walks, but these workouts are max 30 minutes), and 4 days of supplemental zone 2 ranging from an hour to 1.5 hours. (This requires two-a-day workouts on all days except Sunday, which is a full rest day, and one or two three-a-days for max-stimulation days.)

I’m interested in Dr. Stanfield’s trial, but that exercise routine is very relaxed. Three group fitness classes with no periodization is not going to generate many insights for athletes or anyone beyond very sedentary folks.

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#11

Absolutely agree with this

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#12

I concur - it doesn’t look like it would break a sweat. LOL.
I work out every other day - but it is a full hour and a half of lifting 145 to 160 pounds on 11 machines - 3 sets of 30 reps. Then 2 sets of pullups 20 each time. Then bench press 95 pounds 40 lifts and curls 20 times.Just enough to maintain what I have. I have gone up in weights about 10 pounds every 4-6 months. Pretty stable.

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#13

Do we know why some people feel jittery and energetic after a rapamycin dose while others feel a lack of energy? My main exercise is doubles tennis, and I feel absolutely no difference between dosing and non-dosing days. Perhaps my keto diet helps me maintain the energy. I don’t think the problem is insulin resistance, since, on my dosing days, my blood glucose and exogenous insulin needs are usually lower than average.

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#14

And some feel nothing at all. If anything, a low protein/glucose signal diet such as ketogenic should reduce mTOR, thus requiring less Rapamycin to generate inhibition.

Probably some complex genetic interaction, my complete speculation based on many studies showing large inter-person variability with dosing.

Here’s one insight, gleaned from the Glioblastoma/Rapamycin paper.

https://sci-hub.se/10.1371/journal.pmed.0050008

“Whereas this analysis highlights the importance of achieving sufficient mTOR inhibition, it fails to address the fact that adequate intratumoral rapamycin concentrations did not translate into mTOR inhibition in some patients. Such biochemical resistance could be cell-intrinsic (mutation of the drug target, expression of a drug efflux pump in tumor cells, etc.) or host-related (drug bound to serum proteins, sequestration in specific cell types or tissues, etc.)”. Remarkably, S6 phosphorylation was inhibited equally in rapamycin sensitive (patients 1 and 3) and rapamycin-resistant (patients 2 and 12) samples at 0.3 and 3.0 nM concentrations (Figure 3D), indicating that the failure to inhibit mTOR in these patients is not cell-intrinsic. Rather, the data indicate that delivery of rapamycin to tumor cells is impaired in some patients despite achieving adequate concentrations in resected brain tumor tissue. One possibility, based on the fact that rapamycin is sequestered in red blood cells [22], is that the high intratumoral concentrations of rapamycin observed in these resistant patients reflect red cell pooling in highly vascular tumors. Indeed, tumors from resistant patients showed abundant immunohistochemical staining for the vascular marker CD31 (Figure S4) but the sample size is too small to make definitive conclusions. Alternative explanations include variations in penetration of the blood–brain barrier or tumor hydrostatic pressure among patients"

Rapamycin sequestered in blood cells?

Blood Distribution in Rapamycin
https://sci-hub.se/10.1097/00007890-199311000-00029

There are also polymorphisms in mTOR genes

Meta-analysis of the association between mTORC1-related genes polymorphisms and cancer risk

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#15

Agetron, at 7 mg once weekly I don’t notice anything as far as how I feel. I do exercises on the day of dosing the same as any other day. The only day of the week I don’t exercise is Sunday because the gym is closed. Sunday just happens to be the day after my rapamycin dose and maybe a 7 mg dose isn’t enough to create a noticeable effect for me.

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#16

Want to clarify… although I take a gym break after rapa for about 40-44 hours… so MTOR1 restriction can clean… I don’t feel any different… no loss of energy or mood change… nothing… however, physiology of my normally pumped veins (showing high oxygenation from lungs) go shallow… until that work out… 40 hours later… then turn on full of oxygen again, and stay pumped.

Has been a pattern I noticed 6 months ago. Will expect it to happen on Tuesday morning post my rapa intake… on Monday night.

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#17

I’m also mostly keto. I add in a bit of fruit, but it doesn’t knock me out of ketosis. And the rare times it does, I’m so fat adapted that I get back in very easily.

