PBJ
#12
I think the best course of action is to take a Rapamycin blood test the day before you plan on taking a 2nd dosage. Assuming you are not daily dosing. Example, if you test after 6 days and your blood levels are still high, you either need to adjust dosing or timing.
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KarlT
#13
What is high? Should you be aiming for zero?
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Thats a good question for Matt: Questions to Matt Kaeberlein
How low is the optimal “low” blood sirolimus levels before the next dose of weekly rapamycin?
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My view is that ideally the blood level would be low for some days before the next dose.
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Beth
#16
In another thread, I saw multiple options posted a long time ago for purchasing a rapa blood test. Can you simplify this for me and share what a good cost effective option is … TY!
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Why do you believe that when some brilliant people who are MDs or have PhDs in related science take rapamycin weekly?
“Longevity leaders who take Rapamycin”
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PBJ
#18
Marek Health has the best prices I have seen, around $60. Also, you can search and find discount codes online.
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I don’t understand that myself. I have tended to work in the hard science, tech, mathematics and accounting environment (ignoring politics and music for the moment). I cannot understand why when you have a drug that has a half life of around half a week that people take it weekly if they think mTOR (which it inhibits) has any benefit at all.
I see Rapamycin as something that encourages autophagy. That is not something to do all the time.
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As @PBJ suggested, Marek health is probably the best option for the blood sirolimus level test. See details here: How to get a Rapamycin (sirolimus) Blood Level Test
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This is well put. My path to where I am now was:
(1) follow the protocol that almost everyone uses and doesn’t have terrible consequences (goal #1: don’t hurt myself) … 6mg/week
(2) get as much benefit as possible. Increase the dosage until side effects show up (goal #2: don’t waste time on lower dosing than possible: BBB penetration, “I don’t feel anything”)…6mg/week plus fatty meal plus gfj
(3) I want some growth cycles in the mix, right? How to peak the rapa without having it stick around? (Goal #3: high peak, short half-life, periods with no rapa)…4mg/2wks with gfj
I also take an extra week off every 5th week to really focus on growth and zero rapa time.
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PBJ
#22
Our thoughts are pretty much aligned on timing and dosages. With a 2 week dosing protocol, Rapamycin is still in your system about 50% of the time. I am also considering weekly dosing and cycling where time on = time off. With the knowledge we have at this point, I do not see a reason not to try different protocols as long as dosages are kept reasonable.
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Here is my thinking: Rapamycin primarily inhibits mTORC1, which we are trying to modulate.
After taking a dose of rapamycin and then exercising in the next one or two days you will start to negate the effects of rapamycin on mTORC1.
I cannot find any evidence that rapamycin inhibits mTORC2 to any extent when taking rapamycin at the levels we are taking it for life extension. The practical evidence that it does suppress mTORC2 in some members of this forum is the fact that some users experience mouth sores etc. I have been taking rapamycin mostly weekly for the past 2 ½ years and have not experienced this or any negative effect on my immune system. I have caught no bugs even though I am exposed to a diverse population daily.
Other than the reports of mouth sores, a little acne, etc., I do not find many regular users reporting increased illnesses.
“Although mTORC2 is not acutely inhibited by
rapamycin, subsequent studies have shown that mTORC2 is inhibited
in cell culture as well as in vivo in mice when exposed to high concentrations of rapamycin for a prolonged period of time,”
“Though rapamycin does not directly interact with mTORC2, attaching with mTOR in a complex form with FKBP12, it can indirectly affect mTORC2”
Targeting the biology of aging with mTOR inhibitors | Nature Aging.
Recent advances and limitations of mTOR inhibitors in the treatment of cancer | Cancer Cell International | Full Text.
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Beth
#24
How many weeks after my full dose would you recommend I check? Or is even one week fine?
I took 1mg, then 3mg, and this week I took 6mg.
I see I should check the day before the next dose is due. Do you happen to know if that test should be fasted?
KarlT
#25
What you wanna bet that the once a week dosing started as a couple guys after a couple drinks doing a little math on a napkin and saying “how about a week between doses?”
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@约瑟夫_拉维尔 It’s amazing how we’ve followed the same dose trajectory. I am alternating between taking 4 mg + GFJ + fatty meal one week and then a ‘rest’ week of 1 mg + GFJ + fatty meal the next. The question is, does that extra 3 mg equivalent dose do much on the ‘rest’ week or should I just skip it altogether.
The great thing about dosing with Rapamycin is that even if you’re really wrong, you probably won’t cause any permanent damage (Remember that guy who took 500 mg equivalent at one time???). You simply have a less optimal result.
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@DeStrider it’s a good question. For my own program I feel it is important to get to zero rapa in the blood regularly. This can be done with longer periods or holidays. The key, as always, is to measure biomarkers and assess progress. I have a blood test scheduled next week to catch up on my measurements that I had let slide a bit.
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PBJ
#28
I believe there has been some discussion that significant increases in lipids or triglycerides may be caused by mTORC2 inhibition. In Joan Mannick’s studies at 5mg Everolimus per week levels only increased about 3% on average. Maybe it is possible to titrate dosages or timing based on these markers?
Beth
#29
Forgive a question that probably shows how much about this topic I don’t understand!! (Still learning!)
I get that rapa or fasting helps with MTOR
I get that the argument, right or wrong, is that too much meat activates too much MTOR (avoiding an internet fight here 
This would lead me to believe that low protein diets are better for MTOR
But, if that is the case, why would rapa cause lipids to go up? To me it would then track that a low protein diet would do the same, and I don’t think anyone says that.
What am I not understanding?
If I’m WAAAAYY off and this will require a ton of time to explain it, then you really don’t need to!!!
I don’t have a definitive answer on the Rap vs Low protein part but I would be asking this.
Is the “effect” on inhibiting MTOR achieved through the same pathways?
Understanding why a particular compound or dietary intervention has similar results is part of the answer. The pathways for similar results are quite often very different.
My guess is that these 2 “interventions” are operating on different pathways and not directly comparable in how they achieve the result or conversely a “side effect”.
So I would start by looking at how Rapa influences MTOR and how protein restriction influences MTOR.
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I think the main question is how long do we want to inhibit mTORC1.
We don’t know how much it affects mTORC2 except it is dose-dependent.
“mTORC2 is not acutely inhibited by rapamycin”
After taking rapamycin in doses of 4mg with GFJ for 2 1/2 years my body must have become accustomed to it because I don’t really feel much of anything after I take it.
The question is how long do we want mTORC1 to be suppressed?
We can modulate this by the timing of our exercise after taking rapamycin.
Resistance exercise initiates mechanistic target of rapamycin (mTOR) translocation and protein complex co-localisation in human skeletal muscle | Scientific Reports.
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