955 replies to this topic

[QuestforLife]

Rodent studies in medicine often dont tanslate into human beings - they are not as compelling as randomized data on 200+ humans.

I agree, human data though tentative at this point, is very, very promising - rapamycin even seems to reverse some aspects of aging (and the dog aging project seems to report something similar).

I'm going to go back and revisit my calculations on mice to human doses, but it may be that there is more to the mechanism of action than we've uncovered so far.

[XRT doc]

In a lot of fields like cancer, less than 1% of drugs that are efficacious in rats translate into humans. In Alzheimer's rodents models it is 0%. studies often arent even reproducible between labs (especially ones from China) 

 

https://www.nature.c...ibility-1.19970

 

I am new to board, but people are making a lot of false conclusions and failing to contextualize the research. I am excited about rapamycin because of human trials, but mostly the consensus of experts in gerontology.

Edited by XRT doc, 06 March 2018 - 02:35 AM.

[Nate-2004]

 

 

The whole point of using intermittent rapamycin dosing is to get a high Maximum to knock down mTORC1, but a nice low Minimum to avoid knocking down mTORC2. So, for example my dose of 2mg a week assuming a 65 hour half life gives you a Maximum (after repeated dosing) of 2.4mg and a Minimum of 0.4mg. Alan Green takes 6mg a week, so that gives you a Maximum of 7.2mg and a Minimum of 1.2mg.

 
I could swear that in one of these Rapamycin threads someone posted a link to a study that determined intermittent rapamycin for the purpose of avoiding mTORC2 inhibition was not enough to inhibit mTORC1 to any effective degree but now after scouring all the posts and using the search tool I can't find where that was or recall who posted it. It was *the* post that turned me off of rapamycin.

 

 
I expect that you're thinking of a series of posts from me, most notably this one (followed up here and here; but I'd suggest looking at this first, to understand the evidence base behind those).

 

At absolute, bare minimum, people should be investing in therapeutic drug monitoring: between genetic variability and other factors, even getting to levels that might plausibly work without overshooting is a crapshoot.
 

The best evidence for this is the mannick study: 219 pts in australia randomized to different dosing of rapamycin
https://www.ncbi.nlm...pubmed/25540326

As already pointed out by others, that study used everolimus, not rapamycin — a different drug with different pharmacokinetics. It's useful, but the best evidence on using it as an anti-aging drug is still the rodent data, plus human PK data.

 

 

Those are the posts I'm talking about. That's why I decided not to spend my money on it, although the price looks like it has come down a bit since then. I didn't even realize they weren't using rapamycin in that study, I think it just said mTOR inhibition and they think oh rapamycin. 

 

I agree that human trials are better all around but what about this other drug RAD001, everolimus? What's the deal with that one? Why not try that instead?

Edited by Nate-2004, 06 March 2018 - 03:55 AM.

[QuestforLife]

 

I agree that human trials are better all around but what about this other drug RAD001, everolimus? What's the deal with that one? Why not try that instead?

 

 

Expense.

 

The shorter half life would allow you to take a bigger dose, so certainly when the price comes down this will be on my list. A quick online search reveals that all patents will expire on it by 2022.

 

But as I'm only 39 I'm happy with a low dose rapamycin for now.

[Benko]

Quest labs charge $235 for a rapamycin blood level,  Given the cost of the drug and the pharmacokinetic variability it would seem a good idea (as I think Michael pointed out).  You might be able to get it cheaper by contacting one of the online discount labs.

[Benko]

Here is the link to quests info on the pharmacokinetics

http://www.questdiag...limus_Rapamycin

[smithx]

It's an interesting study, but they were using Everolimus, not Rapamycin

The best evidence for this is the mannick study: 219 pts in australia randomized to different dosing of rapamycin
https://www.ncbi.nlm...pubmed/25540326

[FrankT.Hippo]

Hello,

 

I have been taking rapamycin for a mitochondrial disorder (complex I & III). I can say that I am 95% confident that it is having a substantive positive effect. I have increased energy, mental clarity, and stamina. I have cycled on and off since march 2017 and when I am on I rebound and when off I regress.

 

2mg /week, skip every other two week. 

