Animal trials are all on much higher dosages than we are taking

Yes - it can get confusing. The ITP uses ppm in food, but some other studies use mg/kg of body weight of the mice… thankfully, in some studies they estimate the equivalent dosing.

Yes that was the initial study. But that’s what it was. It’s really impossible to extrapolate anything meaningful from mice to human dosages in my opinion.

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“This highlighted that there are not strong and predictive linear correlations between overall and single species animal drug bioavailability and human values”

But, at this stage, we have had many studies of rapamycin studies in transplant patients and the present use of rapamycin by Dr. Green’s patients and forum users to get a broad idea of the range of rapamycin to take for longevity.

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We know what dosages various people are taking, but we have little or nothing meaningful about how well it’s working for people, as this is such a long-term thing. We’re all trusting that somehow it’s working. Yet it makes no sense to me that we imagine dosages such as 6-10-20mg/week will do anything at all when the only evidence that it works comes from animal studies where dosages many many times higher were used. Even were we to raise to 70mg/week, we’d still be far below the levels shown to work in mice, while suffering dangerous and intolerable side-effects (as well as some of us running out of money). I say this although I’m taking the stuff faithfully. I ran the numbers for the first time yesterday and it makes no sense to me. Unless I’m wrong - and I hope I am (please tell me what I’ve missed), it makes no sense for us to be taking it

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I won’t repost my thoughts on dosage, but I do believe 5 - 20 mg/week is effective for some things. Many people, including me, were expecting too much from rapamycin.
I have taken rapamycin from 5 up to 20mg/week with GFJ and EVOO for 9 months and have had some good results.
(Acarbose - Details On Another Top Anti-Aging Drug - #61 by desertshores)

Unfortunately it’s not studied enough. I’m taking it as immunosuppressant after kidney transplant and hope that it serves 2 purposes for me: keeps kidney from being rejected while keeping me young. Once I asked M Blagosklonny if it’s possible to kill 2 birds at the same time, he replied in the affirmative. So I’m hopeful. However, when I suddenly stopped taking Rapa for the whole 4 mo, nothing bad happened to my kidney. All markers were very healthy as if my system did not even notice it.

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This is a concern I share.
To what extent was mTORc1 inhibited in the rodent studies that showed the greatest increases in lifespan? I mean to remember Rapadmin made a post wherein it was discussed what different doses of Rapa resulted in what amount of mTORc1-inhibition in humans. And I thought even relatively lower doses of Rapa had a reasonable effect on suppression of mTORc1-signaling - but I can’t find the post anymore. This may be a silly question, but perhaps we should strive for a similar amount of mTORc1-inhibition - if feasible at all with the doses we are able to take without experiencing dangerous side-effects?

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Greetings Colin,

We had a Portuguese Water Dog (PWD), age 11, that was dying of renal failure. The vet did blood tests and prescribed refined Milk Thistle. Told us that our dog likely had a month of life left. I researched Milk Thistle’s success for canine liver failure and found no valid research. Desperate I researched everything on the Internet and quickly discovered Rapamycin. The vet had never heard of it and it took me 10 days of finding research to convince her to prescribe it for our PWD. She asked me to select the dosage. I used the research on humans as my baseline. I dosed our dog with 4 mg every three days. In a week all her liver failure symptoms went away. We continued on that dosage until the dog was 13.5 years old. At that age, she had lived well past all her litter mates which had died between 8 and 12 years. Because of declining energy, I upped the frequency of the 4 mg to every other day. She was free of all renal failure symptoms at 15.5 years old when we put her down due to severe arthritis.

I recently was diagnosed with severe Gout and minor arthritis at 69 years old. I believe that these autoimmune diseases were stimulated in me due to the COVID-19 vaccine. So I self-prescribed the same dosage that we’d given our PWD. I take one a week. My only side effect was a minor mouth rash the first week. I also have not had a second Gout relapse after two months of Rapamycin. I plan to continue taking it until something better comes along.

Cheers,
Alan Hoshor

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My own experience with various dosages implies that the dosages Dr. Green prescribes are effective. One constant indicator that the dosages prescribed are effective mTORc1 inhibitors is the slow wound healing I experience while on rapamycin dosages as low as 5 mg/week.

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Alan, welcome to the forums and thanks for sharing the positive news on your dog and yourself on rapamycin.

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Boy, I keep increasing the dose on this stuff. From 3 to 8 to 15mg. Who’s ready to try 100mg? :grin:

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IMO, from experience, you will get diarrhea long before you reach 100mg.

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The risks associated with high dosages outweigh the potential benefits in my opinion. Rapamycin levels drop quickly in the blood but we don’t know whether this applies equally to other tissues. There are studies that conclude that the negative effects (e.g., pneumonitis) associated with cycling to Sirolimus negate the benefits for its use for transplant patients. And this is where the drug that they want to cycle off of has significant negative effects.

I discount the studies that show negative effects from chronic use of rapamycin but at some point massive intermittent doses may produce similar effects. The animals that are tested have different metabolism’s than humans. So you can’t just translate dosages by comparing relative weights.

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I would not say with a half life of 60 hours that the levels “drop quickly”. It clearly hangs around for a number of days.

I think potentially a substantial dose followed by a long absence is best. I have so far taken 2mg and have not decided whether to increase the dose or not or when to take the next dose. I think there is an argument for a higher dose, but I wish to take the same dose to compare the results. I would not be surprised if the consensus moves to dosing at a much lower frequency than weekly.

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I take six MG but I am going to start taking five week breaks after eight weeks. The University of Washington studies indicate that the positive benefits are almost equal and there seems to be less risk of negative effects if you cycle off. I would have no concerns about 10 MG weekly. What concerns me is much higher doses coupled with grapefruit juice.

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What did your dog have kidney or liver failure or both?

To Alan Hoshor
As they say, all arthritis is inflammatory disease, whether autoimmune or not. But as for gout, (and I’ve had it, and I’m on allopurinol), I have not heard of any causal relationship with autoimmunity. You know, everyone says organ meats and fish raise uric acid, because of the digestive breakdown of DNA & RNA, that yields the purines, that makes the uric acid, that hurts my foot. But alcohol and especially fructose (which is also =50% of table sugar) drive uric acid and fatty liver (what got me almost dead 5 years ago). Great: Peter Attia 2-hr interview with nephrologist) Rick Johnson re fructose and obesity, and gout. Fasting also potently raises uric acid --all that catabolic recycling, you know. You know, hmm, arthritis and gout…be sure you know your kidney function is good – that might be where a vaccine overreaction could manifest.

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As I read the replies, I don’t see mention of Matt Kaberlein, co-leader of The Dog Aging Project (Rapamycin trials). I think his canine dosing would be sufficiently powerful yet safe. But I don’t know how you humanize the dose to account for size, metabolic rate, etc. What’s the dog-years math for that?

One reason you don’t see him mentioned is because he would never advocate that you do such a thing.