As an older person who takes the highest possible dose without too many unpleasant side effects as per Blagosklonny, I cannot tolerate taking it too often. The pulse dosing has already been thoroughly discussed.
Because: (Quoting from Melih on another thread):
"The reason humans use weekly dosing vs mice daily is because mice have about 7x the metabolism we have. (Someone correct me if I’m wrong)
Basically the 5 half lifes of rapamycin get excreted before it’s the next day and the mice will be ready for the next dose. Humans have to wait a whole week or two for it to be out of their system."
Another excerpt from his paper:
“In theory, high intermittent dose of rapamycin (for example, 30 mg every 3 weeks) may produce a high peak level to ensure that even rapamycin-resistant cells will be targeted. (Probably, everolimus is better for this purpose because of short half-life). A high peak concentration may affect neurons, protected by the blood brain barrier, and stem cells in their niches. A high single dose of rapamycin was shown to maintain lower body weight by shifting the set point long-term in rats [25]."
(Coincidentally 35 mg triweekly has been my dosage for a while, with no intolerable side effects)
"I suggest that optimal dose/schedules are individual, depending on age, gender and spectrum of pre-diseases in each particular person.”
Its not an AUC issue because it is cyclic. The body goes through phases of autophagy/mitophagy and other phases of growth/being fed. If there are no phases it is not clear what is happening.
I wouldn’t necessarily agree as both really are markers that rapamycin is working. Both might be controlled by CR and exercise. Especially lipoproteins IMO reading about rapamycin should get back to normal when you maintain reasonably low BF and when “enough” adiposity was converted by rapamycin induced lipolysis… and this is slow process and it might take some time depending on individual. Same with glucose levels, rapamycin reduces secretion of insulin so glucose levels in blood get higher and are not converted to fat… I believe that while you are taking rapamycin you should have some CR diet and enough exercise and possibly eat low glycemic CH… I might be completly wrong and in a year or so will change my mind but at this point I am still optimistic.
I would be curious to find out if that lady who tried to commit suicide by taking 103 mg of Rapa experienced any beneficial health benefits? If so, that could be cause enough right there…
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.
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.
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.
