I'm a month into taking rapa and already I feel like it's having a noticeable effect. I'm curious what others on this threads dosage looks like. If you prefer to keep it private, you can email me directly (my email is on my profile).
I'm currently taking 2mg once a week on my rest day; I started with 1mg and after 1 month added another MG. I'll continue each month until I reach 8MG once a week, which is the dosage the doc I worked with in Texas to get my prescription recommended and most people seem to take.
Also - I would say that NMN + Rapa is a completely life altering combination for anyone 50+. I feel like I can lift harder and longer now than when I was in my 40's and things seem to be getting easier the farther into my rapa routine I get.
Also also - you can find rapamycin online / overseas under its other name - Sirolimus - and the cost is a little lower than getting a proper US prescription.
I have been taking Rapamycin for 19 weeks and NR and Metformin (for anti-aging) for much longer and I can't see any difference. I'm 50+. I generally, however, feel excellent, as well as I remember when I was younger so long as I have gotten lots of sleep and don't have a cold. When I'm sick or tired I feel much worse than I did, however.
Nicotinamide Mononucleotide, an unregulated supplement.
Note also:
> We found that, when data from all organisms studied were combined for each compound, aspirin resulted in the highest percent increase in average lifespan (52.01%), followed by minocycline (27.30%), N-acetyl cysteine (17.93%), nordihydroguaiaretic acid (17.65%) and rapamycin (15.66%), in average.[0]
Though I'd consider whether flies and worms are good models for your human self.
Yeah as others appointed out it’s a nad+ precursor.
I feel compelled to comment though because anytime I read about how this stuff is only been tested in worms in mice… That automatically discount it’s worth as something to consider.
I’m gonna sah what I said before - I’ve played high-level hockey my whole life, I’m now 55 and I play against guys that barely washed out of their pro career.
When I stop taking nmn for two months my speed dropped from 20+ Mph to the mid teens.
A week after resuming my NMN supplementation my speeds are back in the 23-24 mph range
There’s just no way to fake it against players of this caliber. And to be clear I don’t know anybody even close to my age competing at this level.
Just putting this out there, I am a PharmD and this is totally real and the traditional medical establishment is really behind. It is positive effects are beyond doubt - the argument against it is usually "we don't know what the side effects if 100m+ went on it for 20+ years". (which is also 100% true, but that's where patient autonomy comes in). Also, there are some questions about how much are really the positive effects.
Anyway, I am tinkering with something in that space - feel free to reach out if you want explore being a co-founder. (email in about)
What makes me scared about this is that it's immunosuppressive. The immune system is a very important part of the human body, and I worry that taking it could have terrible health impact after years of acting on your body lines of defense.
Your concern is correct. Suppressing the immune system is a 2-edged sword - a little suppression in the right setting, is extremely beneficial, but go overboard and it is harmful. That's why in a perfect world, we would have large human trials with different dosages and iterate until we can get the maximum benefit and the least harm.
The problem is, no one wants to do those trials because rapamycin is cheap and generic. Why would Pharma spend money on something that they can't patent? Also, these kind of trials have to go on for 10+ years at a minimum - which is cost-prohibitive even if it is patentable (not to go in the weeds, but long trials count in the period of exclusivity given to pharma patents).
I believe the right approach is to use it off-label, be upfront about the potential risks, and collect lots of data so you can improve as you go. Practical anti-aging so to speak.
Another approach is through the NIH grant pathway, but that has a lot of road-blocks as well.
If you think about it, there are specific parts of our immune systems that are likely entirely maladaptive given modern civilization, where people are ~never exposed to parasites, animal venoms, etc.
We can turn those parts off, while leaving everything else on, and be better for it (no allergies, psoriatic arthritis, MS, Chron’s, etc.; and so none of the accelerated cellular senescence those conditions provoke in affected tissue.)
A lot of recent pharma is already focused on doing specific forms of this at low levels. Every other drug ad in the US is for an immune-receptor blocker of some kind. And the side effects of these drugs come down mostly to the fact that they’re too low-level — they stop these parts of the immune system from being called into action at affected sites, but they leave it active and “patrolling”, such that it attacks harder any tissues that don’t absorb the receptor-blocker well, and such that you get withdrawal effects of potential inflammatory crisis if/when it wears off.
Just deactivating the relevant parts of the immune system entirely, on the other hand, provides the same benefits these drugs do, but with none of the “now the rowdy enforcers have nothing better to do, so they go looking for trouble” drawbacks.
According to the abstract of the article, its effects, at least in that form of using it, were not immunosuppresive.
