34 replies to this topic

[Andey]

There are better compounds than metformin to activate AMPK (and control SIRT and mTOR) and better compounds than acarbose to promote beneficial gut microbiome.

What are these ? Sorry for a spin off )

[Hebbeh]

There are better compounds than metformin to activate AMPK (and control SIRT and mTOR) and better compounds than acarbose to promote beneficial gut microbiome.

What are these ? Sorry for a spin off )

One of the better that is becoming commonly used in the athletic community is AICAR. Even aspirin was mentioned earlier in the thread as having a greater median effect on mice lifespan than metformin and the demonstrated anti-cancer effect of aspirin is attributed to AMPK activation. I really don't think metformin is that strong of a AMPK activator.

Most if not all of the positive effects attributed to resveratrol are due to its AMPK activation (and the downstream SIRT target). I use resveratrol to enhance aerobic exercise which is due to its AMPK activation and it's quite a noticeable effect. This effect of resveratrol has been reported by both other individuals I've worked with in addition to elite level athletes including some that have reported on this board. Note that most serious athletes use AICAR and similar compounds now due to the increased efficacy but resveratrol has been used in this capacity (to increase exercise capacity via AMPK). Metformin has never demonstrated increased exercise capacity although many have tested it for this effect and therefore I doubt it's ability to activate AMPK is very strong.

The Holy Grail of AMPK activation may revolve around NAD+ and maintaining a positive NAD/NADH ratio and I believe that the electron transport chain is crucial to maintaining this ratio and may explain at least part of the effect of C60/EVOO (especially in regards to the anecdotal accounts of increased exercise capacity of C60/EVOO...this would also explain the possible anti-tumor effect).
http://www.longecity...in/page__st__90

The best and must sustainable way to manipulate AMPK is via diet and exercise. I believe most of the long term benefits of both CR and exercise is via AMPK activation (and all the downstream targets). And it doesn't take much CR and exercise to start reaping the benefits...just a little bit of discipline and consistency.

Back in my bodybuilding days, I (and others) experimented with metformin in an attempt to manipulate insulin sensitivity (without having to get hard core and inject insulin like the big boys) and it was a big bust. Absolutely no positive results or effects were ever noted and it's never been adapted by healthy athletes for this reason. And it is for this reason that I doubt metformin can improve on already healthy blood sugar levels in already healthy people. And then metformin has that pesky side effect of suppressing testosterone. Metformin is something I'll never use again...I've moved on. And note per above, even aspirin had a better outcome in median lifespan in mice.

[blood]

I picked up some acarbose (50 mg tabs) when I did my last drug order.

I'm taking it before high (ish) carb meals - dinner, occasionally before breakfast too if I eat e.g., oats.

So far, the main effect I've noticed is endless flatulence.

[tunt01]

So far, the main effect I've noticed is endless flatulence.

If I remember correctly from a conference call w/ a scientist on this matter, that should indicate it is working. I think Acarbose interferes w/ the digestion of carbs, thus giving you a CR-like effect while allowing you to still satiate yourself with a meal.

[smithx]

Has anyone tried 17α-Estradiol since this thread was active in 2014?

 

This 2018 mouse study showed a 19% lifespan extension for male mice:

https://www.ncbi.nlm...02/#!po=2.17391

 

It is 100x less estrogenic than the more common isomer form, but since it's available as 98% pure and the other 2% could contain some of the active beta isomer, that could still be problematic.

 

A recent study found that it did feminize male rhesus macaques:

https://pubmed.ncbi....h.gov/36897526/

 

Interestingly, Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation:

https://pubmed.ncbi....h.gov/35105357/

 

This compound is one that Bryan Johnson, the guy who is paying doctors hundreds of thousands of dollars a year to keep him young, is taking, supposedly:

https://www.rapamyci...amycin-use/5350

 

 

The drugs that Bryan is taking, with the strongest medical research behind them, & greatest benefit are:

1. Rapamycin  (up to 15% to 18% lifespan / healthspan improvement if started in late life)
2. Acarbose  (up to 12% to 18% lifespan / healthspan improvement if started in late life)
3. 17 Alpha Estradiol which provides up to 28% lifespan improvements (males)
4. Rapamycin with Acarbose  (up to 37% lifespan improvement if started in early life)

 

 

 

 

Edited by smithx, 19 March 2023 - 08:28 AM.