Rapamycin
Sirolimus
Rapamycin (Sirolimus) is a longevity & bioregulators research compound. mTOR inhibitor — intermittent inhibition of mTORC1 upregulates autophagy and mimics caloric restriction; the most-studied longevity small molecule.
Rapamycin quick facts
| Reported research dose | 1mg-6mg |
| Route | Oral |
| Frequency | 1x Weekly |
| Half-life | ~60 hrs |
| Forms | Oral |
| Evidence level | FDA-approved (transplant); longevity off-label |
Weekly/pulsed, NEVER daily for longevity — the schedule is the whole game. Overdo it and you're just immunosuppressed.
How Rapamycin works
mTOR inhibitor — intermittent inhibition of mTORC1 upregulates autophagy and mimics caloric restriction; the most-studied longevity small molecule.
Proposed benefits
Researched for mitochondrial and cellular-energy support, tissue-specific bioregulation and healthy-aging pathways.
Where to get Rapamycin
Buy Rapamycin at AlgoRx →The evidence for Rapamycin
Graded by what exists behind each claim.
✅ Clinically validated
- FDA-approved since 1999 as sirolimus, for prevention of kidney transplant rejection, with extensive trial data at immunosuppressive doses. Also approved for lymphangioleiomyomatosis and used on drug-eluting coronary stents.
- The longevity use is off-label and not proven in humans. The strongest human hint is a Novartis trial of the rapalog everolimus in adults over 65, which reported improved influenza vaccine response — an immune-ageing endpoint rather than a lifespan one. Trials in dogs (the Dog Aging Project) and human pilots are ongoing.
📊 Correlative data
- The most-replicated lifespan result in mammalian biology — the NIA Interventions Testing Program extended median lifespan in mice across multiple independent sites, including when started in old age.
- Human off-label use for longevity runs at intermittent weekly dosing rather than daily, on the reasoning that it separates the mTORC1 effect from the mTORC2 effects that cause the transplant-dose side effects. That separation is a hypothesis, not a demonstrated fact — the dosing has never been validated against any hard human endpoint.
🧪 Theoretical / extrapolated
- Inhibits mTORC1 by binding FKBP12. mTOR is the cell's nutrient sensor: when it is active, the cell builds; when it is inhibited, the cell switches to autophagy — recycling damaged proteins and organelles. Accumulated cellular damage is a central ageing mechanism, so this is the most mechanistically coherent longevity target that exists.
- The predicted downsides come from the same mechanism. Suppressing building means suppressing immune cell proliferation, wound healing and muscle protein synthesis — which is why it causes immunosuppression, impaired healing, mouth ulcers and dyslipidemia at chronic doses.
- Chronic dosing also inhibits mTORC2, which drives the insulin resistance seen in transplant patients. The whole case for intermittent dosing rests on avoiding that, and the whole uncertainty rests on nobody having proven it does.
How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →
What Rapamycin actually does
Rapamycin is not an mTOR inhibitor in the way that phrase implies. It is an allosteric inhibitor of ONE of the two complexes mTOR forms, and the entire longevity protocol is an attempt to keep it that way. The drug first binds the immunophilin FKBP12; that complex is the actual inhibitor, and it binds the FRB domain of mTOR within mTOR complex 1. It does not block the kinase site. It sits alongside it and sterically restricts substrate access, which is why the inhibition is partial and substrate-selective: S6 kinase 1 is strongly inhibited, 4E-BP1 much less so.
mTORC2 is a different complex with a different partner protein, RICTOR, and rapamycin does not bind it acutely. That is the whole mechanistic basis of intermittent dosing. With prolonged exposure, however, newly synthesized mTOR is captured by FKBP12-rapamycin before it can assemble into mTORC2, so mTORC2 is gradually depleted in a cell-type- and duration-dependent way Ballesteros-Álvarez 2021. mTORC2 is the complex that phosphorylates AKT at serine 473 and carries insulin signaling. So the glucose intolerance and the insulin resistance people fear on rapamycin are not a dose effect. They are a DURATION effect, and duration is the variable a weekly schedule controls.
