To rephrase my question: Are there any studies showing the benefits of very high doses?
I now take 20 to 60 mg nightly and really don’t feel any subjective experience over 1 to 10mg nightly. Can I expect to see any changes in any of my blood markers from taking these higher doses?
AFAIK there are atudies on the anti cancer effects of high doses. My view is that there are no studies implyjng any harm although there is a study about small hamster testes. I have no tested the effects on fertility, but i have 5 children and am not concerned if in improving my health i have lower fertility.
It would be good to have more detailed study of dosing at my level. However, I am happy with my own outcomes. I do weekly bloodwork.
There are more than one areas where i think i am an outlier and i tend to try a lot.
I had not read the 10 mi half life. I would quite like to know the precise details of how melatonin is processed. I think the curve for high doses is different. I have searched this, but not found anything.
Yes - we have a whole thread on increasing the bioavailability of rapamycin, which I guess is somewhat equivalent to the main question @RufusDawes had regarding “enhancing rapamycin”
But - great caution should be exercised here due to potential for liver toxicity… read up and tread carefully: Improve Bioavailability of Rapamycin (2)
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There seem to be quite a few studies on breast cancer reduction, especially at higher doses.
Something women should consider.
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Have used them for years. Great quality testosterone, no prescription needed.
The liver toxicity is not from the GFJ but from the ketacanazole, correct?
No - GFJ interactions with other medicines: The key issue is you have to be very careful if you take other medications in addition to grapefruit juice (or ketocanazole, etc.). Common medications like statins, blood pressure medications and others can have bad effects when taken with grapefruit juice - so talk with your doctor and do research before considering this.
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If you are not taking any other medications that interact with GFJ (or any other medications at all), there should not be any increased liver toxicity from taking Rapamycin + GFJ, correct?
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Right. The concern is for something like some of the statins or blood pressure medications (for example) - you may take what you think it your regular dose, but actually be getting 3 to 5 or more times the regular dose… in rapamycin its a desired outcome, but not necessarily with the other medications.
It would be easy to overdose on on other medications, while taking grapefruit juice, and thus generally why doctors recommend avoiding it while taking medications.
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RapAdmin, are you aware of any info available related to the time the dose multiplyer effect of GFJ lasts in our body?. I ask this because I get a compound injected three days apart from my rapa 6 mg.+ 1 EVOO big gulp and I would like to know if GFJ effect is still active after that 3 days period, which is something I’d dislike deeply. Thanks.
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I’ve read that the dose multiplier effect of GJF can be up to 10 hours. I recommend you review these threads to get more data:
Here: Rapamycin and Grapefruit Juice
Here: The importance of "washout" time for Rapamycin dosing?
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An inexpensive antifungal called Ketoconazole increases the effectiveness of rapamycin by about 5 times. I take 200mg two hours before my rapamycin dose.
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Based on my understanding:
Ketoconazole may cause liver toxicity. If you go this route, please monitor your liver. But it does increase absorption by about 5X.
Grapefruit juice has an optimal enhancement period of 1-4 hours after consumption and a multiplicative effect of 3X. Lower enhancement multiples may be obtained at periods of 5-10 hours after consumption. It should have a negligible effect after 10 hours.
Ingesting Rapamycin with a fat source will increase the absorption by 30%
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Oh my God, I have just got the point across that I have the other compound via injection, not orally. So no interaction possible with my rapa’s GFJ. I am back happy again. 
And to add to the party, the compound I inject doesn’t show up in the list of drugs with which GFJ interacts. Of course sirolimus is in it as immunosuppressant.
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These are great replies, but to clarify, I’m not really looking for supplements to increase the bioavailability of Rap, I use GFJ and that works great for me… rather, once Rap inhibits mTOR1 are there substances that enhance the autophagy and lysosome activity where all the benefits are happening… its seems that Quercetin and Vitamin K2 could enhance the calcium channel activity these other processes utilize. I have been taking K2 along with the D3 as they are synergistic, but just started taking the Quercetin now… see what happens
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Just saw this one as well:
2) AMPK activation:
(for Increased Autophagy, reducing hyperfunction, and reducing insulin resistance)
- fasting, calorie restriction
- metformin, - berberine
I did try metformin for a while but it didn’t behave well with my digestive system… perhaps I should look into Berberine
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Remember there are different types of K2 (Menaquinone 4-13) of which three can be supplemented (4,7,9) and otherwise you need a foodstuff (generally fermented in some form).
I think MK7 is a good tool for autophagy. I don’t think MK4 has the same effect and I know of little research concentrating on MK9.
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I have taken Berberine for some time. I have never tried metformin. I have no personal data on Berberine in isolation, but I am happy with my overall biomarkers.
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Nice! OK I’ll get some K2 as MK7 to add to my stack.
How much Berberine do you take?