Rapamycin - progress so far

Hi all, 

About me: I'm 46 y.o. medical doctor based in Europe and started taking weekly rapamycin 4 months ago. I go to the gym regularly and am in average physical condition for a guy of my age. The last couple of years have brought the first negative signs of physical aging: aches and pains that don't go away, increasing belly fat, a decline in gym performance, wrinkles and increased pigmentation, grey hairs as well as slower wound healing. Am venturing on this rapamycin journey to see whether it can  slow down the inevitable age-related decline and see how it impacts my aging longer term.

Where I'm at now: I started rapamycin 4 months ago at 2mg once weekly and have been slowly increasing the weekly dose by 1mg each month. Now at 5mg per week. I intend to continue on this dose increase scheme until I reach the highest optimal dose, beyond which side effects become an issue.

Currently have experienced zero side effects, not even mouth ulcers.  I have noticed improvements already in body composition (slight reduction in body fat) starting at the 3mg/week dose and most recently increased gym performance (cardio vascular and muscle strength increase) since being on 5 mg/week.

Intend to progress to 6mg/week in September.

Will at some stage probably try topical rapamycin on wrinkle / pigmentation problem areas as well. In Europe a rapamycin solution (Pfizer) is easily available in pharmacies.

Body pictures from today are attached.

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  • go to 10mg at least. studies that show anti aging effect are in mega doses

    Like 1
      • George McMillan
      • MD in Europe self-testing rapamycin
      • George_Malcolm
      • 3 mths ago
      • 2
      • Reported - view

      Mr. Joules 

      Hope to go beyond 10 mg actually.

      I am taking it slow though to find my personal optimal dose, with methodical dose escalation. Mapping my own individual response (efficacy parameters and any adverse events) to each respective dose.  

      Like 2
      • David H
      • David_Hanson
      • 3 mths ago
      • 3
      • Reported - view

      Mr. Joules please give references to the studies you are referring to. I have read dozens of rapamycin studies and have not seen megadosing recommendations. Dr. Alan Greene uses 1 to 6 mg weekly for his patients. He himself takes 12 mg every other week. I take 7.5 mg. I get mouth sores at 8mg.

      The Pearl rapamycin study is using these doses:
      1.
       2.5mg Rapamycin 3 times a week
      2. 5mg Rapamycin once a week
      3. 5mg Rapamycin twice a week
      4. 10mg Rapamycin once a week

      Like 3
      • Van
      • Van
      • 3 mths ago
      • 4
      • Reported - view

      David H Dr. Green and Dr. Bagosklonny are now taking 20 mg. per dose.  Follow on Twitter.  12-14 days between dosing.  The reason for this is they want a spike in the level of rapa in blood to get past the blood/brain barrier to the hypothalamus in the brain to max longevity benefits.  It is believed that the hypothalamus region of the brain is responsible for regulating ageing.

      Like 4
    • Van This is extremely interesting. Do you have a link to Blagasklonny's paper where he discussed this? I apparently missed it on Twitter. Does Dr Green discuss this somewhere? Since this goes against what they recommended previously, I want to understand it better. 

      Like
      • Van
      • Van
      • 3 mths ago
      • 1
      • Reported - view

      chuck stanley https://twitter.com/Blagosklonny/status/1405848090549141507  Will have to look for Green's.  Green always follows Dr. B.  This high dose is also a good way to reset weight "set point"

      Like 1
      • Fred Cloud
      • Fred_Cloud
      • 3 mths ago
      • 1
      • Reported - view

      Van I like the big dose followed by a big break if you can tolerate it.

      Why not add days instead of subtracting mg. when you hit side effects?

      Alot of people say take as much as you can until you hit side effects and then back off 1mg, which seems fine, but strangely no one is saying when you hit side effects, add a day in your cycle until the side effects stop.

      I have seen the reference to large dose to hit hypothalmus and they were in 25mg range or something. So I would think you might be able to do that if you did it monthly. Maybe a rule of thumb would be match the mg dose to the days off.

      Like 1
      • George McMillan
      • MD in Europe self-testing rapamycin
      • George_Malcolm
      • 3 mths ago
      • Reported - view

      Van Really interesting tweet-thread! thanks for sharing.

