#103

My last testing protocol for rapamcyin did not include serum rapamycin. That is partially because my standard labs don’t offer this, but also because I am interested primarily in what effects a dose has on my own systems.

Hence I am happy to use a grapefruit to have an effect, because it is the effect I am measuring not the serum rapamycin.

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#104

Reading some of your posts, I can’t help but picture you like a Hunter S. Thompson of the longevity world, tearing across the country in a car stocked with rapamycin and GFJ, fueled by a heady mix of top-shelf beer and gin. You clearly know what you are doing though. Just makes me chuckle sometimes. :rofl:

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#105

You are in the wrong place for “normal”.

Keep rapamycin weird!

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#106

Actually the gin was already in devon and the beer was from a pub, but i did drive with rapamycin and a grapefruit (and two cgm sensors)

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#107

To measure the exact dose of Rapamycin is the only reason you do not use GFJ?
Sorry to ask so many questions: If you measure, you measure blood test ng/ml too? If yes, your target point at which time? If no, you just do your regular blood lipid tests every couple of months?
Sorry, many people at this forum change their Rapamycin dosage over time and mostly I find only data about how much intake with and without GFJ and little about desired blood levels - since as is the case with me differ as my tests show. Are blood peak levels irrelevant though? Thank you very much!

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#108

I’ve settled recently on taking rapa at night with 100mg melatonin.

The combination feels incredibly restorative, and the melatonin keeps me asleep, as rapa can be both acutely fatiguing (4-6 hours) then energizing (6-48 hours).

I use both piperine and a grapefruit approx 1 hour before, to get the most out of the rapa.

What I notice most, is an “energy floor” particularly the day after. I seem more robust to various stressors as well (less sleep, etc).

39 M

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#109

I’ve not yet measured my blood/sirolimus levels. I’m about to embark on a dose ranging study to see the effect of 10mg/week to 20 mg/week on the exact blood levels and full blood work results. My plan is to test (and I’m still nailing this down) something like 3 hours after initial dose, 24 hours after initial dose, then 48hours, and then daily afterwards for the full week. I after getting a “curve” understanding I may test less frequently. I just want to get a better idea on the exact response rapamycin is having on my body. I will report results when I get them.

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#110

I think you can see from my results from 22mg plus GFJ (say 77mg) that Rapamycin has continuing effects given the half life. Ignoring the effects on the immune system I personally would be very hesitant to take 20mg a week because it is always having an effect.

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#111

Good idea, RapAdmin! But let us never forget, that there is tremendous variation between individuals when it comes to that curve, based not just on individual physiology, but possibly on food intake an quality and the brand of rapa. This means everyone must get tested to get their own individual results.

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#112

100mg Melatonin? You sure?

#113

He is I suppose a bit of a lightweight. Today before I started drinking I took 240mg of melatonin to help deal with the ROS that result from the acetaldehyde. Overnight I normally have another between 1 and 2 grams.

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#114

Hello RapAdmin, thanks for your answer. I was really thinking about what to respond. Five years Rapamycin and founder of this forum and you never made a blood test to find out the Sirolimus levels in your blood but you are not taking GFJ to measure your intake. My conclusion is that either blood tests are not really important or all this is really experimental and no one has a real clue about dosage. Just if side effects kick in, reduce your intake.
So the Sirolimus blood levels I found on my 1,5 years journey on Rapamycin are the one from Kaeberlein, Bryan Johnson and Agetron. Basically the comments of Agetron in this forum induce me to test my blood levels since I was worried I am taking a too high dosage since blood levels obviously vary enormous. Are there other references? Thank you.

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#115

I have some thoughts about this. If you want to know what dose you are taking, relative to yourself, based on other times you take rapamycin, then taking it without grapefruit will give you a more accurate estimation compared to taking it with grapefruit. I mean that if you take say 5 mg without grapefruit then you can be very sure that if you later take 5 mg you will get a very similar concentration.

On the other hand, if you want to know what dose you are taking, relative to others, then I think comparing doses with grapefruit gives you more information. Consider this. Without grapefruit the absorption of rapamycin differs greatly between people depending on their genes that determine how much CYP3A4 they produce. Some produce a lot more and absorb a lot less, others produce little and absorb more. If you and a bunch of other people all take rapamycin with a large dose of GFJ, then all of you will have very low CYP3A4 activity, with much lower variation between you. So my guess is that if a group of people takes 5 mg with GFJ, their blood concentrations will be far more similar than those of a group that takes 5 mg without GFJ.

