If you haven’t read it go to this topic on the forum…More Rapamycin Might Not Be Better – I upped my Rapamycin Dosage and felt it didn’t help. My biological age went up in two tests significantly.
Have reduced to 12 ng/mL will retest in 6 months.
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I have finally upped my dosage to 8 MG. 10 MG would be the max I would go personally.
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Hi - and welcome to the site. We’re all trying to figure out the dose issue right now. We don’t have really good data to go on. The mice seem to live longer the higher the dose goes… so thats guiding the general thinking for many people, but we don’t live in pathogen-free environments so its going to be a little different for humans whatever the case.
There is no “right” solution right now, broadly speaking.
Many people are trying higher higher doses: People pushing the upper limits of Rapamycin Doses - Any One Else?
and here: One User Trying Very High Doses of Rapamycin, and Negative Adverse Events / Results
and other delivery methods: Intramuscular (IM) + Intranasal (IN) Rapamycin - A new paradigm for human longevity translation
Some are reversing that direction: More Rapamycin Might Not Be Better
Here are some protocol ideas here if testing higher doses: Ideas on Protocols for Testing Higher Rapamycin Doses
So - I don’t know what the right approach is for you, I would just urge you to do good pre and post testing to see what the real effect is over time, move relatively slowly (I’ve jumped around up and down 5mg in my dosing without problems). And ideally work with a doctor who understands this stuff, or is interested in learning.
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After having been on 6mg Rapa with Olive oil and metformin for 8 weeks with no side effects (slowly building up to 6mg) I´m about to start again after 4 weeks off.
Any recommendation of a restart / entry dose would be greatly appreciated.
I was planning on starting at 3mg and work my way up to 6mg in three weeeks ?
Thanks so much in advance
Thanks for the links. I’ll go through them tomorrow.
Please know, I’m very clear in the information we “don’t” have so my many questions just go in and process with all the rest.
May I ask what you’ve tried, your dose range having played with it “up and down”, and where you are now? Do you expect to stay at that dose for a while or because we change/grow, you might amend with each test result.
What is highest dose you’ve known or heard about
someone/anyone taking that remains beneficial? Weekly or every other week dosing? Thoughts?
What test(s) will help me stay on top of current dose benefits vs the reversal point I’m seeing here?
I know some people take med vacations and some don’t. What’s your thinking on it - and/or a good protocol?
My concern is I’ve never taken a high enough dose to cross the BBB in order to gain benefits. Even if 6 mg isn’t my sweet spot, is it doing something? Thoughts.
What other anti aging product(s) seem to, or are likely to, benefit synergistically? I read about metformin (not sure of mg) and a few others I’m not familiar with.
Do they add benefits that Rapa alone doesn’t seem to provide? Grapefruit juice? New to me but sounds important. Is it important to take my dose w/gf juice?
Thank you. Thank you.
I love to add others experiences/knowledge to my “brain rapa spot”. I consider it all and believe it helps me make better personal decisions.
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Weekly or every other?
I have paused rapamycin use many times in the past three years and then restart at the same level i stopped at with no issues. I typically have no obvious side effects whether i dose at 6mg /week or 28mg every 10 days to 2 weeks.
But to be cautious if this is the first time you have paused would not be a bad thing. I initially when i paused i think i took two weeks to ramp back up to my normal level. But i have no evidence that this is actually effective.
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Is it important to pause?
Thoughts on “time off” currently?
Thanks.
Most people pause to allow their body to clear up any side effects they are experiencing such as rashes or canker sores. Then they start again and their body usually has a better tolerance for Rapamycin going forward. Good luck and welcome!
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Actually I am dosing every 10 days so my trough can get down to zero from the 12 ng/mL. dose 2mg x 6 due to GFJ taken with it. I consistently get a multiplication of 6 from one 5 fluid ounces of fresh Red Grapefruit juice taken with pill.
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There are different opinions on the issue of planned pulsing (or vacations) from rapamycin. Most doctors who prescribe rapamycin, from what I can tell, don’t tell people to take these rapamycin vacations.
Peter Attia used to do periodic vacations from rapamycin in the first year or two he was using rapamycin, but has since (I believe) stopped doing them.
The general theory right now is that prolonged, frequent (daily) dosing of rapamycin eventually causes mTOR2 inhibition, and that this inhibition causes many of the negative side effects - including immune suppression: Evidence that mTORC2 inhibition is detrimental, by Dudley Lamming
But most of us use weekly dosing - with the belief that we don’t impact mTOR2 much given the schedule.
Rapamycin inhibits mTOR1 immediately upon oral intake, which provides (its believed) the longevity benefits.