 

40 years old, 180 lbs.  Movement disorder, physical and mental fatigue, exercise intolerance, executive function issues, headaches, insomnia, minor sensory-neural hearing loss, etc.

 

Supplements: CoQ10 800mg/day, MitoQ 5mg/ every other day, creatine 5g/day, Curcumin 1000mg/day when cycling of rapmycin, vitamin D/C/B complex, DHA 1000/day (when I can afford it), & cerebral folate (for deficiency diagnosed by spinal tap).

 

The only major issue is that it depresses my immune system and I am susceptible to infections when on (from warts on my hands to colds).

 

 Anyways, I need a resupply. I was wondering if someone has advice regarding a reliable vendor.

 

Thanks upfront for the time. 

 

 

[Nate-2004]

I'd like the same advice as the above, I tried Alibaba but I can never get a response on there.

 

Also another question here on rapamycin. What about instead of intermittently dosing at small amounts once a week, why not do a week of 2mg per day, 7 days, every three to four months instead? Is that long enough to affect mTORC2?

Edited by Nate-2004, 05 April 2018 - 07:33 PM.

[smithx]

Daily doses of rapamycin will suppress your immune system, potentially leading to all kinds of unpleasant things from mouth sores to cancer.

Intermittent is the way to go (if you do it at all, that is).

Also another question here on rapamycin. What about instead of intermittently dosing at small amounts once a week, why not do a week of 2mg per day, 7 days, every three to four months instead? Is that long enough to affect mTORC2?

[StanG]

"Also another question here on rapamycin. What about instead of intermittently dosing at small amounts once a week, why not do a week of 2mg per day, 7 days, every three to four months instead? Is that long enough to affect mTORC2?"

 

A dose of RAPA stays in your system for 6 days so you can only take it weekly. I skip every 5th week to make absolutely sure it doesn't build up in my system.

[Sith]

Does anyone know any cheaper suppliers? The pricing seems ridiculous for long term sustainability.

[PAMPAGUY]

I buy Sirolimus 1 mg. x 300 for $1.60 mg., shipping $8 from dropshipmd.com.  They are very good and reliable.  Have had 3 orders delivered.  If taking 6 mg. week that is $500 yr.  Seems reasonable to me for a drug that can save your life.  This is not a supplement it is a strong Rx drug.  Been taking for 15 months.  Rapa is reserved for people over 60 or someone with a particular disease treated by mTor inhibition.  People younger still strong where mTor has not started to act up.  Delays the onset of most elderly diseases such as Cancer, Alzheimer, renal failure, arthritis, BPH., lack of energy, high blood pressure and frailty.   It is the only treatment that has extended life in every organism tested on.

[RWhigham]

 

 

Rapa is reserved for people over 60 or someone with a particular disease treated by mTor inhibition.  People younger still strong where mTor has not started to act up.  Delays the onset of most elderly diseases such as Cancer, Alzheimer, renal failure, arthritis, BPH., lack of energy, high blood pressure and frailty.   It is the only treatment that has extended life in every organism tested on.

 

The 60 yr old starting age is per Dr Green.  But the father of anti-aging with rapamycin, Mikhail Blagosklonny, is thought to have been taking rapamycin for some time, and he is just now 57 years of age. His early paper was 10 years ago (in 2008), Ros or Tor, in which he points out that rapamycin will inhibit the formation of senescent cells. We know senescent cells don't wait for you to turn 60.

 

 

Edited by RWhigham, 08 April 2018 - 10:52 PM.

[QuestforLife]

I've corresponded with Dr Green many times and he has stated to me that taking low dose rapamycin  in your 40s (2mg per week), is very smart. So its not just for people 60+. Even at 40 (actually I'm 39) I've seen athletic benefits, so I theorize that it isn't just about suppressing geroconversion (arrested cells converted to full senescence). It is clearly also having a beneficial effect on the mitochondria of the heart, based on what I and others I correspond with have experienced. 

 

I got about 3 years supply from dropshipmd. It was a complete arse to do as I had to get my bank to do a wire transfer to India. They kept coming back with more questions, sent the wrong amount etc,. but it eventually got sorted. At least I won't have to do it again for a few years.