On the contrary, the protection of the intestine to aging effects was due to increased autophagy in the intestinal cells, which eliminated the defective cells, and by increased levels of antimicrobial lysozyme, and these effects persisted long after the initial treatment ended.
As someone already said - rapamycin literature is mostly in cancer and transplant patients and with relatively high-doses. The risks are real, but my clinical judgement would lead me to believe that for at least some people the benefits would far outweigh the risks
The bigger story with rapamycin is that the mechanistic target of rapamycin (mTOR) plays an absolutely crucial role in major diseases of modern civilization. One of the ways to inhibit mTOR for free is to simply stop consuming nutrients for extended periods of time.
As added information: metformin, a common anti-diabetic drug, is a inhibitor of mTOR. It potential adverse effects are less severe than rapamycin but are still significant. Specifically, long term usage can cause renal damage. Its mechanism of action has yet to be fully elucidated.
Can you source this? I believe you and I wanted to look into it. I googled this and I did not find anything explicitly saying renal damage. I did find many articles saying it's not safe to take if you already have renal disease but nothing saying that it causes it.
I even found articles that says it doesn't cause renal failure. I'm sure what you said is some real study just not popularized yet.
Ages ago, I had a colleague who was deeply into hacking of his mTOR pathway. Among other things, this included a permanent calorie deficit and removal of all protein from his diet.
I don't know if he's still alive. Maybe it was working a bit too well, I recall he looked like an extremely tall 13 year old with anorexia.
True but after I went very low-carb, I found fasting to be much easier when it had always been very hard for me previously. I know it's more complicated than "carbs cause hunger pangs ~8 hrs later" but my N=1 experience sure feels that way.
It’s simple, but not easy. Intermittent fasting is an easier way to start compared to traditional fasting. Imo it’s still better than other diets due to its simplicity.
> One of the ways to inhibit mTOR for free to simply stop consuming nutrients for extended periods of time.
What is an extended period of time in this context? I happen to consume all my meals within seven hours every day and only drink water in between. Would that help?
(Not doing this for health reasons, it is just a habit.)
This [1] study was pretty thorough on different fasting lengths. They tested 1422 patients for fasting lengths between 4 and 21 days, with a maximum calorie consumption of 200-250kcal and a moderate-intensity lifestyle program.
It concludes that all fasting lengths are beneficial, and are likely going to result in a) reduction in weight and waist circumference, b) beneficial effects on blood lipids, regulation of sugar and other blood-related parameters, including lower blood sugars and higher ketone body levels, c) an increase in physical and emotional well-being and absence of hunger, d) a high probability of decrease of pre-existing health-complaints, e) very limited chance of side-effects.
A good measure is whether or not you feel that empty, churning feeling in your stomach. Another good measure is if you're into the idea of eating something like plain cabbage or oats.
I don't think he _endorsed_ rapamycin or metformin. If he endorsed anything, I'd say it was NMN.
Everything people like Sinclair state should be taken with a grain of salt (as even his peers say he's guilty of making excessive claims) but it's forward-thinkers who change the world, not people following others' steps and afraid to take peek outside their box.
Maybe the guy will achieve something real in the field and maybe it'll be the next guy. No way to know. But I'm far from dismissing someone just because their opinions are not in line with popular knowledge. Boltzmann, Galileo, Copernicus and Wright brothers were discredited or ridiculed.
Lol, why do say that? I had the same impression of him.
It appears that people fall for his niceness is my theory about him. And no doubt he is a nice guy. It's just that his explanations lacked the rigor I generally look for.
Please, people. It's bonkers to jump from fruit fly results to humans.
Before you take any drug chronically - particularly something KNOWN to block a gene cascade receptor - be sure there are good studies (sufficiently powered, peer-reviewed, phase-III studies in humans with actual endpoints and significant positive results).
And be sure the "researchers" you're relying are not just PhD's or retired doctors regurgitating dubious studies.
Remember: the essence of a good scam is that it is partly true.
Readers will get more longevity from walking instead of reading these studies. Avoiding toenail fungus will improve your lives more. Those have real data behind them.
I have taken this drug several times of the past 10 years. Each time it had a different effect on my immune system and body systems. The first attempt, it really helped with ridding my body of sustained fluid in my lungs. In more recent times it had helped with the same thing. I have a lung disease and it's not a simple thing to treat so they take care to treat it with some new treatments like rapamycin. I am simply stating that I had different and somewhat difficult times while being on the drug. The lung disease that I have is not common and I am immunocompromised, so being on an immunosuppressant drug like this really made me feel ill. I had the influenza A one year while being on it, as well as a couple of cases of pneumonia that put me into a funk. I am glad I was on it, though because it got me to where I need to be. The liquid form tastes disgusting( ya gonna need a chaser) but the pill is not so bad. It did really effect my joints and muscle systems, I was taking from 2 mg down to .5 mg and each time the doses made me feel extremely tired. I am glad that this med is helping people and I hope all that are taking it, are taking this medication seriously. It is no easy task to be on. Drink lots of water.
