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

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

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

David H An interview with Dr Green. About dosing.

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

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? 

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.

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. 

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.

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

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.

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

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.

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)

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

David H if grafefruit juice can enhance the uptake if serlimus in +- 350%, if you taje 7.5 mg  with grapefruit, this would be equivalent to 26 mg of pure rapamycin, usn' t it?

Albert L. Barkema Dr. Mark Thimineur used 3 as the multiplier. As of about 2 years ago, he said he ate one grapefruit in the evening and another in the morning before taking rapamycin. YMMV. Personally I eat 2 small or medium grapefruit  30 minutes before rapamycin. 

Van If you find a pharmacy/clinic that has rapamycin topical, please let me know.  Thanks!

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.

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

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? 

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.

Armando in case you dont know about the effect of curcumin on rapamycin, you might want to research it. 

I take an estimated dose of 21 mg biweekly. No rashes. I started out with 6 mg weekly and gradually built up to the dose I now take. 

Ulf Rasmusson mild rashes are listed as a common side effect of rapamycin. I get itchy but no rashes.

Ulf Rasmusson I’m running into the same problem with skin rashes/bumps. I just started the 2mg dose once weekly and in a matter of a few weeks, skin and UR infections started. What did you use to treat your skin, please? 

Ulf Rasmusson Any noticeable increase in oily skin with the rapa?

Maria Molè Thank you. I also restarted exogenous testosterone. That must be the culprit. 

Michael No, no oily skin.

Maria Molè Just ask for an anti-inflammatory cream at any pharmacy, nonprescription. Away from home, so  can't give you any brand name but I don't think it matters which.

Ulf Rasmusson Thank you!! 

Paul Beauchemin but had you done the test before rapamycin? thats what counts

Ulf Rasmusson Incredibly, high dose papaya fruit extract boosted my neutrophils 80 % in three weeks. Can resume rapamycin, whilst continuing with the extract  which upped my lymphocytes as well, by 40 %.

Ulf Rasmusson My neutraphil % went up but my lymph% came down, dropping below normal range with rapa so my doctor recommended a mushroom formula.

It will be some months before I know if it worked.

chuck stanley Could you share the mushroom formula? After the papaya, my neutrophils are in the ok range, but lymphocytes are still way below the normal range after getting drastically hit by dasatinib in D+Q

Ulf Rasmusson This is the blend he recommended, Mushroom Synergy: https://www.amazon.com/gp/product/B081QKG76Q/ref=ppx_yo_dt_b_search_asin_image?ie=UTF8&psc=1

chuck stanley Thanks. Were you recommended two capsules a day? Hard to find clinical evidence, but testning it oneself is the ultimate proof...

I boosted  lymphocytes fairly rapidly with cholera vaccine, but only supposed to take this once a year.

 Ulf Rasmusson Yes, 2 per day, but since it contains silymarin I only take 1/d. I've found in the past that too much silymarin gives me diarrhea. 

Michael Interesting article / info:

All About mTOR + Natural mTOR Inhibitors & Activators

https://selfhacked.com/blog/mtor-natural-mtor-inhibitors/

Michael_B 

Great. Thank you