New users starting up on Rapamycin!

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#4

No grapefruit juice.

Sorry for the long post, this is me, more-or-less, thinking out loud.

Yeah, my proposed dosing schedule is definitely on the conservative side of things. However, we don’t know enough IMHO of this drug, long-term, like 10-30 years. Yes, it’s unlikely my parents are going to make it another 30 years, but still–until we see large-scale, double-blind placebo studies, there’s still a risk, even if I think (or maybe a better word is “feel”) the risk is around 10% that there is a severe side effect lurking under all this seemingly good news, there’s still a too high of a risk for my (maybe overly conservative) conservative mind… Sure, Rapamune has been FDA approved since 1999, and typically given at 6mg on the first day, directly after organ transplant, then 2mg/day after that, then the dose is adjusted after 10-20 days, ending at some point after–month or 2?.. So, that’s great news it has been 24 years since FDA approval… But not hard studies on 6-8mg/week, for a year straight. Really, nothing even close to that in humans.

I just don’t want something to happen to them in 5-10 years, and something somehow points to Rapamycin–I couldn’t live with myself. We just don’t really have enough definitive results. And mouth sores & pimples & rashes all seem like the immune system is being negatively impacted–something that rarely happens at these lower, more conservative numbers.

Also, I saw a video regarding how the modulation of mTORC1 is key–I believe by a guy named Bryan? Can’t find it. But that made sense to me, and if that’s true, then with such a long half-life of 60 hours, there is still 10-15% remaining in the blood if taken weekly, not allowing the body to ‘live’ with a lower %'s in the body for long enough, IMH (and non-medical mind) Opinion.

But more than all that, I just don’t want to do more harm than good, as it’s not my body, it’s my parents. I will let them know they have the option to increase it beyond this conservative starting point if they want to, and I have shown them the polls on this website showing how 75% take it weekly.

Or, perhaps have them take it every 10 days as a nice ‘happy medium.’ Don’t know.

If anyone has any suggestions on exactly the bare minimum of ‘before tests’ to do, please let me know. At this time, the only thing they have done is a lipid test from 6 months ago during their annual check-up/blood draw. I just don’t know where to start. The Sirolimus Zydus in en route, shipping via India Post - so I probably have 1-2 weeks to figure this all out.

It’d be ideal if there were, like, 3 options outlined that the collective genius on this forum could more or less agree on. For example, 3 lists of pre-test/biomarkers before starting Rapa:

  1. Lower data, bare minimum looking at the most important numbers, mainly for safety, lowest cost
  2. Medium data, little more data, little more cost
  3. High data, tons of data, to get a full-meal-deal on all the potential benefits Rapa may have, costs the most

Then new users can choose their own adventure on how much data they want to log.
Also, where to get these? Do we just go to our family doctors and hand them a list? Or are these tests ordered online? This is where my ignorance shines bright, and something like this would make the ‘next steps’ more obvious for new users.

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#5

I am pretty rare in that I do blood tests almost every week, but I am continually changing inputs and so I am particularly interested in identifying whether particular inputs cause particular outcomes.

When it comes to testing, however, what the market offers in any particular jurisdiction is key. Often labs offer panels which are pretty good. You have debates between things like creatinine and cystatin C. Lipid panels vary a bit, but I would try to make sure you have some CRP figures.

However, it is hard to say any more without knowing where you live and even then it is only if you live in the UK that I can make specific suggestions.

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#6

I live in the PNW Pacific NorthWest - Seattle, WA area.

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#7

It seems like a good plan. Definitely do not do grapefruit juice. That is playing with fire. Fine if it is for you, but I would never do that to my parents. The bioavailability of rapamycin varies greatly among individuals. When you add grapefruit juice, you are just compounding the problem.

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#8

Here is my mother’s blood just done a few days ago.
Would this be considered ‘bare minimum’ of tests to be done before starting Rapamycin?

