#21

Look it is not right or wrong, 5 mg every two weeks is a very conservative dosing. But we have no idea what is the correct dosing. If we keep with aging dog study the human dose would be something like 10mg every 10 days, 7mg every 7 days or 14mg every 14 days for a 70kg male respectively or 7mg every 10 days, 5mg every 7 days or 10mg ever two weeks for a 50 kg female. This is also what most experts use. This would be a good guidance. You want as high dose as possible to inhibit MTOR but give enough time between doses to keep MTORC2 not inhibited all the time to keep immune system running. The older you are the more you want to supress MTOR, hence older you are the higher dose would be rational. Finding a good balance between both is a fine personal balance and needs some experimenting. Even transplant patients make fine adjustments on how they react to rapamycin and how they metabolize it and side effects they experience.
I myself was considering 10 days spacing between doses as in my regard gives you this fine balance but it is highly impracticable and difficult to remember and stick to schedule. My next thought was two weeks between doses but since taking first dose of 1mg I experienced really not pleasant effects I did not want to take it to a very high dose so I stick now at 5mg weekly and do not plan to increase that for a while. And I feel this is a conservative dosing and schedule.

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#22

100%
I’ll leave it up to my parents to increase their 2 weeks dosing, and I’ll start them off very conservative. I’d rather start erroring on the too-low vs too-high.
If they want to increase up to 8mg/2 weeks, or 10mg/2weeks, up to them on regarding how they feel, and what their bloodwork is looking like.

Dr Alan Green is at 2 week dosing and he is 79, and has been taking it and prescribing it for ~7 years… And he is only 6 years older than my pops. So, every 2 weeks seems optimal starting point.

Here’s one option for your idea to help you remember taking it every 10 days:

  • Every month take it on the: 1st, 10th, 20th, then 1st again—repeat.
  • Setup recurring reminder in your smart phone for these 3 dates every month.
  • Sure, February you’ll go 8 days, and other days you’ll go 11 days, but likely close enough.
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#23

In terms of shooting holes if the half life is 60 hours (worth working on its a usable figure that is probably not too far out) then it does not go that low after the 5mg dose.

Three half lives is 7 1/2 days, that would be 1/8th of the original dose. 5/8=0.625mg.

Your chart seems to imply something like 0.1mg

Obviously also the 1mg then becomes 0.125mg and your chart implies something like 0.25mg.

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#24

Yah, true you’re right about the “ramp up” area—the troughs or “valley’s” should be a little lower, however the “peaks” seem correct.

During the 2 week dosing though, it’s actually around 5.5 half-lives in 14 days, so that’s about 2%. So 5mg x 2% = 0.1mg.

So the 2 week dosing peaks & valley’s seems correct to me still.
But yah, the ramp up’s valley’s seem slightly off.

#25

The main thing is that it doesn’t go down that far in a week. Two weeks is indeed about 1.5%.

Obviously the half life is likely to be different for different people and it may not have a smooth exponential decay.

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#26

Thanks Admin.

Parents are both talking with their doctor to get:

  1. Full Lipid Panel
  2. Showing the Aging.AI 3.0 - 19-parameter list, in hopes their Dr’s will add whatever additional tests to ensure all 19 parameters are measured.

We’ll see what their docs say.

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#27

You are correct.

The half-life of rapamycin depends on many variables. The quote of 60hrs is probably not that helpful. The only way to determine the half-life of rapamycin in any one individual is to make enough measurements to determine the half-life in that person.

The half-life of rapamycin is not 60 hrs but may vary

“rapamycin; low oral bioavailability (tablet: 14%, solution: 18%) and a long half-life (46–78 h)”

"Half-life (t 1/2) is the oldest but least well understood pharmacokinetic parameter, because most definitions are related to hypothetical 1-compartment body models that don’t describe most drugs in humans. Alternatively, terminal half-life (t 1/2,z) is utilized as the single defining t 1/2 for most drugs. However**, accumulation at steady state may be markedly over predicted utilizing t 1/2, z. An apparent multiple dosing half-life (t 1/2, app) was determined from peak and trough steady-state ratios and found to be significantly less than reported terminal t 1/2s for eight orally dosed drugs with t 1/2,z values longer than one day."

https://www.karger.com/Article/Pdf/528985#:~:text=Rapamycin’s%20analogs%20such%20as%20everolimus,)%20%5B11%E2%80%9313%5D.

