Yes. I take Magnesium in my sleep stack :+1:

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I’m 64 and many of the current “givens” were only so within the last 10 to 15 years.

There were periods of my life that I lived a healthy lifestyle and periods where I really goofed. Only time will tell if I shortened my life.

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This post seems to miss the mark. No one suggested not to take any medication perse.

I’m not sure why you jumped to such suggestions, based on the mere suggestion that the main focus should be on lifestyle factors. It should be, as long as we don’t have proper alternatives. And we currently don’t have them - certainly not gene therapy or slam dunk drugs. Rapamycin seems an interesting lead that most people here take, hoping for the best. But clearly it’s not a panacea, and if meanwhile you’re still eating a crap diet, and/or refuse to exercise, it remains to be seen what the ‘net effects’ are.

The past years I’ve seen a growing number of people go from taking Rapamycin, to taking 5-8+ types of drugs and still thinking ‘it’s not enough’. How do we even know about potential interactions of this self-sought out polypharmacy, potential longterm side-effects, toxicity, or whether one drug is not cancelling out the effects of the other - such as of Rapamycin. We don’t know.
I’m not criticising this, as I understand the feeling of urgency, and the frustrating realisation these lifestyle factors are unlikely to result in meaningful extension of lifespan.
But I miss ‘the other side of the coin’ - the discussion whether such polypharmacy does in fact not potentially result in more harm, and/or whether it may cancel out potential effects of Rapamycin. I don’t believe anyone can currently answer that question, also not based on some bloodwork. Didn’t Brian Kennedy suggest longevity combinations are likely to cancel each other out?

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Rapamycin seems an interesting lead that most people here take, hoping for the best.

As far as humans go, medications that address cholesterol are far more important than rapamycin. And they work even better than exercise.

How do we even know about potential interactions of this self-sought out polypharmacy

Interaction checkers exist.

potential longterm side-effects

We have medications with decades of human use. How much more long term do you want to get? And how do you know that your lifestyle doesn’t have long term side effects?

or whether one drug is not cancelling out the effects of the other - such as of Rapamycin. We don’t know.

We can guesstimate from the ITP and human clinical trials. Combinations such as rapamycin + cana show better results than rapa by itself, for example.

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“We have medications with decades of human use. How much more long term do you want to get? And how do you know that your lifestyle doesn’t have long term side effects?”

I referred to longterm side-effects of such polypharmacy/a cocktail of drugs in my post, Virilius, not just of Rapamycin.

Can we be sure this ITP result translates to humans? For example, in the ITP male rodents had increased lifespan on Cana + Rapa, and if I remember it well female rodents did not. Can we just translate that to humans, as well then? Personally I’m not so sure.
What human clinical trials are there for the combination SGLT2i + Rapa that you are referring to?
And here you are using the example of Rapa + Cana. For what it’s worth we at least still have the ITP when it comes to this combo. But when it comes to the 5-8+ drug cocktail an increasing number of members is taking, we don’t even have rodent studies.

Of course I’d gladly be proven wrong.

I think you can expect to see that on a rapamycin site. Pharmaceutical worshippers who believe that more is always better. Doesn’t mean it’s right.
Prioritizing and human judgement is still the big advantage we have over AI.

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The argument that you can extend your lifespan by incorportating several drugs with different mechanisms that have proven to lower deaths and extend lifespan is fairly compelling though. Much more than the just exercise harder and eat keto/carnivore/vegan/fruitarian approach.

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For rapamycin and the combo of rapamycin and metformin/acarbose, it looks pretty compelling. Beyond that, I’d say address clear blood biomarker problems, then wait and see on the rest.

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Can anyone actually name a combination of things people here take regularly that has been shown to cancel each other out? I really don’t know why people are so quick to assume that you can’t combine a bunch of things together. From what I’ve seen, more combinations have been synergistic, for example: Glycine and NAC, Rapamycin and Acarbose, and CoQ10 and Selenium.

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Many drugs turn out to have pleiotropic effects, many of which were unknown up until discovery. Take as an example the effects of statins on ROCK activation, albeit that has been the subject of many studies by now. But what about other pleiotropic effects of all these drugs that we have no clue about?

Probably a bit off-topic with regard to polypharmacy, but personally I’ve wondered for a while now how all the peptides some members apparently use may affect mTOR. (The same for the high doses of specific amino acids some members take).

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So does food and your environment.

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See this post

The summary was this written by @RapAdmin …'It just reinforces that we still don’t know how all these drug / drug interactions will work out inside our bodies". In a video on this point, a researcher said that they had no way to predict which combinations would be negative. He concluded by saying people should be careful before (in other words, we shouldn’t be) adding multiple drugs together in an attempt to get a longevity benefit.

