Anyone had rapamycin raise their cholesterol?

#1

Just had a physical, and my cholesterol is off the charts. I eat good and I workout with weights and run almost every day.
I vaguely remember Dr. Greene saying something about rapa & cholesterol. I checked AI: Rapamycin can cause hyperlipidemia as a side effect, leading to increases in total cholesterol and triglycerides. My triglycerides were high too.
I’m going to lay off for a while.

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#2

I think it affects most people. If you don’t have a low enough trough then over time it will go up. I think every other week is better for that reason. It affects fasting glucos too.

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#3

Well my TC has been high for 25 years but did not change with rapa. My trigs are quite low ~ 60

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#4

I’ve not seen anyone who has a “big spike” in either glucose/insulin resistance/HbA1C or in lipids. I’ve seen many have a small rise. However, most of my patients are on a selection of the following items:

  1. lipid management and we optimize
  2. Glucose management on a selection of acarbose, SGLT2-i, and/or GLP-1

In the end we usually see improvement in all measures.

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#5

Yah, increased cholesterol is a common side effect. I started taking 10mg Atorvastatin daily and it lowered my cholesterol beneath where it had been before Rapamycin

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#6

I think it depends on the individual. My lipids have improved marginally. Have you tested your Lp(a)? This is determined by genetics so you can find out if you have a greater risk.

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#7

Learned this at a lipid conference. AI says it better than I can:

Yeah — rapamycin inhibits mTOR, and mTOR normally suppresses SREBP (sterol regulatory element-binding protein). So when you block mTOR, SREBP gets upregulated, which drives increased hepatic cholesterol and triglyceride synthesis. It’s essentially taking the brake off the liver’s lipid production pathway.

Somewhat off-topic: 5mg rosuvastatin lowers your LDL about 88% as much as 40mg. That’s a reasonable place to start. (Sorry for the late chime)

#8

I wonder if a SREBP activator drug could be something that combines well with Rapamycin?

U18666A, an activator of sterol regulatory element binding protein pathway, modulates presynaptic dopaminergic phenotype of SH-SY5Y neuroblastoma cells

#9

Yes, rapamycin, while on the Pearl trial (3mg>>10mg) raised my cholesterol, total, LDL, slight change in HGL.

TRT raised it also.