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#28

I was hoping you would jump in. You remind me of a great, intelligent Electrical Engineer mentor I had for 12 years (30 yrs my senior)–who didn’t suffer fools very well! :wink: Something about them uber smart, logic-based/physics-minded EE’s. Great to have you detail-oriented smarty pants sprinkled throughout my life.

Understood. As I said, the graph was me trying to explain the trend line, to reply with an answer exactly why I left a 2-week space between the last ‘ramp-up’ 4mg, to the first 5mg dose. To me, this seems like the best way I could think of to get to 5mg as fast as possible, a happy-medium between speed & safety of ramping up–without immune-system-compromising side effects. If you have a better suggestion, I’m all ears.

The half-life of rapamycin is not 60 hrs but may vary

Sure, but with a range of about 45-75hrs, seems like the nominal number to use for calculations is 60 hrs.

“rapamycin; low oral bioavailability (tablet: 14%, solution: 18%) and a long half-life (46–78 h)”

Super interesting about the 14% tablet and 18% solution oral bioavailability.

"Half-life (t 1/2) is the oldest but least well understood pharmacokinetic parameter, because…

Also interesting about half-life not being an ideal exponential curve every time. But, I suppose, it’s the best we have/easiest way to communicate what typically goes on?
It kind of reminds me of Emissivity–a number between 0 and 1, regarding how susceptible a surface is to emitting (thus also absorbing) or reflecting infrared heat. I thought I fully understood it, created experiments where it would more-or-less show the results I suspected. But then I learned, oh wait, in the real-world, it’s not as simple as a single number between a ‘black body (value=1)’ and a ‘white body’ (value=0). Oh no not that easy–an object has varying emissivity values at each frequency (gray bodies aren’t always as simple as I thought), then to further complicate things, emissivity values change over the surface of an object (think stainless steel, with or without stains, with or without heat markings, with or without oxidation, etc). However, an emissivity table with values between 0-1 is still a simple, easily-understood way to get “90% of the way there, 90% of the time”…
White, gray, and black bodies are “idealized objects.” Similar to half-life.

1 Like
#29

Thanks.
I think you are on the right track to determining the proper dosage for your parents. After taking rapamycin for over a year I am still searching for the ideal dosing regimen. I don’t think your parents are likely to experience any adverse side effects at the dosages you are proposing. The most likely side effects that they might experience are a minor sleep problem on the day of the dose and tiredness for the following day or two. I take rapamycin early in the day to avoid sleep disruption.

I just started again after a hiatus from rapamycin and have been reminded once again of the negative side effects I experience from too large a dose, namely; Mild diarrhea the second day, physical fatigue for three days, and feeling cold for two days.

Because I started late in life I am trying to take the maximum doses possible without too much in the way of unpleasant side effects and not compromising my immune system.

Since I have not experienced any adverse effects on my immune system I am assuming the trough levels are reached sooner than the predicted 60-hour half-live would suggest. I have never experienced any of the cold sores, acne, etc. that many here have reported.
Some of my personal benefits from taking rapamycin for over a year are zero health problems, I am never sick, and I am exposed to the general public nearly every day. I am virtually pain-free and I am able to get a good solid sleep time of 7-8 hrs a night.
I really do expect the rapamycin will result in a better quality of life for your parents.

5 Likes
#30

Just to add to this, I think its important to consider the large variability in terms of an individual’s response to rapamycin (in terms of Cmax, and AUC). As others have mentioned, you have no idea how your body is responding to rapamycin (in terms of it getting into the bloodstream) unless you test.

In the dosing test paper here: What is the Rapamycin Dose / Dosage for Anti-Aging or Longevity?

It showed just how large the variability is… something good to keep in mind. Your blood levels of rapamycin may easily vary from another person’s by 2 or 3X - everyone responds differently in terms of how they absorb rapamycin:

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#31

Thanks.
What is your dosing?

#32

Thank you, Admin-that’s what I’m missing! Fully understood now.