What inhibiting mTORC1 actually does downstream. mTORC1 is the nutrient and growth-factor sensor: amino acids signal to it through the Rag GTPases at the lysosome, growth factors through PI3K-AKT and the TSC complex, and energy status through AMPK. When it is active it drives cap-dependent translation and ribosome biogenesis and it phosphorylates ULK1 to suppress autophagy. Inhibit it and autophagy is released. That single switch — protein synthesis down, cellular self-clearance up — is the entire geroprotective hypothesis, and it is why the intervention is about a trade rather than about a benefit.
Cell, rodent, human — and where it stops
Step one, rodents, where the schedule question was actually answered. The pivotal work is not about whether rapamycin extends lifespan — it is about whether you can keep the lifespan effect and drop the costs. Alternative regimens showed reduced impact on pyruvate tolerance, fasting glucose and insulin, beta cell function and the immune system compared with daily treatment Arriola Apelo 2016, and intermittent feeding recapitulated some effects of continuous treatment while maintaining lifespan extension Baghdadi 2024. That is the primary literature behind the weekly protocol, and it is stronger than most people who run it realize.
Step two, the rodent result that complicates it. Chronic rapamycin attenuated age-related motor deficits in UM-HET3 mice in a sex-dependent manner Singh 2026. The healthspan benefits, like the lifespan benefits of several interventions in this mouse stock, are not the same in both sexes — and no protocol circulating in this space adjusts for that, because nobody knows how it would translate.
Step three, humans, and this is where the Vault page has been years out of date. PEARL randomized healthy adults to low-dose intermittent rapamycin for 48 weeks. It reported significant improvements in lean tissue mass and reduced self-reported pain in women receiving 10 mg weekly, improvements in general health and emotional well-being at 5 mg, and adverse events similar across all groups Moel 2025. That is a randomized, placebo-controlled, year-long human safety and healthspan trial of exactly the protocol this page describes, and it exists.
Step four, the obstacle — and it turns out to be a measurement problem rather than a biology problem. Blood levels were measured in real-world longevity users: commercial rapamycin showed a linear dose-to-blood relationship across 44 participants at 2–8 mg, while compounded formulations across 23 participants at 5–15 mg had lower bioavailability per milligram, estimated at 31.03% of the same dose of commercial Harinath 2025. A compounded 15 mg dose is not a bigger dose than a commercial 5 mg dose — it is roughly the same one. Every protocol quoted in milligrams is silently assuming a formulation, and a third of the people running one are taking something else.
Rapamycin pharmacokinetics — how much of it actually gets in
The card says ~60 hours. That number is the reason a weekly schedule is arithmetically possible, and it is worth showing the calculation.
What clears it. Rapamycin is a large macrolide cleared almost entirely by CYP3A4, in both the gut wall and the liver, and it is a substrate for P-glycoprotein, which pumps it back into the intestinal lumen during absorption. Those two together are why oral bioavailability is low and variable — on the order of 15% — and why the interaction list is long and consequential: grapefruit juice, azole antifungals, macrolide antibiotics and diltiazem raise exposure; rifampicin, carbamazepine and St John's wort lower it. This is the drug in the cohort where a food or a supplement genuinely changes the dose.
The oral barrier and the formulation problem, quantified. Because absorption is gut-wall-limited rather than solubility-limited, formulation matters enormously, and it has now been measured: compounded preparations delivered about 31% of the blood level of the same milligram dose of the commercial tablet Harinath 2025. That is a threefold error hidden inside every dose recommendation that does not name the product.
The arithmetic of a weekly window, done out loud. With a ~60 hour half-life, a weekly dose has decayed through roughly 2.8 half-lives by the next one, leaving about 14% on board — so there is minimal accumulation and a genuine trough. That trough is the point: mTORC1 inhibition is re-established each week, and mTORC2 is given days of uninhibited assembly in between, which is precisely the mechanism by which intermittent dosing spares glucose handling Arriola Apelo 2016 Ballesteros-Álvarez 2021. Daily dosing removes the trough and, with it, the whole rationale.
