Dr. Blagsklonny, one of the biggest proponents of Rapamycin has said you should increase your dosage until you hit side effects and then back off a bit. Of course, he has varied his dosages greatly over the years. Some do a high dose every two weeks while most seem to do about 9 mg weekly.
Mice that took the highest dosages had the best effects. So, I think that’s where the recommendation came from.
Also, some people think that hitting a very high dose will make some permanent physiological effects such as cleansing senescent cells, removing tumors, enhancing brain function, etc… such that they want to hit a very high dose for a short period to gain these effects. However, this is just an assumption as far as I can tell. We are all trying to make the best possible decisions.
I am currently at 4 mg + GFJ + EVOO bi-weekly. I have decided to switch to bi-weekly with the higher dosages. At 3 mg + GFJ + EVOO I was weekly. I plan to try and go up to 6 mg and hold that for a month and then re-evaluate at that point.
@Alex_Barton, welcome! As I see it, the answer is complicated because CFS is complicated. I do a lot to address CFS symptoms, including bioidentical hormones and specific and targeted food and supplements. My research and experiments tell me that CFS has many possible sources, and thus many possible answers.
Could rapamycin be one of them? I think so. I have only been on rapa a couple of months, but my energy and focus is all-over better.
But it might not be the only piece of the puzzle. For you. For me.
Is there a dosing heuristic in the background of the dosing schedules people are using? I’m preparing to start the common schedule, described as 6 mg once a week in AM with periodic vacations. Is it units per kilogram? Most of the people whose use is publicized are men. Therefore they are likely in the 75-80 kg range. Women are more likely in 55-60 kg range. Should the dose be adjusted down based on weight? On age? On anything? Or just titrate from 1mg up until some signal? What’s the signal? Cold sore? Misery? How are people thinking about this?
This is a really good question. Its really early as far as dosing heuristics, but here are some of the ones I’ve seen floating around.
The older the person, the higher the dose needed of rapamycin. This is based on the idea that mTOR tends to get overactivated with age (i.e. doesn’t return to a low baseline after activation), so as you get older mTOR tends to be active all the time, which is not good. Thus the idea that the older you get the more you need to block the mTOR activation so your body isn’t always in “growth” mode. I think this is related to the hyperfunction theory of aging: The hyperfunction theory of aging: three common misconceptions - PMC
The higher the weight / Mass, the Greater the Dose. In the Rapamycin dog trials they dose by mg/kg because there is a relatively large range of weights and sizes (see here: How Do I Get Rapamycin for My Dog? )
In the human medical field I think they tend to go for simplicity, so they may tend to go for simpler dosing strategies to increase adherence, but i also see many doctors increasing the dose of the rapamycin depending on the weight of the person.
Side effects driven by the trough (not the peak) value of rapamycin in the blood. There is a hypothesis that most of the side effects of rapamycin are driven by mTOR2 inhibition, which happens in a non-direct way when mTOR1 is inhibited at a higher level chronically for a longer period of time (I’ve not seen any greater detail on this but would love to see specifics). So if you take rapamycin daily, you have much higher risk of side effects than pulsed dosing weekly or every two weeks.
I take a pretty high dose, ketoconazole + 8mg rapa so I estimate effectively 30-40mg. This longer cycle allows for a complete wash out between cycles. I feel more comfortable with a trough of zero and no need to schedule wash out vacations.
Not long. My 2nd cycle coming up. Previously I was on almost as high a dose biweekly (ketoconazole + 7mg) but when I developed an oral infection I thought it could have been a side effect, so thats when I switched to tri-weekly.
The oral issue was diagnosed as a tiny tear of the cementum of the root. Follow up with periodontist was postponed due to COVID, so we still dont know for sure, but I can tell you it hasnt gotten worse and actually seems to have improved.
I am just at the start of this journey as a 62Y old woman. As a result, I have been taking a deep dive into age-related dosage info and came across this study which would seem to indicate the older we are the more we need. I would be very interested in folks view who are elder and have started rapa.
The difference between Evirolimus and Sirolimus is profound. Evirolimus is much weaker and thus requires more the block Tor 1 than Sirolimus does. So the Mannick study of 20 mg weekly would take a lot less Sirolimus to obtain same results. These rapalogs were really developed for everyday usage to prevent organ transplant rejection. Sirolimus with it much longer 1/2 life is really a much better drug for longevity purposes and it also gives you a much bigger bang for your buck.
First time I heard about this. I’m 65 and taking 5mg / once a week for three months and then a one month break. I realize we’re all different but I am interested to hear what dosage you would be taking if you were a male of 65?
When we are younger, the basal mTOR rate is low, but it spikes given stress, food, etc.
As we get older it seems that mTOR becomes increasingly disregulated and higher, and does not return to the low level after spikes (as quickly or consistently as when young). So the theory is that as you get older you want to suppress mTOR more (though still allow spikes and periodic increases as “appropriate”. See this video with Brian Kennedy here: Make your arguments for Rapamycin dosed weekly vs. biweekly - #12 by RapAdmin
But we are still in the early days of identifying the optimal dosing for people, age groups, weights, etc… so its all more trial and error. What most of us are doing here is starting low, slowly increasing, and doing regular blood testing to see how things are going (and hopefully working with your doctor to try to optimize things).
"Dr Green has moved up from 10mg a week, then 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?
*Note: It appears that Dr. Green was on 6mg 1x / week for 3Y (unk cycling), he then went to 10mg 1x / week for one year. As of the date of the YouTube I/V he had titrated up to 20mg every other week with no side effects. Dr. Green is 80 years old.
the mouth sores issue is a strange side effect. I’m not sure what exactly is driving it. I had one at around 4mg or 5mg/week, and never again, despite going over 28mg dosing. For some people it may be dose related, but for many of us it has no relation at all to dosing. You’ll see many people in the forums dosing very high, with no mouth sores at all.
For myself, I observed side-effects at dose changes, even at 1mg the first time, that don’t repeat. I speculate that there’s some sort of start-up effect.
I am currently on 5 mg + GFJ + EVOO + Metformin bi-weekly, and I developed a new canker sore on the inside of my cheek after the first week. The rash on my hand has also come back mildly as is the rash on my neck. I had hoped to go up to 6 mg next week, so with the GFJ, I’d expect that to be about 20 mg standard without.
I, for one, have been looking for data points for dosage to older adults. Say 75 y o and above. There aren’t as many, so I was glad to see that the Kraig 2018 paper was mentioned (“An RCT to establish the feasibility and safety…”).
I think it’s been mentioned on this site, but --I think-- also in an early Attia interview, that older individuals may not need to take vacations from dosing.
My interest in the older cohort has to do with cachexia and sarcopenia so if anyone’s got insights around rapa’s use there I’d welcome it. Perhaps dosage could need to be altered.
(If it would take us too far off topic message me.)