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

@rivasp12.

Forgive my ignorance, but do you distinguish at all between bacterial and viral in the context of Rapamycin/immune function/response?

re eGFR, we know from a multitude of longevity studies, gene expression/function of liver and kidney appear to be HUGELY correlated with longevity markers. All my liver/kidney function markers significantly improved after Rapamycin. My eGFR is of a 20 yr old, and I’m 57. Of course, I do a lot of healthy things (healthy user bias) as a starting point.

The only really wonky marker is URIC acid…it has plummeted to below lab range. Not sure if this is all Rapamycin because I am normally lowish on a low protein/ketogenic diet.

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Good to know, your n=1 very useful data point.

Would be “nice” to a trough level Sirolimus blood test just before your next dosing/Sirolimus Cmax test. Between these data points and the known half life/pharmacokinetics curve, we can do some modelling of your “dosing” AUC curve.

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I was thinking the same thing. With the 6 fisetin days in between the last two rapamycin doses, that’s 20 days, and I’m pretty sure there wasn’t anything measurable left over from the previous dose. But could there be if measured with 14 days between? I’ll do a trough day test and post it sometime soon.

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Note, on your chart the AUC levels for 20 mg with GFJ are no higher and less than many lower doses without grapefruit juice. That is why I like the idea of not spending too much time at a high-level UAC to avoid affecting mTORC2 and immune function.
If I am reading the table incorrectly please point this out.

Here you go, half life calculator for Rapamycin starting at 42 mg equivalent. Not much left after 20 days.

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This calculator is great, but its also just a rough approximation. The studies have shown very significant variation in people. See this study:

From Here:

Full paper included in the post: Rapamycin Clinical Studies in Healthy People

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@desertshores

The AUC with GFJ is (as concluded in the study) is 350% higher with GFJ (taken the morning of as reference point) vs without GFJ.

“grapefruit juice increased Sirolimus AUC approximately 350%”

If you look at the 15mg row (bottom half of table) and Column 6, AUCoo without GFJ (0), 858, and AUCoo with GFJ (1), 4361.

It’s complicated with alot of overlap but generally cytotoxic T cells and NK killer cells are involved with viruses while neutrophils attack bacteria. Antibodies are involved with both. NK cells also very involved in attacking cancer cells.
With profound neutropenia we get very worried about bacterial infections .

Noted.

Do you put any stock in hormetic stressors and improved resilience in humans? I am talking about normal healthy persons.

Is there any logic (research?) to thinking to running immune markers skimming at lower levels might actually bolster the strength of the intrinsic immune system, with feedback to the thymus, bone marrow, stem cell pool?

@rivasp12

“I take IP6 with inositol”

I’ve never heard of either of these.

Can you share some insight for rationale for taking?

Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic

Ivana Vucenik et al. J Nutr. 2003 Nov.

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Argonaut, thanks for sharing this valuable information. To get a better sense of your rapamycin dosing, may I ask what is your weight?

I thought this excerpt from a twitter thread by @agingdoc1 might be of interest:

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brandy111, I’m male, six feet tall and my weight varies from the high 150s to the mid 160s without attempting to manage it by diet or anything else. I said I had noticed no effects, but now that you mention it, I am trending toward the lower end of that range since starting rapamycin.

My BW has dropped form 78 to 74 since I started rapamycin in January. I’m actually back at racing weight for the first time in 5 years!

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Yeah, so IP 6 is perhaps my favorite supplement. Shamsuddin,MD, PhD is a pathology professor at my old medical school and has been studying this since 1975. He’s written multiple peer reviewed articles on the subject. It stands for inositol hexaphosphate and is abundant in legumes.
It has many benefits and I very highly recommend his book simply titled IP6 + inositol.
Regarding cancer, he found that it actually causes cancer cells to go from a dangerous poorly differentiated state back to a benign well differentiated state. Amazing actually.
Also helps with prevention of kidney stones, osteoporosis,diabetes, and CAD.
I spoke to him at length and he’s a very kind, genuine, and intelligent person. Give the book a go.

I searched clinicaltrials.gov for IP6 and found zero trials for for cancer, kidney stones, osteoporosis, alzheimer. I found a single study for CAD registered in 2010, but never completed/published. I did find several trials on inhibitory effect of phytate on non-heme iron absorption.

So it’s definitely not something on anyone’s therapeutic radar. I’ve read a lot of papers on all manner of interventions to mitigate all cause mortality, have never heard of IP6.

But I am open to all things until swayed otherwise.

Would this be a good proxy in lieu of the book?

Sci-Hub | Protection Against Cancer by Dietary IP6and Inositol. Nutrition and Cancer, 55(2), 109–125 | 10.1207/s15327914nc5502_1 (2006)

At the end of his book he lists about 300 study references.
Mostly on mice.
Couple of years back Mayo Clinic published an anecdotal report on IP 6 completely curing a patient with stage 4 melanoma. Something they described as unheard of.

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As someone who has been dealing with Stage 4 Melanoma since 2014, I thank you for this info. I know it’s only one case, and anecdotal, but I have found a lot of these sorts of inexpensive and non-patentable substances to go under the radar due to lack of profitability. I owe most of my NED (No Evidence of Disease) status to immunotherapy, but my interest in, and use of, many things that have good benefit-to-SEs can’t have hurt. BTW, I wasn’t aware of RAPA for most of my cancer journey, but since have found research that seems to indicate it as a good adjunct to immunotherapy. Plus, it apparently helps to shield healthy cells from DNA damage from radioactivity, and anyone with an advanced cancer diagnosis can tell you - getting regular PET and CT scans is an unavoidable must in regards to addressing any possible recurrences.

Hi Chris. I agree that if it’s benign and might help then why not. One of my associates is taking it after chemotherapy for a lymphoma to prevent recurrence. As with everything else, dosing is all important. Unfortunately, Shamsuddin retired from his capacity as a pathologist in 2020 after 45 years.
That hasn’t stopped him. He’s discovered a very easy, sensitive, and specific test for early cancer detection. Here’s the published article from last year:

Just let me know and I’ll try to track him down for you so that he can advise you on the proper dosage.

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Astaxanthin attenuates total body irradiation-induced hematopoietic system injury in mice via inhibition of oxidative stress and apoptosis

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