      Like
      • Van
      • Van
      • 3 mths ago
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      • Reported - view

      Fred Cloud You do not want to wait a month if taking 20-25 mg.  Just use the half-life calculator and you will see that 20 mg rapa at a 1/2 life of 62 hours is down to around 1 after 14 days.  In my experience, 1-2 mg on calculator and you should have no trouble taking another dose.  We really have been dosing too low in my opinion.  Of course, everyone is different, and you should skip more days if having side effects.  I have been taking 20-25 mg. every 12-14 days.  At 25 mg. after 14 days, you have less than 1 mg. in system.  I download half-life calculator app on my phone which is handy

      Like 2
      • Van
      • Van
      • 3 mths ago
      • 1
      • Reported - view

      Van Many use grapefruit juice to enhance the rapa dose by 300-350% to save money.  You can also have a high fat breakfast such as bacon and eggs and you will get a 35% increase in the dose.  Studies on all of this

      Like 1
      • David H
      • David_Hanson
      • 3 mths ago
      • 2
      • Reported - view

      Van Not Dr. Green per a very recent interview. He said he was taking 12mg at 2 week intervals.

      Like 2
      • Van
      • Van
      • 3 mths ago
      • 3
      • Reported - view

      David H Dr. Green has said he takes 20 mg every 2 weeks. In this latest interview he never says exactly how much he is taking, but "doubled" his dose while stretching out dosing to 2 weeks. We all know he increased his dose to 10-12 mg weekly when he diagnosed his heart condition. Also, he always follows Dr. B. https://www.youtube.com/watch?v=3vszZEifmrA

      Like 3
    • David H the studies that gave the best anti aging effect were mega doses. the study that shower heart regeneration were at 40mg per day when converted to humans. the 60% lifespan increase were also in the 50mg plus per day. so it might be that the rejuvination that comes from rapa is due the demethylation, and thats why the higher doses are needed for effect

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    • Mr. Joules at that dose does it not shutdown the immune system? I thought 12mg a day was for organ transplant?

      Like
    • Arizona Kid no cause i dose every other week, 20mg. Works great so after a few months i did 20mg per week

      Like
    • Mr. Joules you mentioned 40mg a day. That’s what I am interested in. Any information on that higher dosing?

      Like
      • Armando
      • Armando
      • 2 wk ago
      • 1
      • Reported - view

      Fred Cloud Exactly my thoughts! As mentioned below, I’ve been having side effects with just 6mg/week (skin infections), but my first option is going to be to space out that dose to once every 2 weeks rather than reducing it. Maybe I’ll even be able to increase it without side effects. 

      Like 1
    • Armando spacing out doses can deal with mtor2 levels and not shutting down your immune system, but rapamycin in general seems to shut down the innate immunity as dr green said. So if you dont have any luck adding days, you may try subtracting mg. Dr green prescribes 6mg week for all patients. I have been on it for over a year and I have never taken 6mg. I generally taking 4-5mg every 7-14 days. 

       

      From Dr. Green website-

      Side Effects: Bacterial Infection

      Rapamycin is a very potent medication. It should be taken as prescribed under medical supervision.

      One major effect is reduction of activity of innate immune system. The innate immune system is the first line of defense against bacterial infections.

      Increased risk of bacterial infections is natural effect. Everybody taking rapamycin should have antibiotics such as Zithromycin on hand."

      Like
  • Thank you all for sharing, it's all very interesting, and I read your messges only now. I've had to stop after three months in 2020 because of the lack of the medicine. Apparently it's possible to obtain it in parts of Europe. If that holds true, that might change my perspective considerably. Best regards to all

    Like
      • George McMillan
      • MD in Europe self-testing rapamycin
      • George_Malcolm
      • 3 mths ago
      • Reported - view

      Flavio Ferlitz Hi Flavio, yes the Pfizer brand Rapamune (sirolimus) seems to be available in most Western European countries.. Prescription only and the price varies considerably depending on the country you're in.

      Like
  • Hi George, it's good that now quite a few doctors are in the network. It's a pity that the conference we were waiting for, an opportunity to physically meet in EU, hasn't taken place yet and all we have is zoom meetings - e.g. the HEALES meeting. I was the first to say we should have some physical meetup some time - just before COVID.. Longecity had them for years - when I wasn't even aware of these developments we talk about here. Until I read of the RAADfest of 2019. I've been away from the Forum for a while, just trying to find another country where to be able to use these medicines, while waiting for COVID to allow some travel. But having come back today I can see many good changes! I hope meeting becomes an option some time soon. I even spotted an Age Reversal doctor in Spain on the Age Rev. Doctors'list! Unfortunately on this site nothing is encrypted, not even the site's email (I left the social networks and I have only encrypted mail, Signal and  Mastodon). I had seen dr.Green-  that was to get started with the steps suggested as the first ones in the RAAD protocol of 2019. Only problem has been the EU, so I had to stop. Just sent a message to Peter, he says now it's possible to get Rapamycin in Europe - that would make things so much better. Still we can't be completeley on track with the testing to take part in the Netwrok's studies here. Thanks to you too for sharing your experience.

