#21

Is that 20 mg plus grapefruit juice before and after? Or is that the calculated effective dose based on the gfj effect?

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#22

Matt discussed it in this podcast. The results were good - especially on heart function, which I think was the primary endpoint they were looking at. Below is the paper that resulted from it, and the podcast where they discussed the results:

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#23

Itā€™s 20 mg Rapamycin + grapefruit juice.

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#24

Hi desertshores. From my reading of the literature, the grapefruit juice inhibits the intestinal CYP3A4 enzyme, thereby increasing absorption of the sirolimus from the gut. Therefore, the grapefruit juice taken after your dose would not be expected to help absorption much.

For what itā€™s worth, hereā€™s my current biweekly protocol: one whole grapefruit with dinner ~12 hrs prior to dosing, and another grapefruit ~1 hr prior to dosing in the morning (as well as 500 mg metformin and ~1/4 teaspoon of black pepper for potentially more CYP3A4 enzyme inhibition). I take the sirolimus tablets with two small avocados (as a source of fat) in an attempt to further boost the rapamycin levels. Thereā€™s more discussion on this topic in the forum thread titled ā€œImprove Bioavailability of Rapamycin (pt 2).ā€

By the way, thank you so much to RapAdmin for creating this wonderful website! :pray: Your efforts are much appreciated!

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#25

Yes, actually I drink ā€œFlorida Naturalsā€ Ruby Red grapefruit juice quite often because I like it. I make sure I drink about 6 - 8 oz the day before, the day I take Rapamycin and the day after. I donā€™t know the efficacy of the brand I am drinking so I just make sure I have a fair amount in my system. Previously I used to take olive oil with it. I am currently subscribing to the high peak dose protocol and take Rapamycin on an empty stomach and wash it down with some grapefruit juice. Fats lower the peak and spread the time it takes to exit the system. (At least thatā€™s my understanding. I am a retired electrical engineer and my understanding of biology is limited.)
After taking metformin for over 20 years, I have stopped taking it. I believe it is an option for people younger than me. ā€œMetformin Impairs Exercise Training-Related Improvements In Older Adultsā€
I might suggest checking out Michael Lustgarten, Ph.D. on Youtube

He plans on living forever and has excellent videos on most biomarkers and tries to find the sweet spot for all-cause mortality risks.

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#26

Just to make sure I understand, youā€™re taking equivalent to something like 60mg+ of rapamycin by taking 20mg with GFJ? Is that right?

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#27

Desertshores, you may not have seen my post in the other thread regarding optimizing peak dose (Cmax), so Iā€™ll post it for you here.

Taking sirolimus with high-fat food has opposite effects on the Cmax (peak dose in the blood), depending on whether youā€™re taking the Oral Solution or Tablets.

"Food effects: In 22 healthy volunteers receiving Rapamune Oral Solution, a high-fat meal (861.8 kcal, 54.9% kcal from fat) altered the bioavailability characteristics of sirolimus. Compared with fasting, a 34% decrease in the peak blood sirolimus concentration (Cmax), a 3.5-fold increase in the time-to-peak concentration (tmax), and a 35% increase in total exposure (AUC) was observed.

After administration of Rapamune Tablets and a high-fat meal in 24 healthy volunteers, Cmax, tmax, and AUC showed increases of 65%, 32%, and 23%, respectively."

So, depending on whether youā€™re taking the Oral Solution or Tablets, taking it with fat will lower or increase the peak dose, respectively.

Regarding the source of the grapefruit juice, the authors of the research study actually found one of the store bought brands didnā€™t actually contain the active compounds which are necessary to result in the increased rapamycin absorption. From the article: ā€œInterestingly, different grapefruit juice formulations appear to vary in inhibitory potency and therefore, in consultation with the Florida Department of Citrus, we employed a frozen concentrate product that was tested for furanocoumarin levels prior to delivery of each batch.ā€

Just to take that variable out of the equation, I use actual grapefruits rather than relying on store-bought juice which may have different processing methods, pasteurization, etc.

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#28

Thanks. Yes, I know the grapefruit juice I drink is problematic, but as I said: I like it. I really donā€™t like eating grapefruit. That is why I am taking a 20 mg dose. If my grapefruit juice amplifies the dose so much the better, if not, I am still okay.
If you have any insight on what dosage is needed to have some sirolimus cross the blood-brain barrier in a significant way, I would appreciate the info. Right now I am looking for a quick peak spike.

