Peter Attia· MD
but one of the things that's come out of my own research and other research in the field is that the both the benefits and the side effects are strongly linked to dose
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The headline is broadly defensible, but the qualifications matter. Effect sizes vary by population, the strongest claims rest on shorter trials, and credible voices push back on how it's typically framed.
but one of the things that's come out of my own research and other research in the field is that the both the benefits and the side effects are strongly linked to dose
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The "high risk" framing here is the right call. I've had three patients ask about rapa this month and none of them grasped the immunosuppression tradeoff until I walked them through it.
The PEARL trial framing in the dossier is the clearest writeup I've seen for a non-specialist. Worth linking from the AMA pages too.
I'm on 6mg/week, year two. Tracking IL-6, fasting glucose, lipids. Happy to share the spreadsheet if Whalespan wants longitudinal user data.
The dosing variance across the advocate camp is staggering. 3mg, 5mg, 8mg, biweekly, weekly… brief is right that "monitor or specialist only" is the responsible read.
I also feel like because the dose that we gave was so high that again thinking translationally about rapamycin as a drug in the context of aging my feeling is that what we've uncovered here is not going to be relevant at the doses that we would think about giving to
with rapamycin there is a perception out there that I don't share but there's a perception out there that rapamycin has lots of side effects based mostly on the human clinical literature which to be clear is generally in transplant patients transplant patients taking high doses and taking lots of other drugs yeah so sick people taking a high dose of rapamycin in combination with other medications right and it does have side effects there's no question about that
obviously we couldn't do that in healthy volunteers especially healthy elderly volunteers there was some additional information that gave us some confidence we could use much lower doses than what was used in transplant patients yielding much lower exposures
it was developed clinically as an organ transplant immunosuppressant and that's how it was first approved it was used in a dosing protocol and a patient context where there are lots of side effects
for you know the better part of a decade 1999 to 2009 the only experience that the scientific world has with this is in that cont text and yeah you're going to see a lot of side effects but how do you know they're from rap ay I mean and how do you know that they would be the same elsewhere
I do wonder whether the history of rapamycin and the rapidity at which it it it will be eventually tested for other endpoints in clinical trials where it may have benefits has been negatively impacted and slowed down because of the the reputation that the drug got As A Dangerous Drug based on the way it was developed clinically
for you know the better part of a decade 1999 to 2009 the only experience that the scientific world has with this is in that context and yeah you're going to see a lot of side effects but how do you know they're from rapamycin I mean and how do you know that they would be the same elsewhere
we're not seeing an uptick in cancer or something that was unanticipated
Rapamycin extends median and maximum lifespan in mice across multiple lab strains and dosing protocols.
Rapamycin will extend human lifespan by 5+ years at standard weekly dosing.
Weekly rapamycin dosing in healthy adults shows favorable safety and immune markers in early observational data.
Chronic low-dose rapamycin imposes an immune trade-off that outweighs the longevity hypothesis for most healthy adults.
mTORC1 inhibition is the mechanistic backbone for rapamycin's healthspan effects in mammals.
The PEARL trial showed an acceptable 48-week safety profile in healthy adults on weekly rapamycin.