I have tried 20mg with grapefruit juice several times when I first started experimenting with rapamycin.
The result was diarrhea the following day. I did it more than once because I also felt a euphoric effect.
Now I am taking 5mg/week with grapefruit juice but it does not produce any subjective effects.
If you take too high of a dose you will probably have some side effects, but the literature doesn’t show any serious effects from high doses.
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I think over time mtor2 will get dragged down and cause problems. The only 2 ways I know to boost mtor2 is to fast, or also acarbose is supposed to help. I find it easy to fast with the Rapa dose. For some reason I don’t get hungry any way and that could help you too, just an idea to try.
Good Luck,
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Thanks. I’ve spent years trying to improve my microbiome. I’ve done FMT, which seemed to help, but Im not sure it has maintained. I’ve tested many probiotic + prebiotic combinations… and still continue these today. It’s tough for me to know if they are working… but I’ve heard it has to be continued for a long period of time.
Other than Prednisone (which has horrible side-effects), Rapa seems to be the only remedy. It doesnt cure me… but the gut feels far better, and the fatigue isn’t as debilitating. In fact I’m having more and more ‘normal’ days.
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Another case report that may be of interest, related to this thread:
These show notes will accompany the podcast & both be available free-of-charge along with the episode itself.
For updates and announcments in longevity medicine and healthspan, follow me on YouTube and X.
Be sure to subscribe to Agingdoc.com with updates on healthy longevity. The monthly newsletter is free and private, featuring actionable data, protocols and updates for better healthspan.
Sirolimus (rapamycin) has not demonstrated life extension in humans to date (it has not been so evaluated). These protocols are not endorsements and have substantial risks, including & not limited to opportunistic infection & death . The narrative is for research purposes only. Sirolimus use should always be under the medical management and surveillance by qualified prescribing medical providers, and only used when suitable for the patient. Ketoconazole also has risks including liver failure .
In this and subsequent series I describe, with reliably sourced US pharmacy dispensed generic rapamune N=1 experiment. All interventions were performed under intense medical and laboratory surveillance. (1) & (2) have been recorded (unreleased).
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Highest validated sirolimus dose in a human to date 180 mg sirolimus: 10/27/22
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2nd trial by N1: 100 mg sirolimus preceded by ketoconazole. Estimated equivalent dose of 500 mg sirolimus. Highest laboratory confirmed rapamycin concentration in humans to date, exceeding 200 ng/mL in this middle aged male patient, “N1.” 2/20/23.
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Higher dose than #1: Subsequent 200 mg generic rapamune preceded by higher dose ketoconazole : estimated minimum dose equivalent: > 1,000 mg of US pharmacy dispensed generic Rapamune . 11/16/23.
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Setting: N1 on weekly doses up to 30 - 40 mg + / week average > year by 2024.
Purpose: Proof-of-principal
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= One individual (N1) can survive without acute AE a one-time bolus rapamycin bolus.
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Sustained weeks of prolonged substantial sirolimus elevation with optimal lipid & blood glucose control under medical management (N1 at baseline is on pharmacotherapy).
Unresolved:
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Probability of adverse events, including across a diverse population.
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Influence of genetics, environment.
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Long-term reliable safety and efficacy data for long-term use (N1 has been on 30 mg weekly for over 1 year as of 2024).
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Off-label efficacy in humans, if any.
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No hard inferences can be made except for proof-of-principal this scenario is possible for at least one individual/circumstance: “The exception breaks the rule.”
[This case report is not discussed below, but elements are addessed on YouTube Agingdoc Podcast, beginning with Epsidode 7 with Matt Kaeberlein Part 3, Part 4 & beyond].
Enjoy! -Agingdoc
Wow, 1 gram!!! It sounds like everyone is using ketoconazole now.
