Stopping Rapamycin After One Year

Looking to hear if other’s have had a similar experience.

I have been taking 4mg per week of rapamycin for one year. Over the last year my cholesterol level has increased 25% to 220, LDL levels increased 43% to 140. HDL increased 3% to 66. All other blood markers either remained the same or have improved slightly. Based on the cholesterol level increases, i am going to stop and see what i can do to reverse the increases cholestrol and LDL.

My diet has not changed in a year. Body weight and height have remained the same. BMI around 22. I am mid 50s. Activity is same. I exercise 6 days a week for 40 minutes with averge heart rate in Zone 5 to 155 -160 bpm with max heart rate reaching 180bpm.

I have been unable to find data that can convince me to stay on rapamycin with these elevated levels of cholesterol.

Anyone have a similar experience with this?

Thanks.
b

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If I were you I would take at least a six month break from rapamycin and reevaluate. There is data to support the view that one year’s usage of rapamycin with a long break gives roughly the same benefits as sustained usage.

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Rapamycin raises these markers in mice too but in spite of (or maybe because of) these elevated markers they still live longer

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I’ve been taking rapamycin 6mg a week for 6 weeks and my cholesterol has slightly increased as well (LDL/total cholesterol). I’m trying to find some supplements that can lower cholesterol so I can continue rapamycin long term.

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It is the eternal question of cholesterol. My view about Rapamycin is that through autophagy it improves the mitochondria which then have more effective SLC25A1 proteins. As a consequence of that the level of Acetyl-CoA in the cytosol is higher. This is good for a number of things, but it is also the first step in the creation of Cholesterol. So Cholesterol increases.

If you then wish Cholesterol to be lower then you would need either to hit another Cholesterol pathway or inhibiting HMG-CoA reductase as with a statin (or indeed Red Yeast Rice - something I intend testing*).

In a sense any good pro longevity action which increases Acetyl-CoA is likely also to kick up Cholesterol in isolation. Hence the arguments about pterostilbene.

  • This is in fact a statin.

ps My cholesterol is a bit toppy in SI units, but I am not worrying.

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I have historically high cholesterol numbers, too (~400 if left unchecked, which does not vary much with diet). FTR, I’m active, maintain about an 18% body fat, and eat a healthy, balanced diet. On Crestor, my Cholesterol is lowered to about 170. When I added Ezetimibe, that dropped my cholesterol down to 100-102, and adding Rapamycin has not changed those readings for me.

More importantly, adding Ezetimibe dropped my Apo-B from 90-107 down to 52and my LDL from 1539nmol/L down to 917 (adding Omega-3s has helped with the ratios, too). None of that will help with the Lp(a), ofc – that’s going to take a PCSK9 inhibitor (which I’m told is never prescribed without having had an actual cardio event), or gene therapy.

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You have a similar apoB numbers. Just started 20mg Crestor and ApoB dropped to 90. I want to get it down further and was thinking about suggesting Ezetimibe to my Physician. Can I ask how much crestor you take and what the dose of Ezetimibe is that was added?

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I switched from 40mg of Lipitor over to 20mg of Rosuvastatin (Crestor) a few years ago, then upped that to 40gm to get closer to the results I wanted, but my Apo-B remained stubbornly high. Adding 10mg of Ezetimibe made a huge difference in my numbers.