Does anyone know if everolimus is a more selective inhibitor of mtorc1 than mtorc2 compared to rapamycin?
Ive read that daily sirolimus or everolimus does not fully 100% shut down mtorc1, but does everolimus decrease mTOR more than rapamycin (on an equivalent dose basis, whatever that may be)
I’ve not researched this… for what its worth (perhaps a reasonable starting point for your research) - here is the ChatGPT response:
Hi All, my first post… I am new to rapamycin forum group. I plan to start (in Jnauary 2026, after the xmas and New Year festivities) at 1mg per week, and hopefully build up to 6mg. I have read many of you are taking larger doses. But how do you take the 1mg tablets? Do you take them one at a time ? ie take one, drink water, take another, drink water etc until you have reached your weekly dose? Or do you spread the tablet taking over a period of time, maybe over an hour or 2?
Apologies, if this has been asked before
regards
Sapper
Welcome!!! How exciting for you!
I assume everyone does what I do which is taking them all at once.
I even take all 8 pills in one gulp, not that I recommend that!!! Don’t try this at home!
A helpful hint that I learned here…once you get to your 6mg dose, if you are in the US, you can get a $25 sirolimus test (at gethealthspan.com) to see if that dose is optimal for you. I was on it for almost a year and discovered 6mg was not enough for me. For others, it’s too much. On dosing day, make sure you are not consuming things that will magnify your dose, unless it’s on purpose, like grapefruit or pomegranate juice
I take mine with some liquid. I cannot take them at the same swallow because there are too many, but I wash them down with something or other. Normally not alcoholic, however.
Those are rookie numbers, Beth. I’ve swallowed 20 pills total in one gulp before (I don’t recommend anyone copy this though).
Exactly… my supplements… all at once with milk at bedtime… easily 15 pills… multiple of boron… lithium… lecithin… lol.
HA, I did not say that was my max, now did I 
My epitaph will read:
Died while choking on too many longevity supplements
Thank you all for your wonderful advice and anecdotes.
My current thinking (prone to change with more education) is that I will build up to 6mg or 8mg if I can tolerate it - once a week, and cycle for eight weeks, followed by a four week break.
I am still doing further reading and research, but I am very eager to start on rapamycin in January 2026
Sapper
With a hiatal hernia (swallowing constriction) I grind with water in a blend-jet blender my 3x daily pill regimens. Before my carnivore move I ate raw carrots at work and my swallowing problem had me almost choke many times, trying to eat healthy. I’m with you re choking on pills. ;(
How very scary!!! Do you need to blend your meat or are you good about chewing that really well? I often eat way too quickly and could foresee having a problem.
My only experience with choking was my mom when she had late stage Parkinson’s… it happened too often for comfort. Her aide would give her the heimlich.
See research study using Rapamycin at 1 mg per day and blood testing of subjects regarding T cells still within average range for test subjects after 8 weeks of 1mg per day dose.
I switched to this protocol 2 or 3 months ago and no issues for me or my wife.
No concern about blood levels stabilizing at ~6 ng/mL (per the article)? I remember @DrFraser conjecturing that one should probably spend a max of 1/3 of their time above 3 ng/mL because it results in some degree of immunosuppression. But maybe ~6mg/mL is just fine?
Did you, @Steve_Combi (or your spouse), take any breaks during that 2-3 months?
Time will tell - 6 ng/mL is immunosuppressive, not just immunomodulatory. It’s less risk than having higher levels (such as 12-20 ng/mL) by 30% or so, but there are risks. I’m certainly not going to have this as a protocol for my patients as I don’t think there is evidence of safety - but we’ve got a lot of folks experimenting on this board, and I’m happy to see what happens.
On a speculative therapy, I’d not be pushing it that hard. Rapamycin is one of many great options that probably end up improving length/quality of life. I have enough data at this point to say what I’m doing has at least short term safety in a couple of hundred individuals over a period of 18 months.
What protocol are you doing personally?
Interestingly the study notes on blood work indicate that this level is safe and not immosuppressive:
"The researchers’ first priority was to determine whether a low-dose rapamycin protocol—closer to the longevity-focused “healthspan” regimens than to high-dose transplant protocols—could be administered safely in older adults. All six participants tolerated the 1 mg/day oral dose without incident over the eight-week treatment period. Rapamycin blood levels stabilized at 6.21 ± 1.58 ng/mL after one week and remained consistent through week eight (5.94 ± 1.29 ng/mL, p = 0.67). These values fall within the lower therapeutic range used in transplant medicine but are well below concentrations typically associated with immunosuppression. No participant reported adverse effects related to treatment.
Routine laboratory testing revealed only minor, statistically significant shifts: small decreases in white blood cell count (WBC), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), and slight increases in hemoglobin A1C and low-density lipoprotein cholesterol (LDL). All values remained within normal clinical limits and were judged to be biologically insignificant. Importantly, no cases of hyperglycemia or immune suppression were observed—findings that distinguish this regimen from the metabolic complications often seen with higher-dose, chronic mTOR inhibition.
Taken together, these results confirm that low-dose rapamycin was safe and well tolerated in this cohort of healthy septuagenarian men. The absence of immune compromise or metabolic disruption supports the idea that mTOR can be modulated within a “geroprotective zone”—a therapeutic range that engages longevity mechanisms without crossing into the immunosuppressive territory for which the drug was originally designed."
do you take any breaks?
I agree that it’s immunosuppressive. Mine is 5ng/mL and it provides enough immunosuppression to support my transplanted kidney. Also, it there are no breaks and 1mg/day dose is consistent it will eventually accumulate. I use a simple spreadsheet to trace my levels and have breaks as soon as trough exceeds 5ng/mL.