There is a lot of uncertainty right now with regard to the optimal dosing levels and schedules for rapamycin in humans (for anti-aging). Doctors and other people have generally standardized on the range of 3mg to 10mg a week in a single weekly dose, but there is little confidence that that is an optimal level and dosing protocol. The current standard dosing for rapamycin does seem to be a highly tolerable level in terms of side effects which is a great start. But - longer term it would be very valuable to better identify the benefits (and potential risks) more precisely of other dosing regimens.
Obviously, we really need to find out the optimal dosing levels and protocols for the best anti-aging effects. We get a hint on this issue from animal studies - so I think it would be good a good start for us to crowdsource all the animal data we can find in the research literature and try to convert it to dose equivalency in humans (to the degree possible).
And then over time we should also track the dosing levels being tested in different people (and outcomes) so we can all learn from past research and also from each other.
When we get all this information compiled we can dig in deeper on questions related to dose equivalency with the researchers to get a better understanding of how the doses map to each other (obviously very roughly) between species.
In this paper it was noted:
In most studies, mice were treated with 1.5ā2 mg/kg rapamycin. Importantly, the clearance of rapamycin is much faster in mice than in humans. For example, in mice levels of rapamycin drop 20-folds the next day after injection,14 whereas in humans its terminal half-life is about 2.5 d.38,39 It was estimated that a 1.5 mg/kg injection in mice corresponds to the therapeutic oral dose in humans.
With regard to the half-life of rapamycin in mice - here is what the study mentioned above states:
Although these results showed that Ndufs4ā/ā mice benefit from rapamycin treatment, we noted that by 24 hours after injection, rapamycin levels in blood were reduced by more than 95% (fig. S3). We therefore performed a follow-up study delivering rapamycin (8 mg/kg) daily by intra-peritoneal injection starting at P10, which resulted in blood levels ranging from >1800 ng/ml immediately after injection to 45 ng/ml trough levels (fig. S3). For comparison, an encapsulated rapamycin diet that extends life span in wild-type mice by about 15% achieves steady-state blood levels of about 60 to 70 ng/ml, and trough levels between 3 and 30 ng/ml are recommended for [human organ transplant] patients receiving rapamycin.
Dudley Lammingās lab reported this half-life for rapamycin in mice:
We calculate that the half-life of rapamycin in mouse blood is approximately 15 h , with blood levels of rapamycin reaching 4.9 nM 3 days after injection, a concentration capable of inhibiting mTOR signaling in tissue culture cell lines (Sarbassov et al., 2006)
And this paper provides a way to translate ppm (the dosing calculation provided in all the ITP studies on rapamycin in lifespan extension) to mg/kg:
Rapamycin is at 14 mg per kg (ppm) food, which is approximately equivalent to 2.24 mg/kg/mouse/day based on the assumption that an average mouse weighs 30 g and consumes 5 g of food per day.
Below is a summary of the dog and marmoset (monkey) studies with rapamycin, and the doses theyāve used. In the healthy dogs and marmosets, we see pretty high doses, with few side effects which suggests that healthy humans are likely to have similar outcomes. Also included below are the dosing used in transplant applications, just as a point of comparison:
| Dose Equivalency |
Daily Dose (mg/kg) |
Dosing Sched. |
Total Dose mg/kg/wk |
Wkly Mg. Dose for 170lb/77kg |
| Dog Aging Project |
|
|
|
|
| Dogs - Low |
0.05 |
M/W/F |
0.15 |
11.55 |
| Dogs - High |
0.1 |
M/W/F |
0.3 |
23.1 |
|
|
|
|
|
| Pauloni study: |
|
|
|
|
| Low |
0.08 |
Daily |
0.56 |
43.12 |
| Yi Study: |
|
|
|
|
| Med, .5mg/kg |
0.5 |
Daily |
3.5 |
269.5 |
| Hi, 3 month, |
1 |
Daily |
7 |
539 |
|
|
|
|
|
| Dose Equivalency |
Daily Dose (mg/kg) |
Dosing Sched. |
Total Dose/wk |
Wkly Mg Dose for 170lb/77kg |
| Marmosets |
1 |
Daily (week days) |
5 |
385 |
|
|
|
|
|
|
|
|
|
|
| People: |
Dose (Mg/kg) |
Daily Dose (mg/kg) for 77kg person |
Dosing Sched. |
Total Dose mg/wk for 77kg person |
| Transplant w/Cyclosporin |
|
|
|
|
| Transplant - 2mg/day |
0.03 |
2 |
Daily |
14 |
| Transplant - 5mg/day |
0.07 |
5 |
Daily |
35 |
| Trans w/o Cyclosporin |
|
|
|
|
| Transplant (low) - 8mg/day |
0.11 |
8 |
Daily |
56 |
| Transplant (Hi) - 20mg/day |
0.29 |
20 |
Daily |
140 |
| Max - 40mg / day |
0.57 |
40 |
Daily |
280 |
Following is a link to a google spreadsheet Iāve created where people can add information.
Please join in and contribute on this small project:
Also - please post in a reply to this message your rapamycin dose right now and what it works out to mg/kg or mg/lb
