A lot of evidence that grapefruit increases rapamycin absorption and it’s suggested it does so by inhibiting CYP3A4.
Piperine does that too and is noted to increase absorption of other supplements like curcumin.
Will a bit of pepper increase effective rapamycin dosage like grapefruit does?
I would guess that it probably does
I’m not sure what the dose/response relationship is, but there is some effect. See this thread: Rapamycin Interactions with Other Food, Drinks, Supplements and Drugs
Tested piperine’s effect on rapamycin absorption, for me it increases bioavailability by 75% (see table below)
| Date | Rapamycin (mg) | Piperine (mg) | 48h sirolimus, blood (ng/ml) |
|---|---|---|---|
| 3/15/2025 | 6 | 0 | 1.9 |
| 3/22/2025 | 2 | 10 | 1.1 |
The 3/15 dose was standalone, just rapamycin and water. On 3/22, rapamycin and piperine were taken at the same time.
Any thoughts on a reasonable target blood level 48h after dosing when rapamycin is taken weekly?
Thank you for testing this!
Appreciate the info, but would be more meaningful if the rapa dose had been the same each time. Just to account for any potential saturation of absorption at higher doses. (I’m not actually aware of any saturation effect, as you get with drugs like gabapentin, but interpersonal variability of rapa bioavailability is so large, who knows if it can be discounted completely.) Or at the very least, blood levels might not be proportional to dose.
If you are trying to increase the rapamycin blood levels, you may want to take the peperine 30 minutes to 1 hour prior to the rapamycin. Based on this information:
Based on pharmacokinetic data from human clinical trials, the time to reach maximum plasma concentration (Tmax) for piperine is approximately 1.0 hour post-ingestion.
Primary Tmax: Research indicates a median Tmax of 1.0 hour following a single oral dose. This rapid absorption profile is consistent across varying dosages (e.g., 100 mg vs. 200 mg formulations).
Biphasic Absorption: Evidence suggests piperine may exhibit a biphasic absorption pattern or enterohepatic recirculation. One study observed a secondary peak (Cmax−2nd) occurring approximately 9 hours post-dosing.
Half-Life (t1/2): While reports vary based on formulation, animal models suggest a half-life of approximately 18 hours, though human elimination kinetics can vary significantly based on metabolic status and concurrent supplementation.