Side Effects of Rapamycin (part 2)

So, fellow travelers, unfortunately, diarrhea is one of the top five side effects of the following:
Acarbose
Metformin
Rapamycin

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Since I have switched to my new protocol, I no longer have any rashes. I am now on 2 mg + GFJ. Could be I was taking too much or my body has gotten used to Rapa. Probably the latter since Iā€™ve been taking it over a year.

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Transcriptome profiling utilizing a Rapa resistant cell line as a control indicates that Rapa is incredibly specific inhibitor of mTOR.

So I worry when supplements to counteract the ā€œside effectsā€ experienced when taking Rapamycin are proposed. My own opinion is that most ā€œeffectsā€ of Rapa are direct effects of mTOR inhibition rather than side effects. In other words it is possible that all effects of rapamycin are downstream of mTOR inhibition.

Supplements to ameliorate the annoying effects of Rapa may also reduce the beneficial effects, there is really no way to know at this point. It seems possible that mTOR can be over-inhibited with intolerable effects but then I would think the solution would be to reduce the dose rather than counteract the intolerable effects.

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are you referring mTOR1 here? or mTOR2 as well?

Jonas you are correct that sentence doesnā€™t quite make sense. mTOR is a protein present in both mTORC1 and mTORC2 protein complexes. It is the activity of the mTORC1 and mTORC2 complexes that can be inhibited by rapamycin. My point is that inhibition of either complex is a direct effect of Rapamycin binding to FKBP12 and mTOR.

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A short update on my rapamune journey since april 2023 : last week ( Tuesday, 5 September) I had my first 3 mg dose with again huge and disgusting skinrash (on Wedsnesday 6 September)

I have been going slow mainly due to this side effect but being so happy I didnā€™t have any from last 2 mg dose ( but maybe this could also be since I was on holidays so surely less stressed etc), on 5 September I finally tried 3 mg. I have been trying several suggestions from this site for the skinrash (as described above;with bubbles, reddish painful skin and always the worse on exact same place) but have the feeling what works ( ā€œbestā€, letā€™s say) for me so far is simply red light and inotyol ointment (my grand mum always recommended me) which seems to be a mere zink oxide and titanium oxide cream: it still takes time (now 1,5 week passed and still not totally gone but antibiotics, antiviral, etc ( everything I found on this blog more or less; tried different brands for each) did not seem to go faster either and are more invasive, I think?

Just sharing for what its worth, and interested in your thoughts if any. Of course I am still on the look out for sth that could solve faster obviously, but so far that is what I experienced.

Will now wait till clearing up and then take 2 or 3 mg again, not sure yet :sweat_smile:

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Maybe just stick to 2mg for a few months and then build up the dose slowly. Alternatively, everyone responds differently. 2mg might be ā€˜about rightā€™ for youā€¦.

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Just sharing. I am ramping up to 6mg dose and after 4 mg got a mouth ulcer, like many have. Just using kanka to keep it from hurting too much. Also have a feeling of euphoria occassionally (but that could be the long meditation practice :slight_smile:

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Hello, I wanted to update everyone on my rapamycin use. I have been taking 5mg 1x a week for 33 weeks. I have lost 15 pounds which i am happy with. My blood pressure has been elevated 138/93 and it was always 120/80. I started taking magnesium and berberine to try and lower it. I have also started running. I donā€™t think the rapamycin is to blame and neither does my primary doctor. I feel way better than I did and am continuing my 5mg dosage for another 15 weeks. I will keep you updated.

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My BP was improved with nitric oxide and potassium. Worth a try if you havenā€™t. Good luck.

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On my new dose of 6 mg + GFJ + EVOO + Metformin (21 mg equivalent) bi-weekly. The first couple of days after dosing, my feet and ankles were mildly swollen upon waking from sleep.

Also had a weird headache in the lower left side of my head while sleeping which I am not sure if it is related. It lasted only one day, but it seemed to go away if I turned my head to the left and came back if I turned it to the right. Quite strange as I have never had that before. Anyone else have this?

I am not getting the fatigue any more (thanks taurine!) but it appears I am not getting as much euphoria as before either. I do have a general sense of well being though.

Also, definitely slow wound healing. Of course, the night after I took my dose, I scratched up my wrist and palm pretty badly. The four open wounds are all red, irritated, inflammed and infected even though I applied neosporin and bandages. (although the bandages fall off quickly. Hard to stick on an active joint!) They are healing, but at a noticeably slower rate than if I didnā€™t have as much Rapa in my system.

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Rapamycin, if overdosed, can be hard on kidneys. You may be overdosing with GFJ. Your swollen ankles point to possible kidney problems. And if you have kidney problems, thereā€™s a greater risk of lactic acidosis with Metformin. Have you checked your kidneys recently?

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I have checked my kidneys via blood tests. They are fine. But, itā€™s good to know and watch out for. If I continue to have this problem, I will cut down on my Rapamycin dosage.

The point of this experiment is to see how a high dose of Rapamycin affects my health over a 2-month period. Iā€™ll be getting a complete physical and blood work at the end of December. I was originally going to try 40 mg over 3 weeks, but I didnā€™t want to risk rebound, so decided to try 21 mg. It is possible that it is higher beyond the calculation, but without a Rapamycin blood test here, Iā€™m using the computed values.

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17 posts were merged into an existing topic: Improve Bioavailability of Rapamycin (2)

Why do you think you are having a problem with mTORC2? Are you experiencing increased infections, etc?

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Immunosupression. Lowered neutrophils and in particular lowered lymphocytes. Mild pneumonia, solved with an antibiotic.

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Mostly theoretical. I have had neck acne a few times (a single pimple each time), a couple mouth ulcers, and a single instance of gum inflammation that lasted a few days. I worry more about what is happening that I canā€™t feel.

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life extension has a blood test for rapamycin levels. unfortunately, they only do it in the Fort Lauderdale lab. the last time I did it there it was $95

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There are a few companies in the US that provide inexpensive blood sirolimus level testing: How to get a Rapamycin (sirolimus) Blood Level Test

In Europe and elsewhere it can be more difficult. If you find one outside of the US, please post information about the lab and cost.

People have said that in the UK this is an option: Doctap.co.uk charges Ā£134 (plus the Ā£50-Ā£70 consultation fee - obviously not extra if having other tests done) in the UK.

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There is still some swelling in the bottom of my left foot which is odd. I think I may need to dial down my Rapamycin dosage to 5 mg + GFJ when I take my next dose in 2 weeks.

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