@Krister_Kauppi Are you saying to be careful about doing too many interventions at one time? I worry about that.
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Its more that some are concerned about that rapamycin may promote cancer but I want to point out that its not that easy to just stop taking rapamycin and do other longevity interventions instead. They can back fire also because of the double edge sword effect. There is no easy solution here. Are hope is to track cancer early and my guess is also if we track it early that longevity interventions then needs to be adapted and changed to handle this new situations.
Regarding your concern about doing too much of different longevity interventions is another interesting topic. Lets start a thread about that. I can do it when I’m home again.
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Thanks! I would like to further explore the “how to avoid doing too much” angle with you and others on this site. Let us know when you are available.
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Why against making yoghurt? It’s easy, fast, takes no time.
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Overtreatment and being overly ambitious with many interventions at the same time can backfire and create unintended negative consequences. It is impossible to predict the effect of many medications given at the same time. When it is done it needs regular and professional medical supervision and follow-up. When it comes to the complex interventions that we practice (with lots of supplements), there are not many professionals to turn to. I would personally really like to reduce my stack. And I do my best to do so. But I am far from done.
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No specific reasons. I am not yet in a place in life/wisdom where I can reliably make yogurt. I am working hard to do what I can from where I am with what I have. I’ll get better from here.
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The problem with multiple interventions is that we can’t measure things reliably like autophagy and even senescence. Senescent cells for instance have great value in tissue regeneration and wound healing, but when they hang around they cause even more senescence and chronic inflammation. But we think of them as “zombies” that should be attacked from all angles, so we inhibit their formation with rapa and then we try to wipe them out with fisetin, quercetin and dasatinib. This can be excessive and harmful since we don’t really know what we’re doing.
As I pointed out, the same can be said of our efforts to induce autophagy. It can be excessive and harmful.
Some people toy with the idea of adding methylene blue to their regimen. Do they know that it is a powerful MAO inhibitor that can lead to the potentially fatal serotonin syndrome when combined with antidepressants? I doubt it. We need to be careful messing around too much with our finely tuned physiologic systems.
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Isn’t wheat germ extremely high in oxalates?
Thanks for pointing this out. In looking this up I discovered that several things I consume regularly have high oxylates: cacao, spinach, beetroot. I’ll have to look into to this further.
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Check this out:
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Is it well known that Rapamyin induces autophagy? In what tissues? And what sorts of autophagy? Are we even certain that most sorts of autophagy are good? As far I’ve read, these things are total guesswork.
I can’t point out the video, but it’s one of Peter Atia’s with Matt K on it. Peter asked Matt point blank if rapaymcin induces any kind of autophagy. Matt gave him a point blank “no”. It’s only the suppressing of SASP that causes it’s good effects. At least that’s what’s actually known. Instead of guessed at.
I don’t think we even have a clear understanding of the different autophagy mechanisms, do we?
I mean I’m no doctor. But Matt K keeps going on about how much really is NOT proven and not even understood to ANY extent. Only guessed at and taken as fact later 
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It’s well known that mTOR suppresses autophagy and that rapamycin is an inhibitor of mTOR. Here’s one of many references
Like I said, autophagy is absolutely essential to recycle misfolded proteins and damaged organelles, but it’s a finely tuned process and can be damaging in excess.
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I listened to that podcast with Matt K on it as well where Matt seems to state that he doesn’t see evidence of Rapa inducing significant autophagy. Peter Attia has had another guest, Lloyd Klickstein, who I believed stated he thought Rapa was a modest activator of autophagy. So perhaps there is a diversity of opinions on how much Rapa actually activates autophagy. I’m hoping it significantly activates autophagy, but if it was only suppressing SASPs, I’d be cool with that too. If it does get proven that Rapa is a strong activator of autophagy, I may consider taking longer breaks from taking Rapa, as I wouldn’t think autophagy is a process that was meant to be stuck in the “on” position 24/7.
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Could you point out that podcast?
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Yes, that’s the one I was thinking about, thank you. I think the Matt K podcast is this one, but not 100% sure -
Additionally, Joan Mannick (a noted Rapa researcher) states that “rapalogs don’t consistently induce autophagy” and in many cell lines (that she presumably studied) “there was no induction of autophagy”.
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Popular science report:
scientific report:
https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00383-2
We don’t want dysfunctional autophagy in the brain. And this knowledge makes it important that, when we age, we make sure that our NAD levels isn’t to low in the brain.
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Is low dose rapamycin more beneficial than high dose?
I think generally no. The mouse studies do not indicate so. They show greater benefits at higher doses, and the most effective doses are pretty massive compared to what humans normally use. I think one reason for this is that rapamycin only inhibits mTOR partially. Even massive doses do not fully inhibit mTOR.
Is the combination of CR, and even fasting, with rapa excessive?
Possibly but I would think not unless we’re talking about moderate to large CR which is very uncommon for humans to practice. The reason I think this is because rapamycin appears to mainly inhibit mTOR when it’s moderate or elevated. When mTOR is already low such as during fasting, it doesn’t seem to reduce it any further.
Do we need to be careful combining rapa with autophagy inducing supplements and phytochemicals?
I don’t think so. The reason I don’t think so is that there aren’t any supplements that are well proven to induce autophagy in humans in vivo. If such supplements existed, then it would be logical to be careful combining them with rapamycin. But no such supplements exist. The supplements you hear about that are claimed to increase autophagy most likely do not inhibit it vivo in humans to any significant degree. An example is spermidine. It may increase autophagy in vitro but in vivo it appears to be not effective at all. Note that in the ITP studies, they tried giving spermidine to mice but found out that none of it was found in the blood after ingestion so they abandoned it.
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BTW I have been on the lookout for interventions that increase autophagy for 15 years. I’m not aware of any supplements that are likely to increase it significantly upon ingestion of reasonable doses in humans.
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I believe tempeh is relatively high in spermidine.