How to Know When You're Taking Too Much Rapamycin?

Here’s Joan Mannicks thoughts.

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Food for thoughts. Thank you @DeStrider.

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So impaired glucose tolerance and hyperlipidemia. It might be really interesting for people to post in this thread, hba1c and ldl/apob results before and after specific rapa dose and duration.

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I don’t mind posting my HbA1c figures for the past couple of years (each week), but they are not only affected by rapamycin. They are also affected by the amount of alcohol I drink which does vary. They are also averages over 30 days and can increase in a metabolising blood sample (so if the sample is not tested on the same day it is taken HbA1c goes up). I use some postal labs and relatively few same day testing labs. Hence I don’t think you can pick up anything particularly from the HbA1c.

I am currently taking 5 or 6mg of Rapamycin every 3 weeks with a slice of Pomelo.

I think this has probably nudged up my HbA1c which is now around 4.9.

These are the 2024 figures

29.2 Rapa 9th Jan 32 delay 29 28.58 Rapa 30th Jan (5mg + Pomelo) 31.03 28 31.57 29

31 is 5, 29 is 4.8

It is perhaps popping up a bit after Rapamycin, but I think testing delay is having the biggest influence on the result.

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Thanks John, which units are you using for hba1c? Mmol/l or %

If Joan Maddick is correct that impaired glucose tolerance and hyperlipidemia from taking Rapamycin are signs that mtorc2 is engaged, then I suspect a LOT people need to pay attention. Anecdotally, it seems that a number of the most active threads, ie the gargantuan staten thread, has dozens of people taking moderate amounts of Rapamycin on a regular basis and reporting higher, sometimes significantly higher, glucose and lipid levels.

I think I’ve read, or listened to, a number of notables including, Blagosklonny, Matt K and Alan Green, describing slight increases in glucose as common but not necessarily threatening.

Certainly large increases in glucose or hyperlipidemia would be alarming. Joan Maddick is one of the most respected Rapamycin researchers and she’s regularly encouraging caution in the use of Rapamycin. Perhaps this is wise for people experimenting with excessive doses or long term dosing?

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Yes, and the PEARL trial will provide invaluable info on the dosing levels. Because hba1c and lipids were tested across a range of doses

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baseline:
HbA1c 4.7
apoB 64

3 months (6mg weekly + acaborse 50mg/meal)
HbA1c 4.9
apob 78

6 months (6mg weekly + acarbose 100mg/meal)
HbA1c 4.8
apob 58

9 months (1mg daily 21 days / 7 days off + acarbose 100mg/meal)
HbA1c 4.8
apoB 60

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The reported values are mmol/l. I used an online converter to give the % figures. That convertor may not have been precise.

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green = no rapa
light yellow = 5mg or so rapa
darker yellow = 10mg rapa

Feb 10 was four weeks after starting rapa. I had averaged maybe 5mg/wk over that time period.
Jun 20 is after four months continuous 10mg/wk.
There were some pauses from Jun-Oct for dental work. Also, I took pantethine for a short while, which I think accounts for the dip in ldl and apob in Aug.

I started 10mg rosuvostatin Oct 1. It seems to have ‘kicked in’ in Dec, as the triglycerides cratered and hdl jumped. (But ldl went up?)

No rapa during Nov and Dec because I hurt my leg.

I restarted rapa in Jan at half my prior dose, 5mg/wk. So Feb 2, Feb 22, and Mar 1 reflect 10mg rosu and 5mg rapa. (I also took ezetimibe for a few days in the last half of Feb, so that might have had an impact.)

In sum, ldl went up on 10mg/wk rapa with no offsetting interventions, now on 5mg/wk maybe not, or it’s more than offset by statin/ezetimibe. If rapa isn’t the source of my current neutropenia, maybe I will try 10mg every other week and see what happens.

Blagosklonny addressed concerns about this stuff. But it seems his influence has faded out around here.

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Baseline before Rapa
LDL at 2.5 mmol/L (and on a statin 20mg/day)
A1C 5.7

After 6 months of Rapa 6mg/week
LDL 3.1 mmol/L (still a 20mg/day statin)
A1C unchanged
Noticeable mouth sores

After a break for a few months, lowered Rapa 5mg/week and increased statin to 40mg/day
LDL 2.6
A1C unchanged.
Mouth sores gone

Debating now whether to take an extended break from Rapa.

After

Great data thank you. It seems to support the theory that rapa has a short term only negative impact on blood lipids?

I’m interested in how little extra benefit you had from doubling your dose of acarbose.

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One thing I get from weekly tests is an idea as to how much variation in a biomarker is noise. Another is an idea how much metabolising samples can vary. I don’t think I would read much into a variation in HbA1c of 0.2%.

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You’re right. The impact on blood lipids was interesting though. A 22% increase in apob which then fell back. It will be interesting to see what data comes out of the Pearl trial on this

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