 

Any company in India selling at dropshipmd prices and smart enough to set up a PayPal or Bitcoin account is going to make a lot of money!

[PAMPAGUY]

I've corresponded with Dr Green many times and he has stated to me that taking low dose rapamycin  in your 40s (2mg per week), is very smart. So its not just for people 60+. Even at 40 (actually I'm 39) I've seen athletic benefits, so I theorize that it isn't just about suppressing geroconversion (arrested cells converted to full senescence). It is clearly also having a beneficial effect on the mitochondria of the heart, based on what I and others I correspond with have experienced. 

 

I got about 3 years supply from dropshipmd. It was a complete arse to do as I had to get my bank to do a wire transfer to India. They kept coming back with more questions, sent the wrong amount etc,. but it eventually got sorted. At least I won't have to do it again for a few years.

 

Any company in India selling at dropshipmd prices and smart enough to set up a PayPal or Bitcoin account is going to make a lot of money

Guess Dr. Green changed his mind on over 60 for rapa.   I visited Dr. Green last June for a physical and Rx's. I have also used dropshipmd and was pleased.  No Rx. Your right, wiring money is a pain in the ass.  I think the India Mart has a program where Indian pharmacy companies can charge on Visa/MC by going thru them,  and India Mart guarantees delivery.  Going to check it out and will post.

 

PS -Anyone not using Nicotinamide + Riboside (NAD precussor) is missing the other half of the equation for long and healthy life.

[Nate-2004]

I realize this is a rapamycin thread but why is nobody talking about Everolimus, which showed more promise in human studies than Rapa did? I'd like to know where I can get Everolimus.

 

Wiki:

 

 

Compared with the parent compound rapamycin, everolimus is more selective for the mTORC1 protein complex, with little impact on the mTORC2 complex.^[15] This can lead to a hyper-activation of the kinase AKT via inhibition on the mTORC1 negative feedback loop, while not inhibiting the mTORC2 positive feedback to AKT. This AKT elevation can lead to longer survival in some cell types. Thus, everolimus has important effects on cell growth, cell proliferation and cell survival.

Edited by Nate-2004, 09 April 2018 - 12:21 PM.

[PAMPAGUY]

I realize this is a rapamycin thread but why is nobody talking about Everolimus, which showed more promise in human studies than Rapa did? I'd like to know where I can get Everolimus.

 

Wiki:

$10 mg last price I saw for the rapalog Everolimus.  Also, Tor2 is a non event for weekly rapa users.  Been on it for 15 months.  Reason Everolimus was used is because drug companies sponsored the trials and want to sell it.  Just like NR, stick with drugs or supplements you can make money on.

[Nate-2004]

$10 mg last price I saw for the rapalog Everolimus.  Also, Tor2 is a non event for weekly rapa users.  Been on it for 15 months.  Reason Everolimus was used is because drug companies sponsored the trials and want to sell it.  Just like NR, stick with drugs or supplements you can make money on.

 

True, but nevertheless it's still the only human data we have on intermittent dosing.

[DbCooper]

I have done two months of Rapamycin (1mg per week Rocas brand from India) thus far. The way Ive been doing it is 1mg every 6-7 days for one month, then take a month off. My "on" month started again today and I purposely ate a 1 small grapefruit 15 min before taking my Rapa. I am 39 and in good condition.

 

I assumed that because I started my Rapa a few months back, in the midst of one of the more serve cold and flu seasons, I would be constantly sick.  Completely subjective, but I am amazed that I wasn't sick once.  Usually I come down with a seasonal sickness once or twice a winter, but as of this writing, nothing. I even have a small medical procedure with the potential for infection and I healed quickly and without incident. Anyone else experience this?

[poonja]

In regard to your drinking grapefruit juice.  I assume you are trying to increase the impact of the rapamycin.  It is my understanding that if that is, in fact, your intention, you should wait three to four hours between the grapefruit juice and the rapamycin.  That is what I do.

[DbCooper]

In regard to your drinking grapefruit juice.  I assume you are trying to increase the impact of the rapamycin.  It is my understanding that if that is, in fact, your intention, you should wait three to four hours between the grapefruit juice and the rapamycin.  That is what I do.

