DeStrider's Rapamycin Protocol

Updated July 2, 2023

After using Rapa for about a year and seeing the results along the way, I thought I’d share what I’ve experienced. For me, I use a combination of Rapamycin, Acarbose and Metformin. I use my euphoric fatigue as a bellwether for effectiveness. If I take too little, there isn’t much euphoria. If I take too much, the euphoria turns into nausea.

So, this is what I do to maximize the euphoria.

  1. I start by eating 2 whole grapefruits and taking 1 g of Metformin.
  2. I take 2 mg of Rapamycin in a shot of EVOO 1-4 hours after the grapefruit and Metformin. I used to take 3 mg.
  3. The next day I take 500 mg of Metformin and then stop the Metformin.
  4. I take 100 mg of Acarbose with each meal every day.
  5. Repeat in 7 days

Of course there are other supplements I take, but this is how I handle my off label prescriptions. I have found the Metformin is useful only on the first two days and if I continue after that, I experience hypoglycemia.

I have decided not to take large doses of Rapamycin anymore.

I started my protocol with 1 mg a week for 4 weeks. After that, I upped it to 2 mg a week for 4 weeks. Then I upped it to 3 mg a week for 4 weeks. So, I eased into the 3 mg over time. Remember that grapefruit juice increases the equivalent dose by roughly 3-3.5X. With 2 grapefruits, EVOO and Metformin, I would say it is closer to 3.5X. After news of Dr. Bs cancer metastasis, I have decided to go back down to 2 mg. However I had gone up to 6 mg (18-21 mg effective dose) using this method without any serious side effects. But for any dose over 3 mg I waited 2 weeks for the Rapa to clear my system.

That’s what I have found works for me. However I am a 5’11" 206 lbs male and you may have to adjust your dose accordingly. I am not a doctor and this is not medical advice. It’s just what has worked for me.

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I am curious about your HGA1C and fasting insulin levels before and during this protocol if you don’t mind sharing the data.

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My fasting glucose was 4.7 mmol/L before I began Rapamycin. A normal range is 4.1-5.9. I was taking 1 g of Metformin daily when I had this bloodwork. I haven’t had my annual blood draw this year, but I will in September. All I can say is that if I take 500 mg of Metformin daily, it causes hypoglycemic symptoms.

Hey DeStrider,

I’m on a very similar track.

My fasting glucose is a bit higher, mid 5s. I’m 1.78 (5’10") and 72kg. Family history of skinny diabetics, so I eat accordingly.

I don’t use GFJ. I’m concerned with a lack of a clear dosage control and the variations in individuals.

Same protocol rapamycin, acerbose and metformin but with variations.

6 to 8 mg rapa with olive oil each week.
3 days a week 1x500mg metformin (with B12). On low exercise rest days.
I use acerbose for meals that warrant the effects. That’s usually 1 a day.

I particularly want to avoid completely suppressing MTORC2 all the time. I’m outside of the USA so there’s no easy access to regular blood tests to monitor the peaks and troughs of rapa that persists in my blood over the long haul.

There’s obviously an accumulated weekly rapamycin amount given the long 63hr half life. I can’t find any solid data on the levels of trough rapamycin that might suppress MTORC2 longer term so the only safe approach seems to be getting back to zero. So, I’m due a rapa holiday.

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I apologize for my ignorance, but what do you mean by “ euphoric fatigue”? — is this a common description of Rapamycin effects? (I’m not yet taking Rapamycin so perhaps it’s obvious.)

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Its interesting… not something I’ve ever experienced, but quite a number of people here report feelings of eurphoria after taking moderate to higher levels of rapamycin. At really high dosing, many people report GI issues (diarrhea, etc.).

You can do a search on the term “euphoria” in our forums and see the mentions: https://www.rapamycin.news/search?q=euphoria

I’m not sure exactly what he’s talking about when he mentions “europhoric fatigue”…

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The best way to describe euphoric fatigue for me is the feeling that you get after sex. Except it lasts for a couple days. You feel a bit tired but very satisfied and just want to take a nap. The feeling wanes slowly with time.

Yes, I also experience some GI issues sometimes with pain on the first day and diarrhea (like yesterday ). The GI issues usually clear up by the second day and they do not always occur. I still have a bit of the euphoria going…

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Hmm unfortunately, no feelings of euphoria or fatigue for me.

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Everyone has a different biology and a different experience with Rapamycin. Just because you don’t have it doesn’t mean anything is wrong.

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Sorry, tongue in cheek response to the illuminating description of your euphoria. I’m very happy with rapamycin benefits.

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Updated the original post to reflect my new thoughts on Rapamycin.

I often wondered if the euphoria was from elevated blood sugar

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Some people asked, so I updated it with the following info:

I have used this method with up to 6 mg of Rapa (18-21 mg effective dose) without any serious side effects. But for any dose over 3 mg, I waited 2 weeks before the next dose to allow it time to clear my system.