    Like 1
  • Besides reducing rapa dosage at the point you experience side effects, or adding days between doses there may be a third option to reach the maximum dosage without side effects. 


    Recall that Fahy showed in his TRIIM studies that growth hormone regenerates the thymus, which is pretty much gone by age 40. Most people don’t have access to growth hormone but if you did, what if you were to take a once a week dose of HGH? That is not enough to regenerate the thymus, which requires 3 doses per week, but it may be enough to retard thymus involution and have cumulative beneficial effects as well over time. 


    This is pure speculation, but I did discuss with Fahy, that since HGH is a TOR, if you take rapa on Sunday and HGH the following Saturday night, the small amount of rapa that is left in the system is effectively offset by HGH, thus dis-inhibiting TOR for a brief period until the next day's rapa dose. To the extent that is true, then you might be able to tolerate a larger dose of rapa. Anyway, I just started cycling sirolimus with growth hormone. I'll see how it goes.  Maybe it will be beneficial. Maybe not.   

    Like 1
    • chuck stanley keep me updated on this, I have low IGF for my age. I took semorlin for a month and lab tests doubled, but I did not feel the effects. I am told by a hormone doctor, it can take 3-6 months to feel those effects. Anyways, I dumped the semorlin for MK-677

      Like
    • @Arizona Kid.  Will do.  I should have lab results in late October. 

      Like
  • Just read through last several months of Dr. Blagosklonny's Twitter tweets.  
    1. He wrote that it's best to take as much as you without side effects.
    2. He showed a video of him taking 20mg Rapamycin. I didn't find the time between doses.
    3. Someone else reported that they corresponded with Dr.Green by email and he written that he was taking 20mg every 2 weeks.(this is different than what he said in a more recent interview in which he said 12mg).
    After reading this, I plan to to slowly increase my dose. I do eat a whole grapefruit 30 minutes before I take 7.5mg weekly. 
    I admit I was skeptical.about the higher doses.  Thank you to the members who posted about the higher doses.

    PS These are not my recommendations for anyone else. I suggest people should always do their own research.  I always feel better about dosing when I read original documentation directly from the Rapamycin experts.

    Like
    • David H An interview with Dr Green. About dosing.

       

      Rapamycin: Practical Dosage & Benefits | Dr Alan Green Episode 4 - YouTube

      Like
    • David H I'm seriously considering starting Rapamycin now.  Can you say, David, you feel better, healthier since you have been on it for a while? 

      Like
      • David H
      • David_Hanson
      • 3 mths ago
      • Reported - view

      Dorian Gray I feel the same with rapamycin but I am not that concerned about how I feel. My biological age per the Levine epigenetic clock for aging and life expectancy is 19 years less than my chronological age(70). But I don't know what that clock calculation was before I started rapamycin.

      I recently increased my NMN daily intake to 1.5gr/day from 1.0gr/day.That has made me feel more energetic and clear minded starting the next day. That makes NMN the only supplement that that I feel. I am going to try to raise my rapamycin dose from 7.5mg/week to 10mg/week(matching the dose that Dr. Alan Green uses for himself before he changed to 20mg every other week). Dr. Green does a senolytic treatment with dasatinib and fisetin during the weeks he doesn't take rapamycin. Dr. Blagosklonny, a well known rapamycin expert, also takes 20mg every 2 weeks per his tweet which includes a video.

      Like
    • David H Is there a rationale you know of that suggests it is better not to take D&F the same week as rapamycin? I cant think of any benefit. I alternate D&F but I take rapa weekly. 

      Like
      • David H
      • David_Hanson
      • 3 mths ago
      • 3
      • Reported - view

      chuck stanley Look at the Modern Healthspan channel on youtube. Today this channel posted a video in which Dr. Alan Green gave longevity protocol.  His rational is that D/Q's purpose is to kill senescent cells while rapamycin increases autophagy as one of its effects. Autophagy is a cell renewel process. It is Dr. Green's view that these should not occur at the same time. Dr. Green's voice is a little difficult to understand because of poor quality as audio equipment IMHO.  
      I highly recommend the Modern Healthspan channel. The owner has interviewed many longevity experts.

      Like 3
    • David H Yes, I did see that. I respect his opinion but dont know the rationale. 

      Like
      • David H
      • David_Hanson
      • 3 mths ago
      • Reported - view

      chuck stanley From the video, I understand that Dr. Green believes that the Rapamycin would or could keep senolytic cells from being eliminated by the D/Q if both are taken about the same time. He thought one week apart would be ok.