Best wishes
When somebody asks about what is the next big thing, I always think on anti-aging. If you think that you don’t want to live forever, imagine that today when you arrive home you find a note saying that you will die exactly 1531[^1] days from today. How would you feel?
With that said, I would stay away from miracle drugs, because no two human beings have the same physiology. But that’s not an unsolvable problem.
[^1]: It’s a random number to “erase hope”. Not knowing when we are going to die keep us slightly hopeful and perky, our mind away from the problem.
Honestly, at peace lol. I don't really care about living.
My primary desire for living atm is keeping my family safe, providing for them, etc. Beyond that, i am living just because i am - and i enjoy life as much as i don't want to _not_ enjoy time i'm here anyway.
I would argue that a miracle anti aging drug would work well for the majority of the population, much like NSAIDs work well for the majority of the population. Bonus points for being cheap and easy to synthesize.
I think this is a great example of "what's good for the individual, is bad for humanity as a whole". Imagine we'd discovered a drug that adds 100 years to a persons natural life. Now imagine this drug was discovered 100 years ago. J.D. Rockefeller and the likes would still be alive and influencing politics. I can't even begin to think how much humanity would stagnate after such an invention.
See also the Planck principle: "A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it"
People don't need life-extending drugs to hold onto power or ways of doing things, that's what dynasties are for. And if in a democracy somebody like J.D. Rockefeller gets a voice that is too loud, then the democracy is flawed and we the citizens are ultimately at fault.
I'm 35, have been taking 6mg of rapamycin per week for about a year. It's hard to assign the effects directly to it since I've been taking other supplements and also fixing up my diet + exercise. That being said, I am quite sure that it has reduced general aches and pains, reduced visceral fat and I now have less gray hair compared to when I started. It did slightly increase my glucose and lipids, but still within safe ranges AFAICT. I'll continue to take it until I notice real adverse effects.
This comment is quintessential to the issue with HN.
So you are quite young, just had a complete change of lifestyle and your take away is that the beneficial effect comes from the drug you take randomly amongst a cocktail of other things.
Readit News
I'm currently taking 2mg once a week on my rest day; I started with 1mg and after 1 month added another MG. I'll continue each month until I reach 8MG once a week, which is the dosage the doc I worked with in Texas to get my prescription recommended and most people seem to take.
Also - I would say that NMN + Rapa is a completely life altering combination for anyone 50+. I feel like I can lift harder and longer now than when I was in my 40's and things seem to be getting easier the farther into my rapa routine I get.
Also also - you can find rapamycin online / overseas under its other name - Sirolimus - and the cost is a little lower than getting a proper US prescription.
I read up ok it. It can literally cause cancer.
Note also:
> We found that, when data from all organisms studied were combined for each compound, aspirin resulted in the highest percent increase in average lifespan (52.01%), followed by minocycline (27.30%), N-acetyl cysteine (17.93%), nordihydroguaiaretic acid (17.65%) and rapamycin (15.66%), in average.[0]
Though I'd consider whether flies and worms are good models for your human self.
0: https://pubmed.ncbi.nlm.nih.gov/34687363/
I feel compelled to comment though because anytime I read about how this stuff is only been tested in worms in mice… That automatically discount it’s worth as something to consider.
I’m gonna sah what I said before - I’ve played high-level hockey my whole life, I’m now 55 and I play against guys that barely washed out of their pro career.
When I stop taking nmn for two months my speed dropped from 20+ Mph to the mid teens.
A week after resuming my NMN supplementation my speeds are back in the 23-24 mph range
There’s just no way to fake it against players of this caliber. And to be clear I don’t know anybody even close to my age competing at this level.
Dead Comment
Anyway, I am tinkering with something in that space - feel free to reach out if you want explore being a co-founder. (email in about)
What can you tell me about it?
The problem is, no one wants to do those trials because rapamycin is cheap and generic. Why would Pharma spend money on something that they can't patent? Also, these kind of trials have to go on for 10+ years at a minimum - which is cost-prohibitive even if it is patentable (not to go in the weeds, but long trials count in the period of exclusivity given to pharma patents).
