People pushing the upper limits of Rapamycin Doses - Any One Else?

Good points and I very much agree. For those very reasons I don’t think that a blood level has much value. It works better for things like digoxin and gentamicin that have narrow windows.
For visceral fat rapamycin wasn’t a miracle But when I combined it with a once a week fast and exercise on an empty stomach, the visceral fat loss was very impressive. Wasn’t possible without the rapamycin.

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Thanks. Hoping that with some more time I’ll see fat help!!

Doing 18 hr IF 2x a week. Do you think 24 hour 1x a week is better?

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From what I first read about rapa and then what I have seen in the 3 people that I know personally on rapa - all were re-setting their weight point - is nothing seemed to change at all until after 3-months use – nothing at all… then at approximately 15 weeks… that first pound goes, and a few days later another and another a few each week - it continues to take off the weight from 15 to 20 pounds over the next month. I will be curious if this happens to you. I developed an Adonis Belt and some abs (I do not do ab exercises at all). I want to add that not a bit of actual arm or chest muscle diminished for me or them… just the adipose tissue - FAT!

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So there is hope. Tks for the feedback on duration until something seen…that is an important point. I am assuming I have real rapa as got with script in USA pharmacy. I’ll keep on it as just getting to where you say it should kick in.
I do plank stuff and abs, some light free weights and walk a lot…nothing like you, but should be enough for an old guy!

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FYI - All were doing three 2mg pills – 6mg total once a week to get changes.

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I just completed my second round of using rapamycin bi-weekly at a dose of 20mg with grapefruit juice. At this dosage, I experienced adverse side effects of diarrhea and slow wound healing. I am now doing a washout period of 30 days or more. I am going to have a medical procedure so I want to be sure I don’t have any adverse effects from rapamycin. Each round of rapamycin for me is the use of 100, 1mg tablets I receive from India.
I am going to get some comprehensive blood tests in the next two weeks to see what I have accomplished by taking a high dose of rapamycin every two weeks with grapefruit juice. Some possible positive effects I didn’t expect were a loss of weight due to a loss of appetite and a decreased resting heart rate. My resting heart rate is 48 bpm. I now have to force myself to eat enough to keep from going below my recommended weight range. My next round of rapamycin will start at 10mg with grapefruit juice and I will adjust accordingly to the point of having some adverse side effects. I am 81 yrs old.

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Wow - I think thats a record in this group. I have not heard of anyone reaching this blood sirolimus level before. Do you get any side effects? How long between doses? Have you been doing this high a level for a while, or just this one time?

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I’ve been taking 12 mg with grapefruit or grapefruit juice for the last 6 or 7 months, every two weeks. The last two months, I did stop for the 3 day fisetin Mayo clinic regimen, starting rapamycin again three days after the last fisetin dose. So, those times, twenty days passed between rapamycin doses. As far as side effects and benefits, there’s been nothing of note. I was hoping my arthritic knees would improve, but they still hurt.

I don’t think I have the dosage record. Look just above. Desert Shores was taking 20 mg with grapefruit juice every two weeks. My ng/mL level was higher than I expected, since another person on here took 5 mg with grapefruit and got 17 ng/mL.

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That would be me.

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EnrQay, yours is the only other peak ng/mL test I’ve seen here so far. Since it isn’t all that expensive and takes very little time, we may begin to see a few more.

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Wow you were out to absolutely CRUSH the CYPA34 enzyme!

Is this your normal dosing protocol?

Can you advise for how long you were on the 12mg/GFJ/2 weeks regiment before this test?

Cmax at 2 hrs 68 ng/mL at 12mg with GFJ+

Note: Definition of Cmax:

Data From This Paper:

Looking at the 15mg, Cmax 50.3 without GFJ, and 127.9 with GFJ. Of course, it’s very hard to capture peak unless your’re doing many short interval blood draws after dosing.

Just to put your single data point in reference, you’re definitely in some type of therapeutic range, and no apparent side effects.

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MAC, I’ve been doing it this way for the last 6 or 7 months. The only change has been that sometimes I used bottled grapefruit juice and other times whole grapefruit. I think next dose I’ll just have one grapefruit or glass of juice with the pills.

@rivasp12.

Forgive my ignorance, but do you distinguish at all between bacterial and viral in the context of Rapamycin/immune function/response?

re eGFR, we know from a multitude of longevity studies, gene expression/function of liver and kidney appear to be HUGELY correlated with longevity markers. All my liver/kidney function markers significantly improved after Rapamycin. My eGFR is of a 20 yr old, and I’m 57. Of course, I do a lot of healthy things (healthy user bias) as a starting point.

The only really wonky marker is URIC acid…it has plummeted to below lab range. Not sure if this is all Rapamycin because I am normally lowish on a low protein/ketogenic diet.

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Good to know, your n=1 very useful data point.

Would be “nice” to a trough level Sirolimus blood test just before your next dosing/Sirolimus Cmax test. Between these data points and the known half life/pharmacokinetics curve, we can do some modelling of your “dosing” AUC curve.

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I was thinking the same thing. With the 6 fisetin days in between the last two rapamycin doses, that’s 20 days, and I’m pretty sure there wasn’t anything measurable left over from the previous dose. But could there be if measured with 14 days between? I’ll do a trough day test and post it sometime soon.

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Note, on your chart the AUC levels for 20 mg with GFJ are no higher and less than many lower doses without grapefruit juice. That is why I like the idea of not spending too much time at a high-level UAC to avoid affecting mTORC2 and immune function.
If I am reading the table incorrectly please point this out.

Here you go, half life calculator for Rapamycin starting at 42 mg equivalent. Not much left after 20 days.

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This calculator is great, but its also just a rough approximation. The studies have shown very significant variation in people. See this study:

From Here:

Full paper included in the post: Rapamycin Clinical Studies in Healthy People

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@desertshores

The AUC with GFJ is (as concluded in the study) is 350% higher with GFJ (taken the morning of as reference point) vs without GFJ.

“grapefruit juice increased Sirolimus AUC approximately 350%”

If you look at the 15mg row (bottom half of table) and Column 6, AUCoo without GFJ (0), 858, and AUCoo with GFJ (1), 4361.

It’s complicated with alot of overlap but generally cytotoxic T cells and NK killer cells are involved with viruses while neutrophils attack bacteria. Antibodies are involved with both. NK cells also very involved in attacking cancer cells.
With profound neutropenia we get very worried about bacterial infections .