I'm considering experimenting with very large doses of Rapa due to its effect on my Crohns/fatigue

I’ve been on 15mg/week for 4 months and I’ve noticed a very obvious improvement with my autoimmunity problems. 5mg/week did nothing, but 15mg seems to work.

But I want to experiment with higher doses… maybe 20 or 30mg per week. Has anyone else here tried such high doses before?

Thanks.

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Some past discussions / threads you may want to review:

Here: One User Trying Very High Doses of Rapamycin, and Negative Adverse Events / Results

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

Here: Ideas on Protocols for Testing Higher Rapamycin Doses

Here: 20 Mg of Rapamycin every other week

Here: More Rapamycin Might Not Be Better

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Have you considered daily dosing?
Maybe 2 weeks on 1 or two weeks off?

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I regularly take ~22-25 mg every 2 weeks by using 5mg plus ketoconazole. I take a “maintenance dose” of 4 mg between the large doses.

I have had no noticeable side effects at this dosage.

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I wonder if you want or expect too much from Rapamycin.

While Rapamycin appears to affect autoimmune conditions, it appears to have only a small affect.
In my case I’ve suspected it has helped my autoimmune issues, but again not by much.

I’ve seen no specific studies on Rapamycin doing so.

Assuming it does have an affect, I think it would do so because (conjectures follow):

  • Imbalances in the composition of the gut microbiome lead to low butyrate production, which in turn leads to permeability of the colon, which leads to autoimmune reactions (more complicated than this summary, but you take my point).

  • Rapamycin (which has a weak antibiotic affect) may contribute to rebalancing the microbiome by killing off some of problematic bacterial overgrowth (e.g., of firmicutes apparently coincident if not causal of all cases of psoriasis. I’d expect something similar with Crohn’s).

Other approaches can more effectively rebalance the microbiome and doing so can contribute to significantly mitigating autoimmune issues.

These can include:

  • Purging the microbiome. This can include things like bowel preps followed by antibiotics targeting problematic bacterial overgrowth. Alternatively - 7 days of raw fibrous vegetables and egg whites (this really works).

  • Restoring the microbiome balance, with prebiotics (e.g., resistant starch) to feed healthy bacteria supporting butyrate production.

  • Supporting the microbiome with: probiotics, Vitamin D3, MCT oil, and Grass fed butter.

Probiotics if not properly designed to get through stomach acid don’t seem to do much. Taking them with resistant starch might help.

Worth researching.

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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).

  1. Highest validated sirolimus dose in a human to date 180 mg sirolimus: 10/27/22

  2. 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.

  3. 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.

  4. Setting: N1 on weekly doses up to 30 - 40 mg + / week average > year by 2024.

Purpose: Proof-of-principal

  1. = One individual (N1) can survive without acute AE a one-time bolus rapamycin bolus.

  2. Sustained weeks of prolonged substantial sirolimus elevation with optimal lipid & blood glucose control under medical management (N1 at baseline is on pharmacotherapy).

Unresolved:

  1. Probability of adverse events, including across a diverse population.

  2. Influence of genetics, environment.

  3. 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).

  4. Off-label efficacy in humans, if any.

  5. 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

See: https://www.barzilaiconsulting.com/rapamycin

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.

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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