#294

Soon it’ll be only sleep, diet and exercise.

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#295

I presume he has given no reasoning for this.

Dropping Melatonin may be a bigger mistake than dropping Rapamycin.

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#296

If we’re going to say it’s only reasonable to take a drug when there’s clinical trials showing benefits in a given population, then hardly any of the Rx drugs discussed here can be reasonably taken by healthy people. Clearly, people are inferring that these drugs will also provide benefits in healthy individuals and that healthy individuals often may better tolerate -ve side-effects.

The same goes for the risks. Where are the trials finding cutaneous bacterial infection is a side-effect of longevity-dose rapa? They don’t exist—you’re inferring that. They’ve been shown to occur in individuals taking higher, immunosuppressive doses of rapamycin (often in combination with other more powerful immunosuppressants+preexisting conditions). There aren’t subjective reports on this forum of this occurring. If they did, it would be a bigger issue in older individuals with weakened immune systems, thinner skin, preexisting conditions. Why isn’t that a concern for you? Similar reasoning goes for glucose intolerance.

Sure, a study in diseased humans is more likely to translate to translate to humans than a study in animals, but it’s still just a guess. And as far as lifespan extension, the only explicit evidence for that is going to come from animal studies. There isn’t an RCT for every drug in every population (and even if someone lies within an RCT population, it’s no guarantee that said drug will work for them).

It’s an inexact science and we’re all just making guesses on literally every decision (of course, some guesses are far better than others). But when you come in here acting like you’re obviously right (e.g yelling/caps lock and “>>>>>>>>>>>>>>>>>>>>>>>>>>”), it’s not going to provoke a nice response. Especially when you’ve made inferences yourself or just not engaged with certain points (e.g many drugs are going to be better tolerated by healthy, young individuals).

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#297

Did he explain the reason?

#298

I think he was only taking like 3 mcg anyway. It was tiny. He didn’t change much.

#299

He seems to like devices

Perhaps he is testing one of the new ones like Elemind or Somnee - with some small initial clinical data saying they beat melatonin in head to head comparison for sleep

(Although melatonin might be good for other things that sleep onset and quality)

For those not following those threads see eg here: The Everything Technology and Longevity Thread - #45 by Neo

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#300

Actually, Kaeberlein’s

Evaluation of off-label rapamycin use to promote healthspan in 333 adults

showed 3 times increase in skin infections among causal rapa users over non-users.

However, it’s the unknown adverse effects that could be potentially more sinister.

Let’s consider this hypothetical scenario for a twenty year old male:

MTOR pathways play important roles in regulating multiple aspects of skeletal development and homeostasis. Most people reach their peak bone mass around age 30.
The 20 year old stats taking weekly rapamycin, mind you that MTOR pathway in a twenty year olds are mostly well regulated, and not over-active like in individuals in their 60s.
This 20 year old is an avid cyclist so he turns down the mTOR even further but he is not in to resistance training. This individual never reached his maximal potential bone density by his 30s and by his 60s he is diagnosed with osteoporosis.

This is just some hypothetical scenario with sound reasoning to illustrate potential for harm with very early use of rapamycin. There are other potential harmful scenarios, reduced fertility comes to mind too.
Why take the risk for a young, healthy person?

How can you possibly justify the potential risk with dubious benefit over suppressing a well regulated M-tor pathway of a healthy twenty year old individual ?

BTW, I used caps (and deleted the post after few minutes of consideration) for emphasis. I guess as a physician I am just naturally inclined to protect the public against what I consider a bad medical advice. I have 2 boys, one that just turned 20 and there is no way in hell I would ever recommend rapamycin to them.

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#301

I don’t think we know, which then violates the “first do no harm.” I certainly don’t advocate for people in their 20’s being on Rapamycin. I have one patient in his late 20’s on Rapamycin. This was with him begging for it and eyes open on potential risks/benefits.

I’m not so worried about cyclic mTOR inhibition in regard to muscle loss or osteoporosis. I think we’ll see where Dr. Stanfield’s trial goes on this. The overall experience has been improved lean body mass; but this is typically in individuals who are a bit older.

Apart from the one 20 year old, I think my next youngest is in their 50’s, I believe.

In regard to adverse effects - my patient’s keep in pretty close contact with me and I have >100 on Rapamycin now, and I had 2 cases of infection in the last year, both interestingly with eyelids, with a stye with cellulitis for both of them. I suspect this is random, but will continue to track.