#33

My last dose was 3 mg with GFJ + EVOO. I plan to dose every two weeks.
My next dose will be 10 mg without GFJ but with EVOO. I plan to test my rapamycin level the day before my next dose. Unfortunately, there are just too many variables associated with GFJ. I don’t know if I am getting the same dose every time when I combine it with GFJ because I don’t actually know when or where, within Florida, it is sourced from or when it was harvested, or the furanocoumarin it contains. The main reason I was using GFJ was just to extend my supply of rapamycin so that I don’t have to order so often.

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#34

I am on my 3rd week at 6mg every Monday. On your knee you might find something by youtube - Dr. Berg Knee

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#35

Hi there. I am a 63 female, weighing ftom 102 to 105 lbs. I have been taking rapamycin 4mg every 7 days with resvaratrol on an empty stomach. I started last Dec. I have had no side effects. I think I will go to 5mg weekly. I only took 4mg as I got 2mg size pills, and did not know if they can be split. I got mine from Big Y, and they were costly. Can you provide your source from India Post and about how much they are? Is it safe to pay with a credit card or paypal? Thank you very much for sharing all your knowledge here.

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#36

Hi and welcome to the forum.

Just a note - you get about 30% increased bioavailability with rapamycin when you take it with a fatty meal (some people here take it with a shot glass of olive oil, some times a can of sardines). See here: Improve Bioavailability of Rapamycin (2)

Also - Here are details about importing rapamycin from India: Importing Rapamycin to Save Money (pt 2)

Here is our list of online pharmacies that people have had good results with: 在线购买雷帕霉素 - 可靠药店列表

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#37

Hi Brett, congrats. I some here mention no grapefruit juice. I’ll comment from my own journey. I was taking 20mg every other week, and I took the LEF.org sirolimus test for blood levels 24 hr after taking 20mg ground up in a blender and water. I can’t swallow any pills even these small ones.

ZERO rapa in my blood. Zero! I took maybe 6-8 rapa blood tests, as some reco’ed take the rapa in the morning test in the after noon. Maybe 0.5 (?? units) blood levels. Thats next to zero.

It wasnt till after I read the GF threads that I whipped up my own GFJ plus a boat load of other compounds that act in a similar way to GFJ, like 1g of berberine + 1 gr of quercitin + 20mg or so of peperine, an a few more THEN took 20mg then blood tested <6 hrs later; Finally got a blood level in the 20-30 (??) range. BTW I may have missed Dr Green or any researcher’s suggested blood level of rapa, but I’ve not read what a good anti aging goal should be??

But I do know my initial zero blood level was not going to do my aging any good.

The point of this; your parents may not be getting any benefits if they don’t blood test at least once to verify;

#1 the product you bought actually has rapa in it?? Yes fake rapa is sold.

#2 its being absorbed, the biggest issue for me.

Best of luck, curt

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#38

Desert, FWIW only me, I buy pink frozen concentrate GFJ and use 1/4 a can each rapa pre dose by 2 hrs. Plus a boat load of other adjunivents for absorbtion like and including olive oil. I posted on the GF thread / or was it the testing thread. That I ran a lef.org blood test post my mix. I agree re repeatability and consistency in future blood levels.

I was absorbing zero so was happy (enough) when I got 20-30(??) blood levels of rapa post my GFJ + much more.

I’ve not read what target blood levels of rapa we should target?

good luck to all, curt

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#39

70 year old female here weighing 125 lbs. I’ve been on rapamycin 1 1/2 years and personally. I have had no problems with 6mg a week. I’ve had ONE single mouth sore which happened on the first dose. Nothing since. Alternating your parents 5 mg to every other week seems unnecessary and might reduce the benefits.

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#40

Thank you.

  • Have your lipids been in good ranges?
  • Did they increase/decrease pre/post Rapa?

My mom’s lipids are a little high (see blood panel above), so her (Medicine 3.0) Doc is going to watch it.
I think after talking with several others here, my goal has changed a bit, and it’s now to increase their dosage from 4mg/2weeks (mom) and 6mg/2weeks (dad) up higher and higher to their preference. I think a good goal would be to double their numbers (8mg/2weeks, 12mg/2weeks), but only if they want to/feel up to it.
But ramp up very slow, maybe increase 1mg every month. But I still feel good about every 2 weeks intervals with the long half-life of Rapa–erroring on the side of giving the body time without too much mTOR2C inhibition, while creating higher peaks & valleys of “modulation” of mTORC1.

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