Good question! Rapa sounds like a two edged sword for cardiovascular disease – probably helps by decreasing inflammation and boosting autophagy but partially detrimental by negatively affecting lipids. Maybe it doesn’t matter as long as you start addressing elevated lipids ASAP. High LDL isn’t likely to kill you at age 24, but neither is a lack of rapamycin.
Yeah , well the reason I wanted to take rapamycin now, is to protect a lot of my functions especially as I begin to age. I definitely am going to address the lipids as I was shocked when I found out about it. It is humbling because it shows that I have something to improve on(not saying I didn’t in other areas) but also how Im glad I have been doing some of the things I have been doing as my lipids/ lp(a) couldve been way worse if I wasnt eating healthy or exercising constantly. I am wondering if the rapamycin may be able to combat potential complications from LDL particles or protect the arterial walls.
Well, you have plenty of effective options for lowering LDL particles (less for Lp(a), but hopefully the new drug will be available in the next couple of years!), so it doesn’t have to be either/or rapamycin vs lipid control, IMO.
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Might be worth keeping discussions of your blood work to the other thread? Keep this one focused on people’s experience exercising on Rapamycin?
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I completely agree and I apologize for that. In fact I was trying to figure out how to move answers to different posts, Unless that is a @RapAdmin thing.
I’m guessing you’re aware of MitoQ as well. Does it seem like it’s not really worth it?
My take on MitoQ (unless or until I see differently) is that it unfortunately hasn’t lived up to the hype/hope. (But as previous person said, let’s try to keep this thread to rapa/exercise since we veered way off topic)
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Taking Rapamycin prevents Atherosclerosis which is good for cardiovascular health.
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I thought it might be of interest to some to hear my experiences of using Rapamycin whilst training seriously for endurance.
I began rapamycin in January and increased by 1mg/week up to 10mg before dropping back down to 8mg in the last few weeks. During that time I increased training volume from ~6hrs to ~8.5 hours per week. Historically that increase would yield significant improvements in performance yet my CP20 (maximum power for 20 minutes) has declined by 5 to 10w.
In contrast, from a strength perspective, I do a single set of press ups twice per week and have continued to add a repetition almost every session. I now do >30 with a 15kg back pack. I am not currently able to do lower body strength movements (KB swings) because I am rehabbing a strained hamstring.
I am conscious that anecdotally many people report increased endurance from rapamycin but would question whether these people are quantifying their performance so precisely. I note that anemia and microcytosis are listed as side effects of daily rapamycin intake. The article below has the following statement which would obviously result in a reduction in oxygen carrying capacity:
https://www.sciencedirect.com/topics/medicine-and-dentistry/rapamycin
There was dose-related erythrocyte microcytosis within 1 month of treatment and increasing with time on sirolimus, independently of the concurrent use of other immunosuppressives.
And then there is this statement that suggests that the body will adapt given time:
In 119 patients taking sirolimus, thrombocytopenia (defined as a platelet count below 150 × 109/l) and leukopenia (white blood cell count below 5.0 × 109/l) occurred in 78% and 63% respectively [37]. The incidence, but not the severity, of these reactions correlated with sirolimus whole blood trough concentrations. Most cases occurred within the first 4 weeks of treatment and the severity was usually limited. There was spontaneous resolution in 89% of the patients and sirolimus dosage reduction or temporary withdrawal was necessary in only 7% and 4% of the patients respectively. None of the patients required permanent withdrawal.
In retrospect I should have taken before/after blood tests to track these parameters but I’m posting here in case others have this data? I am reluctant to discontinue rapamycin but will probably reduce to 6mg/week. I understand this is the dose used by both Peter Attia and Matt Kaeberlein so would be interested to know whether they have any data that is applicable…
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Very interesting - thanks for posting, and for the details. can you share exactly the equipment you use to measure your CP20 and how frequently you are measuring this? Has it been a steady decline? Do you measure it weekly? As you lower your dose of rapamycin to 6mg/week please report your ongoing results on this.
Its this type of data that can really help us understand results - I hope more people can share this type of data here.
