At the risk of beating a dead horse, discussion in another thread made me realize how little I know about the correct dose. So, two specific questions:
actuallyā¦ how little all of us know about the ācorrectā dose.
Based on the information presented in this thread: The Key issue of Dosing Levels and Intervals for Best Rapamycin Outcomes
I have decided that I donāt think Iāll truly āknowā if Iām taking enough rapamycin ever (or at least for the next decade or moreā¦
Given that - that āhigher generally tends to result in bettter longevity resultsā in all the animal studies (except one, where they maxed out in female mice and the longevity gains plateaued at 128ppm, if I recall correctly)ā¦
My belief is that the best we can do is test different dosing levels and timing approaches on our own bodies, track blood test and functional results closely - and modulate in a way that we think will optimize results.
I think daily dosing in mice is roughly equivalent to about once every 4 days or so in human terms given the speed that mice metabolize rapamycin is about 4 times faster.
| Sirolimus Dose |
Mouse mg/kg/day Dose |
Mouse: Blood/Sirolimus Level |
Human mg/kg/day Dose |
Dose for 60kg Human | Daily Dose adjusted for longer half-life (/4) |
|---|---|---|---|---|---|
| 4.7ppm | ā¼2.24 | 3 to 4 ng/mL | 0.182 mg/kg | 10.92 mg | 2.73 mg |
| 14ppm | ~6.67 | 9-16 ng/mL | 0.542 mg/kg | 32.54 mg | 8.135 mg |
| 42ppm | ~20 | 23-80 ng/mL | 1.626 mg/kg | 97.56 mg | 24.39 mg |
| 126ppm | ~60 | 4.878 mg/kg | 292.68 mg | 73.17 mg | |
| 378ppm | ~180 | 45 to 1800 ng/mL | 14.634 mg/kg | 878.04 mg | 218 mg |
| Sirolimus Dose |
mg/kg/day Dose |
Blood/Sirolimus Level |
Male Median LS Increase | Female Median LS Increase | |
| 4.7ppm | ā¼2.24 | 3 to 4 ng/mL | 3% | 16% | |
| 14ppm | ~6.67 | 9-16 ng/mL | 13% | 21% | |
| 42ppm | ~20 | 23-80 ng/mL | 23% | 26% |
Based on the FDA animal to human dosing conversion guide here.
Note: Ā½ life for sirolimus in mice is approx. 15 hours, vs. approx. 62 hours in humans. So, mice metabolize sirolimus approximately 4 times faster than humans.
My approach has been increasingly to optimize around avoiding the ātoo muchā issue, and doing this by tracking and mitigating all the possible negative side effects, which for me seem to be around lipid increases. Iām in the phase of testing and monitoring different rapamycin doses, and lipid management approaches, from diet to medications and supplements - testing them all. Iām early in this process, so nothing to report yet.
The problem with increasing dose, if my math is right, is that if you double your dose, you add a full half life to clearance time which is another 62 hrs.
Of course we donāt even know how much clearance is needed.
Yes - so as part of this new plan Iāll also try adopting the blood/sirolimus level testing that was suggested by @McAlister in his post: Rapamycin Cycling (Time Off) - Who Is Right? - #4 by McAlister
I like the three test approach to blood / sirolimus levels. With the Mareck testing at $59, the triple test approach is not too expensive:
So, when you get results, do you have peak levels that are too high, too low? Do you have trough levels that are too high?
I would love to do the same, but Sirolimus blood tests are unavailable in my location. 
However I am very interested in everyoneās results
@RapAdmin what is your current Rapa dosing schedule?
Check with hospital labs (especially transplant clinics) they do this test routinely. I was also thinking it is not available but phoned the transplant clinic and they have it and it is quite inexpensive out of pocket too.
Thanks. I will check it out.
Nothing ventured. Nothing gained.