Hm Im starting to think if I should experiment with 0.5mg every day - for 3 days than 4 days off and then the next week take 6mg and then 7 days later start 0.5 every 3 day for 3 days. I think changing up the dose around is probably a good thing as we don’t really know if the typical weekly dose is the best. Might give it a try will see. I’ll have to get a script for the 0.5mg pills as I only got 1mg and 2mg pills, and breaking the 1mg in half will probably destroy the coating so it wont get absorbed correctly.
Anyone else also changing up their dosage schedules? or just sticking to the weekly/bi weekly typical dose?
I think it does help to have an idea as to what the mechanism is that you are looking for from Rapamycin and whether that implies trying to keep a highish level relatively continually or for the level to go up and down in a multiday cycle.
Chat GPT4 says: "The half-life of rapamycin (also known as sirolimus) varies across different mammalian species due to differences in metabolism, clearance rates, and other factors. Generally, the half-life of rapamycin in mammals ranges from a few hours to a couple of days.
For example, in humans, the half-life of rapamycin is estimated to be around 62 hours. In rats, the half-life is reported to be between 9 and 16 hours, while in mice it’s around 5 hours. In dogs, the half-life can be between 18 to 24 hours. These figures are approximate and can vary based on factors such as age, sex, body weight, and individual metabolism.
Please note that these values are not absolute, and they may differ based on experimental conditions, dosing regimens, and the specific study. Always consult relevant scientific literature and professional advice when interpreting pharmacokinetic data."
In quoting from this I don’t know whether or not it is hallucinating. It is, however, a good source. It would be nice to have a reference to a range of half life calculations.
It does make the point, however, that daily dosing for mice with a half life which is in a number of hours is arguably sensible where doing so for humans is not.
please don’t use chatGPT as information is really unreliable…
Also with rapamycin half life and absorption there are so much individual differences that it really hardly makes sense to talk in general terms. I personally think after reviewing some literature on this that the only way to be sure what is happening in your body is to test yourself. Even when we talk about half life in humans to be around 60 hours it is in reality not helpful as in most people tested it gets metabolized or cleared out of organism in 5-7 days after initial dose. The only way to know how your specific organism is absorbing the particular form of rapamycin you are taking and how you are metabolizing it is to test. Even with transplant patients dosing and scheduling is personalized on test results.
I’m 28 so I just want to preserve what I currently have for long as possible. Also want to gain a little muscle so I need to think what dosage would be best for me. Some say you cant gain much muscle if you inhibit mTOR but Im not to sure if this is true. Does anyone else gain muscle on rapamycin? If so whats your dose schedule?
GPT4 gives a starting position which enables more detailed searches to be done. As to the simple question as to whether the half life in Mice is materially less than Human Beings it appears that it is.
Mice: its dose dependent 2.1 - 4.8 h.
Looking at other papers it is a work of some hours to run through the papers and get a short review on pharmacokinetics of Rapamycin in various species. It is, however, clear that it is not just a simple exponential decay curve.
I use Rapa 5 mg once per week and have had muscle and strength gains over the past year. Rapa inhibits mTor, but mTor isn’t the only mechanism responsible for hypertrophy.
Nice article by two experts. They suggest that the hyperlipedemic effect of rapamycin can be modified by dosing adjustments. However, this study suggests that the lipid dysfunction, seen in 3-20% of patients, is Not corrected by dosing reduction. Furthermore, the elevation of triglycerides in particular isn’t responsive to lipid lowering therapies. Discontinuation of rapamycin would seem to be the only solution to the triglycerides.
On the other hand, as I’ve argued on multiple occasions, the cardio protection of rapamycin seems to trump the lipid abnormalities in this group of patients.
@ Jensen_Achilles From the various scientific studies I have read inhibiting mTORc1 does not inhibit muscle growth in mature animals, to the contrary inhibition actually helps preserve muscle in elderly animals, for example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751631/
It is always tempting to use logic to figure out how the body works, but not knowing precisely how the whole system functions it does not always work out and sometimes the opposite is true. Only direct observation is reliable with this level of complexity.
Also of note, being in my early 50’s I have no problem building muscle, in fact I would subjectively say I build muscle at the same rate as when I was 18. After an injury I have built back different muscle groups with ease (had to switch from cycling to swimming). If I could give my younger 28 year old self one warning it would be to protect joints from injury, both repetitive and traumatic. Joints are the biggest thing to worry about with aging, not muscle - just my experience.
I’d like to know whether things like fructooligosaccharides can help us against this kind of infection. Anyway, now I take 4g of fructooligosaccharides everyday even during the period I don’t take Rapamycin. Berberine also inhibits E. coli, but I hesitate to use it because of its side effects.
Maybe this is the answer, youngsters can afford to take Rapamycin very infrequently whilst the older we become the more often we should take it (albeit in lower doses).
Like everyone else though, just a guess on my part, and I did notice that Blagosklonny constantly used the word “may” so he is still guessing like the rest of us.
I would think the glucose handling is probably going to feed into mTOR activation. As glucose handling deteriorates then mTOR spends more time activated
I might be temped to try it daily as well. There might be more benefits in daily dosing especially in cancer prevention and autoimmunity, but there is potential higher risk of bacterial infection. Bacterial infections have potential to kill you, so does it outweigh the risk? Having antibiotics on hand might be helpful I guess. @blsm how long have you been on pulsed dosing?
