2mg Rapa+GF(J) quantification and poll

#1

I am a bit frustrated by the usage of GFJ because I don’t know if its effect can be quantified and replicated in private usage.
Desertshores wrote something like he tested Rapa+GFJ and in some instances he got diarrhoe and sometimes not, which gives us a hint that the furanocumarin contents aren’t that constant. It may depend on the cultivation time, growing region and, the time of the year.

(In this case I just ignore that this may be caused by different absorbtion or that the side effects aren’t that constant too.)

So I am asking around:

Have you quantified your sirolimus level with a blood test while on Rapa+GFJ (maybe in comparision to Rapa without GF(J))?

And exactly when after taking Rapa did you do the test?
And did you use a fresh GF, only its juice or did you drink a concentrate?

And a little poll (ignoring that we all may be experiencing placebo effects):

  • Using Rapa with GFJ (2mg Rapa + 350ml GFJ = ~7mg Rapa) WITH health benefits for about 6 months or more
  • Using Rapa with GFJ (2mg Rapa + 350ml GFJ = ~7mg Rapa) WITHOUT health benefits for about 6 months or more

0 voters

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#2

Took a Labcorp test a few weeks ago. Trough - this is 7 days after consuming 4 mg rapamycin and GFJ of one red grapefruit - trough was 1.1

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Then took 2mg and GFJ of one red grapefruit - tested 2 hours after dose. C-Max 4.2.
Not sure why I didn’t get more of a bump.

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Got a 2x’s increase.

This is why we test. I will now be doing 4 mg with GFJ… hoping to get a consistent 8 mg each week.

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#3

Awesome Agetron, bringing data/science to your rapamycin intervention!

But this is why GFJ is fraught with metabolic reproducibility. The physiological gastric dynamic, most especially the critical CYPA34 enzyme that impacts rapamycin availability changes every time you take your next dose. What’s exactly in that next grapefruit, or juice bottle, what’s in your digestive tract from the days before, sleep, exercise, hormones, etc…these all impact your intestinal enzymes.

Recall the seminal cancer/GFJ trial…they went to GREAT lengths to get controlled GFJ concentrate (no raw fruit). They understood full well the challenge.

"We employed a frozen concentrate product that was tested for furanocoumarin levels prior to delivery of each batch. This ensured consistency across cohorts and is something that must be kept in mind for future studies or applications

You surely aren’t doing this level of GFJ control. And even if you did, you’d probably still have variation in your GFJ dosing AUC due to your weekly changes in digestive dynamics. At an absolute min, buy a few cases of frozen GFJ with same lot #, and take from this, and TRY HARD to reproduce the timing between ingestion, rapamycin taking, AND blood draw lab testing. How hard will this be, and you still get it wrong. The Cmax peak after oral rapamycin is VERY sharp, +/- 15 mins has huge impact on the snapshot. Why go through all this effort if you’re trying to be rigorous? Just focus on reproducing your 1 week trough level, that should be your steady state goal. Clinical trials don’t normally mess with GFJ nor Cmax, only trough levels…and dosing is adjusted accordingly to new trough target (you know each person has different rapamycin absorption profile due to genetics).

Unless you are trying to save $, I would do ONLY rapamycin so you have a far better controlled intervention. And now think, all the metabolic parameters you are spending time/money on, that are MASSIVELY impacted by the steady state rapamycin AUC signal are ALL going wonky because you cannot control your weekly rapamycin AUC. Blood markers, aging tests, you name it.

Ditch the GFJ, eliminate variability in your amazing rigorous n=1 experiment. You will only confound forward data, and may make the wrong next interventional decision.

Good science does not rely on “hope”. :wink:

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#4

FWIW

First I would prefer fresh squeezed GFJ. The less processed more furanocoumarin in the juice.
.
Science?

In my view I agree with Stuart Firestein.

Yes, I am posting it again.

“Pursuit of Ignorance ” Drives All Science: presentation by Neuroscientist Stuart Firestein see;

#5

You propably still have the variations with or without GFJ. It doesn’t matter. GFJ is just a additional variable.

So if we have more data, we can maybe calculate the variability of GFJ and do a little math:

N mg intake + min inc from GFJ in %= lowest possible dose that works
N mg intake + max inc from GFJ in %= highest not detrimental dose

That’s what I am trying to do here.

and of course I am doing this to save money.

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#6

Exactly. Rapamycin absorption by itself is a random variable and by adding GFJ, this is another random variable. Also, we don’t have an actual agreed upon target for blood levels as everyone has a different biology. So hitting a random target with random variables is where we are.

Great thing about Rapamycin is that if you are accidentally too high, there aren’t many bad side effects.

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#7

What are the desired peak and trough levels?

#8

For me I want a trough of under 1.
C-max… or peak…8 mg to12 mg range… every 10 days.

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#9

Ok. But if you’re dosing once a week, don’t you need peak and trough within those 7 days?

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#10

If I do 6mg no GFJ… or 2mg and GFJ… I redose in a week.

If I dose 4mg with GFJ… I redose at 1 week and 3 days.

Narrowing the 6mg to 12mg regular dosing. Going on 3 years and still figuring it out.

I am off anything that might be in the 20 mg or higher range after negative biological test from 7 months in that range.

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#11

This isn’t directly to the GFJ comparison, but’s a data point.
I’m on 1 mg/day Sirolimus (Rapamune) / day, 5yr post liver transplant, and my 24-hr trough level averages 6 ng/ml, at a major transplant hospital.

We’re following a protocol described here, to use rapamycin to get off of immunosuppression drugs all together: Immunosuppression Withdrawal in Liver Transplant Recipients on Sirolimus (Josh Levitsky, et al).

Some day I’ll do a different protocol, maybe with GFJ, but I will make sure my level goes to zero for a few days, at least, before the next dose.

You don’t want to be always on the sauce: those rejuvenated stem cells need to divide and flourish, and that ain’t happening when mTOR is squashed.

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#12

I would get processed junk if only for the consistency

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#13

I am planning to buy 5kg of instant GFJ concentrate if they tested it for furanocumarins (if I won’t take ritanovir instead)

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#14

FWIW

If you have not seen, review;

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#15
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#16

indicates that the highest concentration is in the pulp.

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#17

Did you do any research into this? I am playing with an idea to use ritanovir too as it it relatively easy obtainable, non liver toxic… but might need to measure the effect in vivo as ritanovir irreversibly blocks CYP3A4… meaning it probably extends the AUC for 48-72h (time to CYP3A4 recover)…

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#18

I have no problem in extending the half-life. My concern is just that the peak is to high for to long.
Maybe it’s okay if I take Rapa only every other week. So I can make sure that the sirolimus blood level is at ~0 if I have my next dose.

The question in general is:
should I modifiy the curve or should I not?
We haven’t got even one paper about longevity and Rapa+GFJ or Rapa+Ritanovir. I think its just a shot in the dark. Or maybe only a shot in the dusk.

kind regards from the cage
A labratory mouse

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#19

Do you have any tests done with 6mg no GFJ?

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#20

Its generally believed that its not the peak sirolimus levels that cause any issues, its the trough levels… if the trough levels don’t go low enough between doses, there is risk that mTORC2 is inhibited longer term and that is the issue that has been identified as potentially problematic, as the cause for the immune suppression, etc.

See this thread: How to get a Rapamycin (sirolimus) Blood Level Test

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