Rapamycin induced insulin resistance and drop in testosterone

You can calculate HOMA IR using insulin and glucose numbers.

https://thebloodcode.com/homa-ir-calculator/

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Another example of polypharmacy and supports my argument that we should only test one variable at a time.

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Maveric78, just to be clear, the only variable that was changed between his recent and previous insulin, glucose, and testosterone lab test results (performed 11 months ago) was the initiation of rapamycin (Sirolimus for 9 months, at a dosage of 12 mg every two weeks / 0.2 mg/kg). He has been taking metformin, acarbose, and canagliflozin for the past 3 years, with no dosage changes.

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Exactly polypharmacyā€¦ He hasnā€™t tested the effect of rapamycin, heā€™s tested the effect of Rapamycin in conjunction with Metformin, acarbose AND canagliflozin. For example, based on the paper above, metformin inhibits CYP3A4 and therefore increases rapamycin blood levels. Who knows what other interactions may be occurring.

Why is his taking three separate diabetes medications? Is he even diabetic?

Btw, back calculating 0.2mg/kg he must only be 60kg? How tall is he?

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Heā€™s not diabetic or even prediabetic. Heā€™s taking low doses of metformin, acarbose, and canagliflozin for their purported/theoretical longevity benefits.

Height 5ā€™ 8" . Approximately 62 kg

Rapamycin/Metformin and rapamycin/acarbose have both been tested by ITP and both did better than Rapamycin alone. Neither were used to increase rapamycin blood levels or as some silly proxy for grapefruit juice.

12:40
ā€œAcarbose and Rapamycin did not improve on Rapamycin (alone) in femalesā€

In males, median lifespan extension were:
R = 23%
A = 22%
R+A = 29%.

So you can see that the benefits were not truly additive. Why introduce another variable when there are already so many unknowns and when the additional benefit is minimal?

Metformin plus medium dose rapamycin produced similar results to high dose rapamycin. We donā€™t know the mechanism and, to my knowledge, metformin has not been tested with high dose rapamycin.

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I wouldnā€™t call a 7% increase in median lifespan ā€œminimalā€. Thatā€™s 5 extra years in a 70 year life span and well worth some polypharmacy. Also since the other meds were being taken for years, the only new variable introduced was the rapamycin. The point would be a lot more valid if heā€™d started 2 or more meds all at the same time or even within months of each other rather than years. Yes it still makes the analysis more complicated but also more interesting IMO.

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The additional 6% (R Vs R+A) increase was to median lifespan so 90th percentile (data unknown but extrapolating) will be ~3%.

When did you hear this? I am under the impression that Matt is now taking rapamycin full time, as is Peter Attia, that is with no breaks, just weekly dosing. Can anyone point to source material regarding this?

After discussing this with Alan Green , I believe that his results arenā€™t typical.

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Brandy, thanks for posting this personā€™s experience. More data points are always better here, so that we can see the range of responses to rapamycin.

Just a small comment on terminology: I think most of us here would call what we are doing ā€œpulsed rapamycin dosingā€ (that is, either weekly or every two week dosing). Generally, as @LaraPo mentioned, its the daily rapamycin dosing that organ transplant patients engage in that we call ā€œchronic rapamycin treatmentā€ because its daily, for their entire lives (potentially).

Peter Attia and some others used to take ā€œrapamycin vacationsā€, where every few months they take a longer break in their dosing, but generally what weā€™ve seen among the doctors and others like Peter Attia, etc. is the elimination of the vacations, with minimal or no negative impacts. For example, doctor Allen Green, who has over 800 patients on rapamycin for longevity, does not recommend these rapamycin vacations, and has seen no ill effects in his patient population.

Of course, everyoneā€™s biology is different, so some people may still need to take these rapamycin vacations.

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Does Dr. Green also look at the HOMA-IR values of all of those patients?

Iā€™m not sure ā€œfreeā€ testosterone testing is very reliable unless someone is following a strict sleep schedule and has it tested at the right time in the morning with each test.

I donā€™t know, Iā€™m not a patient of his. Iā€™ve never heard of the HOMA-IR before. Not sure if its used at all in the USA and Canada.

I see the test was developed in the UK. Are you in the UK? Is it more commonly used there?

A thirty minute walk right after eating seems to control postprandial glucose levels significantly well. No meds required.

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Is it your own experience or the information from the literature, podcasts?

I know he advises that you get an insulin and glucose and then calculate it on your own. He gave me the distinct impression that rapamycin isnā€™t an issue.

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ā€œA thirty minute walk right after eating seems to control postprandial glucose levels significantly well. No meds required.ā€

This has also been my anecdotal experience when I measured my BG-levels throughout the days. Albeit this was before I started taking Rapamycin. Whereas different herbal supplements, Ceylon cinnamon with each meal, sulforaphane, seemingly had no effects on my post-prandial BG-levels, being active for 10-15 minutes after eating did. (I did a more active short dance workout though).
On the other hand Iā€™m grazing too much during the day, probably eat too much fruit, so I still opted to add an anti-diabetic drug. Perhaps I should reconsider, but I was worried about the discussed effects of Rapamycin on glucose levels.

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