Rapamycin (aka Sirolimus) is a very interesting drug of diverse effects. It is being explored in early trials for PC because of positive effects demonstrated in cell cultures of PC cell lines and in animal model (mice). A phase I dosing study in human PC patients demonstrated a safe profile in moderate doses (up to 3.5 mg per week).
There is much interest in Rapamycin for promoting "health-span" in aging and age related diseases. So many of which intersect with our APC population including myself. So I am considering adding a weekly dose to my regimen on an intermittent basis. The following "Opinion" article covers the considerations well with special focus on actual risks and "the fear of rapamycin".
This will not be applicable for many here who are on various intense regimens to control their APC. And I am certainly not recommending it. Just considering it for my own (for now) stable and indolent case. I post this to invite perspectives and thoughts from this community. Thank you. -Paul
I've been taking 2 mg / week of Sirolimus for about 2 and 1/2 years. Seems like there is a fair amount of support for it being an inhibitor of mTOR. My NMD first told me about it and research panned out.
It's one of the few things that I have been consistent with.
I haven't seen any side effects. At least nothing that I can pin down to Sirolimus. The dosing you sent me is for SOC immunosuppressive transplant rejection prevention. That is very different than the once-a-week 2 mg dose that I take for immunity enhancement and mTOR inhibition.
I have not started taking it yet. Still investigating. But I believe your 2 mg per week dosing would be the sweet spot, below reported side effects threshold. Monitoring CBC counts for first few months.
This is a great Forum - thanks for starting this thread, Paul. I had been thinking of rapamycin for some time your post makes me finally act.
For Alan Green the rapamycin experimenter the proper anti-aging dose of rapamycin is 2-6 mg, and the proper interval 1-3 weeks, so your 2mg per week is right in the middle of that. He is/was using 6 mg per week himself, at least initially, and Scott 1963 here is using that too. Have you seen side-effect reports from more than 2 mg? Have been thinking of 3-4 mg initially, checking neutrophils.
My immediate family over 50 and good friends are nearly all taking Rapamycin pulse dosing. As are my anti-aging doctors. No side effects. Should not feel anything. Safer than aspirin.
Rapamune Tablets and a high-fat meal in 24 healthy volunteers, Cmax, tmax, and AUC showed increases
of 65%, 32%, and 23%, respectively."
I do know that there is a threshold. Higher than a certain amount it becomes immunosuppressive and is used as SOC to prevent organ transplant rejection. Lower than the threshold the action changes and it inhibits mTOR and boosts the immune system. 2 mg is a standard dose for cancer. I'm not sure if I would want to rely on marketing to tell me that they figured out a way to boost absorption and therefore I can take less with the same effect.
But taking it with a meal seems safe. A modest increase in AUC.
That´s a wealth of info. In particular I appreciated the link to Alan Green´s rapamycin treatments of himself and patients. He has started to use dasatinib+quercetin to kill senescent cells, adding it to mTOR-inhibitor rapamycin. I will go the opposite way, adding rapamycin to my D+Q combo.
I did this ten days ago. Rapamycin and Dasatinib have a synergistic effect. I had toxicity the first day. I would take Rapamycin day 0, take Dasatinib day 1 if you are doing a pulse dose of rapamycin.
Nothing convincing. The resveratrol, metformin and NMN advocated by Sinclair may downregulate PI3k/AKT/mTOR, and I have used those. But Sirolimus is much more direct and long history of use in humans at higher doses ( but with higher risks). There’s the rub.
I get an Rx from my NMD and then go through goodrx (free). $145 for 15 2mg tabs. 1 a week. About the same but more of a hassle (I already went through the hassle so no issue now). What is the online pharmacy and do they have an online doc to do the Rx?
Thanks Paul. I have had these discussions w RSH1 in the past. You seem to be exploring mBAT, and now mTOR inhibitors, kind of as a 1 man trial (both you and RSH1). I/we have to appreciate you sharing your Wins & Losses. I am convinced that SOC has not kept up w the many scientific and Medical advancements in combination. Thanks. Please continue to keep us posted.Mike
Found this: “Rapamycin is the main mTOR inhibitor, but deforolimus (AP23573), everolimus (RAD001), and temsirolimus (CCI-779), are the newly developed rapamycin analogs.”
mTOR for many who have not looked up: “The mammalian target of rapamycin (mTOR),[5] also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the MTOR gene.[6][7][8] mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases.[9]”
Dr David Sinclair talks often about the use of Metformin, Resveratol, and NMN for anti aging. His videos w Joe Rogan are fascinating to watch.
