Dr Green new Rapamycin high dose

Dr Green has moved up from 10mg a week to 20mg every 2 weeks. Technically that is the same dose, he just doubles it up and waits twice as long before redosing.

I am shocked that he isnt getting the mouth sores at that kind of dose. I wonder if the older you are and the slower your cell division is that maybe you can tolerate these higher doses without side effects?

Is anyone else experimenting with extreme doses or what is your limit?

Here is the clip discussing it.

https://youtu.be/JiyJ_X3YBew?t=2197

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  • Fred, I am taking about 30mg/week. I base that on 10mg actual sirolimus plus 6 to 8oz of grapefruit juice, so thats an approximation. You may be correct that older users tolerate higher doses without side effects. Why would that be so?

    Like 1
      • Van
      • Van
      • 2 yrs ago
      • Reported - view

      chuck stanley An older persons Tor signal is much stronger as they grow older.  It takes much more Tor inhibition to lower it.  If the rapa has to lower Tor 1 so much there might not be enough left to affect Tor 2 for side effects.

      Like
  • I understand that Blagosklonny is also taking approximately 20mg every other week without negative side effects.

    Like 1
    • THOMAS DECICCO yeah dr green follows dr blagoskonnys research and dosing, so I think he got inspired from him. Watch the rest of the video. 

      Like
  • Side effects seem to be highly individual - I got a canker sore at 3mg, but never again and I'm now on 10mg/week and have tried up to 25 or 30mg (two week schedule) with no side effects.  In the Study on Everolimus (rapalog) only 9 people out of 53 got canker sores at 20mg a week.  Details here:

    https://www.rapamycin.news/t/everolimus-instead-of-sirolimus-rapamycin-anyone-else-trying/128/9?u=rapadmin

    Like 2
    • Michael
    • Michael.1
    • 2 yrs ago
    • Reported - view

    He just seems to blather on about nothing as a physician providing observed data. He couldn't even adequately describe why upping his own dose was better.

    Like 3
    • True! Not very impressive. He was rambling on in an unscientific way. I was hoping for more.

      But watch the video from the start, as I had fast forwarded it to that point and you will actually be impressed with what he knows about rapamycin. It’s probably the most thorough I have seen.

      Like 2
      • Michael
      • Michael.1
      • 2 yrs ago
      • Reported - view

      Fred Cloud Shall do!

      Like
  • Anyone experience unusual blood tests results after being on Rapamycin? My dog is on Rapamycin, and since then, his kidney disease (in early stages) has normalized! He is peppy and energetic, with no apparent adverse effects. But his blood counts of Lipase and Alk. Phos. began to elevate shortly after and now are very high. I have no idea if  this is a coincidence or not. Any thoughts would be appreciated.

    Like 1
  • Started at 5 two years ago and bumped up to 10 mg per week last dec.

    Went up to 15 mg every two weeks in June and then took 20 mg Nov 1

    Have never gotten a side effect. Big changes to kidney eGFR and creatinine

    Like 2
  • Dr. Green has a particular interest in APOE-ε4, and I believe that he is recommending the higher dosing for APOE-ε4 carriers only, especially homozygotes (or perhaps recommending it particularly strongly for APOE-ε4 carriers).

    @michael.1 I, too, would love to see more detailed data and rationale from Dr. Green. There are patient confidentiality issues that he needs to navigate, which might be part of why he hasn't released data yet.

    Like 1
    • JH
    • green_cloud
    • 2 yrs ago
    • Reported - view

    Dr. Blagosklonny posted in Tweeter that he plans to take 24 mg every two weeks.

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      • Michael
      • Michael.1
      • 2 yrs ago
      • Reported - view

      JH Blagosklonny has one ride at the carnival with very few paying riders: Dr. Green  (largely incoherent) and sometimes, the extremely annoying, Pete Attia; though he's as clueless as everyone else in the minefield of rapamycin.

       

      The most important thing anyone on this forum can do is post before and after photos and extensive blood work, collate it into a spread sheet and jeep a running log. Otherwise it's just a subjective shit show.

      Like 1
      • JH
      • green_cloud
      • 2 yrs ago
      • Reported - view

      Michael unlike you still young, old men like us are desperate and dont want to wait until FDA approves the usage and dosage after 10 years from now.