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On the contrary, I did not miss the mark.

Someone did. As I quoted that poster:

Taking no medication should not be anyone’s goal. The goal should be maximum health and lifespan. There is zero reason to favor interventions that don’t involve medication. Medications are just a tool. A very useful tool. They can allow us to accomplish lifespan and health enhancement results not possible without them, and even more powerful interventions such as genetic manipulation should be used as soon as available. By any means necessary.

The rest of the post’s points I have addressed previously, so won’t repeat here.

The fact that there are possible interactions in polypharmacy is a reason to keep studying them, to keep progressing, to keep enhancing our knowledge, not to give up on medication because complications might arise. That’s a Luddite attitude. New interventions, progress necessarily will involve complications and failure. That is not a reason to not try, or to discourage attempts at experimentation. Climbing down from trees involved novelty, dangers, risk, challanges, occasional failure, but ultimately was the only way to make forward progress. The existence of such danger is not grounds for discouraging polypharmacy, or fearfully clinging to a conservative naturalistc fallacy.

Yep, polypharmacy has dangers and challenges. We are acutely aware of this. I myself frequently cite Matt Kaeberlein on the dangers and unknowns of stacking molecules/interventions/medications - geometrically increased complication potential. And so I research interactions and dangers of combining interventions extensively to the best of my ability, eagerly learning from the wise people on this board and elsewhere. Many, if not most threads here discuss side effects, gain vs loss. We move forward with caution.

But not moving forward also has its risks. Imagine you are trapped in an underground cave that is slowly filling with water - in time you will certainly drown. There are two folks with you. One of them listens to the roaring outside the cave and says, let’s take a leap out - we might save ourselves, as the roar might be only of a herbivore. The other says, but the roar might be that of a terrible predator and we’ll die instantly, lets stay here and make the best of what we have, build a platform and so last a bit longer before we drown.

That’s a different approach, life philosophy, tolerance for risk. Some of us are willing to take a leap into the unknown - we make our best assessment and accept the risk of losing. “Better to try and not succeed, than never try at all”. Some prefer to stay with the known, and maximise current conditions, safety first, leave the bleeding edge for those who are willing to bleed.

Just a different approach. I belong to those who are willing to risk emerging from the cave. Everyone must make their own assessment. I don’t judge those who prefer to stay within the limits (however narrow) of that which is known for sure. It’s not for me, but each of us is responsible for our own lives. I expect the same courtesy in return, and am happy to hear from the other side: “CronosTempi, you’re welcome to bleed at your bleeding edge, but I like my couch free of liquids”.

We are here to hopefully exchange knowledge and points of view for mutual benefit.

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Yes, I did a search too but didn’t come up with anything great except that the question is often asked. I’ve seen lots of answers sprinkled around the forum but no good summary.
Like @LukeMV I know of more synergistic combinations than outright cancelling out. Certainly the obvious like not combining mTOR activators with inhibitors but that’s more of a cycling/timing issue, just like not taking certain amino acids that use the same receptor/pathway at the same time. Also that Vtamin C (strong antioxidant interfere with the bioavailability of berberine. A good complete listing of interactions (not known drug interactions) in one place would be helpful.

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Even the original discovery by Dr. Charles Brenner of NR that’s in TruNiagen and other products?

Would you use a hammer to kill a fly? There’s more than one way to skin a cat. I’m a risk taker…but a “careful” risk taker. I’m going to choose the path with the best risk/reward ratio.

“maximum health and lifespan” is what we’re here (on the forum) for, so that is the assumed goal, taking the least medication to achieve that is perfectly reasonable because, as has been said many times here, “every drug comes with a risk”.

I won’t be the first one signing up. I’ll wait til there is plenty of evidence (like rapamycin).

makes it sound like you are fearful of nature…you could live in a lab.

Exactly! Matt doesn’t take a lot of pharmaceuticals beyond rapamycin…last I heard, he said that he was leaning toward trying tadalafil, not sure if he did.

Ca 100 grams of onions daily gives me the inilin I need

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NR has failed the ITP and various human clinical trials. NMN has also failed various human clinical trials. NAD+ boosters don’t even increase NAD levels in the muscles while simple exercise does. That is why excitement around them died down a while ago.

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makes it sound like you are fearful of nature…you could live in a lab.

To be fair, nature is incredibly deadly for us complex, multi-cellular life forms. The surface of this planet is basically the only place where we can survive and even that is constantly trying to kill us.

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And I thought I was weird…