Dr. David Sinclair is a now professor in the Department of Genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. He is an inventor on 35 patents and has received more than 35 awards and honors. ... David's fight against aging hasn't been easy.
I am not sure the exact benefits of just the rapamune. I am also on Xgeva, Dr.Kubler Immuno therapy treatments, and The dreaded ADT. I am 5 years in with 1 Met to spine at T11. PSA is staying undetectable and other than hot flashes and missing testosterone I think I am healthier now than before the diagnosis. ( I did try ADT vacation 2 years ago, 8 months in PSA spiked and bone pain was on the increase. Cyber knife to T11 after PSMA PET CT found accelerated growth to the lesion brought it under control. Back on ADT full time since then).
Interesting how rapamycin was discovered.From Wiki
It is produced by the bacterium Streptomyces hygroscopicus and was isolated for the first time in 1972 by Surendra Nath Sehgal and colleagues from samples of Streptomyces hygroscopicus found on Easter Island.[8][9][10]
This doctor does tele-consults for $50. Will prescribe Rapamycin/ Sirolimus if indicated. He is big on peptides as well.
My 6mg a week costs me less than $50 a month. My meds are coming from a compound pharmacy through Dr Julio.
If you have labs you can send them to him in advance. It will be very helpful. His $50 consult fee is a bargain for even just a lab review. He spends half an hour or so.
Julio L Garcia, M.D.
5735 S. Fort Apache Rd.Suite B
Las Vegas, NV 89148
Past-President of the Aesthetic Surgery Education and Research Foundation
practice devoted to cosmetic surgery and age management therapies
dedicated to helping patients with mesenchymal stem cell/ cytokine/ growth factor therapies and peptides for the treatment of acute and chronic medical issues
Does anybody know of a doc/clinic in the EU that prescribes and/or supplies rapamycin for off-label use? With the info from Scott1963 I can get hold of it in the U.S, but will have a hassle in customs.
I read your description. Perhaps ask your doctor to put you on combined Dasatinib and Rapamycin. Then it will be up to you to pulse dose once you have the meds.
My doc will not prescribe rapamycin since it´s not indicated to treat PC. Do you think it is better to get it from India than the addresses you gave in the U.S.? I get my Dasatinib from India. I had telephone contact with the supplier there who seems trustworthy, but, perhaps from prejudice, I can´t be totally 100 % sure it´s the right stuff. I have been thinking of sending a tablet to a lab in the U.S. that can determine if it´s the right thing.
I am planning to get some rapamycin while I am here in Mexico, no Rx needed. Plan to take 2 mg weekly for 8 weeks while I am on my modified cyclic testosterone. Then while off the T, take fisetin and quercetin daily for a month in lieu of dasatinib to clear senescent cells.
The small clinical trials on dasatinib+quercetin are three consecutive days only, and I believe similar with fisetin. The assumption is that medication is only needed every 2-6 weeks, with senescent cells taking that time to reemerge, at least in preclinical trials.
Once again, right on Scott1963. I can't wait to start rapa weekly. Hearing about Mexico and India, a possible obvious solution struck me. Shortly traveling to Brazil, will start looking there. Thankfully rx is not as strict everywhere as where I live.
Thanks for the lead on TaylorMade Compounding. Rapamycin seems totally unavailable both in Mexico and in Canada, even the US brands like Rapamune. I’m plugged in with TaylorMade now for Sirolimus and Dasatinib. Very good prices on their compounded products. 👍🙏
From my experience, there is nothing like the Dasatinib plus Quercetin and Fisetin. You just can't get that same hit with the Quercetin and Fisetin alone. Do some research on Dasatinib and you will find that it too is used with PCa.
Right on! As soon as I figure out best way to get high bioavailability of Fisetin which I understand is an issue, I will add intermittent (I believe high-dose) Fisetin in between the D+Q.Does the hit from using all three manifest itself in any particular way?
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Sirolimus/Rapamycin availability
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