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#302

With younger people there may be an argument for rapamycin once a year.

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#303

Yes, AGE is the key. Stanfield is concerned about lean body mass loss in OLDER individuals. His study participants are aged 65-85.
Healthy 20 year olds do not typically have lean body mass issues.

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#304

Preventing hip fractures by having strong bones, avoiding falls when so, is probably one of the greatest tail risk prevention strategies. So anything that weakens bones over time might be a terrible idea unless there’s protection against hip fractures despite weaker bones.

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#305

I don’t see a lot of harm there, I guess it would be similar to yearly fasting.

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#306

That’s the idea. I think it would probably be best to take a reasonably high dose rather than just a milligram.

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#307

Actually, Kaeberlein’s

Evaluation of off-label rapamycin use to promote healthspan in 333 adults

showed 3 times increase in skin infections among causal rapa users over non-users.

It’s a survey study (more prone to bias) and while there was a trend toward increased skin infections, it did not reach statistical significance. Did you not actually read the paper? Because otherwise it’s disingenuous to mention that finding and not qualify it.

I’m almost 31 fwiw and I’m not advocating 20 y.o’s take rapa for longevity. I wasn’t close to fully developed when I was 20 (brain being prime example).

This is just some hypothetical scenario with sound reasoning to illustrate potential for harm with very early use of rapamycin. There are other potential harmful scenarios, reduced fertility comes to mind too.
Why take the risk for a young, healthy person?

If the healthspan and lifespan added (and/or if there was slowing of aesthetic changes) are proportional to the “rapamycin-years”, then you would want to start earlier than later. To me that means 30s or 40s. Another possibility is getting most of the lifespan extension with short-term dosing later in life ( e.g Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice). The first approach obviously carries more risk of side-effects, while the second approach leaves more of the possible benefits on the table.

That’s not me advocating people take a specific approach (or that they take it at all), just laying out my personal thought process.

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#308

You do understand that p value is completely arbitrary. Typically set them at 5% or 1%, it’s just a bullshit standard. People that decide absolute truth based on made up numbers sound like cultists to me, but I digress. This is why I like looking at the actual data.

  1. 3 times as many people had skin infections in the survey
  2. There is plenty of anecdotal data that skin infections occurs with “longevity” dosing of rapamycin, and that’s coming from Matt K. the rapa King himself
  3. Dr. Green used to routinely prescribe antibiotics to his rapa patients

So are you going to continue to argue that skin infections are not more likely in healthy people taking “longevity” dosing of rapa just because the “survey” study didn’t meet the “magic” percentage?

It’s a known risk.

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#309

No duh it’s arbitrary, that doesn’t make it useless. Nobody in science thinks they can get at absolute truth, and using p values gets you closer to the truth/minimizes errors far better than “looking at the data.”

That data doesn’t conclusively demonstrate longevity rapa causes skin infections, and neither does a doctor prescribing antibiotics with it. Okay maybe there’s some anecdotal evidence, and I’m not saying that it doesn’t, but you act like it’s a closed case despite having provided very little evidence (one paper that doesn’t support your claims+”trust me bro”)

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#310

Thank you for this information. I mentioned somewhere here before my N of 1 experience - was taking 4 mg rapamycin per month, no problem. Raised to 5 mg and experienced large purulent boils such as I never had - one was on my, ahem, never mind. Previous dosing/frequency experiments ended up with aphthous ulcers, which I consider dose limiting since it is evidence of immune dysregulation, plus they hurt like hell. So back to 4 mg/month without any discernible problems. FWIW, I occasionally get a CBC, plt counts, comprehensive metabolic panels, CRP and all have been unremarkable.

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#311

Not a closed case but very simple equation.

Anecdotal evidence of risk of rapamycin and/or theoretical possibility of adverse event based on mechanism of action FAR OUTWIEGHS zero evidence (based on human studies or experience or even in theory since m-tor pathway are typically not dysfunctional in this cohort) of any benefit in a 20 year old. And BTW we were talking about 20 year olds, I saw that you tried backtracking to 30-40s.

Thus KNOWN and/or POSSIBLE RISK of rapamycin >>>>>>>>>>>>>>>>>>>>>>>>> Dubious benefit in a 20 year old human being.

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#312

Sodium hypochlorite solutions are useful to use periodically if one is prone to furuncles/carbuncles.

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#313

I’m not backtracking. You’re the one repeatedly bringing up 20 y.o.'s which is why I clarified that I’m in my 30’s.