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      • David H
      • David_Hanson
      • 3 mths ago
      • Reported - view

      chuck stanley It has been reported that Dr. Green often follows what Dr. Blagosklonny does.  Here are some tweets that Dr. Blagosklonny made this year:

       

      Mikhail Blagosklonny

      @Blagosklonny

      ·

      Jun 11

      Next week, I may try a new schedule: 20 mg rapamycin once per 10-12 days. High peak blood concentration is important to affect the brain due to blood-brain barrier I never had side effects so did not reach optimal dose yet

      Quote Tweet

       

      Mikhail Blagosklonny

      @Blagosklonny

      · Mar 2

      Yesterday. Rapamycin (10 mg/week), very low carb/high animal fat diet, daily exercise Rapamycin-based anti-aging formula includes non-prescription: vitamin B3 (Nad+ booster), DHEA, L-ornithine, lithium, aspirin Cannot reveal prescription drugs now

      Like
    • David H 

      Okay, that explains Dr Green’s reasons for moving to biweekly dosage. I just cant find any scientific basis for cycling the timing of D&F to coincide with a low blood level of rapa. Maybe there is a study or a correspondence we don’t know about. I cant find anything in Blagosklonny to suggest that taking senolytics during rapamycin therapy is contraindicated. My impression is that Blagaklonny thinks senolytics may be explained in part by inhibiting mTOR.  If that is the case, then senolytics and rapamycin are complementary rather than antagonistic, not just because they are both geroprotective but because they both are inhibiting TOR.  

      If anything I would expect that taking them together might be beneficial, maybe synergistic in that inhibition of mTOR is increased without the side effects of a higher dose of rapamycin.

      Like
      • David H
      • David_Hanson
      • 3 mths ago
      • 1
      • Reported - view

      chuck stanley It seems that Dr. Blagosklonny doesn't believe in senolytics. I downloaded his recent paper on senolytics but have only read the abstract. Paper title is Anti-aging: senolytics or gerostatics (unconventional view)

      Like 1
      • Fred Cloud
      • Fred_Cloud
      • 2 mths ago
      • Reported - view

      David H Well thats odd because rapamycin acts on senescent cells too and contributes to some of the antiaging effect of rapamycin. It doesnt kill them like a senolytic, instead it acts as a senomorphic which means it puts the senescent cells to sleep for a couple of weeks, like fisetin does.

      https://www.nature.com/articles/nrd.2018.44

      Like
  • Hi, I live in Spain.  Can you give me the name of the topical rapamycin solution available in pharmacy.  Tried looking for it and could not find.  i'm sure it has a brand name.  Thanks again

    Like
  • Hey George.

    Not sure if you've done this already - but it's definitely worth (also) measuring your weight circumference. Which is the point just above your hip bones.

    It fluctuates a bit based on time of day - certainly post meal it'll be wider. Morning, before eating or drinking much may be the best measurement to use.

    You'll like notice a change on this measurement before you notice much change in the mirror.

    It's something I'm doing personally anyhow.

    Like
    • rapa_experimenter Edit: I appreciate there are such things as weighing scales :) But the reason for mentioning waist circumference, is that if you're a gym go-er, it's a cheap and easy way to avoid conflating loss/gain of muscle that affects your overall weight.

      Changes in waist circumference are almost exclusively related to changes in fat storage.

      Like
      • George McMillan
      • MD in Europe self-testing rapamycin
      • George_Malcolm
      • 2 mths ago
      • Reported - view

      rapa_experimenter Thanks for the tip, I'll do that for sure!

      Definitely have the impression that the bacon around the middle is slowly (or not so slowly) melting away.. Will probably continue to post pics too though, every 3 months..

      Like
  • Increase the cardio to lower body fat %. Maybe add a trt dose of test (then increase the cardio even more from the resultant bloat). Dump the rapamycin. It's fools gold.

    Like
    • Michael This seems more like your personal experience? He just told you his benefits, why would he toss it ? 

      Like
  • Rapamycin can reduce body fat, but there are more suitable means for this purpose.

    I agree with Michael.

    Like
  • UPDATE  #2

     

    Hey folks,

    So, it’s time for the monthly update.

    I increased the weekly dose from 5 to 6 mg on the 1st September and still have had no identifiable adverse reactions. Nothing at all, not even a solitary mucosal ulcer..

    Yes, this is subjective, but I do have the impression that I am already experiencing several benefits..

    Firstly I have stopped putting on fat, regardless of how unhealthy my diet. I am also reasonably certain that abdominal fat and fat otherwise around my middle is becoming less. At the suggestion of a number of you I will start taking waist measurement and post these with future updates. 