ā€œSirolimus was absorbed more slowly when administered after a high-fat meal than when administered after fasting, as shown by statistically significant reductions in peak concentration (Cmax) and the ratio of Cmax to the area under the curve (AUC), and lengthening of the time to peak concentrationā€ The effect of a high-fat meal on the oral bioavailability of the immunosuppressant sirolimus (rapamycin) - PubMed

mTOR Attenuation with Rapamycin Reverses Neurovascular Uncoupling and Memory Deficits in Mice Modeling Alzheimerā€™s Disease

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#29

FWIWā€¦

ā€œDrug transport across the bloodā€“brain barrierā€

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#30

Hi, I must have been his third patient since my 5 year anniversary is this June. I had a pronounced increase in exercise stamina after only 3 months of 3 mg / week dosing. Iā€™m a specialist in Internal Medicine and it reminded me of my patients who had an increase in their cardiac ejection fractions. I canā€™t say that itā€™s on a dose response curve, since my results havenā€™t really improved even up to 12 mgā€™s, but havenā€™t deteriorated either. Thatā€™s not to say that higher doses wonā€™t result in greater lifespan.

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#31

Based on what you and Desertshores have provided here I may have to rethink my method of dosing. Iā€™ve been mixing 6 mg rapamycin with 1 tbs olivado avocado oil, then blending it with my keto coffee which I drink over a time span of one hour in the early morning once weekly. Itā€™s been convenient and with breakfast at least an hour later it seemed like a good way to get the rapamycin more easily absorbed than by taking it with a meal. Any thoughts?

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#32

Effect of a High-Fat Meal on the Oral Bioavailability of Sirolimus (Rapamycin).pdf (69.2 KB)

Desertshores, in the study you referenced, they used the oral solution (Iā€™ve attached the full text here). Iā€™m assuming that you take tablets, so taking it with a source of fat would be expected to increase your peak levels.

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#33

Iā€™m sorry, maybe Iā€™m reading table 1 and chart 1 incorrectly. Table 1 and chart 1 seem to indicate a higher peak when 15 mg is taken after fasting. Parameter (units) After Fasting. Cmax = (ng/mL) 67.4 Ā± 22.8 After a High-Fat Meal Cmax = (ng/mL) 44.4 Ā± 15.5 0.0001
As they say on Reddit:
Explain to me like I am 5yrs old.
Peak value is what I am looking for.
I am not looking for the total volume under the curve.
I thank you for your input and as I said before; biology is not my forte.
Since I am old and past the stage of major responsibilities, I can afford to experiment a little bit. Currently, I am ā€œexperimentingā€ with high peak values after oral intake.

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#34

you reported the adverse side effects of taking 20mg with GFJ,
how about the positive effects you have compared with low dose before?

#35

Please read my previous posts in this thread again, and the linked references if you want more details.

Sirolimus can be prescribed in two different forms: an Oral Solution (liquid), or Tablets.

If you are taking Sirolimus Oral Solution, then a high-fat meal will decrease the peak (Cmax). You read Table 1 correctly, but if you look at the rest of the paper you will see that all the subjects were administered the Oral Solution form of Sirolimus.

If you are taking Sirolimus Tablets, then a high-fat meal will increase the peak (Cmax). See reference linked in my previous post.

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#36

How did you quantify your increased endurance?

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#37

Iā€™m a creature of habit and walk the same trails. After several months of rapamycin I was quite suddenly able to double my distance with very minimal fatigue. Prior studies on ultra athletes has shown a clear association between exercise stamina and cardiac ejection fraction/ stroke volume. Itā€™s a similar effect that Matt is seeing in his dog study but Iā€™m not sure of the mechanism.

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#38

I measure power output for all my cycling training. Most is performed around VT1 (~80% threshold) so any difference in PE is difficult to determine but once a week I do a Z5 session where any improvements would be immediately evidentā€¦ Iā€™ve seen no change so far.

That said Iā€™ve only been taking Rapa for 9 weeks and have ramped up slowly by 1mg/wk (9mg on Monday).

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#39

You must take into account your baseline ejection fraction. The normal ranges from 60-90% of blood ejected with each beat. My pre rapamycin EF was about 65%, so I would be very aware of an increase to 75% or greater, but you may well have a high baseline and wouldnā€™t notice a small change.

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#40

That makes sense, thanks for responding.

You must be one of the earliest adopters so your feedback is valuable. Have you experienced any other benefits? Are you on 12mg per week or per fortnight?

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