I believe the right approach is to use it off-label, be upfront about the potential risks, and collect lots of data so you can improve as you go. Practical anti-aging so to speak.
Another approach is through the NIH grant pathway, but that has a lot of road-blocks as well.
We can turn those parts off, while leaving everything else on, and be better for it (no allergies, psoriatic arthritis, MS, Chron’s, etc.; and so none of the accelerated cellular senescence those conditions provoke in affected tissue.)
A lot of recent pharma is already focused on doing specific forms of this at low levels. Every other drug ad in the US is for an immune-receptor blocker of some kind. And the side effects of these drugs come down mostly to the fact that they’re too low-level — they stop these parts of the immune system from being called into action at affected sites, but they leave it active and “patrolling”, such that it attacks harder any tissues that don’t absorb the receptor-blocker well, and such that you get withdrawal effects of potential inflammatory crisis if/when it wears off.
Just deactivating the relevant parts of the immune system entirely, on the other hand, provides the same benefits these drugs do, but with none of the “now the rowdy enforcers have nothing better to do, so they go looking for trouble” drawbacks.
Edit: it's an opinion article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/
On the contrary, the protection of the intestine to aging effects was due to increased autophagy in the intestinal cells, which eliminated the defective cells, and by increased levels of antimicrobial lysozyme, and these effects persisted long after the initial treatment ended.
It seems pretty safe anyway from my understanding…
Which is suggesting Ashwagandha might a candidate for Rapamycin and Metformin mimcry.
I even found articles that says it doesn't cause renal failure. I'm sure what you said is some real study just not popularized yet.
I don't know if he's still alive. Maybe it was working a bit too well, I recall he looked like an extremely tall 13 year old with anorexia.
That is not simple for most people.
What is an extended period of time in this context? I happen to consume all my meals within seven hours every day and only drink water in between. Would that help?
(Not doing this for health reasons, it is just a habit.)
It concludes that all fasting lengths are beneficial, and are likely going to result in a) reduction in weight and waist circumference, b) beneficial effects on blood lipids, regulation of sugar and other blood-related parameters, including lower blood sugars and higher ketone body levels, c) an increase in physical and emotional well-being and absence of hunger, d) a high probability of decrease of pre-existing health-complaints, e) very limited chance of side-effects.
[1] https://journals.plos.org/plosone/article?id=10.1371/journal...
Around day 3 or day 4 of a water-only fast or (the potentially easier but still effective option of) of a fasting-mimicking diet fast.
How frequently and for how long must one fast to see this?
Deleted Comment
[1] https://en.wikipedia.org/wiki/Lifespan_(book)
[2] https://lifespanbook.com/
Everything people like Sinclair state should be taken with a grain of salt (as even his peers say he's guilty of making excessive claims) but it's forward-thinkers who change the world, not people following others' steps and afraid to take peek outside their box.
Maybe the guy will achieve something real in the field and maybe it'll be the next guy. No way to know. But I'm far from dismissing someone just because their opinions are not in line with popular knowledge. Boltzmann, Galileo, Copernicus and Wright brothers were discredited or ridiculed.
It appears that people fall for his niceness is my theory about him. And no doubt he is a nice guy. It's just that his explanations lacked the rigor I generally look for.
Before you take any drug chronically - particularly something KNOWN to block a gene cascade receptor - be sure there are good studies (sufficiently powered, peer-reviewed, phase-III studies in humans with actual endpoints and significant positive results).
And be sure the "researchers" you're relying are not just PhD's or retired doctors regurgitating dubious studies.
Remember: the essence of a good scam is that it is partly true.
Readers will get more longevity from walking instead of reading these studies. Avoiding toenail fungus will improve your lives more. Those have real data behind them.
With that said, I would stay away from miracle drugs, because no two human beings have the same physiology. But that’s not an unsolvable problem.
[^1]: It’s a random number to “erase hope”. Not knowing when we are going to die keep us slightly hopeful and perky, our mind away from the problem.
My primary desire for living atm is keeping my family safe, providing for them, etc. Beyond that, i am living just because i am - and i enjoy life as much as i don't want to _not_ enjoy time i'm here anyway.
See also the Planck principle: "A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it"
https://en.wikipedia.org/wiki/Planck%27s_principle
So you are quite young, just had a complete change of lifestyle and your take away is that the beneficial effect comes from the drug you take randomly amongst a cocktail of other things.
Interesting.
I've never taken rapamycin nor even heard of it before today. I have less gray hair than I had twenty years ago.
My understanding is that gray hair suggests a B vitamin deficiency, especially PABA, and a need for adrenal support.