The comparator, and it is not an injection. There is no injectable rapamycin in this context; the meaningful comparator is the transplant dosing regimen, which is daily and targets a whole-blood trough concentration. That is the exposure at which immunosuppression, mouth ulcers and dyslipidemia are expected — and it is a completely different pharmacokinetic state from a weekly pulse, which is why transplant adverse-event rates should not be quoted directly onto a longevity protocol.
What would have to be true, and how you would know it was not
Three predictions with markers, directions and windows. The second is the one almost nobody in this space runs; the third cuts against the intervention.
1. Sirolimus level is the missing measurement, and it is a routine, cheap, widely available assay. Sirolimus (rapamycin), whole blood is ordered every day in transplant medicine. The real-world data shows a linear dose-to-level relationship for commercial product and roughly a third of that per milligram for compounded Harinath 2025. Draw it 24 hours after a dose, once, early. Prediction: people on compounded product will be far lower than they assume, and some on commercial product at higher doses will be higher. This single test converts a milligram protocol into an exposure protocol, and it is the highest-value blood draw on this page.
2. The lipid panel should drift upward and fasting insulin should not — and the gap between them is the test of whether the schedule is working. Rapamycin raises triglycerides and LDL reliably at continuous exposure; mTORC2 depletion drives the insulin resistance and it is duration-dependent Ballesteros-Álvarez 2021 Arriola Apelo 2016. Draw a lipid panel, ApoB, fasting insulin and HbA1c at baseline, 12 weeks and 24 weeks. Prediction on a weekly schedule: some lipid drift, flat insulin and flat HbA1c. If fasting insulin climbs, the schedule is not delivering the trough it is designed around and the interval, not the dose, is the thing to change.
3. The prediction that cuts against it: immune measures are the cost, and they are measurable rather than theoretical. mTORC1 inhibition is immunomodulatory by design. Order a CBC with differential and a lymphocyte subset panel at baseline and 24 weeks. PEARL reported adverse events similar across groups over 48 weeks Moel 2025, which is genuinely reassuring at that dose and duration — but it is one trial, and the population running this off-label is older, longer-exposed and mostly unmonitored. A falling lymphocyte count, delayed wound healing or recurrent mouth ulcers are the mechanism showing up, not bad luck.
What nobody has tested yet
Four questions with no answer, and the first is the one everyone assumes has been settled.
Nobody knows the optimal interval. The rodent work established that intermittent beats daily Arriola Apelo 2016 Baghdadi 2024; PEARL tested weekly at two doses Moel 2025. Whether every 10 days, or every two weeks, or a cyclical block schedule preserves the autophagy benefit while further sparing mTORC2 has never been compared in any species. The weekly interval is a convention, not a result.
Nobody has paired sirolimus levels with outcomes in a longevity cohort. The levels have now been measured Harinath 2025 and the outcomes have now been measured Moel 2025, in different studies. Putting them together — does exposure predict who improves? — is an analysis waiting for a dataset that half exists.
Nobody has resolved the sex question in humans. Chronic rapamycin's motor-deficit benefit was sex-dependent in mice Singh 2026, and PEARL's lean-mass and pain findings were reported in women at 10 mg weekly Moel 2025. Whether men and women should run different doses or different intervals is completely open, and it affects half of everyone taking it.
Nobody has measured autophagy in a person on this protocol. The entire mechanistic case is that mTORC1 inhibition releases autophagy. Autophagic flux markers are measurable in peripheral blood mononuclear cells. No published study has confirmed that a weekly oral dose in a healthy adult actually does the thing the whole rationale depends on.
Rapamycin — its own safety story, not its class's
This drug's risk story is entirely about exposure duration, and the class block below cannot express that because no other compound in the Vault has this shape.
