Rapamycin in humans

I'm cautious on pharmaceuticals but am considering Rapamycin. Downsides are cost, difficulty to source and potential side effects (some people suffer from stomach issues IIRC). So balancing that I'm looking at potential benefits, aging being the benefit. Let's take this explanation of the benefits as an example, in particular

It has been known since the 1930s that caloric restriction extends lifespan and slows aging. Rapamycin could be characterized as caloric restriction in a pill. In a mouse study discussed in the "Cardiomyopathy" section, rapamycin had similar effect in aged mice as 40% caloric restriction in restoring the dysfunction of old hearts to normal function of young hearts.

Now separately we know that research has determined that caloric restriction does not have the effect for humans/chimps that you see with shorter lived species in life extension. It can increase health span (e.g. making you less prone to heart disease) but it won't add years to your life. AFAIK the Rapamycin studies have been done on mice and dogs which have a much shorter life span than humans. 

Anybody have any data that says otherwise? If the main effect is  to decrease TOR, well there are other ways to do that (periodic fasting which also has other benefits). 

So at the moment I'm remaining skeptical of the benefit of Rapamycin in humans, adding in the other difficulties I'm holding off using it, but am open to research and evidence to the contrary. 

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      • angie4life
      • angie4life
      • 6 yrs agoSat. November 3, 2018 - 12:26 pm
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      Thanks for the info, as I’ve been vegan 18 years and always wonder about whether it matters with supplements.  The supplement I feel had helped the most is the NMN sublingual powder ... I take several scoops a day , and a pesky long term tendinitis disappeared after a month or so .  I’ve been doing intermittent fasting and taking Metformin for two months , and my pup and I added low dose Rapaymycin this week after we did high dose Fisetin a few weeks ago ..maybe now add CoQ 10 , or even better , ubinquinol .

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        • are we there yet
        • are_we_there_yet
        • 6 yrs agoWed. November 21, 2018 - 2:15 am
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        angie4life did you spell tindionitus correctly? did you mean tinitus as in ear ringing?

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      • angie4life
      • angie4life
      • 6 yrs agoWed. November 21, 2018 - 12:31 pm
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      Hey, sorry , was typing fast late at night ... tendinitis, as in bicep tendinitis from too many yoga pushups haha .

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      • are we there yet
      • are_we_there_yet
      • 6 yrs agoThu. December 6, 2018 - 3:48 pm
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      I found a dr in my city, houston that gave me script for rapamycin (sirolimus) and started taking it at 1mg starting yesterday, followed by 9 days off, then increasing to 2 milligrams for the second 10 day cycle, etc... I also take 500 mg metformin daily and did another full blood panel before starting rapamycin.

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      • are we there yet
      • are_we_there_yet
      • 6 yrs agoSun. December 9, 2018 - 12:13 am
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      I was lucky, the first doctor I asked wrote script for rapamycin (sirolimus) after reviewing Dr. Green's website protocalls.

      I have already been taking 500 mg,d metformin. My Rapamycin schedule is conservative at a 10 day intermitant dosing starting at 1mg, then 2, then 3.... I have been keeping detailed records.

      Possiblble side effects I may have seen from mapamycin are a reduction in left knee arthritus, a slight ocasional dry cough on the first day or two of the 10 day cycle, a bruse that I got on my arm may have taken longer to go away. I have extensive full med panel data befor testing as a baseline I can refer to later as I have a longer dose history. 

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      • are we there yet
      • are_we_there_yet
      • 6 yrs agoWed. December 12, 2018 - 6:34 am
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      The half life if rapamycin-sirolimus is 67 hours or about 2.5 days. 

      A week = under 3 half lives

      10 days = 4 half lives

      15 days (twice a month) = 6 half lives

      I use 10 days for intermitant dosing for now

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        • Danmoderator
        • skipping my funeral
        • dantheman
        • 6 yrs agoWed. December 12, 2018 - 1:11 pm
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        are we there yet Don't forget that the gene CYP3A5 (rs776746) for those with the CC variant the half life of rapamycin is likely longer, ref

         

        https://www.pharmgkb.org/pathway/PA166165039

        CYP3A5

        Similar to CYP3A4 variants, kidney transplant patients with the CYP3A5 rs776746 CC (also known as CYP3A5*3/*3 or a non-expressor) genotype may also require lower daily doses of sirolimus to obtain optimal trough blood concentrations as opposed to those with the CT or TT (*1/*1 or *1/*3, expressor) genotypes [Articles:15707415168153171794105226543771]. One study has found no association between CYP3A5 rs776746 and sirolimus metabolism [Article:23974086].