 

 

I never said I drank grapefruit juice.  Anybody who's used grapefruit ingestion to enhance the kick of magic mushrooms can tell you, you don't need to wait 3 hours after eating a grapefruit to dose. 15 minutes is plenty more than enough to enhance things. 

[QuestforLife]

True, but nevertheless it's still the only human data we have on intermittent dosing.

 

We've discussed everolimus before - it is better than rapamycin because of its shorter half life, which allows one to take a larger dose and suppress TOR1 more profoundly, with less chance of suppressing TOR2. But we'll have to wait till 2022/3 for it to be off patent.

[Nate-2004]

We've discussed everolimus before - it is better than rapamycin because of its shorter half life, which allows one to take a larger dose and suppress TOR1 more profoundly, with less chance of suppressing TOR2. But we'll have to wait till 2022/3 for it to be off patent.

 

I hate the patent system.

 

Is it that expensive? Maybe it's worth just waiting till then, that's only 4 years or so. I'll be 47 or 48.

[tintinet]

I hate the patent system.

 

Is it that expensive? Maybe it's worth just waiting till then, that's only 4 years or so. I'll be 47 or 48.

 

 

Nah- just wait for the next more expensive drug to follow everolimus!

[Painkillerrr]

Sorry i wrote some pointless stuff

Please if you can, delete this post

Edited by Painkillerrr, 11 April 2018 - 07:40 PM.

[BioHacker=Life]

Just ordered some rapamycin tabs to try out. What's everyone using for dosing?  2.5 to 5 mg a week is what I've been told.

[Nate-2004]

So 6mg a day with a 30 hr half life for a week is obviously way too much as indicated in a reply to my earlier post. However, what if you were to instead go a week starting with 5mg, followed by 2mg every other day and ending after a week, waiting a month then going again? This would also be coupled with berberine + MCT oil OR perhaps metformin, 400mg, 3x daily.

 

Also what if you throw in fasting or time restricted eating of some kind and perhaps also maybe NR + Liposomal Resveratrol?

 

Not recommending this, just asking what if.

 

Just trying some of the alternatives to the dosing schedule in the earlier posts by Michael on what hasn't worked so far.

Edited by Nate-2004, 12 April 2018 - 08:52 PM.

[BioHacker=Life]

I hate the patent system.

 

Is it that expensive? Maybe it's worth just waiting till then, that's only 4 years or so. I'll be 47 or 48.

 

I got 12 5 mg rapamycin tabs for $90. It's not cheap but if I only need to take it for a few months to kill all my zombie cells I'm ok with it.

So 6mg a day with a 30 hr half life for a week is obviously way too much as indicated in a reply to my earlier post. However, what if you were to instead go a week starting with 5mg, followed by 2mg every other day and ending after a week, waiting a month then going again? This would also be coupled with berberine + MCT oil OR perhaps metformin, 400mg, 3x daily.

 

Also what if you throw in fasting or time restricted eating of some kind and perhaps also maybe NR + Liposomal Resveratrol?

 

Not recommending this, just asking what if.

 

Just trying some of the alternatives to the dosing schedule in the earlier posts by Michael on what hasn't worked so far.

 

Seems on the high side based on what I've read. I currently do modified CR and the best form of transresveratrol.

[Nate-2004]

I got 12 5 mg rapamycin tabs for $90. It's not cheap but if I only need to take it for a few months to kill all my zombie cells I'm ok with it.

 

Yeah same, I also got quoted on x100 1mg tabs for $250, which is 20 5mg tabs basically. Definitely more expensive than yours. Wish we had a good recommended U.S. located lab to test sources.

 

 

 

Seems on the high side based on what I've read. I currently do modified CR and the best form of transresveratrol.

 

Well, basically this would just be maintaining roughly a 5mg level in your system for a week then stopping for a month, vs going once a week with 5mg, which would be around .03mg left in the system by day 7.

 

In my proposed method you'd have it in your system for longer than a week but you would be cycling it in a way that gives you a longer break.

Edited by Nate-2004, 12 April 2018 - 08:57 PM.