I Started Rapamycin Today

Does anyone know the basis for 6-8 mg recommendation by those who specialize in Rapa? I’ve been trying to convert the mouse study dosing to human dosing and get a much higher number, but I’m probably overlooking something. For example, in the ITP studies they used 42 ppm which converts to 7mg/kg for mice. I thought, probably mistakenly, that the conversion factor for human equivalent dosing was to divide this number by about 12. So for a 80 kg person this would be 47 mg. That seems awful high but I’ve read that the optimal dosing for cancer patients in 90 mg!

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I’m curious of this as well. I’m wondering if it was just… someone arbitrarily picked it… and then a bunch of people followed suit. I’m tempted to push it way up.

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Dr Blagosklonny likes to say that the proper dose is the highest dose an individual can take without side effects. I’m not sure how literally he means that, but I think the principle is that it might be different for different people and that most people will hit side effects before they run out of dosing that would give them more benefit.

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From Dr. Attia and Kaeberlein The Drive Interview. Here is the study where the idea of 6-8mg once a week comes from. Joan and Team looking a rapamycin boosting the flu virus immune/vaccination response in elderly people 65 years or older. Link: 175 - The biology of aging, rapamycin, and other interventions that target the aging process - YouTube Go to this part of the show 45:17 in the podcast for rapamycin dosing information. Pretty much this is it!

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The weekly dosing schedule, and that dose range is roughly based off the clinical studies of Everolimus done by ResTORBio in 2017 and 2018 time period, where that range seemed effective in terms of improving immune response, but with minimal side effects.

It has nothing to do with the mouse studies (which are much higher, but mice are kept in sterile and pathogen free cage environments - so high immune suppression may be less of an issue for them than for humans who interact with outside world).

The dosing is discussed in this thread: What is the Rapamycin Dosing / Dosage for Anti-Aging or Longevity, and Life Extension?

Full ResTORbio paper here: Sci-Hub | TORC1 inhibition enhances immune function and reduces infections in the elderly | 10.1126/scitranslmed.aaq1564

(note RAD001 is Everolimus, a rapalog). More details on Everolimus here: Everolimus instead of Sirolimus / Rapamycin? Anyone else trying?

Summary of paper:

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More generally, there is significant evidence that higher doses (at least in male mice) result in better lifespan results. The issue is that the side effect at some point when you go higher (at least if you go higher for any length of time) is immune system suppression… and if you are exposed to a serious infection at that point, you’ll likely get that serious infection, and the results could be … well, serious.

Its a balancing act. And at some point it would be really valuable to understand this - and its likely to be variable by person, and their environment and exposure to germs, etc…

Here are some past discussions on the higher doses issue.
Here: One User Trying Very High Doses of Rapamycin, and Negative Adverse Events / Results
Here: What Questions Do You Have on Higher Doses of Rapamycin, 60% Remaining Life Expectancy Improvement Study?
Here: Ideas on Protocols for Testing Higher Rapamycin Doses

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Peter also has good interviews with people directly involved in the ResTORBio clinical studies - (Joan Mannick and Lloyd Klickstein ) good listening too for the details on the clinical trials:

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With immune suppression, not only are you more likely to get infections, but you’re also less likely to be able to wipe out cancer cells via immune surveillance.

Of course, there’s some debate now on whether rapamycin actually is an immune modulator rather than an actual suppressant. Blagosklonny has written that rapamycin suppresses hyper immunity or the type that would be seen in autoimmune diseases.

As far as dosing is concerned, Alan Green was one of the clinical pioneers using weekly doses in humans about 6 years ago and his dose at that time was 6 mg’s per week. Many of us just emulated his dosing, especially since his response was so remarkable.

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Dose twenty-six 8mg{2mg X 4, Dr. Reddy’s Brand] - 08/16/2022 was two day late. Had to get refill. Normally I take on Sundays.

With wild sardines in OO. Had no adverse effect with last week’s dose. Did not have the GF/GFJ, did not have time.

This is the six months mark.

At 6mg / week does Alan Green have his patients take Rapamycin fasted, food in general, or specifically with fatty meal?

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He’s never given me specific advice in that regard, but maybe he has with others.

Thanks. I’ll do a little digging myself. I just started last week and i’ve already ruled out grapfruit juice because i don’t want to add any more variables, there seems to already be so many unkowns with this medicine i feel theres no need to complicate it, and I’m still fairly young (40)

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Dose twenty-seven 8mg{2mg X 4, Dr. Reddy’s Brand] - 08/21/2022

Had 14oz GFJ, waited approximately 45 minutes. Took with wild sardines in OO. Then took another 14oz of GFJ approximately 1½ hour later. Had no adverse effect with last week’s dose.

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Out of curiosity, why do you take GFJ after taking Rapamycin? Shouldn’t you take it all beforehand as you are trying to knock out the enzymes before your Rapa is absorbed?

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Dose twenty-eight 8mg{2mg X 4, Dr. Reddy’s Brand] - 08/28/2022

Had one large organic GF, waited approximately 1 hour.

Had with wild sardines in OO.

Had no adverse effect with last week’s dose.

Am planning on increasing dose in the near future.

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Dose twenty-nine 8mg{2mg X 4, Dr. Reddy’s Brand] - 09/04/2022

Had 14oz of GFJ, waited approximately 1 hour.

Had with wild sardines in OO.

Had no adverse effect with last week’s dose.

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Thanks for doing this Joesph! These updates provide a great record for the rest of us!

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Dose thirty 8mg{2mg X 4, Dr. Reddy’s Brand] - 09/11/2022

Had ¾ of a large organic GF, waited approximately 45 minutes

Took with wild sardines in OO.

Yes, I still took my weekly dose.

Last week several time start adding /using my rapamycin/DMSO{amount is around 1.5mg per ml of rapamycin in DMSO, diluted with 0.9 sterile saline, DMSO around 30%] topical on skin dip finger in solution rub on inside wrist radial artery area. Also around my left front knee area, under the knee cap. Also a dab behind each ear and rub some on my forehead hair line area.

I do not think it was more the 1ml total liquid amount used.

Late Friday have a very small ulcer in my gum upper inside lip area side where the gum and inner lip join. First time since talking rapamycin, started on 02/20/2022

FWIW, the DMSO is transporting the rapamycin very well through the skin.

This was going to be the solution for intranasal at a lower % of DMSO, I had an issue while mixing, when I added the 0.9% saline saline had instant crystallization develop in the solution. So I increased DMSO amount, just to use topical on skin area.

Still working on a intranasal solution mix.

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FWIW

Dose thirty one 8mg{2mg X 4, Dr. Reddy’s Brand] - 09/18/2022

Had 16oz of GFJ, waited approximately 1 hour.

Took with wild sardines in OO.

Also added my rapamycin/DMSO{amount is around 1.5mg per ml of rapamycin in DMSO, diluted with 0.9 sterile saline, DMSO around 30%] topical on skin, dip finger in solution rub on inside wrist radial artery area and the top of both hands. Also a dab behind each ear and rub some on my forehead hair line area.
The total amount was less than 1ml.

Had no adverse effect this past week.

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Instant crystallisation when diluting a DMSO/Rapa-mixture with saline (in his case I mean to remember it was demineralised water), is also what MAC mentioned. This is a pity, as there doesn’t seem to be an easy way to avoid using 99.9% DMSO.