I am running another CGM session with Rapamycin. It is difficult to tell as Freestyle I am told overstates its measurements in the first couple of days, but I do think there remains a trend for Rapamycin to cause slightly higher glucose levels.
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…in other words, if markers are not changing “in the wrong direction” rapamycin is not working?
btw do you have a copy of the article? I can not access it trough my institution.
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The ever insightful Blagosklonny brought up a very interesting point about the possible dangers of every other week dosing. He mentions that he believes that this gives an opportunity for the body to overcompensate and as a result have an excessive mTOR response.
He states that this may be particularly true in the vascular endothelium leading to excessive thrombosis, ie. heart attacks and strokes.
A good argument for weekly dosing.
As for bacterial infections, the MK study failed to reveal anything greater than placebo. Some people get gram negative sepsis from something like a serious urinary tract infection, having nothing to do with rapamycin.
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I wonder if there is any research that underpins this. It does not sound that rational to me.
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Similar to elite athletes perhaps when they overcompensate and store excessive glycogen and aerobic enzymes in their muscles in anticipation of the next work out.
So if you hit mTOR hard every 14 days, your body may produce more TOR in anticipation.
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Wondering how much of an increase would in ApoB or A1C would cause you to dial back dose or frequency of rapa.
Why would that not apply for weekly?
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cause mTOR is suppressed most of the time because of long half life I guess?
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The weekly dose is much less than biweekly, making it less likely for the body to overcompensate.
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Blagosklonny only takes 8 mg per week. I wonder why he doesn’t take more given what he said in the article.
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Exactly.
First 1.5 years took rapa 6mg weekly… I got great biological gains in age. Upped to 36-38 mg weekly…
after Dr. B’s recommended higher rapa is better… for 7 months, and I lost some of my biological gains. I began aging faster.
Lowered to 13 mg weekly for 4 months …regained back biological gains. More is not better for me…obviously.
Based on this chart I could be currently as low as 49 years biologically. Cool!
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While I respect Dr. Blagosklonny the optimal dosing at this stage is still speculative at this time.
As regards the harmful effects of high pulse dosing i.e. “this gives an opportunity for the body to overcompensate and as a result have an excessive mTOR response” is pure speculation and no studies either in animals or humans to back this up."
“I believe that rebound of mTOR in endothelial cells may increase thrombosis, arterial permeability and arterial spasm”. Pure speculation.
I have been following Dr. Blagosklonny on Twitter for quite some time and he doesn’t seem to be able to make up his mind on some things such as maximum dosing.
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Dr. Blagosklonny once tweeted at me that I was taking too much rapamycin for my age. I was 27 years old & taking 7mg a week at the time with no side effects.
He tweeted " I would not expect any side effects even at high doses, but Its probably not necessary to inhibit mTOR too much at a young age"… However he also once tweeted that rapamycin should be started at 25+ & he also knows the animals started on rapamycin at a young age live longer so he sometimes contradicts him self & I don’t mean that disrespectfully but its true and when I replied back to his tweet asking him what dose is best for my age he replied “I cant give medical info, seek medical advice from a doctor” , so idk why he commented in the first place if he couldn’t give me useful information but anyway I think he doesn’t know what dose is a beneficial for aging just like the rest of us.
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I think the main takeaway from the paper is that there is no ideal dosing schedule, and there is no aging. First you need to know which age related disease is going to kill you, and then you dose Rapamycin in a manner that delays that disease. Perhaps smaller and more frequent for cancer prevention and larger less frequent doses for dementia…
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My advice? Start young and stay on it. Better to preserve a 27-year-old body than a 60-year-old body. Rapamycin does not actually reverse age in spite of some improved biological markers. At best it slows down aging.
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@desertshores I completely agree with you. I wish I found out about Rapa when I was 25. However, until they invent that time machine, I’m going to have to preserve what I currently have!
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Of course it’s all speculation because, as you say, there’s no human studies on optimal longevity dosing, and there will probably never be such a study.
He changes his mind in degree, not in kind. He reads, studies, thinks and speculates. He then gives his opinion which is worth a great deal more than most other opinions on this subject.
I read 2 hours of medical studies a day relating to preventive medicine and change my mind , to some extent on some topic, maybe weekly.
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Very good point and that’s why family history is so very valuable.
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The possibility of MTOR rebound w/ periodic dosing &/or discontinuing rapa is obviously concerning. If this is a real risk, as Blagosklonny implies, then rapa doesn’t seem quite as safe as all of us have to take a break at times. Are we at risk if we discontinue when we have an infection? surgery? Or does B recommend never stopping? Is weekly dosing safe or are we best to do it daily? Surely there must be some data on rebound risk.
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Do we have an opinion on James W. Clement’s book ‘The switch’?
To summarize, it speculates that people should fast and feast for longer time intervals, like months. E.g. Fast and eat only sparse amounts of food during summer and winter. Rebuild your body and feast during spring and autumn.
Clement also speculates, that we should time these fasting or feasting intervals like our ancestors.
Nobody knows the optimal fasting/ rapamycin protocol, this is just another idea I am thinking of.
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