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…

Yeah, guess what. I did consider tadalafil, but am not leaning toward it, I’m leaning away from it. I am unconvinced of its benefits (outside of ED), and find possibly concerning side effect (there is are threads here dedicated to tadalafil, where these issues have been explored). I am awaiting further data. That said, I don’t think that others are wrong in taking it for possible pleiotropic benefits. It just for me it hasn’t reached a sufficient benefits/risks ratio.

And risk of taking a med has to be seen in the context of the risk of not taking it. If you suffer from a big liability, you might be willing to take a bigger risk to alleviate it. If I’m dying of cancer and conventional therapy can not help me, I would take the big risk of an experimental drug with many unknowns and dangers.

Each drug and each case must be evaluated on its own merits, as objectively as possible, without ideological biases such as “meds bad”, “nature always good” and so forth. If in opposing the naturalistc fallacy bias, you perceive me to be somehow biased in the opposite direction, then it is a perception I dispute. I am attempting to chart a course of action that is as evidence based as I can manage, with the risk balanced to the best of my ability. Perhaps your ability is superior, and if so, I can only congratulate you, while I continue on my inferior path, as sadly I must always be limited by my own judgement - in short, it rocks to be you!

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As long as you know the least amount of medication.
As new life-extension drugs are found almost daily, trying to take the least amount is theoretically plausible, but it is probably not practical.
As @Joseph has stated if we wait for proof it may too late, especially for us older folks.

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As far as pharmaceutical (generally prescription) drugs go, the rapamycin combo (with acarbose or metformin) meets the burden of evidence for me. Then I take a few vitamin/supplements (D&K, magnesium, omega 3, lithium…ok, a few more) for insurance to reach healthy levels with little risk. But at 70, I’m healthy, my blood markers, BP, Homa-IR, HsCRP, ApoB, sleep score, HRV, daily exercise monitor, DEXA, are all good. What should push me to add more pharmaceuticals? (beyond rapa). At this point I just don’t see it…I’ll work on doing even better or at least maintaining my high level of diet, exercise, sleep and positive mental state (more joy, more social engagement, more mental challenges to sharpen my mind and memory). I want to live longer because I really enjoy where I’m at. Sure, I want to be even more creative and productive and achieve more…show me a pharmaceutical that provides that with no downside and I’m in (something like coffee but better). As far as top 5 interventions, I like things like hiking the Pacific Crest Trail, Shinrin-Yoku (Forest Bathing), Onsens (nude, natural mountain hot springs), and beautiful, young women, if for no other reason than just looking at them is invigorating - for men of all ages - and I don’t see anything unnatural or creepy about that. If it brings back old memories or stimulates your hormones, great…of course we realize that (at my age anyway) it’s like looking at art, but no harm in that. And if women do the same thing, more power to them. Play pickle ball, ping pong, badminton, whatever. These are things that make me happy…all natural.
**Oh, and a couple of science links because, after all, this is RapaNews.

Effects of forest environment (Shinrin-yoku/Forest bathing) on health promotion and disease prevention

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9665958/

Shinrin-Yoku (Forest Bathing) and Nature Therapy: A State-of-the-Art Review

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580555/

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In regards to Inulin, this is response I got from Pendulum:

The observations attributed to akkermansia in this study were collected under artificial conditions which may not translate to humans. First, the inflammatory colitis was induced chemically in a rodent model that may not reliably relate to any human condition. A second extreme condition was then superimposed by largely eliminating the gut microbiome with broad-spectrum antibiotics prior to introducing akkermansia in excess in this setting. This severely limits the normal network of microbes within which akkermansia normally operates. These factors limit the interpretation of the data. And…perhaps most importantly, there are multiple other studies that suggest akkermansia delivers benefits in relation to colorectal cancer in mice. Thus, it is my assessment that this study has very little impact related to the use of our products in humans.

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If you’re going to quote me, please try to be somewhat accurate. Saying that 67% of interventions are non medication, leaves 33% as medicine. That’s hardly what I would consider “no medication”.

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LOL, so that’s what you now claim to have meant? I get it, you meant the goal should be 67% non-medication interventions! How could I have possibly not understood your meaning! Yep, you intentionally left “33%” for medication, when you said:

you meant that out of 9 interventions, everyone’s goal should be 6 non-medication, carefully leaving “33%” for medication! Now I get it!

I think it’s clear what’s going on here. I’m going to leave your quote without any further future commentary, as I’m worried that twisting yourself into an increasingly absurd logic pretzel is going to result in your breaking something, and that might necessitate a 33% drug assisted intervention. Peace!

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