The take away is if you want to be extremely careful you might want to take rapamycin vacations - but that may also decrease the benefit (since you aren’t taking the rapamycin during that period).
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No, it’s not important to dose with grapefruit juice. If you want the multiplication effect that it has with absorption of rapamycin, then use it. But, my point of view is that is safer when establishing a suitable weekly dose to simply take rapamycin with a fatty meal. In my case that’s keto coffee before breakfast. If I feel the need to reduce rapamycin costs then I’ll consider lowering the dose and adding grapefruit juice to bump the absorption rate up. That will likely involve more rapamycin blood testing to determine what the grapefruit juice is actually doing to my blood levels. It is, however, a logical step to save money, and if there are more reasons I’m sure someone will add their thoughts.
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I understand we’re all kinda guessing here. I’d like to think we’re making educated and informed choices.
Having said that, is there a specific level/dosage to strive for - knowing we are at a dose providing brain clean up? Lowest, highest?
Any broad range on Rapa levels when testing one day before next dose that would cause concern? Show benefits? Lower than __? Higher than……? Things to hone in on? What tests might I request?
Is there any general statement you could make regarding “getting closest to one’s optimal dose/and how to”? Do you consider our highest dose to be most beneficial or does it stops adding benefits at certain point seen in serum levels or specific bloodwork?
I’ve been taking 5 mg Rapa weekly for approx 9 months. I no longer experience any problem or my one and only side effect, feeling whooshy and tired for a day. This doesn’t factor in any CFS/fibromyalgia symptoms. Yes, I’m one of those.
I’m very in tune with my body and able to discern even the slightest change ie: two types of headaches I get, regular and whooshy, along with many other things, slight changes . This is because of my 18 year journey w/this dx, ongoing research, and trying anything, to date. I’ve been on my own trying to “fix” myself for quite some time. My findings are more effective than any tx/pill ever tried. And, I’ve tried all I could tolerate. Just a little background.
The same day i started my increase, early am, whooshy was back.
That same morning, I increased 2 mgs vs 1 mg, as I’ve titrated before. This is how/why I arrived here, taking Rapa, and increasing the dose. Mainly.
I can’t test for baseline, 8-9 mos later. I’d prefer not to stop and start over. I do believe my insides are likely doing better. Just a “gut feeling” and those come from a “knowing area” of our brain, not our gut, btw.
I’ll be 61 in Feb. And as many have said here,
“told I look in my 40s”, but I was always that way. Not a Rapa change. My thinking was more clear for a handful of months in the middle of this time period. I’d love that back please. And lotsa other stuff.
You said the least amount of change noticed was usually seen in younger/healthier people.
Doesn’t describe my situation:)
I’ll compare this/last year’s annual bloodwork for any improvements. I hadn’t begun Rapa at that point. Do you recommend any testing that’s not a “normal” annual old person physical test? Which of the standard tests (last year’s) could tell me something about Rapa working or not, in this moment?
I started a topic on the subject of health and Rapa usage. Not sure what was written specifically but it’s important to know that many symptoms overlap in several dx: Lymes, CFS/ME, Fibromyalgia, and so on. I’d love to hear about anyone who has a health thing, taking Rapa.
Is there any way to know I’ve increased too much or if I’m at my sweet spot? I’ve read about mouth sores, diarrhea… side effects, but I’ve not experienced any.
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Your opinion on where Rapa levels should be (range?) the day before next dose? What if result is 0?
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Is there an easy way to know one should STOP THE INCREASING
or is there a DO NOT exceed X mg weekly, parameter.
Anything that might dictate an increase?
Basically, having some information on when to stop increasing or when to consider increasing for optimal benefit, would be valuable info for all of us. Even if the info is a very large range of an educated guess.
I really enjoy reading everyone’s experiences, the receptiveness, and the crazy quick responses!
I could stay on here and read all day.
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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.
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Hi, I have CFS. Has rapamycin helped your CFS please? I’m considering trying it. Thank you.
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@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.
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Are you saying that in 9 months, your CFS + fibro have not improved using rapamycin?
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?
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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.
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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
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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.
Some related threads that may be of interest:
here: To have less side effects, are there any ways to increase Rapamycin elimination rate? (Ex: drugs? fasting?...)
here: Make your arguments for Rapamycin dosed Once Weekly vs. Once Every Two Weeks
here: Rapamycin Update - Summary of Recent Matt Kaeberlein, Dr. Green, Blagosklonny Conference Call (June, 2022)
here: Rapamycin and Beyond: Presentation by Dudley Lamming & Adam Konopka
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I would suggest that inhibiting mTORC1 in itself has downsides and that cycling is the key.
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