Curious
#1
I used perplexity with the question “Name the most promising natural polyphenolic mTOR inhibitors.”. And this is a summary of what I got. When using a multitude of supplements, I think it is easy to venture into a territory where we inhibit mTOR 2. And some commonly used supplements also inhibit CYP3A4. This made think even more about how to not inhibit mTOR 2. I see a real risk of doing so when I use to many supplements, even if most of them have rather weak effects on mTOR 2. Some of them inhibit CYP3A4 to. This makes calculating the risk even more difficult.
Summary Table
| Compound |
mTORC1 Inhibition |
mTORC2 Inhibition |
Mechanism of Action |
| Curcumin |
Yes |
Yes (at high doses) |
Reduces phosphorylation of S6K1/4E-BP1; affects Akt |
| EGCG |
Yes |
Possibly |
Suppresses phosphorylated S6; neuroprotective |
| Fisetin |
Yes |
Yes |
Downregulates Raptor/Rictor |
| Quercetin |
Yes |
Yes |
Blocks PI3K/Ras; activates AMPK/TSC1 |
| Resveratrol |
Yes |
Indirectly |
Inhibits PI3K/Akt; activates AMPK-TSC |
| Myricetin |
Yes |
Less defined |
Inhibits PI3K/Akt/mTOR pathway |
| Kaempferol |
Yes |
Less defined |
Modulates upstream signaling |
| Apigenin |
Yes |
Less defined |
Affects PI3K/Akt/mTOR pathway |
These compounds demonstrate promising potential as natural inhibitors of the mTOR pathway, with varying degrees of efficacy against both complexes. Further research is needed to fully elucidate their specific mechanisms and therapeutic applications.
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Interesting. More herbals.
I don’t think I want longer time of mTOR inhibition on top of my 1x/14-21 day rapamycin dosing. Is the idea to dose along with rapamycin to get a bigger effect than just taking more rapamycin (If that is possible)? I only seek a hit and run effect.
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Curious
#3
Even though these compounds are weaker mTOR inhibitors than rapamycin, it is hard to get a clear view of what happens in our bodies when you combine them with rapamycin. Especially since some of them, are known inhibitors of CYP3A4. This indicates that when using herbal supplements, we can’t foresee the effect we get on mTOR 2. I should add that follow-up questions to perplexity or to consensus gave similar but far from identical information on the effect polyphenols have on mTOR 2. Curcumin in low doses seems to be safe when it comes to avoiding mTOR 2 activation.
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