20 Mg of Rapamycin every other week

Been on 20 mg of Rapamycin every other week since end of September. No issues whatsoever and perhaps placebo here—but feel more energetic and sleeping better. Just an update. Anyone taking higher dose out there? IF so, results?

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Blagosklonny said in his latest Tweet that he is going to take Rapamycin up to 24 mg soon.

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I was at 20mg every two weeks, but I adjusted to 12 mg. last week and will take a few weeks break prior to my covid booster shot.

I also started 20 mg bi-weekly in Sept. Blagosklonny and Green both went to that dosing protocol. I take it with 400 grams. Grapefruit Juice. I cannot get pills in Spain so I order Rapa powder and mixed with Lactose. That was 2 years ago and it works well. Tried to go to 23-27 mgs, but did not feel good also had trouble staying asleep at night so I went back to 20 and have been happy.

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Is 6mg rapamycin + grapefruit equivalent to pure 20 mg rapamycin? Due to 350% bioavailability?

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Everything I have read indicates that yes 6 mg rapamycin with grapefruit juice is equivalent to approximately a 20 mg (some variability in grapefruit juice contents of the key chemical) dose of rapamycin. But I would like to hear what other people on this site have to say on the subject.

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Why did you adjust to go down to 12 mg? For covid shot only?

Yes - the 12mg rapamycin will wash out over 2 weeks, whereas I’m not so sure about a 20mg dose.

Understood. I was thinking of trying to increase to 22 or 24 mg to see if any side effects, but not sure at this moment.

I’ve taken 9mg rapamycin with grapefruit juice a few times - no noticeable side effects.

We should try to think about a good protocol for testing new dosage levels to try to push the knowledge base for everyone here. Please - I’d like everyone’s input on this. Many of us will all, at some point, probably want to test increased doses for rapamycin, we should think about, and discuss with the researchers and clinicians, about the best way to slowly and safety increase rapamycin dosing in a way that captures as much information, and helps us track the true effects on our bodies.

I notice we have a number of doctor’s on this site, and researchers - so perhaps everyone can chime in here (or if needed, I’ll create a new thread just for this purpose).

perhaps something like:

  1. Stabilize at your existing dose for at least 2 months
  2. Increase dose by 5mg (e.g. from 20 to 25mg)
  3. Do blood test after 1 or 2 weeks (or whatever your protocol timing is given that dosage).
  4. Track blood pressure immediately prior to dosing, and 20 minutes, 40 minute, 1 hour, 2 hours, 4 hours after dose. (I’ve heard some people have spikes in blood pressure - so I’d like to monitor this more)
  5. Check self daily for any new side effects / benefits noticeable - I will develop a standard checklist for this - rash, mouth canker sore, energy level, etc.
  6. Note any changes in blood variables, and track changes (share on this forum)
  7. Calculate Levine Phenotypic age using spreadsheet (see attached)

Spreadsheet I downloaded from Mike Lustgarten’s website for calculating your Levine Phenotypic Age:
3ba41-dnamphenoage_gen-1.xls (31.5 KB)

More about the Levine Phenotypic Age calculation:

Research Paper Describing the Calculations:

“An epigenetic biomarker of aging for lifespan and healthspan” describes a technique for combining nine blood-work values with calendar age to calculate your Mortality Score (probability of death in the next ten years) and your Phenotypic Age, i.e., your apparent biological age as implied by your blood variables.

Levine, et al., also used an elaborate DNA analysis of many blood samples to find what they call the DNAm PhenoAge, a measure of the degree of DNA methylation present, a phenomenon associated with aging. They correlate this measure with the Phenotypic Age, showing that they track very well. My spreadsheet uses a fit to their plots to estimate your DNAm PhenoAge and the modified Mortality Score that it implies.

More of a description from Mike Lustgarten:

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From his Twitter post:·




Mikhail Blagosklonny
@Blagosklonny

4h

Doses and schedules are individual and must be personalized under doctor supervision. They may range widely. In my case, I never had side effects at relatively high doses (20 mg/2 weeks) compared to typical 6 mg/week. Will shift to 24, probably. But do not do that on your own

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Why grapefruit juice rather than just grapefruit? Grapefruit itself is lower GI.

I always just eat a whole grapefruit when I’m doing the grapefruit juice protocol with rapamycin. I’m not sure why they used grapefruit juice in the study. Given our typical weekly dose - you only need a few glasses a week, so I’ve found grapefruit juice to be a pain because the fresh stuff doesn’t stay fresh that long (a typical carton / container of GFJ is a half gallon) - far too much.

So yes, the actual fruit is best I think.

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What about taking rapamycin immediately before an important high-calorie, high-ROS meal, like Thanksgiving dinner? Would it help blunt much of the excess ROS?

Good question - I don’t know. Perhaps the doctors on our forum can chime in with a response to your question…

@DrRoss
@mTORdocTOR

While I imagine rapamycin might help, the phrase “high-calorie, high-ROS meal” makes me think “that sounds a bit more like what the diabetes drugs are for.” Acarbose, metformin, and antioxidants seem like the more obvious tools for that kind of application.

That said, yeah, beyond the focus on calories, such a meal would likely also be rich in protein, and the the rapamycin would presumably help counteract the mTOR activation from the onslaught of excess amino acids in the meal. The quelling of mTORC1 would in turn quiet the innate immune system a bit, so yes, I suppose rapamycin would be expected to blunt some of the excess ROS that are likely being generated by neutrophils in response to the meal.

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Huh, does it quiet the innate immune system more than the activated immune system?

I just started a couple months ago & am currently taking 6 mg/wk. I’m wondering what meaning we should give to ‘wash out’. At a 72 hr half-life, after a few weeks at 6 mg’s, the steady state low will be 1.87mg. Should we think of this as a good ‘washout’ level? Seems high to me. I’m thinking of changing my regimen so that I won’t do the next dose until the in-body level drops to less than 0.5 which at 6 mg is 11 days. I show 20 mg as 16 days. I’m not a doctor so it’s just my current thoughts from what I’m reading but weekly dosing doesn’t seem ideal unless the definition of safe washout is 2 mg’s or so.

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I wouldn’t specifically use rapa to blunt the acute postprandial (after-meal) oxidative stress/inflammation. There are plenty of studies out there showing that including foods with a high density of antioxidants (dark berries especially) in the pro-oxidative meal can mitigate the increases in ox stress/inflammation and impairment of vascular endothelial function. Leafy greens in the meal would also likely help via increased production of nitric oxide from their high content of inorganic nitrate. Or you could do what I do – take a capsule or two of organic grape seed extract with the occasional so-called “cheat meal”. A multitude of other supplements would likely also work (curcumin, ginger, etc etc).

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Do nuts have those antioxidants too? I mean, I once got my CRP measured after a 2200 calorie almond binge and it was 0.01…

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