Rapamycin vs Metformin

I've got a supportive MD who runs an aging clinic I'm seeing soon and am considering next steps. So far I've ...

  • Fixed all the basics (hormones, glucose, BP, ...)
  • Taking 2000 metformin daily
  • Did the NAD patches, plus daily booster


Canonically the next step would be Rapamycin, however I've heard rumors that if you're good with Metformin activating AMPK that perhaps Rapamycin isn't necessary. If it's still 'a good idea' or at least not a bad idea, thoughts? 

From the March Life Extension magazine page 98

Human Strategies to Suppress Excess mTOR

Rapamycin is being studied in humans to assess its ability to suppress excess mTOR and potentially reverse age-related pathologies. 

The most efficient way for people to suppress mTOR today is to activate cellular AMPK.

This can be done with the drug metformin, intermittent fasting/calorie restriction, and/or AMPK activating nutrients like gynostemma and hesperidia

The interesting thing is that the article is about the Canine Rapamycin project to suppress mTOR, yet at the end seems to be saying that Metformin is the best way to go about it via AMPK 

Further in this article from Feb 2018 by Bill, the sequence is

  1. Living causes cellular waste, which is removed via autophagy
  2. "Recent discoveries show that almost every intervention proven to extend healthy lifespan involves activation of autophagy (removing toxic cellular waste)"
  3. "One of the safest and most effective methods to optimize autophagy is by activating an enzyme in our cells called AMPK"
  4. "AMPK performs its fat-removing process, in part, by regulating a protein called mTOR"
  5. The most studied mechanism of metformin action is its ability to boost AMPK activity.


So it would seem you can use Metformin to activate AMPK and thereby regulate mTOR. Or you can go after mTOR directly with Rapamycin. Given the track record of Metformin that would seem the better route, and if you're already taking it then, in the absence of other information, adding Rapamycin would seem to be overdoing it. 

Addition: OK I found a reference

BF: Most people eat too much and this causes mTOR to be chronically elevated, which may preclude optimal results using the other interventions. Rapamycin directly suppresses mTOR. So we believe that inducing autophagy (removal of accumulated cellular waste), which happens when mTOR is suppressed, is a logical first step. What we are finding, however, is that most of our supporters already take metformin, practice intermittent fasting, and/or ingest nutrients that boost a cellular enzyme called AMPK, which indirectly suppresses mTOR. So we feel they may be able to skip rapamycin at first and proceed to boosting their NAD+ as I next describe. We will know more about the additive benefits of rapamycin when a clinical trial we are helping fund wraps up in a few months.

There you go, if you are taking Metformin, practice fasting, supplements and diet, then the expense and trouble of Rapamycin is probably not necessary. 

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