The study that I linked is very favorable towards rapamycin effects in mice re insulin. Short term usage is bad but longer-term usage turns favorable.
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The day after I read this I got my labs for a PE. Been on on Rapa about three months (2.5mg MWF initially , then 7.5mg once weekly more recently. Lo and behold, both Total and Free T 2/3 lower than six months ago. I have been on HRT for a several years (72yo, male) and have had levels consistently in high normal range for the lab).
My skeletal muscle mass has also declined. I train cardio and strength regularly. My trainer has noted that since taking rapa, I have plateaued in my lifting where I had been hitting PRās on a fairly regular basis.
Going off rapa, and will retest in three months to rule out that variable (the other variable being the compounding pharmacy that makes up the cream for topical application; cannot do injections as on anti-coaguant).
PS My doc was blown away by significant improvement in my lipids. WBC/neutrophils down a bit.
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Thank you for sharing this important info dogdoc!
Please let us know if your testosterone levels return to your normal baseline after going off rapamycin for 3 months. Hopefully the apparent detrimental effect of rapamycin on testosterone levels is reversible.
Thatās just weird because if you are on Trt your endogenous testosterone production stops which means that if you didnāt change your Trt dosing schedule your testosterone gets used up or broken down quickerā¦
Testosterone levels drop quickly at the end of the weekly dosing interval. So, day of testing relative to the date of administration can make a big difference.
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To clarify, I have been taking testosterone via a compounded topical cream applied daily which for some years has maintained good levels of total and free T. I have also had my blood draws three hours post-application as my doctor said that should be a peak levels. I am getting blood drawn next week to recheck my T which will be seven weeks off rapa (I am thinking that is a sufficient number of half-lives.) I am not ruling out the possibility of an issue with the compounding pharmacy as my initial trials with proprietary topicals were ineffective which is why I ended up using a comounded product. Maybe they have changed something in the prep of the cream. My current doc does not see an issue with getting testosterone by injection. May get an endo consult.
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You may choose injection for a more reliable delivery of the dose. By the way it doesnāt need to be IM. Sub cutaneous injection works fine and is less painful although the instructions are for IM.
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After 61/2 weeks off rapa, my total and free T have recover to 78% and 75% of pre-rapa levels respectively. Will recheck in the next few months. Not sure re restarting at any time. The consequences of low T are wide ranging, not to mention the direct effect of the increased catabolism from rapa on skeletal muscle mass, bone density, WBC counts, etc . Will look for more data, both scientific and anecdotal on this issue.
DD
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Thanks dogdoc for the update. Please keep us posted. I believe the potential adverse effects of rapamycin on male testosterone levels is underappreciated. Rapamycin has been shown to decrease the size of testes in rodents. I suspect only a small fraction of men have routinely been testing their total and free testosterone levels prior to starting rapamycin, and regularly afterwards.
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I am a 72 y/o, 86 kg male. Exercise 12/hrs weekly with cardio and weights. 3 months of rapamycin 6 mg once weekly. Have seen my HbA1c increase from 5.7 to 6.0, glucose from 83-93 and insulin resistance from 6.7 to 10.7. I take 5mg rosusvastatin daily. I am wondering if my rapamycin dose of 6 mg once weekly is an overdose for me when viewed through my labs. It appears with 6 mg that I am in mTORC-2 inhibition which is causing the above lab changes? What is the consensus here? Would 4 mg once weekly be better or an approach similar to Matt Kaberlein with a drug holiday of several weeks from rapamycin? I plan to also combine the lower (4 mg) with Kaberleinās suggested protocol of 10 weeks on rapa followed by 8 weeks off as mentioned above. Also, does anyone know the % of slow metabolizers of rapamycin as this could also be contributing to the elevated levels of insulin and glucose. Thank you.
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My opinion is that it is sensible to back off the Rapa dose or frequency to get side effects to where you are happy. Then, if you want a higher dose, build back up to see if the problem actually was Rapa.
Side effects Iām aware of:
LDL increase
Glucose / HbA1c increase
Lower leg swelling
Acne
Mouth sores
Skin or other infections
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Agree with you. Iāve attempted to research as much as possible. I will cycle off for 8 weeks and then when I resume, after repeating lab work, it will be 4 mg/weekly & I may with further reading, opt for 8 mg every other week. Iāve had one aphthous ulcer along with the worsening lab tests. Thanks,
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This statin is known to raise blood sugar and might increase the risk of developing type 2 diabetes. Have you been long on rosusvastatin? Maybe check this with your doctor and maybe change statin, I believe atorvastatin is much better in this regardā¦
Thank you. Yes, Iāve been taking the minimal dose of rosusvastatin and my metabolic profile was stable. After 3 months of rapamycin, I checked my labs and was disturbed to find that they had worsened. Reading different articles and will take an 8 week vacation (cycle) from the rapamycin, recheck all my labs and then, because I believe that the 6 mg was actually triggering mTORC2 inhibition, I will start back up with 4 mg once weekly and then repeat labs 10 weeks after resumption. If the labs after resumption on this dose worsen once again then I will probably give up on the rapamycin.
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That is why I was asking how long are you taking it. If I remember right median new onset diabetes diagnosis in rosusvastatin is around year and a half / two years into taking it in about 5% of users. I might remembered the numbers wrongly, but it is a statistically significant increased risk.
All my metabolic biomarkers (lipids and glucose control) worsened 3 months into my rapamycin regimen. At 6 months they were around baseline. At 9 months lipids were better than baseline. Maybe also something to consider.
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Yes. That is very encouraging data. I hope that mine do the same.
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I had my A1C taken again yesterday. I am holding steady at 5.7 which is right at the line of starting to be concerning. Again, my rapa dose is 2 mg with GFJ week and 4 MG with GFJ in alternating pulse doses. I am slightly concerned but have seen the Blago research. Question: Is NOMA-IR a test you ask for individually from your lab/provider or calculate yourself based on the formula GlucoseXInsulin/405? I am considering booking a session with Dr green to get his opinion. Iād like to be fully informed on the risks of a high-ish A1C. I can always lower my rapa dose or spread farther apart too.
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You just need a fasting glucose and insulin testā¦use an online calculator (link below) to find your HOMA-IR result.
https://www.rdm.ox.ac.uk/about/our-clinical-facilities-and-mrc-units/DTU/software/homa
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