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From animal clinic trials, higher the dosage, better the life extension effect, some experts recommended to up your dosage until side effect shows up.
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Better brain blood barrier pass through in higher dosage of sirolimus.
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My father got autoimmune issues, spinal stiffness inflammatory disease. To avoid the same situation, I believe immunosuppressant is the solution.
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Are you still on this protocol and still no issue?
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I have cycled that 1mg per day schedule.
2 months on 1 month off since then.
I experienced no issues at all when I did this for 3 consecutive months
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How did you find this compared to intermittent?
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Subjectively I’ve never had any “feelings” related to intermittent or continuous dosing with Rapa. No side effects that other people experience either.
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extremely interesting, especially if keeping in mind that RCT where 2 months regime of 1mg per day have increased volume of hippocampus (or maybe another part of a brain, may recollect incorrectly).
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I feel quite good and noticably “younger” if this makes any sense, but it leaves me prone to more respiratory infections. I’m not sure I can justify the good feelings I get for the regular respiratory sickness.
My last hope on this as far as I can think of is reducing the frequency of dosage even more. Maybe once every 2/3/4 weeks.
Never had an issue every 2 weeks but once a week really leaves me vulnerable to sickness it seems. I believe this to be more of a personal issue than a general issue.
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I understand the theory that rapamycin lowers the immune system. But are there any significant studies that back this up in humans?
Was I just born lucky? I have been taking high doses of rapamycin once weekly for almost 5 years and haven’t had as much as a sniffle.
In an n=1 five-year experiment, I find that rapamycin does not compromise my immune system.
Recently, after reading some posts, I decided to try a biweekly dose. I have done this for several weeks, but I find I just don’t feel as good on the biweekly dose. Am I addicted to rapamycin? I have started back on a weekly dose of 6 mg in enteric capsules with GFJ.
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Since the thymus involution and regrowth due to rapamycin in mice, I use rapamycin 6mg once a month or every 45 days it depends. I want to let ly thymus recover and maybe regrow
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I’ve got some autoimmune issues. I think I just need to be more cautious with immune modulators.
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Remember the trough matters. Incidentally the lab has just emailed me after my last blood test because my WBC is under 2. I am pleased.
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A study that might be relevant to this discussion:
Less Is More: Pulsed Rapamycin Shrinks Precancerous Polyps Where Daily Dosing Fails
Thirty patients with familial adenomatous polyposis, an inherited condition that carpets the colon with precancerous polyps and makes cancer nearly inevitable without surgery, took a slow-release oral form of rapamycin for one year across three dosing schedules. The two intermittent schedules reduced polyp burden while the continuous daily schedule did not, and the daily schedule also produced the most toxicity. The largest single result was a median 39 percent reduction in colorectal polyp burden at six months on every-other-day dosing, but that result did not reach statistical significance and patient-to-patient variability was enormous. The trial had no placebo arm, so patients served as their own controls. The authors have selected the one-week-on, one-week-off schedule for a 168-patient phase III trial. This is a safety and dose-selection study that produced a hypothesis, not proof of benefit.
Rapamycin has spent two decades as the most credentialed drug in longevity biology and the most awkward one to actually use. It extends lifespan in every model organism tested, but the continuous dosing that transplant medicine relies on brings immunosuppression, metabolic disruption, and mouth ulcers. The field’s working hypothesis has been that pulsed dosing captures most of the benefit and little of the cost, because intermittent exposure inhibits mTOR complex 1 while largely sparing mTOR complex 2, the branch responsible for insulin resistance and immune suppression. That hypothesis has been tested extensively in mice. It has rarely been tested head to head in humans.
This trial does exactly that, in a population where the biology is unusually legible. Familial adenomatous polyposis is caused by loss of the APC tumor suppressor, which drives Wnt signaling and, downstream, mTOR activation. Patients develop hundreds to thousands of colorectal adenomas and face near-certain colorectal cancer without prophylactic colectomy. Even after surgery, polyps continue growing in the retained rectum, ileal pouch, and duodenum, requiring endoscopy every year for life. There is no approved drug for these patients.
Investigators at Brooke Army Medical Center and seven other centers gave thirty patients a 0.5 mg encapsulated rapamycin formulation on one of three schedules: every other day, one week on and one week off, or every day. They measured polyp burden by endoscopy at six and twelve months against each patient’s own baseline.
The pattern was consistent and unexpected in direction. The every-other-day group showed the largest six-month reduction in colorectal polyp burden at a median of 39 percent. The one-week-on group showed the largest twelve-month reduction at 29 percent. The daily group showed no reduction at either timepoint and in fact showed net progression, despite receiving the highest drug exposure and having the best pill compliance. Intermittent dosing beat daily dosing on duodenal polyp burden at six months and on total polyp burden at twelve months.
Toxicity followed the same gradient. Nearly half of all participants had a grade 3 or higher adverse event. Treatment-related grade 3 events occurred in 40 percent of the daily group versus 10 percent of the intermittent groups. More drug produced more harm and less benefit.
The caveats are severe. Ten patients per arm, no placebo, open label, and only one of the many polyp burden comparisons reached conventional statistical significance. What this trial establishes is a tolerable dose and a testable schedule. Whether it prevents cancer or surgery is the phase III question.
Context and Source
Paywalled paper: Phase II Trial of Encapsulated Rapamycin to Reduce Polyp Burden Associated with Familial Adenomatous Polyposis
Authors: Broderick JC, Samadder NJ, Stoffel E, Fang JC, Stanich PP, Wise P, Wright R, Clifton T, Peoples G, Burke CA
Journal: Clinical Cancer Research, volume 32, issue 15, pages 3146 to 3156, August 1, 2026.
Lead institution: Brooke Army Medical Center, Department of Surgery, Fort Sam Houston, Texas, United States. Multicenter with Mayo Clinic Arizona, University of Michigan, University of Utah, Saint Louis University, Ohio State University Wexner Medical Center, UT Health San Antonio, LumaBridge, and Cleveland Clinic.
Journal impact: The impact score of this journal is 10.9 (2025 Journal Impact Factor; CiteScore 19.8), evaluated against a typical high-end range of 0 to 60+ for top general science, therefore this is a High impact journal.
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Yeah… years ago I overdosed rapamycin for 7 months 17 mg = 51 ng/mL.
Bad on my bio-markers. Would expect daily 1 mg rapamycin to not be good ether.
I like my 6 mg weekly. Just hit 5 full years dosing. Lol.
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Interesting. I wonder what @DeStrider thinks about this. This again points to how important it is to get the dosing and protocol right. Not the best study, but something is better than nothing.
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Unfortunately, Rapamycin hasn’t had a noticeable effect on my polyps in terms of quantity. I’m not sure if it affected their size.
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Have you contemplated adjusting the dose to see if it affects the # of polyps or their size? You should have the records of every colonoscopy - number of polyps removed, their sizes and pathology characterization. Presumably you can go through your records and see patterns if there are any.
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IMO it’s not the dose but rather trough that affects everything. Ppl can be on the same dose, let’s say 6 mg/week like @Agetron, but their trough could be different.
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True… true.
If your system clears the rapamycin fast … more weekly or every other day low dose 1 mg might not be an issue.
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