Saw a healthspan posting about a study of Rapamycin’s effect on aging hearts. Study had people taking 1mg per day rather than a weekly dose. Most people on this site are taking a weekly dose rather than a daily dose it seems. Any thoughts on this? See below link to article and excerpt concerning dosing.
"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."
I actually just read that same article this morning myself. It definitely explained it exceptionally well and gave me a better understanding of exactly what the study showed. It’s very interesting that they used a 1mg daily dose. Perhaps low daily dosing isn’t such a bad strategy like we thought it was. I’m curious what other people think.
We don’t really know. My view is that the target is a “spring clean” of selective mitophagy and the key factor is the intensity of mTOR inhibition. My view also is that most of the time you don’t want mTOR inhibition. Hence I go for a really high dose, but really infrequently (currently at least 6 weeks between doses).
Different people have different views and we don’t have comparative results to enable us to come to solid conclusions.
Why would it be bad? Over the past two years I took rapamycin at 1 mg daily with brief weekly breaks. I had no adverse effects. My labs improved especially inflammatory markers and both total cholesterol and LDL dropped below baseline eventually. Glucose control stayed the same. I also gained muscle and saw measurable improvements in strength, endurance, and VO2max while on it.
True, but most animal lifespan work used chronic rapamycin; dogs were 3×/week; the human everolimus vaccine study had daily and weekly arms. Weekly rapamycin is a pragmatic choice IMO to balance effects and side effects (avoiding sustained mTORC2 inhibition while still getting multi-day exposure thanks to rapamaycin’s long half-life and oncology’s experience with weekly mTOR inhibitors), not settled doctrine. We currently have far more data on chronic administration than on intermittent schedules.