Rapamycin and Grapefruit Juice

I don’t intend to come off as a mean-spirited, puritanical miser but to be particular, I’ve read sort of the opposite and I’m not particularly a fan of the “happily ever after” philosophy either.

I see painful emotions (including temporary dissatisfaction, anxieties and/or distress) as not an indicator of a failure of happiness, similar to Kant: “Everything in life is determinate and finite, so we will never meet the infinite criteria we establish for happiness”

Happier people appear to be more risk-averse in general and more specifically in financial decisions, and choose accordingly safer investments. This might be explained by the fact that happy people take more time for making decisions and have more self-control. In addition, predicted happiness affects expectations about longevity and inflation. Happy people expect to live longer and accordingly seem more concerned about the future than the present, and expect less inflation.”

Rain or shine: Happiness and risk-taking - ScienceDirect!

Not only that, plenty of successful seasoned business folks/entrepreneurs are risk averse:

“There’s a reason that seasoned entrepreneurs don’t think of themselves as risk takers, even though everyone else does.”

I simply find that one must take calculated risks when there is no treatment for a disease and you are certain that you have that disease. I find other people prefer to keep their heads in the sand when it comes to what they deem impossible to treat.

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MAC you are correct on getting an absolute Cmax and AUC… My dilemma is I can get a rough estimate with my one shot test - as it is sent out. I could wait long enough that the rapamycin is completely cleared get a blood draw that would confirm and take rapamycin and return for a second blood draw 3 hours later. Which would be very telling. I have gone from 6 mg nothing with it weekly for over a year; then to 8-10 mg with nothing added for about 3 months, when I did the 8 mg with Grapefruit juice my last check up 3 months ago in April I had 9,2 ng/mL 3 days later. So I anticipated getting a 300% increase. Which I have been consistent with my dosing amount - meal - amount of GFJ and same time of day… which is why the 700% increase surprised me base on my past number.
Ultimately, for now my high goal is a 24 ng/mL Then do my biological test Glycans and - DNA methylation in 6 months.

Wanted the post to alert others their numbers could be much higher than they think or even want. That is all.

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Yes, we are all infected with ‘aging’. We are looking for a cure or at least a way to slow the disease. I still can’t believe that so many people out there just accept this fact instead of putting their all into finding a cure. At least there are some people who are trying now as compared to 20 years ago…

It still boggles my mind that people are still smoking and abusing their bodies… That’s the real risk in life.

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Great info, thanks for sharing.

Looking at that data I feel even more strongly that rapamycin should not be taken with GFJ. If you want to increase the dose, take more pills!

A recent anecdote. I happened to try some CBD on the same day as my rapamycin dose a fortnight ago… Within 48 hours I had developed bad acne all around my temples. I was initially pretty confused… and then I read that CBD also inhibits CYP3A4

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Appreciate your methodical diligence, actually doing a sirolimus blood test, and posting! Now you can manage going forward with this important biomarker data point.

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MAC wrote - "You didn’t do a trough, might want to do next time… "

The trough level is the lowest concentration in the patient’s bloodstream, therefore, the specimen should be collected just prior to administration of the drug. The peak level is the highest concentration of a drug in the patient’s bloodstream.

I no doubt have the most amazing Primary Care Physician on this site. We met today and went over my Cornary Calcium report Zero; GylcanAge 37 years biological, TruMe 51 years biological; TRT perfect and even my high sirolimus result 56.9 ng/mL. As soon as I told him that was after a 2.5 hours Tmax to reach that as a Cmax peak. He was like cool. He thought it was my trough - not cool…lol. Two years in on rapamycin there is nothing to say but amazing. He always has a new PA or doctor doing a residency when I get my review and he enjoys showing me off as what you can do to reverse age and have excellent health.

When I said, "It is my rapamycin day - can I take a blood draw and get my trough. Take my rapamycin and GFJ and then return in 2.5 hours for a second blood draw? He was like yes - let’s see. Will be excited to share my pre-medication trough and Cmax peak with everyone. Sure it is N=1. But, will give people an idea of what is happening in us. And, maybe encourage others to do the pre and post rapamycin LabCorp test. Should have my results to share in 3-days.

Any bets on where I will land - trough and Cmax? Have been past month – weekly taking 6mg rapamycin with one fresh squeezed Pink grapefruit (about 1 cup of juice taken with the pills). I am hoping to hit 28 ng/mL as my Cmax … my trough should be 5-6.

Will soon know.