Oh, not at all. These are the outliers. Most people are much lower doses and no bioavailability enhancers like grapefruit juice or Ketoconazole - the higher the dose the greater the risks…
The person (n of 1) example above is working with David Barzelai (AgingDoc), a doctor and specialist in longevity medicine.
from an August, 2022 user poll here on our site)
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@hamtaro 4 months isn’t actually that long when you are talking about global alterations in cell division and metabolism. These changes take time to settle into a steady state. In the case Crohns you may be altering a very complex relationship between your immune system and your microbiome. I would suggest you give it more time at your already fairly high dose before you experiment with even higher doses. Things may continue to improve and you may even be able to reduce the dose eventually. Try not to think of it like a steroid but more a fundamental tweek to your immune system that may (hopefully) result in an immune state that is similar to before you developed Crohns.
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I think you may be right about that. I may wait another 4-6 months before I make any changes, if any.
One thing I’ve noticed is both times I took a rapa break, I start to feel things get worse again after about 3 weeks.
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Well now we know you probably can’t kill yourself with Rapamycin. 500 mg equivalent dosing is crazy. I’d say the ketaconazole was probably more dangerous than the Rapamycin! We probably hit saturation, but it appears to be non-lethal.
Interesting that LDL jumped 38 pts for N1. So it seems that a jump in LDL is associated with Rapa.
Is N1 on this forum? If so, hats off to you sir. I would never do it myself, but thank you for doing it for us.
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Have you tried Low dose naltrexone ?? WOrks so well in inflammaotrybowel disease. As a physician , I think using things like thymosin alpha 1, low dose naltrexone would go much further for you
Here’s a study showing ramamycin/sirolimus improves rheumatoid arthritis, an autoimmune condition: Low-Dose Sirolimus Immunoregulation Therapy in Patients with Active Rheumatoid Arthritis: A 24-Week Follow-Up of the Randomized, Open-Label, Parallel-Controlled Trial - PMC
Also see https://www.mdpi.com/1422-0067/21/19/7015 (search: “rapamycin”)
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Are you able to provide more info on why you think these things might be helpful for autoimmune disease? Thank you.
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I am on 15mg - 24mg weekly, since July 2023. At first it seems worsening my autoimmune problem, psoriasis between my eyebrows, when i began rapamycin in 6mg. However, when i gradually up the dosage to 24mg, it’s gone. However, i am a little bit of worry about rapamycin inhibit the sperm generation, i can feel the decrease of semen amount…
The consolation is average speaking eunuch lives 10-20 years longer…
Rapamycin inhibits spermatogenesis by changing the autophagy status through suppressing mechanistic target of rapamycin-p70S6 kinase in male rats
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See this thread, the issue with spermatogenesis seems to go away when you stop the rapamycin. Many cases of men with organ transplants and on rapamycin, go off and have children: Possible Rapamycin Risks for Healthy Humans (Part 2)
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Is itt possible that in this case (or in the case of autoimmune disease prevention) that Rapamycin is simply doing its approved indicative effect: reducing immune response? And this is why it is helping people who’s immune system is attacking their own bodies? And this is also why there may be a dose response for you? If this is the case, rapamycin wont “cure” anything but will need to be taken forever to correct this “symptom”. (Still could be amazing for you)
Or is there evidence that raamycin actually changes the autoimmune response and “cures” it? That would be amazing.I have a daughter with (fairly recent) TiD and id love to find a way back for her.
I know keto/carnivore isn’t popular on this forum, but many of the people who come to it have been very sick — many with autoimmune diseases — and whatever aspect of this diet (elimination diet, nervous system quelling) seems to work for many of them (not a clinical research trial). And there is some ancillary evidence that if youve been on the diet for some time that you can ease your way off it without losing the effects. There is some speculation that all this diet really does is get you metabolically heathy but not much else. Not suggesting anyone try this. Also i have vitiligo (a minor autoimmune) and i still have it after three-ish years of mostly low carb so it did nothing in this respect for me. (By the way: “keto/carnivore” has been mentioned as terrific for many people with crohns disease, and nervous system disorders — first medically used for epilepsy — but not sure there’s much mention outside of this in autoimmune.)
have you considered daily dosing instead of weekly?
No, one purpose to take high dose is to expect the rapamycin can pass blood brain barrier to reach my brain…
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My father used to have “back stiffness”, a chronicle spine inflammation caused by autoimmune attack. I am willing to take rapamycin for the rest of my life in exchange of free movement…
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Absolutely with you.
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