The distinction that governs everything: mTORC1 inhibition is the intervention, mTORC2 depletion is the toxicity, and only the second is duration-dependent. Ballesteros-Álvarez 2021 Arriola Apelo 2016. That is why a weekly protocol is not a lower dose of a transplant regimen — it is a different pharmacological state. It is also why the failure mode is not overdose but schedule creep: moving from weekly to twice weekly to daily, a step at a time, converts a geroprotective protocol into immunosuppression without any single step feeling like a change.
The infection question, stated at the right size. PEARL found adverse events similar across groups over 48 weeks Moel 2025, which is the best available evidence that weekly low-dose exposure is not meaningfully immunosuppressive in healthy adults. Against that, mTORC1 inhibition does modulate T-cell responses, and the honest framing is: the trial data is reassuring for that dose and duration, the mechanism is real, and the people most likely to be running this off-label are older than the trial population and less monitored.
Wound healing and surgery are the concrete, plannable risk. Impaired wound healing is a documented effect of mTOR inhibition and it is the reason transplant protocols hold the drug around surgery. With a ~60 hour half-life, holding a weekly dose for two to three weeks before an elective procedure clears essentially all of it — which makes this a manageable interaction rather than a contraindication, provided the surgical team is told. They will not know unless they are.
The interaction risk here is unusually large and unusually ordinary. CYP3A4 and P-glycoprotein carry the clearance, so grapefruit, azole antifungals, clarithromycin and diltiazem all raise exposure substantially, and the whole schedule argument depends on exposure. A CYP3A4 inhibitor does not just raise the peak — it lengthens the tail, which is precisely the variable that determines mTORC2 depletion. That is the single most consequential interaction in this cohort and it can be caused by a breakfast drink.
Mouth ulcers are the early warning and they are worth knowing by name. Aphthous stomatitis is the commonest and earliest dose-related effect of mTOR inhibition, it appears before the metabolic changes, and it is a direct signal that exposure has risen. Rapamycin is a prescription medicine; none of this is medical advice or a recommendation for use.
Sources read for this page
- Moel M, et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging (Albany NY) 2025 · PMID 40188830
- Harinath G, et al. The bioavailability and blood levels of low-dose rapamycin for longevity in real-world cohorts of normative aging individuals. GeroScience 2025 · PMID 39873920
- Arriola Apelo SI, et al. Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system. Aging Cell 2016 · PMID 26463117
- Baghdadi M, et al. Intermittent rapamycin feeding recapitulates some effects of continuous treatment while maintaining lifespan extension. Molecular Metabolism 2024 · PMID 38360109
- Singh R, et al. Chronic rapamycin treatment attenuates age-related motor deficits in sex-dependent manner in UM-HET3 mice. Journals of Gerontology Series A 2026 · PMID 41863332
- Ballesteros-Álvarez J, et al. mTORC2: The other mTOR in autophagy regulation. Aging Cell 2021 · PMID 34250734
Rapamycin — safety, from the human record
Not a prediction. This one has been studied in people. What follows is drawn from the human record — trials, labels and pharmacovigilance — rather than from what the mechanism implies. Where the way it is used here differs from what was studied, the card says so. How evidence is graded here →
What the mechanism predicts
Derived from the molecule, not a trial.
- Inhibiting mTORC1 upregulates autophagy and reproduces much of the transcriptional signature of caloric restriction. That is the longevity argument and it is the best-evidenced one in the whole field in animals.
- The same mechanism predicts the problem no other profile in this file is written to warn about: mTORC1 is required for lymphocyte proliferation, so inhibiting it is immunosuppression. That is not a side effect discovered in trials — it is the licensed indication. Sirolimus exists to stop people rejecting transplanted organs.
- Continuous dosing also inhibits mTORC2, which is where the insulin resistance and dyslipidemia come from. The intermittent weekly schedule used in longevity protocols is an attempt to hit mTORC1 and spare mTORC2 — a coherent hypothesis with limited human confirmation.