    The most interesting improvement though is a definite improvement in cardiovascular performance. I am not out of breath as easily and exertive activities are noticeably more easily mastered. Example: treadmill. For years I’ve been doing a once weekly session of 50mins on the treadmill. For the last 5 years my top speed had a consistent ceiling of  8.0-8.5 km/hr. Within two weeks of starting the 5mg / week dose (6 weeks ago) I upped that to an average tempo of 9.0km/hr and on Friday, when I last trained, I averaged 9.2 km/hr. While these improvements are small, they are noticeable and prior to starting on this journey, unachievable. There is no plausible alternative explanation in my routine for this improvement.

    All things going well I will increase to 7mg / weekly beginning of October.  What I am most of all keen to see is whether there is any improvement in various inflammatory conditions that I deal with: skin, sacroiliac joint, prostate.. From a health and longevity perspective inflammation is the concerning point on my agenda and am curious as to whether there’ll be any impact at higher doses.

    I will post photos again in November and then quarterly thereafter.

     

    Waist Circumference:

    18.09.2021:       104 cm / 41 inches

    Like 3
  •  ^  Very interesting.......keep the updates coming.

    Like
  • I’ve spent a lot of time training, but even after lots of practice, I couldn’t see a pleasant result for me. I didn’t know what was the problem until I figure it out. The biggest problem for me was the unsuitable fitness machine. Especially I couldn’t understand why the calves were so hard to gain. Therefore I advised the gym to change the calf raise machine. They bought some from https://fitbodybuzz.com/best-calf-raise-machine-reviews/, and now, all customers are more than happy. Their equipment is high quality and perfect for gym exercises. Highly recommend them!

    Like
      • George McMillan
      • MD in Europe self-testing rapamycin
      • George_Malcolm
      • 2 mths ago
      • Reported - view

      Lime Star yeah thanks but I'm not primarily in this for muscle gains..

      I share photos and will continue to do because that's only visual content that can be shared showing positive progress. I saw that several folks in the past had complained that there was a lack of photo documentation here so I figure fotos might be helpful.

      Like
  • NEW ANTI-AGEING FORMULA FROM DR. BLAGOSKLONNY
    TWITTER SEPT. 25TH. 2021

    4/5 
    Rapamycin high dose intermittently
    Low-Carb or Low Carb/Cal diets, time-restricted, IF 
    Physical exercise daily
    Sun, Sunbath/Vit D3
    Metformin low/medium dose  
    Angiotensin II inhibitors 
    Aspirin low dose
    Lithium low dose
    DHEA, L-Ornithine
    NAD boosters
    PDE5 inhibitor

    5/5 Other agents to consider:
    Alpha-estradiol for men when become clinically available
    Acarbose  (if cannot adhere to Low carb diet)
    Fisetin
    Doxycyclin (once/twice a month)
    And other compounds depending on conditions


    Goes on to say evidence on NAD boosters, and Fistein is weak, but will not hurt you except for pocketbook

    He also states, "These recommendations are for medical doctors to consider for there patients."  He does not make recommendations directly to people because not practicing medicine.  That is why you will see no dosing recommendations, leaves that up to your doctor.

    Like 6
    • Van I would really like to see more self experimentation with Fisetin at 2grams a day or more. 
       

      What is the purpose of once monthly antibiotics? 

      Like
  • George McMillan  hi I am also in the Western EU, where did you get the prescription from? I have tried many doctors but they refuse to provide a prescription unless I am getting organ transplants.

    Like
      • Spasov
      • Spasov
      • 1 mth ago
      • Reported - view

      Peter Jenkins 

      If you have a friend in Turkey, he can send you Rapamune. I am from Bulgaria and here you can not do without a prescription, and they send it to me from there. Another option is from Ukraine or India ... Sorry for my bad English.

      Like
  • Hi George, I was wondering if you’ve had any problems with skin infections (which would indicate a weakened innate immune system).  I’m 59 y/o and have been taking 6mg/week over past 9 months and gotten 2 infections that seemed to proceed quite quickly. Treated both with antibiotics successfully, but am concerned that I’m weakening my immune system too much (too much MTOR inhibition?).  I’m going to start taking 6mg every 2 weeks to allow the rapa to fully exit my system.  Also seems logical that we should fully alternate between low MTOR and normal MTOR levels. 
     

    What might also be complicating my situation is that I take other things that reduce MTOR (eg metformin, curcumin extract, etc).  I’m not diabetic, but take the above for life extension purposes.

    Any thoughts given your experience?

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