Burgundy Summer 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

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.

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. 

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"

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.

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

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

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

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

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

Burgundy Summer at that dose does it not shutdown the immune system? I thought 12mg a day was for organ transplant?

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

Burgundy Summer you mentioned 40mg a day. That’s what I am interested in. Any information on that higher dosing?

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. 

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."

Fred Cloud Dr. Green prescribed 2mg once weekly for me. At the 4 week mark, I’m starting to experience skin and UR issues.

Maria Molè Thats a very low dose, I am surprised you are having side effects with it.

Maria Molè Fred Cloud

I just started up on it again (5 mg 1x weekly), mainly for whatever periodontal benefit it might provide, and noticed over the past 4 weeks I'm now scratching my forearms. 

Fred Cloud  During my consult with him, he decided to start me off really low. I have a history of side effects from meds. So I guess we’ll now be looking at lower dose or more time between doses. 

Maria Molè What's 'UR'?

Raya Kofman Upper Respiratory 😁

Maria Molè Aah.. thank you!

Raya Kofman You’re welcome. I went on ZPack for a few days and all is good again. Stopped Rapa for now. Not sure if I will restart at this time.

David , just so you know, the PEARL trial currently has two cohorts for rapamycin dosing:
Cohort 1: 5mg 1x/week
Cohort 2: 10mg 1x/week