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#18

Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance

“We conclude that the doses of rapamycin required to extend life do not cause overt mitochondrial dysfunction in skeletal muscle”

Just a random straggler I came across…

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#19

I have only been taking rapamycin for a couple of months now but I have not noticed any difference in energy with or without rapamycin. My blood glucose is typically quite low and very steady (as is my insulin). I do not follow a keto diet.

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#20

In this post. Rhonda Patrick says that muscle protein synthesis is driven by mTORC 1 & 2 under different circumstances. mTORC1 triggered by leucine. mTORC2 triggered by resistance training.

Details hidden behind her membership firewall. Does anyone have access to collect the research behind this? Perhaps this is why rapamycin does not inhibit muscle building unless mTORC2 is inhibited via too big of a dose or too short of a dosing period.

https://x.com/fmfclips/status/1758567520959623375?s=46&t=g51H5gL_rX6JIVg_7VgkQg

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#21

Again, has anyone found papers on this description of mtorc2?

From Rhonda Patrick:

Muscle protein synthesis (MPS), simplified:

  1. When lifting weights, MPS is halted. Afterward, you get an explosion of MPS via mTOR Complex 2 (mTORC2).

  2. The amino acid leucine activates MPS via mTOR Complex 1 (mTORC1)

So, protein + resistance training = a magical combo

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#22

So, what about Creatine? Keep reading that Creatine is well studied, good for the brain as well as muscle. Creatine stimulates mTORc1. Lots of advocates, Layne Morton and?? Attia? But Attia takes Rapa. Rapamycin down regulates mTorc1. Can someone please helpme reconcile all this? Is it a matter of just choosing between longer life (but lower protein synthesis and muscle) then take Rap/Met, versus more robust physical/muscle (then take Creatine)??? If my top priority is geroprotection, because I have family history of Alzheimers, should I take RAP or Creatine? would taking both just be counter-productive?

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#23

I found this study on mice. Claims that Rapamycin abolishes the up-regulation of MTORC1 anti-depressive effect of creatine. No mention of muscle effects though.

https://www.sciencedirect.com/science/article/abs/pii/S0009279720306505?__cf_chl_tk=W9Uzl6h1kxtvV8ZDNeK8bNdkheJnmj82LjtoaTkO7Qc-1714209624-0.0.1.1-1407

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#24

Curious if anyone has thoughts on how long after strenuous exercise one should take Rapa?

I typically have a strenuous workout on Saturday morning 9-10am. And then take Rapa with lunch at 1pm.

I hadn’t seen the above that exercise increases mTORC2. I was avoiding taking Rapa before exercise, but this makes me wonder about how long after I should wait.

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#25

FWIW: I don’t let taking rapamycin interfere with my exercise routine. If my exercise schedule coincides with my rapamycin schedule, I exercise first then take rapamycin about 2 hrs later. I don’t know if this is good or bad. I exercise in the morning and I take rapamycin in the morning.

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#26

Hello - I have been using Sirolimus for the past year and a half. I have noticed benefits of increased sex drive - it seems to enhance my bio-identical HRT. I play a lot of tennis 3-4 hrs/ day and lift weights. I have not seen any decline in my ability to gain muscle. What I have seen is a significant decline in my endurance and ability to climb mountains on bikes, skis or foot. I get winded easily whereas 2 years ago I could easily do the climbing. My blood results showed low B12 despite constant supplementation as well as low glutathione. Has anyone else had these type of problems with endurance, respiratory and low B vit. absorption?

Thank you,
Maggie

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#27

Hi, and welcome to the forums. I have heard some people talk about some level of exhaustion/fatigue the day of (or day after) dosing rapamycin (though I don’t experience that). Some others say it impacts their exercise abilities / endurance.

I think you may find some interesting discussions here related to this topic:

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#28

You wrote: blood results showed low B12

If you are taking Metformin…it can significantly reduce your B-12.

Learned this from Dr. Yelena Budovskaya… Stanford anti-aging professor.

Otherwise, I haven’t had anything negative like you’re describing.

#29

That sounds like you are over exercising - I’d be exhausted at that rate.

My fitness levels have noticeably improved whilst being on Rapamycin.
I do weights 3 days a week, 15 minutes HIIT per week and 2 hrs zone 2 cycling and 2-3 hours table tennis per week.
Your 3-4 hrs / day plus weights I think is overdoing it and you are suffering from exhaustion.

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