One implication of this is that if someone wants to get a dose that is equivalent to 7 mg without GFJ for an average adult, he could either take 7 mg without GFJ, or he could take 2 mg with GFJ (assuming an average of 3.5x increased absorption with GFJ). If he takes 7 mg without GFJ, he has higher chances of being far from the blood concentrations of rapamycin that the average person would experience after ingestion of 7 mg without GFJ. If on the other hand he takes 2 mg with GFJ he is likelier to not deviate so much from the average level experienced by someone taking 7 mg without GFJ. I think if everyone were taking large doses of GFJ with rapamycin, the blood levels we experience would be more similar and more easily compared. Note that this of course is only true if the people are taking a large enough dose of GFJ to be very certian of a strong inhibitory effect on CYP3A4. That would mean not just 200 ml but 300-400 ml.

5 Likes
#116

I would say the blood sirolimus tests right now are of most value when taken just before your next dose, to see what your trough levels are. You want to get low trough levels before repeated dosing so that over time you are not significantly blocking mTORC2, and thus triggering the negative effects that go along with it. But if you’re doing regular (say quarterly) blood testing on CBC/HS-CRP, etc. and getting good results - then perhaps you don’t really need the blood sirolimus trough levels. Certainly I’ve been getting along with out doing the blood sirolimus testing. Most of us here probably have not done the blood sirolimus testing.

On the optimal dose side of the equation; absolutely we have little idea on what the optimal dose for healthy humans for longevity purposes is. We have lots of data on lab-based mice and soon monkeys, but they live in largely pathogen-free environments so I’m not sure how well those data translate to us (and it will likely be highly variable - if you’re a software engineer working at home you have a low risk profile, if you’re a medical professional working in an ER room you may have an entirely different and higher risk profile due to exposure risks).

I’m going to be testing higher dosing, and different dosing periods, with extensive blood testing before and after, just so I get a good handle on how my body processes rapamycin and what my “curves” look like in terms of blood levels over time. And I’ll track all the standard CBC, blood test results to see how things are impacted over time (I may also add a CGM to the mix to track blood sugars).

You mention “Just if side effects kick in, reduce your intake.”

I would say that this is also an area of lack of consensus. There are two types of side effects we see; physical side effects (e.g. rashes, mouth sores, etc.), and blood-based marker side effects (eg. lipid increases, blood glucose increase, etc.).

For the first type of side effects - its going to be a personal decision on what is tolerable… I had a mouth sore once it went away, no big deal. I’ve had rashes that persisted for weeks… a bit bigger deal, but still tolerable and they eventually went away. Its going to be a personal decision depending on the severity and frequency of the side effect.

Then on the blood-based marker side effect - you face a decision; do you lower the dose, or do you tolerate the side effect (within a given range), or do you treat the side effect (eg. by adding a statin, or other lipid management medication). There are no standards and no studies on this type of thing - so again, its going to be an individual’s call on what to do here. I had higher LDL-C lipids prior to starting rapamycin and had been off and on statins for years. When my lipids when higher I became more rigorous about taking my statin and I added bempadoic acid and ezetimibe - and now I’m in the low 60s for LDL-C (down from the 140 to 200 range prior). This has just been my approach, but I’m not necessarily recommending it to anyone else. You need to do your research and figure out what works for you.

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#117

What i found really useful was the CGM readings and blood tests that showed how long rapamycin was active. I will do a similar CGM test for UA. However, that will have to wait at least 4 weeks.

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#118

What is clear from my recent test is that the lipid/glucose effects are of a limited duration.

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#119

Do you think the impact of Urolithin A can be seen on CGM? (I didn’t notice anything when I tried it)

#120

I think it is likely to be dose dependent. Hence i intend taking a highish dose for a few days.

#121

Likewise my vision hasn’t improved after taking rapa for 5 years. Also I haven’t seen any study showing that rapa improves vision. Whether rapa “works” or not for humans is tbd and we are the part of the experiment.

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#122

Thank you very much for the answer. Now I got my blood test back 7 days post intake of 4mg Pfizer Rapamune with GFJ. It was 0,6ng/ml.
Is it safe to take then the next dose of Sirolimus?