      Like 1
    • Michael  There is vastly more information in favor of rapamycin than you speak of.  Interventions Testing Program of the National Institute on Aging, Matt Kaeberlein, and even David Sinclair may be taking it as he has recently been dodging the question.  There are many, many other pieces of favorable research.  There is vastly more to the subject than just Blagosklonny being a proponent of rapamycin.

      Like 2
    • C B
    • C_B
    • 2 yrs ago
    • Reported - view

    I’m up to 8mg + freshly squeezed grapefruit juice so ~24mg equivalent. Zero issues. 

    Like 1
  • 30mg every two weeks for about one year. Experimented with 90mg every 6 weeks (30mg with fresh grapefruit) for about 6 months before, and weekly dose of 15mg prior to that. People that I have placed on a sirolimus regimen generally do fine on either weekly or biweekly dosing. Weekly dose is calculated at .18mg/kg and biweekly is just double that. Bloodwork in all patients has been fine except a bump in total cholesterol. Even on 90mg every 6 weeks I never had side effects. Some patients have a little mood change if they are on a biweekly dose for the first 2 days presumably from alteration in biogenic amines which is probably more pronounced at higher dose. Logic for taking higher dose less frequently is to expose cells to a higher level of mtor inhibition transiently which seems to have been more beneficial in rodent studies using higher levels with longer intervals. Other than reporting on short term adverse effects, I don't think we have any basis on a personal experience level to comment on benefits - maybe after about 10-15 years on sirolimus we will see some differences in "aging". However, it does seem to make some people feel better - again, probably just the biogenic amine effect (more dopamine, norepinephrine, seratonin) in the midbrain.

    Like 3
    • Mark Thimineur I'd just like to clarify, when you say "30mg every two weeks for about one year" am I correct in saying that you took 10mg of actual rapamycin tablets with grapefruit juice and therefore got the effect of taking 30mg of rapamycin and did that every two weeks for approximately one year?

      Also, are you saying you experimented with 30mg of rapamycin tablets taken with grapefruit juice therefore giving the effect of 90mg of rapamycin all at once, at 6 week intervals and continued this for 6 months?

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    • Mark Thimineur .18mg/kg per week! Wow.  I am on .05mg/kg week.

      Have you ever run any of your bloodwork through one of these levine phenotype calculator to see if your are getting any phenoage drops? I am thinking about doing a rapamycin dose escalation experiment and increase dose by 1mg and map out a dose response curve relative to phenoage. I think this will give me a good idea of what the optimal dose is and if there are any hidden threshold doses or diminishing returns on increased dose past a certain point.

      Like 1
      • MAC.
      • MAC2
      • 2 yrs ago
      • Reported - view

      Mark Thimineur Thank you for posting your experience, very informative for this community.

      Regarding "bloodwork", you only mentioned TC as apparently being somewhat dysregulated. But I recall Dr Green, who has a lot of patients/experience with Rapamycin, indicating that lipids, glucose dyregulation, risk of infection (thus, need for statins and/or metformin and/or antibiotics), was highly prevalent in his Rapamycin population? This experience I assume was a "proxy" marker for Rapamycin/Tor1/Tor2 impact? Thoughts vs your population? 

      Does your bloodwork panel include other than lipids/glucose?

      I've noticed a significant drop in my liver enzymes (GGT, ALT), improved kidney function (eGFR), much lower uric acid, with very little change in my lipids. Perhaps a slight rise in TC, but my TG/HDL and remnant cholesterol (both CVD proxies) are excellent.

      Like 1
      • Van
      • Van
      • 2 yrs ago
      • Reported - view

      Mark Thimineur I have read that higher doses of Rapa such as 20+ mg. (for the "spike" ) to get past the blood/brain barrier in order to inhibit Tor 1 in the hippocampus portion of brain where many believe ageing is controlled from.  Mark, do you know of any studies to support this theory?  I personally have used Rapa for almost 5 years, (was Dr. Green's 2nd. patient) and now take 7 mg Rapa with GFJ protocol set out by Dr. Thimineur twice a month without any side effects.  The main difference is I actually take 400 grams of GFJ juice and pulp divided into 2 doses as suggested by you.  1/2 night before and 1/2 next morning, 30 minutes before taking Rapa.  Starting weighing GFJ because of variability of size between grapefruits.  I am a healthy 75 yo male without issues.  Phenoage of 62 yo. 

