Rapa: new hints for dosages

[mccoy]

In his recent podcast with Joan Mannick and Nir Barzilai, Peter Attia discusses the dosages of Rapalogs.

https://peterattiamd.com/joanmannick-nirbarzilai/

He also speaks about his own experience, from 5 mg single dose per week to 6 mg single per week, cycling with some weeks on, some off. I don't remember if he cited the exact rapalog he's using, probably everolimus, the object of Mannick's article. There is no difference in the perception of well-being, whereas he's having, even at these intermittent relatively low dosages, the side effect of mouth ulcers. I'm a little skeptical after this, mouth ulcers are not very pleasant.

Quote

Joan’s 2014 paper at Novartis

• Knowing that the only way this will ever move forward is if the drug was safe and did not suppress the immune system, they started with a very low dose with intermittent dosing 
• They were looking to see if the patients had an enhanced immune response to the flu vaccine 

-Study details 

• The drug used was RAD001 (a.k.a. everolimus)
• The doses given to the 4 different arms—
  • 1) Placebo arm 
  • 2) 0.5 mgs of RAD001 daily
  • 3) 5 mgs once a week 
  • 4) 20 mgs once a week
• The goal was to partially inhibit mTOR, because when you completely inhibit mTOR, you stop T cells from proliferating and you’ll get immunosuppressed

-The ending observations: 

• • The two lower doses (0.5 mgs daily and 5 mgs once a week) were the best
  • Turning mTOR down (not off) in the elderly is the best for enhancing immune function

 

Edited August 17, 2020 by mccoy

[Saul]

I don't take rapa and don't intend to.

It is true that rapa slightly lowers the effectiveness of the immune system -- but according to Matt Kaeberlein, of the University of Washington, who the negative effects to the immune system is insignificant for healthy adults.

Dr. Kaeberlein believes in using rapa as an antiaging drug -- he's trying it out on pet dogs.

    --  Saul

[TomBAvoider]

mccoy, Peter Attia takes it for 8 weeks and then takes a break of 5 weeks according to that podcast. He finds no benefits that he can pinpoint (something that I've read repeatedly on websites frequented by those who do take rapa - it's pretty universal that nobody can report any obvious benefits, while mouth ulcers are ultra common). One effect he mentioned was that it seems to him his fingernails grow slower on the drug, which isn't surprising since it is generally assumed that it inhibits growth and protein synthesis in general. In that respect it's similar in effect to CR - it has also been my experience that on more strict and severe CR, things like fingernails and hair tend to grow more slowly, something that has also been reported by other CRONies. Such lower growth might translate into less cancer, perhaps, among a myriad of other effects. But yeah, dosing and the whole protocol are critical elements with a drug that seems to have a pretty narrow range of where it is good for you and it's very easy to step outside of it and either get no effect or a bad effect... you have to get it just right.

[Saul]

According to Kaeberlein, the weekening of the immune system is insignificant for healthy adults.

  --  Saul

[mccoy]

9 hours ago, TomBAvoider said:

it's pretty universal that nobody can report any obvious benefits, while mouth ulcers are ultra common

MMMmmmmm... I wonder then if rapalogs are taken on the faith we have on David Sabatini's studies and the assumption that a chronical, slight inhibition of the mTorc-1 complex will trigger the exact metabolic cascades benefitting healthspan and longevity. A leap of faith, as it were. Or maybe some people are closely observing some of the effects on some of their blood parameters?