The Key issue of Dosing Levels and Intervals for Best Rapamycin Outcomes

i weight 160lb (40 years old) and usually do 7mg a week

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its $5-6 a mg

FWIW…

62yo - male
190lb, 6’1" height
6mg{currently 2mg x3}
Eat one GF wait one hour, then take with sardines in OO

Have been think/considering to increase the dose.

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I currently am taking sirolimus every two weeks, at a dose of ~0.35 mg/kg.
I decided to do biweekly dosing after reading this article and doing a rough extrapolation of the half-life of sirolimus in humans vs. mice.

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system - Lamming Lab.pdf (574.9 KB)

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I think that’s the highest dosage I’ve heard of. It would equate to 26mg/fortnight for me

So using this data to extrapolate from MKs TRIAD dog dosing you get:

0.15mg/kg/wk x 0.541 = 0.081mg/kg/ wk

Or 6mg for a 75kg individual

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Has anyone else looked into the effectiveness of the actual grapefruit rind and peel in contrast to the fruit and juice? I usually blend one-half of a white grapefruit, skin and all, before taking my rapa dose. I use a natural low-glycemic sweetener to mask the extra bitter taste. (Is “bitter taste” a chemical hint?). I base my method on a few studies I’ve come across that seem to indicate it may be beneficial. I don’t like getting a bunch of sugar from the juice either and it might be more reliable than bottled and processed juice. Identification of epoxybergamottin as a CYP3A4 inhibitor in grapefruit peel - PubMed

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The effect of grapefruit juice on drug disposition

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As usual, we need a study that shows peak and AUC effects of GFJ and now GF peel. It’s hard to say what the equivalence between the two might be.

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I share your concern of eating an entire grapefruit for the CYP3A4 inhibition, as I’m strict keto, eschew anything sugar/glycemic. I eat no fruit, except for some blueberries/blackberries. But I bite the bullet for the longevity hack. I do the dual GFJ protocol…one the night before, and one the morning of rapa dosing.

Not sure the absolute level of inhibitors just in the skin vs the major juice meat. I am going to guess the peel has much less absolute inhibitor, and in the context of maximizing the Rapamycin signal, I’d not risk just going with rind only. You may never find this experiment done with Rapamycin.

Unless you don’t want to consume anything sugar, why not just completely reduce your “sugary” consumption in the day(s) leading to the Rapa dosing, and then just eat the grapefruit as a compromise?

Bottled grapefruit juice is normally loaded with sugar.

Do you eat any fruits or carbs? If you do, you surely are getting a glycemic spike at other times.

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Just wondered whether you uncovered any additional data on CBD’s potential interaction with Rapamycin?

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I have not looked - but I have seen people talk about it in the forums:

See: Improve Bioavailability of Rapamycin (pt 2) - #41 by KFISH

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I paid $400 for 100 but then found a supplier who will sell me 200 of the same brand Biocon ( not generic) for $300

Dee, just to clarify. The “brand” version of rapamycin is the Pfizer Rapamune. This was the first version of the drug that came out in the late 1990s and is still produced today. All the other versions of rapamycin (sirolimus) are generally referred to as generic (though of course they are made by companies / brands). I know, its confusing. We have a full list of all the different companies that produce rapamycin / sirolimus which I will link to below.

As far as pricing - there are many online pharmacies that sell Biocon and other generic versions of rapamycin for typically $0.75 to $1.25 per 1 mg. See the list and people’s discussions here: Rapamycin Naming Conventions (part 2)

Full list of all the vendors / versions of rapamycin and related molecules here:

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I’m not a fan broadly but I can see the rationale for longer 3+ day fasts. Feels like this is typically only practiced once a quarter else the ‘side effects’ would outweigh the benefits?

Perhaps Rapamycin could be administered in a similar style. One huge dose per month perhaps?

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Hi Diana
A good book for Rap is Rapamycin mTor Autophagy & treating mTor syndrome , on Amazon $14.99 , a great read

I am 82kg and taking 6mg per week.

Those transplant doses are comparatively very high - but they want to be immunosuppressed and we don’t (right?) so we should take significantly less than that…

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Indeed transplant or cancer therapy doses are very high…typically several mg PER DAY to hit target trough/AUC. Your 6mg/week is likely low immunosuppression.

The unknown question is immuno-dampened vs immuno-suppressed vs immuno-comprised vs human longevity? Is one of these (or other modality) OVER LONG TERM associated with lifespan extension? Can we inhibit mTOR sufficiently, accept a major immuno perturbation, and yet side step a premature morbidity to escape into lifespan extension??

Do one of these setpoints actually contribute to the longevity signal?

Here’s a very in depth immuno study on transgenic immunocomprimised mice on rapamycin, levels that in parallel to immuno exploration extend lifespan as validation model.

Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune-deficient mice (2015)

“Our extensive data show that longterm rapamycin is a potent immune modulator and not clinicallyimmunosuppressive in numerous scenarios. Our demonstrations of preserved na€ıve phenotypes in B and T cells in aged mice on eRapa support potential benefits for antigen-specific immunity and could be related to its reported rejuvenating effect on hematopoietic stem cells

The lifespan figure below is 2 models of IMMUNO COMPROMISED mice:

As you can imagine, it’s incredibly complicated, we don’t have the answer. Will submit that escalating dosing will surely impact immuno markers further, and only a sufficient sample size of n=1 will elucidate some further insight to this important question. We will need some brave (crazy?) soldiers.

66 y/o female
115 lbs, 5’4" height
4mg (2mg x 2)
Dasatinib 50mg once a month 60 hrs after weekly dose of Rapa)
Will test for trough levels & possibly increase by 2mg.
No side effects

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This is interesting and complicated. We assume that dampening organ rejection means immunosuppression, but it might mean immune modulation which is really a whole other animal.
MAC, I saw on one of your other posts that patients on chronic everolimus has fewer viral infections ( CMV). So maybe you can have less organ rejection while boosting anti viral and anti cancer fighting.

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