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        • are we there yet
        • are_we_there_yet
        • 6 yrs agoFri. December 14, 2018 - 5:59 am
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        DanMcL ... thank you.... I have a 23 and me kit... I will submit it soon. I did it for my mom and it took about 2 and a half months but was well worth it for several reasons. I’m doing a slow steeped ramp up of sirolimus on my self test with no notable problems. Saturday is my next dose. 

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      • albedo
      • albedo
      • 6 yrs agoMon. December 17, 2018 - 7:26 am
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      Don said:
      albedo Do you have a link to that clinical study?

       Sorry Don, I do not.

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      • are we there yet
      • are_we_there_yet
      • 6 yrs agoSun. January 6, 2019 - 6:22 am
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      update...I am 70, my dosage is metformin 1000 mg per day and 4 mg sirolimus every 10 days, statin 20 mg twice per day. Rapmycin greately reduces inflamation and arthritus in my left knee. Subjectively my walking gate and posture feel younger and more energetic. no negative side effects. would like to use dasatinib but its price of thousands of dollars gives pause. Sadly, no weight loss from sirolimus and metformin from my 265pound weight that runs in my family. My oldest great aunt lived to 106 years old.

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        • Alex
        • Alex.2
        • 1 yr agoThu. April 13, 2023 - 6:13 pm
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        are we there yet Hi are you still taking rapamycin and did it make your face look younger? Thanks

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      • RobH
      • RobH
      • 6 yrs agoSun. January 6, 2019 - 9:10 am
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      I'm happy with the Dasatinib that I got from Bonhoa for $200.  It's enough for 6 dosages, so about $33 each.  Much more effect (positive) than Rapamycin or Metformin.  Age 74, so younger people probably would notice less.

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        • peterc
        • peterc
        • 6 yrs agoSun. January 6, 2019 - 5:52 pm
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        RobH was the positive effect from just one dose? If so, do you plan to take multiple doses to possibly get more effect, or was 6 dosages just the minimum that you could purchase?

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        • RobH
        • RobH
        • 6 yrs agoSun. January 6, 2019 - 11:16 pm
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        peterc Details over in the Dasatinib thread https://forum.age-reversal.net/t/182sb1/dasatinib

        The Dasatinib came as 60 20mg tablets.  Single dose of 200 mg was 10 tablets, leaving 50 tablets for the future.  So I took 10 tablets of Dasatinib + 3 800mg of Quercetin.  Two weeks later I did another dose.  As I recall, I was a bit queasy 2-4 hours after the first dose.  Nothing I remember after the second.  After several weeks I noticed that I was swimming further and not taking Wednesday off.  Instead of swimming about a mile 4 days a week, I'm now swimming a mile and a half 5 days a week.  It varies according to how I feel at the time, but I clearly have better endurance and faster recovery.

        Given my positive experience, I plan on taking another 2 doses (about a week apart) every 6 months.

        I'm continuing to take 4.5 mg Rapamycin (my dog gets the other 0.5) every 8-9 days.  That will probably change when we get further guidance, but I'm staying with the original recommendation for now.  I had great hopes for an easy weight loss given Dr. Green's experience, but it didn't happen.  It must be his severe diet that delivered his weight loss.

        I have Metformin, but haven't managed to take it on a regular basis.  There are a number of recommendations to take it that I respect.  It hasn't done anything I noticed when I did take it.  

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        • peterc
        • peterc
        • 6 yrs agoMon. January 7, 2019 - 5:36 am
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        RobH Thanks for the reply Rob, that's interesting to hear that you have noted a difference. I also take Metformin 500mg/day and Rapamycin 4-5 mg each Sunday, though I may stop for a while they are working out the dose. For senescent cells so far just fisetin 600mg/dx5 days, then 1500mg/dx2 days a week later. Didn't notice anything. Considering dasatinib. Seems like I recently read a precaution that some stem cells are also eliminated by some senolytics, which gives me pause in terms of being too aggressive. 

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      • are we there yet
      • are_we_there_yet
      • 6 yrs agoTue. January 8, 2019 - 8:14 am
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      It should be mentioned on this site that rapamycin (sirolimus) on its boxed warning says to avoid direct sunlight on your skin as increasing skin cancer risk.... I use a light windbreaker jacket when necessary. So avoid tanning booths and sun tanning. Sirolimus half life is 67 hours or about 2.5 days. A week is about 3 half lives attenuation in your blood. 

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