Would be nice if I don’t need reading glasses. I’m finally targeting about 10ng/mL after 24 hours. See how I go in 12 weeks.
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I haven’t been using reading glasses for over a year now. Can’t be 100% sure it was the rapa but one way or another I’m good to go. I do attribute part of the help to getting a smart phone that refreshes 120 times a second. When scrolling, 60hz screens appear to stutter which was killer for my eyes. Also I stopped playing video games on my phone, as I had a tendency to over-intensely focus to such a degree that my eyes would be sore the next day.
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I wrote this before. I have myopia. Definitely my visual acuity improved tremendously after rapamycin. I take 2mg a week and I started noticing this effect in the first week. Colors are more vivid, I see distances more clearly. I had slight dry eyes and even that fixed it. I don’t have to use as many artificial tears as I used to.
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I’m in the “haven’t noticed any changes, good or bad” group. No side effects. I didn’t have any “old age problems” (aches pains etc) that were cured. Far as I know my vision hasn’t gotten better, and I do get an eye test every year. This leaves me wondering - is the rapa actually working? I guess the only way to tell is if I don’t die. =)
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I have been increasing my dosage, and I am feeling more fatigued but not in a euphoric way. I think it’s my body signalling that I need to cut back. I will try a 14 mg equivalent (4 mg + GFJ) bi-weekly protocol to see if that helps the fatigue.
Or it could just be that life has gotten more stressful. 
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Destrider, have you ever done a blood test after 2 hours or 24 hours?
I definitely feel fatigue on the day. I know my psoriasis has definitely reduced, more on the first day and it creeps back later from say 4th day onwards. One of my problematic joint pain in my left finger is almost gone. The other more severe one is at 50% of the original pain.
I’m currently on 12mg with GFJ. I know from the blood test it peaks well over 30ng/L and around 10ng/L after 24 hours.
Should I increase to 14mg or should I keep the current weekly at 12mg for another 6 weeks first?
Patience is definitely not one of my virtue 
.
Perhaps another 10 weeks and then decide. I’m of the opinion that a higher dosage and maybe a longer delay in-between dosage is better than continuous low dosage.
Are you taking 12 mg + GFJ? That’s be 36 mg equivalent. If so, you’re definitely running the risk of MTOR2 inhibition.
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I know people who have taken much more … I am only taking that amount because of the stupid brand… Siroboon. I monitor based on the level of siromilus in my blood after 24 hours. I am within the safe limits that Bryan Johnson described. He takes 13mg, then 6mg on alternating weeks.
“Blood Rapamycin levels:
90 min: 26.5 ng/mL
4.1 days: 2.5 ng/mL
13 days: not detected”
I dont think my rapamycin quality is that good despite of all the steps I take. I now just need a history to convince the local doctor to prescribe to me. lol
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All you needed to mention was Siroboon. I understand now. 
Your 15 mg of Siroboon is 1.5 mg normally.
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If you know your blood rapa levels, what do you do with that information?
Do we truly know what that level “should” be, and thus can use it to adjust our dosage as needed?
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I measured my blood level a couple hours after a dose (no idea what the “target” would be, but I know I am taking real stuff) and on the morning before a dose (below detection threshold). I think making sure the trough was zero was the more actionable of the two.
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I think the 24 hour target is around 10 ng/L. That means the peak will be just over 30 ng/L. By the end of the week I am sitting around 2.4 ng/L. There isn’t a lot of information out there… do I wait till I hit 0 before starting again? As long as the pain in my finger becomes less… I will keep on it.
I think we want to target a trough dose significantly lower than the trough dose (and maintenance blood level target) in organ transplant patients whose goal is immune suppression.
So… “The usual maintenance dose of Sirolimus in these patients is 2 to 5 mg/d and its optimal maintenance trough level is 5 to 10 ng/mL.”. Source: Sirolimus Dose Requirement in Kidney Transplant Recipients in Iran - PubMed
So I think we probably want to target at least a trough level of 2 ng/mL, and perhaps 1 ng/ML. My rough thinking is that we want at least half the trough blood levels that the organ transplant patients are targeting so we’re getting at least half the immune suppression. And perhaps 1 mg/mL because it seems lower might be better when thinking of immune suppression. It seems to be a risk/reward trade-off. The higher the trough, the greater the risk of immune suppression, but the higher the trough the higher the potential longevity benefits (if you don’t die from infection).
Other people’s thoughts?
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It seems like some of these questions will be impossible to answer without studies of different doses – or even varying the doses as necessary to target different peak levels – in generally healthy people. It seems like answering some of the questions people are asking on this forum might require studies stratified by age and body composition too.
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The dosing is an individual decision.
Risk tolerance etc.
Following Dr. Mikhail Blagosklonny’s thoughts as expressed through opinion articles, which is the highest tolerable dose, especially for older people.
For many of us, he is the Godfather of rapamycin in humans for life extension.
Because I am old I started at a high dose (I knew very high doses hadn’t killed anyone so far) and titrated down to the maximum weekly dose I could take without adverse side effects. I have been taking 5 mg/week with GFJ for quite some time.
This is the maximum dose I can take without experiencing diarrhea.
IMO: Younger people need smaller doses.
Dr. Blagosklonny
Dr. Mikhail Blagosklonny from www.mikhailblagosklonny.com
Professor of Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York. Editor-in-Chief, Cell Cycle, Aging, Oncotarget, Oncoscience. Dr. Mikh
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Presently we are all making choices in the absence of some of the information that would help us make better decisions with greater confidence. Like most of the people who frequent this forum, I have decided to take certain drugs or supplements based on my best evaluation of the possible risks and possible benefits. I think it’s possible to make a decision under uncertainty while wishing there were less uncertainty. I am just saying I think we are all making guesses about a variety of things that should be susceptible to elucidation by the scientific method were the budget available to run the studies. E.g. don’t you agree that its conceivable the results of the PEARL trial could make you update your priors and revise your dosing regimen?
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Really, the PEARL study is the only one that will be revealing results in the near future (i.e. next year) that will give us more information.
But, it was a short study (1 or 2 years) with loss of visceral fat as the key endpoint. The dosing of 5mg and 10mg per week is interesting. But really, this study doesn’t give us a whole lot to go on, for the end point we really care about; healthy longevity. Really the ResTORbio clinical study probably gives us more data with higher quality than the PEARL study. I’ll take any data I can get, but we have to put the data in perspective.
I’m sure the 10mg/week will show slightly higher side effects than the 5mg/week. And the 10mg likely shows slightly more efficacy than the 5mg in terms of the primary endpoint. But beyond that I’m not too sure of the value we’ll get from PEARL.
What do you see as the potential benefits of the PEARL results? Do you see it differently?
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I think by day 9 or 10 I will be heading below 1 ng/L. But I think for now I will try to maintain my dosage as it is for a few more weeks before changing. At least 30ng/L peak is not that bad but I do feel fatigue on the first day. If I have to feel like that every week to keep my psoriasis suppressed I am happy to keep doing it but at some point I will increase the cycle from 7 days to 8 days and 9 days etc.
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I don’t have specific expectations of the PEARL trial other than seeing if there are differences in “benefits” between the 5mg and 10mg wings; it was just the first that came to mind. My point is simply that there is a lot more we could know, and while this forum offers some of the best and most enjoyable available speculation about what little we know, we would benefit from more data from thoughtfully constructed studies.
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Absolutely. We need real clinical studies on rapamycin, ideally a TAME like trial for rapamycin. Unfortunately, since rapamycin is off-patent, people don’t want to fund these types of studies so I think we may be on our own… or limited to small studies like PEARL that don’t really answer the questions we want answered.
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