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Amazing, he’s gonna let you do another Sirolimus test just to capture trough!

“Guess my trough”, live sirolimus sports betting…

With only one Cmax test, impossible to capture peak. Consider doing it at 2 hours. And take your GFJ at least an hour before to give enough time to blunt the enzyme. But since you want to keep things constant for this round, don’t change anything.

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You kill me MAC - asking my PCP to stop and have his nurse take a blood draw on the spot for a trough and then return 2.5 hours for a second blood draw felt like enough of an imposition - to go for a 3rd or 4th draw an hour later. LOL Will be close enough for me. You are obviously a solid researcher… I am a bit more loosey-goosey on it.

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Sorry I misunderstood. You keep driving that bus!!

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Brahahaha! Exactly!!

Your signature…

The Agetron protocol!

"Nothing else is even close."™

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Well, blood draws are good for your health. I wonder if a 3rd or 4th daily blood draw would affect your biomarkers and reduce your age?

Just kidding… Kind of…

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Have my results today and I hope this helps some of you figure this whole grapefruit juice and dosing thing out.

I have been keeping it simple with the grapefruit juice (GFJ). Simultaneously I have taken 6 mg (that is three 2 mg pills) Sirolimus/rapamycin with one pink grapefruit - sliced into four pieces and fresh squeezed by hand into a glass. You get about one cup of fresh GFJ. Pop the pills chase them down with GFJ.

My goal is to more consistently hit about 20 ng/mL of Sirolimus/rapa in my blood. Figuring I get about a 3.5 increase to my dose = my t-max or peak.

This past Monday - it has been 7 days since my last dose of 6 mg Sirolimus/rapa and a cup of GFJ.
I should be at my trough. Took a blood draw and LabCorp test - I found that I was at 2.2 ng/mL

That same morning I took one pink grapefurit squeezed it and drank it with my popped 6 mg (three 2 mg pills) Sirolimus/rapamycin. Went back and 2 1/2 hours later had my second blood draw and LabCorp test - I was at 31 ng/mL . So my dosage was multipled by 5. This is good to know.

My physician was cool with the 31 ng/mL number as long as I have no side effects. And I don’t.

My plan is to stay on the 6mg and a cup of fresh GFJ once a week for the next 6 months. I will then taken my Glycan Test again and TruMe test and get my biological age. If it is the same (I have not aged at all since my previous test) or I am better - meaning I have regressed another year or so younger - I will stick to this as my dose.

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I would worry very much about someone who is new to rapamycin that comes to this forum for advice and reads this thread or the one on daily dosing and takes instruction from either or both.

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I currently take 8mg once a week with GF and or GFJ and sardine’s in OO. Started at 6mg on February 20, 2022 a total of 25 doses{almost all with the GF/GFJ and the sardines] as of this week August 07, 2022. And I received ALL the information from this forum. Including getting prescription’s

And am planning a higer dose.

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Agreed… I was at 6mg for 1 1/2 years. Only upped my dosage in the last 6 months… with no negative issues. I get my positive health information from spending the $$ for additional tests. Coronary Calcium scan, DEXA, GlycanAge and TruMe

I have the guidance of a physician that is truly interested and there 24/7 for me.

Full blood workups every 3 months since on Rapamycin. That’s a lot of scrutiny this day and age. Despite not a single blip… we keep the testing. It is serious stuff being on a medication with limited healthy person trials.

Caution is good.

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Joseph, if I may ask, how old are you?
Thanks,

62 years, 7 month, 190lb, 6’1"

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Thank you everyone for all of your valuable information! I truly appreciate all of the insights I have gained here from all of you.

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You are taking a relatively high dose (with GFJ) although a trough level of 2.2 isn’t that high. This is an excellent data point to build from.

I would venture to guess most everyone on this forum is at much lower trough levels on a weekly dosing, sans GFJ. If you aren’t approaching 5 ng/L trough, may not be much sustained mTOR inhibition.

Do not confuse mg multiples with GFJ scaling…it’s an AUC thing. GFL increases the AUC approx 350%, but your trough is still low.

MB mantra dictates “takes as much as you can tolerate”. Mice longevity is correlated with dose. How do we navigate re effective translation?

Seems you aren’t complaining too much about side effects, correct? Certainly tolerable?

Have you shared a CBC, curious about these markers, a typical negative side effect? Would be very interested.

Do you have a health reserve given your age that allows you to take a high dose and not have side effects? Is 2.2 ng/L indicative of “not doing much” re dysregulation of your markers and/or side effects?

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