      Like
    • MAC. I've limited sirolimus prescribing to family and friends and about 50 patients so my observations are limited. No observations of glucose elevation above normal. Definitely have seen TC elevations above norms and a tendency for decreases in RBC count to borderline levels in some patients. As a rule, most of us take metformin as well (for its own benefit) except those who experienced GI side effects on metformin.

      Does any of this concern me - answer is no. Heart disease and cancer cause 700K and 600K deaths per year in U.S. (respectively) far outpacing all other disease related deaths. Benefits of sirolimus in regards to heart disease are assumed and these assumptions are strengthened by preliminary data in "The Dog Aging Project" run by Matt Kaeberlein. Similar to humans, and probably other large mammals, heart failure in dogs is a primary mortality cause. The experience of Dr. Green in which his AHC, which would have likely been fatal, going from symptomatic to asymptomatic is also notable. My current assumption is that TC elevation is a harmless SE of sirolimus. i.e. the benefits far outweighs the risk (if any) in regards to the heart. Some of us, me included, choose to treat with a small statin dose. 

      Data from rodent studies are instructive for cancer as this is the primary mortality in these small mammals. Sirolimus related lifespan extension is associated with a delay in cancer among these small mammals thereby extending lifespan on average. I make the assumption that sirolimus will act as a cancer deterrent in large mammals as well. 

      After "covid" and accidents, the next major causes of mortality are CVD (stroke) at 160K, pulmonary disease (150K), and Alzheimers (135K). Animal studies also provide insight that sirolimus may delay or prevent these diseases in humans and I make that assumption. If CVD and Alzheimers are combined, brain disease is the third leading cause of death and perhaps the one we all fear the most. All of the brain specific studies in rodents showed the treatment group retained a normative brain compared to controls (histological and behavioral)

      In short, the deviations in RBC and TC measures are not concerning to me at this point but I try and keep an open mind.

      One other issue is the innate immune system which may be affected negatively and thus make us more prone to bacterial infections. I have not seen this express itself over the past 3 years with one possible exception. A patient who had spinal hardware developed a bacterial infection and had the hardware removed. Amongst chronic pain patients many have had multiple spinal and joint surgeries and these events happen with some regularity. Was sirolimus contributory in this case - possibly - again, I keep an open mind.

      Like 1
      • MAC.
      • MAC2
      • 2 yrs ago
      • Reported - view

      Mark Thimineur I wasn't casting aspersion to the anti-aging benefits of Rapamycin, otherwise I wouldn't be taking it. As you say, wild type mice only die of cancer, and in pretty much every study on mice/Rapamycin, their lifespan is significantly increased! 

      My point was very specific as to whether the "proxy" signals of your dosing interventions in your population cohort was actually "cellularly" directly connected and translatable/meaningful vs say Dr Greens cohort (far lower doses), which he seems to imply AND conclude (by way of the lipid/glucose dysregulation) is at the limit of triggering cellular dis-homeostatis. Namely, Rapamycin had gone too far, at the risk of outweighing benefits? I think that's what I am trying to learn from your amazing work...is your dosing regiment something for us (say the majority taking FAR lower doses) to learn/explore from? Do we keep upping dose until what...TC goes out of whack or other? You don't seem to have reached the same threshold as Dr Green at such high doses?

      Perhaps Dr Green has a much higher baseline comorbidity population base, thus Rapamycin intervention does indeed trigger much higher metabolic side effects? I think you intimated a pro longevity (genetic predisposition AND healthy confounders?) baseline cohort in your patients, thus allowing for a much greater Rapamycin dosing tolerance?

      It's too bad we don't have a readily available cellular "longevity" lab assay to individually guide in this intervention journey. There are those that question the method-type, reproducibility, and validity of DNA methylation as a definitive anti-aging proxy. 

      Like 1
      • MAC.
      • MAC2
      • 2 yrs ago
      • Reported - view

      Van Go Van!! Perhaps you meant hypothalamus? As far as I know, the hippocampus is only a short term memory associated storage region, not a master cellular homeostasis signaller.

      Role of hypothalamus in aging and its underlying cellular mechanisms

      https://www.sciencedirect.com/science/article/abs/pii/S0047637418300502

      Like 1
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