People pushing the upper limits of Rapamycin Doses - Any One Else?

I ordered the book! Thank you for posting this.

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Bill Sardi wrote a book ā€œThe Iron Time Bombā€ which is about IP6 but now out of print. I knew Bill and he passed away a few months ago. He was a very smart guy. I periodically take IP6 to control my iron level.

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This was my formula to protect against radiation before my CT scan.

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Can you provide a link to the paper for this drink combination please?

Yes. Here it is.

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@rivasp12
I think Kaeberlein said that he will be using 0.15mg/kg once per week and that he uses that dosage for himself too. I heard this in his interviews with Attia. Am I right?

Regards,

@argonaut
Thanks for sharing your lab results! Please keep reporting how are you feeling and what benefits are you getting from Rapa!
Although I do think your dose is too high when combined with GFJ. There are so many things in life and medicine where more is not better. Take care.

Donā€™t know what Matt K is taking, but for an 80 kg man that would be 12 mgā€™s per week which seems high for a weekly dosage.

You may be right. Iā€™ve considered weekly or daily dosage, or staying on my current dose and stretching out the intervals to three or four weeks. If I knew the optimum way to go about this, I would do it. There are many opinions. Dr. Blagosklonny at one time suggested taking the highest dose that doesnā€™t produce side effects. After fourteen months, I havenā€™t experienced any side effects or any subjective benefits. I continue to hope my insides are better for it.

My current thinking tends toward staying at the current dose and schedule and starting to do occasional washouts of six or eight weeks. But Iā€™m one of the least scientifically literate members of this august group - just making it up as I go along, so nobody should take me too seriously.

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I thought Matt K was in the 5ā€“6 MG range.

@argonaut
No worries, thanks a lot for sharing your experience.
Matt Kaeberlein interviews with Peter Attia are a fantastic source of info. And, as said, he will be using 0.15mg/kg for his dog aging project (TRIAD), and also suggested he is using this dose for himself. (Previously he was using 8mg weekly, I estimate this means ~0.1mg/kg).

@rivasp12
Maybe, but at least these are the numbers he mentioned for his dog project (and for himself in between the lines of the interviews with Attia).

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@RapAdmin ,

In the paper they say that only the 0.5mg daily and the 5mg weekly met the primary end point of the study. And in Attia interview to Klickstein they mention that the 20mg weekly was not showing improvements vs the 5mg weekly dosage (sort of a U response to dosage). Also, they mention that the 20 mg weekly of everolimus inhibited MTOR1 100% during the treatment interval, while the 5mg weekly inhibited at around 50% during the treatment.

This to me suggests that we should try to mimic the 5mg everolimus weekly dosage (~8mg Rapamycin?)

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That sounds reasonable. If mTOR is 100% inhibited (surprising if the case as one would expect to get close, but not to 100%) then there is no sense going further.

Any inhibition of mTOR will assist in encouraging autophagy, but to me this argues probably for a 5mg dose, but I would not take it more frequently than 4 weekly anyway.

Iā€™m not so sure. The studies done by ResTORbio (Mannick / Klicksetein) were only a few weeks long. There is evidence to suggest that there would not have been 100% mTOR inhibition over time. See the complexities of mTOR inhibition in this discussion by Brian Kennedy below,.

Dr. Brian Kennedy covers the mTOR modulation issue in this video here:

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I have seen that before. The thing I take from this is that the effect of Rapamycin is lasting. This immediately asks the question as to why it needs to be taken with any frequency higher than say every year. If it improves mitochondrial quality (and that I think is what people think) then how often to we need to induce autophagy/mitophagy to make a material difference.

What is your reasoning behind not dosing 5 mg of Sirolimus more frequently than once every 4 weeks?

My reasons for dosing at 4 weeks is that the half life is quite long (viz about 60 hours). There is a disadvantage to inhibiting mTOR as well as a temporary advantage (best timed with fasting as well). I have good reason to believe that it knocks down my White Blood Cell count. I am a bit short of WBCs at the moment anyway and want to minimise the time with a low WBC.

I am not saying my analysis is perfect, but this is not a substance that only has a short term effect.

Long breaks seems to be where University of Washington researchers are headed. Matt K seems to take breaks also. Reasoning being that the positive effects are just as great and the risk of side effects are decreased.

Great interview. But the thing is, as prof. Brian Kennedy states: we donā€™t know whether intermitted doses or Rapa will have longer lasting effects in humans also.
Werenā€™t the maximum increases in lifespan seen in rodents that received the highest doses - or was there a U-curve response as someone mentioned in this thread?