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Unrelated to rapamycin - but very related to exercise and muscle growth/maintainence:
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I measure power with a crank based power meter called a Quarq. The tests are performed a couple of times per month on my Kickr turbo trainer. There is natural variance from test to test so it’s actually the lack of improvement from the increased training load that is most concerning/frustrating.
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It sounds like you have a setup very similar to that which Peter Attia uses. If you are a member of his website, perhaps post a question related to this to his AMA forum:
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It has been my experience over years of resistance training that I have often hit plateaus where I have had to change my training or diet to move forward.
It is difficult to measure minor changes in muscle mass, but max vol and max strength are a little easier to measure. I usually do three sets of progressive resistance training. I keep increasing weights and do the third set to exhaustion which is about 4 to 10 reps.
I haven’t really noticed any decrease in performance since taking rapamycin for approx. 6 months nor have I noticed any performance increases that couldn’t be attributed to anything other than continuing to exercise on a regular basis. I continue to set new personal bests.
My opinion is that rapamycin has little effect on strength training one way or another.
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An interesting new paper that suggests to me that it maybe its Rapamycin’s anti-inflammatory effect that helps maintain muscle strength during aging…
For example, leucine, the branched-chain amino acid that most effectively stimulates muscle protein synthesis in healthy muscle by directly modulating activity of the mechanistic target of rapamycin complex 1 (mTORC1) to initiate mRNA translation, cannot stimulate protein synthesis in models of acute inflammation. Strategies to overcome this form of ‘anabolic resistance’ may be needed to enhance the efficacy of other pharmacotherapies for sarcopenia
Full paper here:
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Any idea what the composition of the EAA supplement was? It looks like they combined the EAA+EGCG supplement together, so we don’t know how much of the effect is due to one vs the other (was the EGCG or the EAA even necessary, for instance?). I can only get the abstract.
haemopoiesis - the production of blood cells and platelets, which occurs in the bone marrow.
Microcytosis - red blood cells that are smaller than normal.
I’m prepared to say with fairly high confidence that, in the short term, rapamycin inhibits adaptation from endurance exercise. Hopefully it bounces back quickly when treatment is paused (or dosage reduced).
For most here I’m sure this will not be a major concern. Indeed there may be health and longevity benefits from a reduction in circulating iron…
Regarding dosage, this is seen with patients on ~2mg/day (14mg/week) but it’s obviously unknown how significant the effect is at say 8mg once per week.
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I put the question of microcytosis directly to MK, here is his (very generous) response:
Hi David,
I don’t know of any data to suggest that once weekly dosing increases risk of microcytosis, but you are correct that this is a relatively common side effect at higher daily dosing of rapamycin or other mTOR inhibitors. I think most people consider the cause to be reduced iron uptake/availability, although mTORC1 inhibition is also known to reduce cell size pretty much across the board, so it could also be a more direct effect that way.
We did see a statistically significant decrease in MCV in our published dog study with 3X per week dosing, but it was not enough to push dogs out of the reference range, so would not have been clinically diagnosed. We’re still blinded in the ongoing once per week dosing trial, so I don’t have any data for that to point to yet.
My guess is that 6 mg/wk might induce a similar small change in MCV within the reference range, but the only way to know for sure would be to have it measured, and it would certainly be subject to individual variation. Whether a small change would affect O2 carrying capacity or not, I don’t know.
Matt
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Thanks for sharing this insight, even MK dosen’t know.
I agree that at “some point”, severely impacting the red blood cell oxygenation homeostasis would impact endurance/VO2 max. I imagine Tour de France competitors spend most of their professional lives managing their blood metrics down to the minute detail for maximum edge.
Most moderate exercisers might not notice, depends on markers status/power/duration load, but perhaps elite might?
I have not noticed in either resistance or endurance, but I’m not a competitive athlete, but neither have I comfortably crossed over into major dysregulation.
Without monitoring all your markers, one is flying blind. I have no fear of crossing into dysregulation, can certainly just back off.
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That’s very interesting! Could impaired haemopoiesis and microcytosis explain higher resting heart rate and lower heart rate variability?