MommaBlood
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#9

Well, obviously there is not hard and fast rule on what the minimum is. I tend to think that at a minimum you want the information provided by CBC and hsCRP blood tests. This at least allows you to track ongoing biological age testing results using the free Levine Phenotypic Age Calculator (out of Yale), and the Aging.AI biological age calculator. I wouldn’t put a ton of value in the absolute values these calculators provide, but they at least provide a good tracking mechanism to gauge how things are going over time, based on some solid science. I would be more interested in how things change over time, than the absolute numbers.

More details here: A Friendly, Biological Age Reduction Competition?

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#10

I think it is great what you are doing. Do keep in mind that I believe it is technically against state and federal laws to give prescription drugs to others (without a medical license). Obviously your parents would not cause you a problem, but one never knows what sort of busy-body person might. Possibly even a family medical doctor if they were irked at losing control of their precious “power of prescription”, or, for instance, the person you gave the Rapamycin to ended up in the ER for something unrelated but reveled they were taking this prescription medication that you gave them. Maybe the ER doctor is legally required to inform the police, who knows. My own policy is to tell only very close family and friends exactly how I have purchased Rapamycin, but to let them buy it themselves.
Being prosecuted is probably an outlier, but I tend to be a bit careful about such things in this crazy world.

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#11

I think you may be talking about the following video. Dr. Brian Kennedy covers the mTOR modulation issue in this video here, queued up to the discussion on mTOR modulation:

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#12

ad. 1 I would do Levine blood panel markers (google it or search this forum, there is a lot debated about it, here is the link to spreadsheet)

ad. 2 I would take http://aging.ai/ their Aging.AI3.0. blood panel with 19 parameters (you can take the blood test anywhere just use their website to evaluate results, which is free)

additionally I would test lipoproteins, apoB and apoA1 and glucose (especially HbA1c test)
this two would give you a good insight IMO.

Regarding rapamycin dosing, this is highly individual. But there are common wisdoms I gathered reading this forum, podcasts, twitter and research papers is that you should take the maximum dose without unwanted side effects (you need to test this in vivo) and space the doses that your level of rapamycin before next dose is almost zero not to suppress MTORC2 all the time. If you space doses to two weeks, you can take considerably higher dose than weekly.

This post below can give you an idea what experts and rapamycin researchers are taking and their schedule. In any case it is worthwhile monitoring blood biomarkers while taking rapamycin and I would consider testing the trough level of serum rapamycin at the end of dosing period too to see that you are not suppressing MTORC2, but other biomarkers and probably side effects and rise in bacterial infections would be a telltale sign that the dose is too high or spaced too close. One can also take vacations from rapamycin (eg 8-12 weeks on / 4 weeks off) to make sure immune system is not inhibited.

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#13

btw how did you get to 6mg/week for your dog? If I am not mistaken the dosage for dog in Dog Aging Project TRIAD Study is roughly 0,15mg/kg… if your dog is around 18-23kg (I googled average weight of golden doodle) you are looking at 2-3mg per week.

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#14

You need a good baseline. That’s just the lipids.

Getting at least the phenoage biomarkers is a good idea.

Albumin ALP Creatinine Overnight fasting glucose CRP Lymphocyte % of total WBCs WBC (total) MCV RDW

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#15

I would say an absolute minimum is a full blood count (FBC) just to ensure that the immune system is in good working order and not already compromised in any way.

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#16

My dog weighs 70 lbs, and read 2mg/20lbs once every week, so figured 6mg/week.

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#17

You should check your hip mobility. Often these issues are related to lake of internal rotation mobility in the hip. See a good PT.

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#18

Why did you decide skipping Rapamycin every second week after reaching the desirable end dose for your parents? Why not to continue with the dose on a weekly basis?

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#19

That is some heavy pooch :sweat_smile: 5mg is more correct using 15mg/kg formula I guess.

#20

I want very minimal side effects regarding mTORC2 inhibition. I find this to be a good starting point, “ooching” into this Rapamycin off-label new world.

See sketch below. I understand bioavailability is different from the pill’s mg’s—but this is the idea/trend I’m going for. Shoot holes in it.

Rapamycin_Graph.PNG
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#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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