If your concerned about rebound and want to keep your dose low and consistent, is there any proof that it brings your immune system to an unhealthy low? Did I read that pretty much all the studies in other animals are in daily dosing with proven results? A lot of us don’t want to play around with the dosing and what we are taking during the dosing, we just want a set and forget approach
All the organ transplantation / immune suppression studies and applications are daily dosing. We have a member here, @LaraPo who is a kidney transplant recipient and she uses Rapamycin to keep her immune system a little lower (I think she takes 1mg/day most days) to help prevent rejection of the kidney. She is also very careful about potential infections… avoiding crowds, etc.
So the biggest downside is immune suppression as a risk (unless you only do a few days a week, or pause every week or two for a while). Also - I think its likely you’ll inhibit mTORC2 with increased risk of lipid and blood glucose disregulation, which are thought to be caused by ongoing, persistent regular dosing of rapamycin.
The daily dosing in animals don’t really translate well to humans for two reasons; mice have a much faster 1/2 life for rapamycin (I think something like 15 hours), vs. 60 hours for humans, so in a sense one day for a mouse (from a rapamycin dosing perspective) is like 4 days for a human.
Also - all the animal studies have the animals in pathogen-free environments (very clean, antiseptic environments) so the risk of infection is low. Most people don’t live in this type of environment, so even if the animals are immune-compromised, they are still like the “boy in the bubble” and not exposed to germs, so don’t have to worry about infections.
There’s no proof that low and consistent dosing, with occasional breaks, brings your immune system to unhealthy low. I’m on a more or less consistent dose of 0.5mg at this time. Before it was 1 mg. I take it 4 days a week and break for 3 days. My monthly bloodwork doesn’t show that my immune system is over suppressed. In fact all biomarkers on my CBC with differential and renal panel are very healthy.
I would not take daily dosing at age 77 with a natural degeneration of my immune system due to ageing. Maybe for young or treating specific diseases. The only disease I have is ageing. In Mannick, elderly took .5 mg daily, but did not get as good a response to the flu vaccine vs 5 or 20 mg weekly.
From the recent Peter Attia / Matt Kaeberlein / David Sabbatini podcast episode, they said that the practice of one a week dosing comes from the Joan Mannick study with Everolimus and showing enhanced immune function with weekly dosing. Apparently daily dosing worked as well. But there is theorizing that daily dosing can suppress Mtorc2 while intermittent only suppresses Mtorc1, which is what we care about for longevity. It’s not proven to be the best regimen and our current dosing is also just a guess based on the limited human information available.
so are there concrete immune suppression studies for the organ transplantation necessity for rapamycin? or is it a hypothesis since rapamycin works for the organ transplant that it lowers the immune system?
Rapamycin was originally approved by the FDA for immune suppression and use by organ transplant patients, so yes, lots of studies on this prior to approval by the FDA.
You can see all the documents FDA documents submitted as part of its approval, they are here if you want to look at the actual research that was done:
With a specific focus on the pharmacology aspects, such as in this document here: