The Key issue of Dosing Levels and Intervals for Best Rapamycin Outcomes

yes, 2 x 1mg pills of rapamycin. Yes, the equivalence might well be in the 6mg/week range. Possible side effects (though not definitely rapamycin-caused): 2 or 3 tiny red sores on the tip of my tongue, a small sore on the inner cheek caused by my biting myself but is surprisingly long-lasting, and a bruise under the base of one fingernail with accompanying damage to the base of the nail (I was not aware it had been injured). I think I’ll wait a few days extra for my next dose.

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I think using Grapefruit with a single dose does not increase the peak serum concentration. It just increases the halflife/clearance.

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I guess that could be true - I haven’t studied the paper in depth. I think the key measure may be the AUC (Area under the curve) - i.e. how much exposure you get to the drug via the blood stream.

Whatever the case - the important point is that that you can get by with a lower dose of rapamycin and effectively get a higher dose - thus saving money and potentially decreasing side effects.

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Certainly more exposure. In this paper the patients are taking everyday, thus it’s building up with a lower clearance rate. I use grapefruit with my Sirolimus too. 15mg q 10 days.

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Although popular science reporting like this might sometimes be inaccurate, this article clearly says the grapefruit increases absorption (thus peak levels?) and does not mention half-life. Another article quoted one of the scientists as saying the grapefruit effects were high within a few hours of consuming the juice, so I don’t think continually daily consumption is needed.

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I’ve been taking 30mg of CBD for the past year and started rapamycin last month increasing now to 6 mg/week. Some research has been published showing that CBD increases the blood level of rapa similar to grapefruit–to the extent of 200% or more. But they don’t talk of how much CBD does this. Does anyone have any input on how much CBD is needed to have this effect? I’m a patient of Dr Green & he thinks 30mg of CBD is not a problem but he didn’t have any direct knowledge of the issue. Any feedback would be appreciated as I’d like to keep taking CBD but don’t want to overdose on rapa. Thanks
Jim

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Hi Jim,
Welcome to the site, and thanks for posting on this. I had not heard of this - but a quick check on Pubmed shows you are absolutely right. I will dig deeper into this to see if I can find more and answer your questions - but you should definitely be careful:

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Thanks! I’ve stopped taking CBD starting last week until I get more info. The best news would be that 30mg of CBD is reliably synergistic w/ rapa & consistently increases its biological effect by some known percentage. I could then continue w CBD & cut my rapa dose. But so many unknowns. Don’t want to overdose or underdose!

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After reading the Dog aging project update recently, I took 13 mg Pfizer Rapamune (0,15 mg/ kg) at the start of a 3 day fast in the morning on an empty stomach with water and experienced no sides. In the past I also took 6 mg with 2 glasses grapefruit juice also without sides. I am 44 years old and exercise daily.

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Looking to hear more. My issue with grapefruit juice is that it comes with a bunch of sugar

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Yes - I agree on the sugar issue. There is also the issue of the large amount of variability (in terms of its effectiveness in increasing the bioavailability) in the grape fruit juice that you buy.

When I have done the grapefruit with rapamycin dosing I eat the actual fruit an hour before I take the rapamycin. That seems like it might be better, and I’m guaranteed to get “fresh grapefruit juice” - and all the fiber from the fruit.

I have also done more research on the drug called “ketoconazole” that is mentioned in the same research study that used the grapefruit juice. This drug also is very good at increasing the bioavailability of the rapamycin - by a pretty consistent 5.6 X it says in the study. In the study they were giving it to cancer patients who were taking 90mg of rapamycin / Sirolimus a day - a huge amount, but with the ketoconazole they only needed to use 16mg / day to achieve the same blood Sirolimus levels.

ketoconazole is a cheap, and easily available generic medication - so if that is something that is of interest to you, talk to your doctor about it. The key issue the mention in the study that they were concerned about with regard to the ketoconazole, was toxicity or overdosing because they were using it every day. This wouldn’t be an issue in the sirolimus / anti-aging protocol I suspect because it would only be used once every week or two.

More information here:

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Hi, my name is Ross Pelton and I am The Natural Pharmacist. I have written a book titled Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome which is in the final stages of editing and will soon be published.

Regarding “optimal” dose of rapamycin. I think this needs to be individualized. Everyone is different…ie. biochemical individuality.

I was taking 6 mg once weekly. My lab tests revealed that I had become anemic…so I have reduced my dose to 6 mg every other week. I just had a blood draw today. I will post the outcome when I get the results.

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Welcome to the forum Dr. Ross. Please post a link to the book once its available. More information is great.

What is your opinion about doing peak and trough sirolimus blood level tracking or testing? Since there is quite a variation in half-lifes (between people) and dependent on diet, etc. - and the risk of mTORC2 inhibition over time.

Life Extension now offers a cheap $95 blood sirolimus test that we could use for this purpose.

I think testing peak and trough sirolimus would provide very important information for the LIfe Extension community. We are truly in the very beginning of this new frontier. I think ultimately, we will find that there is great biochemical individuality in what is the optimal dose and frequency for different individuals. I just made a comment earlier about reducing my dose from 6 mg weekly to 6 mg every other week…based on labs that revealed I had become anemic (low iron & hemoglobin). Lots to learn…Ross

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Did switching to a 2 week interval reverse the anemia? Is your book out yet?

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What optimal iron/ferritin levels and hemoglobin levels do you aim for?

Could you provide a link to the Life Extension, sirolimus blood test? I tried looking it up but no luck:(

For those interested, here is a link to Ross Pelton’s book:

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Here is a post with information about the blood sirolimus test, you need to call them and specify the test number. It may take a bit of work - some the lab test people don’t seem too familiar with it:

See this post for details on how to identify the test (you have to call their lab test customer support, its not yet listed on their website): Life Extension Blood Sirolimus Test

also mentioned here:

Hi Rapamycin enthusiasts,
I’ve encountered a delay in getting my book published. New books need to get a registration number and bar code from the Library of Congress. This process has traditionally taken 8-10 days. Currently, due to COVID and staffing problems, the wait is 1-2 months. Stay tuned…I’ll shout out as soon as Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome is available. Healthy regards, Ross

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