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I took my dose of Rapamycin according to my protocol yesterday afternoon. In the afternoon I was a bit sluggish, but today I feel invigorated. I feel healthy and energetic. In two words - simply amazing. Before I felt a euphoric fatigue. Now it’s just euphoria. It’s just pure joy and energy. I feel amazing. The only change I made between before and now is the addition of taurine. I am wondering if the taurine is working synergistically with the Rapamycin to get rid of the fatigue?

Either way, I feel damn good… Almost too good if that’s possible.

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Hi, I like your regime and thanks for sharing. I want to try myself. And forgive me if I missed you or someone else already answered this. I tried searching for Enteric coating of 1mg Sirolimus pills… I found many discussions on powder/compounded form. My question is has anyone tried or is it advised to put the small pills inside an enteric coated pill? Not sure of what would happen if 2x Enteric encountered… I called the pharmacist and they said the pills are coated but they are not sure with what… My hope is that the capsule would help the pills be better absorbed.

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Update

I had blood work done and found that my LDL had increased from 81 to 122 and my HBA1C moved into barely pre-diabetic levels. I do believe that this was caused by the Rapamycin as it was the only major change after my last blood work that could explain this.

I took my results to my GP and we have concluded that the best course of action is to resume 500 mg Metformin daily and start 5 mg of Crestor statin daily. We will test again in 6 months. This sounds like a good course of action to me.

Rapamycin plus Metformin has shown to be synergistic so I believe that the statin will as well. We won’t truly know as mice don’t get heart disease. However, to me it makes sense. My doctor said things were not bad yet, but that I am taking a good proactive approach.

I also had an arterial plaque scan, carotid artery scan, and afib test. Everything came back normal.

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After watching the Matt Kaberlein, Attia and Sabitini podcast, I have decided to do another large dosage of Rapa. Just now I have taken 7 mg + GFJ + EVOO + Spermidine + 500 mg Metformin. I will wait 14 days before dosing Rapa again.

An hour in, heavy on the fatigue with a mild euphoria. This has been the largest dose I have taken at a 21 mg equivalence.

Took my other supplements and the euphoria is enhanced. I guess there is an interesting interaction between my supplements and Rapa. Probably the lithium, NAC, or selenium. Or the nap I just took. :wink:

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Will you continue with this strategy of high dosing, or will you do it on an intermittent basis?

After listening to the podcast, I am also about to review my dosing. Before listening to their conversation, I was constantly set on a lower dose, 4-5 mg a week. This is in line with the Manning study that showed effects from this dosing.

(PDF) mTOR inhibition improves immune function in the elderly (researchgate.net)

Then came the conversation between Attia. Kaeberlein and Sabatini and they argued that there are most likely tissue-specific needs and higher doses are most likely to have a broader effect when it comes to reaching different tissues in the body. (This thinking is also in line with the theories of Blagosklonny). And I got the impression that they speculated that higher doses also provide a better effect than lower doses do in the same tissue.

This makes me rethink my dosing. But according to the Manning Study, dosing with 20 mg per week creates an increased probability of unhealthy side effects (already seen within 6 weeks). So that strategy does not come with an acceptable risk reward profile for me. Avoiding negative effects on glucose metabolism and high lipids is a high priority for me.

I consider two dosing strategies:

  1. A few months with 5-6 mg per week and then a couple of booster sessions with 15 – 20 mg with two weeks between and then a break with 6-8 weeks off rapamycin. Then start over again.
  2. A few months with 5-6 mg per week, and then a few months with 10 mg every two weeks. Then take some time off.

Right now dosing is a guessing game and I want to cover as many tissues as possible with a low risk of side effects. But nobody knows the optimal dosing. Optimal risk reward for me is most likely low doses that are interrupted with a short term of higher dosing and then taking time off rapa.

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I firmly believe 20 mg a week is a poor choice due to MTOR2 inhibition. However a 20 mg intermittent dose followed by a flush out week should be able to avoid that. I am debating adding a 3rd week as well to purge all Rapamycin. Thoughts?

@Curious I think we have the same line of thinking. I am not planning on doing 21 mg a week or bi-weekly all the time. I am doing it one time and not dosing again for 2-3 weeks when I will switch back to 6-9 mg weekly. I am thinking of doing a large dose every 6 months or so.

I think modulating in this manner probably has the highest chance of hitting the sweet spot wherever that is and not shutting down MTOR2 too long. I want to make sure that my blood concentration is high enough to rejuvenate all of my organs at least twice a year (and if not all, then at least a few more).

I am interested in seeing what happens. So far, just more fatigue.

Also, I am still experiencing some muscle pain from my failed statin experience and I am hoping Rapa can help with that. So far it feels promising. Rapa euphoria trumps statin pain? We shall see in a couple of days.

Also mildly twisted my ankle yesterday (not too severe, yet painful) so curious if a high dose of Rapa will help that too. Un-ergonomic dress work shoes seem to reduce healthspan. :wink:

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This sounds like an interesting plan and I might adapt for my dosing too. Just out of interest did you drop the statin completely or have you tried a different one? I persevered with the muscle pain and it definitely eased after a few months although three years on I do still get muscle aches but I put up with it. I’ve also added Ezetimibe 10mg which really helped bring down my LDL a lot further than Atorvastatin on its own (and I’m on the maximum 80mg).

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