By inflammation, are you referring to joint pains?
Yes, basically what I would call old guy aches and pains 
.
As long as I take rapamycin I really donāt feel any joint pain or stiffness. Iām 72 and Iāve been an athlete of one kind or another most of my life.
Now I basically lift, walk, and do high intensity interval training on a Schwinn Airdyne. After a hard workout, I sometimes feel a little stiffness and muscle soreness the next day, but almost none. Certainly less than when I was doing this in my 20s and 30s.
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So youāre saying that on rapamycin youāre actually having less joint pains at 72 than you were in your 20ās while doing essentially the same things? What dose?
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I took 6 mg a week for 3 years. Now Iām taking 8 mg a week.
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Dosing is a very complicated issue. Mannick got an immune response on just the equivalent of 4 mg per week. A phase 1 prostate cancer trial saw a trend towards an increase in certain immune cells at just 0.5-1.0 mg per week. This suggests a rather potent drug.
As we age it would seem that our TOR levels increase, so it would stand to reason that our dosage should go up some. This is counterintuitive since the elderly usually need less of a dose, not more.
Besides the lipid and glucose concerns, autophagy is a major consideration. At low levels itās absolutely necessary to fight cancer, but at high levels it does seem to be cancer promoting. This seems particularly true in the prostate stroma.
Dosing remains a difficult problem but studies on humans certainly suggests that itās a potent drug .
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Larry
#26
week 4 coming for me stable at 3mg , going for 4 on Tuesday, as I noted last week I felt a slight increase of arthritis pain and joints as day 5 and 6 approached but much less than no R at all , as Charles says above he is very active and feeling pretty good , I have 5 years on him and concur !
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Before u go think itās ok to keep reducing dosage and doing the tiny amounts that most people on this forum do and thinking doing less is always safer than doing more. I suggest you read the article
Low Dose Rapamycin Exacerbates Autoimmune Experimental Uveitis
Zili Zhang, 1 , * Xiumei Wu, 1 Jie Duan, 1 David Hinrichs, 2 Keith Wegmann, 2 Gary L. Zhang, 1 Mark Hall, 1 and James T. Rosenbaum 3 , 4 , *
Matthias G. von Herrath, Editor
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jimo3
#28
Iāve lowered my intake of late mostly out of concern of a mtor rebound risk. Do you have an opinion on what the āsafestā or best-odds dosage would be? And what does ālow doseā in terms of this article even mean for humans? 6mg/week would probably qualify, no?
āthe daily administration of 1.5 Āµg rapamycin significantly augmented the severity of EAU, whereas the treatment with 7.5 Āµg rapamycin virtually inhibited IRBPā
They used female-only mice in this study.
That is indeed a very low dose. Translated to humans that is way below what anyone here is taking. The paper is from 2012 and I cannot find any similar papers since warning humans of such a low dose.
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jimo3
#30
For what itās worth, Iāve lately been taking 2mg every 3 to 5 days w/ the interval based on the estimated blood level declining to 1.50 to 1.75 mg, assuming a 3 day half life. I changed it from 6mg/week after reading of some fears of tor rebound. Who knows?..
Just read the article carefully and try to estimate how it translates using the say 10 to 1 factor as far as mg per kg of body weight vs that for small rat. It is somewhat unclear as to exactly quantify it in my opinion but yea i would say for sure less than 7 mg per week is low dose. i did a calculation per that article months ago but forgot how i did it but see the reply to desertshores person for a quantitative calculation for human. Also donāt go thinking taking grapefruit juice will make your dose higher with respect to that article. I am no expert on the subject but posted the article to see what you may think about it as i have not read anywhere else about someone mentioning that article or issue of low dose worse than higher dose. Seems to me yea it was somewhat concocted experiment for a single issue purpose but if true for that then it is likely not the only case in which low dose is worse than no dose or higher dose. Also that was considering rapaā¦ by intraperiontal injection which is way more effective than oral and even more effective than subcutaneous or intramuscular injection.
jimo3
#32
Iām taking 2mg every 4-5 days based on a targeted trough level of 1.4-1.8 mg, using a 3 day half life calc. Perhaps that could work?
ok translate to a 70 kg person a 2 microgram daily dose using a 20g mouse then get 70,000/20/10 times 2*10^(-6)=0.7 mg for a human per day. And that was intraperiontal injection for the mice which is much more effective than oral so that does translate into an appreciable amount for a human . Say it is 4 times as effective as oral then that translates into 7 times 4 times 0.7 or 19.6mg per week for human. So it is NOT less than what anyone else here is taking !
Or ok using a 12.3 factor rather than 10 then it still results in 15.9 mg per week. To make it even more in your favor for human say everyday for mouse is every 2 days for human then still get about 8 mg per week for 70kg human.
The fact that it was in 2012 does not make it untrue nor does the fact that few if any articles have been written since then warning humans does not mean it is not an issue. O
i donāt know exactly what you mean by 'would work ā but that is certainly low dose according to that article. See my quantitative calculation below or above ? but its here.
seems that ā tor reboundā that guy said in the article is quite opinionated. Like someone said i donāt see any proof or anything to really to substantiate that.
jimo3
#36
I was responding to Larry earlier in the thread & to his specific symptoms. Not sure why it shows up here as well.
The title says it exacerbates autoimmune āexperimentalā uveitis.
āWhat is uveitis? Uveitis is inflammation inside your eye. Inflammation usually happens when your immune system is fighting an infectionā
So how many of us have āexperimentalā uveitis
Unless you had red eyes from autoimmune disease before taking low-dose rapamycin maybe rapamycin might exacerbate the problem.
I really donāt see your point.
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Seems to hit about 1 out of every 4500 people from the Wikipedia articleā¦ so yes, not a big issue for most of usā¦
Of course, there are always going to be edge cases where rapamycin may hurt people - thats true for any type of supplement or drug.
I do think people who have pre-existing conditions have to be extra careful in researching rapamycin before trying it to make sure its impact on the conditions, and interactions with other drugs, are not negative.
there are later papers than that of same subject such as
Inhibition of mTOR by Rapamycin Aggravates Corneal Epithelial Stem Cell Deficiency by Upregulating Inflammatory Response
https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/stem.3036
by JW Park Ā· 2019 Ā· Cited by 8 ā Corneal opacity, neutrophil infiltration, and pro- inflammatory cytokine expression were significantly reduced in the cornea by rIL-10 (Fig. 6Bā ā¦
I DID not necessarily say it was a problem but as i said prior out of all the near infinite possibilities it would be very unlikely that such an issue is true for that one and only that one issue. It is almost for sure going to be true for some other scenarios other than uveitis.