What has actually been reported
- In transplant use at continuous doses: mouth ulcers (stomatitis), impaired wound healing, hyperlipidemia, hyperglycemia, proteinuria, cytopenias, peripheral edema and a raised rate of infection. Non-infectious pneumonitis is uncommon and serious.
- Stomatitis is the most common complaint at intermittent longevity doses and is usually the first thing to appear.
- In older adults, a rapalogue improved the antibody response to influenza vaccination in a randomized trial — the strongest human evidence that intermittent mTOR inhibition can enhance rather than suppress an immune response. It was a different molecule and a specific endpoint, and it is the reason the field takes the intermittent schedule seriously.
How to reduce the risk
Same mechanism as the prediction.
- Treat any fever or infection as a reason to pause and seek advice, not to push through. This is the single most important line here.
- Stop it well before elective surgery and until wounds have healed, on a clinician's timing.
- Baseline and periodic lipids, glucose, CBC, CMP and urine protein — every one of the predicted problems is invisible without them.
- No grapefruit, and check every new medicine against CYP3A4 before adding it.
- This is a prescription immunosuppressant. Running it without a clinician who knows you are on it is the version of this that goes wrong.
What it does to your bloodwork
A fact about the assay.
- A full lipid panel with ApoB, fasting glucose and HbA1c — hyperlipidemia and hyperglycemia are the two metabolic effects most likely to appear.
- CBC for cytopenias, CMP for liver and kidney, and a urinalysis for protein — proteinuria is a recognized effect and is silent.
- See the sirolimus marker page for why the drug level printed on a lab report is a transplant target and not a longevity one. There is no established therapeutic range for this use.
What it overlaps with
- Strong CYP3A4 and P-glycoprotein inhibitors — including ketoconazole, clarithromycin and grapefruit juice — raise exposure substantially, and strong inducers such as rifampicin cut it. This is the interaction class that turns a modest dose into a large one.
- Stacking it with any other immunosuppressive or with a senolytic is compounding effects on the same immune axis.
Don't run this if
- Active infection of any kind, and the period around any surgery or significant wound — impaired healing is a documented effect, not a theoretical one.
- Pregnancy, breastfeeding or trying to conceive.
- Live vaccines, unless the timing has been planned with a clinician.
- Poorly controlled diabetes or dyslipidemia, without monitoring.
The honest unknown
- Whether intermittent dosing in healthy people is net beneficial, and at what interval. There is no human lifespan or healthspan trial. The dose-response for the immune effect appears to be biphasic — low intermittent exposure enhanced vaccine response while continuous exposure suppresses immunity — and nobody can currently tell you where the line is for an individual. Unproven is not ineffective; it is also not safe by default.
Not medical advice. If you take prescription medication or have a diagnosed condition, check this with a pharmacist or doctor.
Rapamycin — interference & stacking
Predicted from mechanism, not from an interaction study. How mechanism-predicted claims are made →
What Rapamycin moves on your bloodwork
Expected direction, not a measured one.
- hs-CRP (High-Sensitivity C-Reactive Protein) — ↓ expected to fall
Where these work, systemic inflammation is the plausible readout.
What to do: hs-CRP is cheap and moves. Baseline and 12 weeks. - HbA1c (Hemoglobin A1c) — ↓ expected to fall
Improved mitochondrial and metabolic function should show here if the effect is real at all.
What to do: The honest use of these markers is as a falsification test: if nothing moves in 12 weeks, the compound is not doing much for you. - Comprehensive Metabolic Panel (CMP) — ◆ worth watching
Liver and kidney function — the standard baseline for anything run long term.
What to do: Twice a year is enough on a stable protocol.
This class is where honest expectation-setting matters most: the markers above are how you find out whether anything happened, and for most of these compounds that question is genuinely open.
- How to work up to it, and when not to
- When to take it, and why that window
- Cycle length
- Time off between cycles
- Fasted or fed, and when in the day
- Coach Cam's personal notes
- Which compounds push the same lever, and why the dose adds up faster than people count
- What blunts it — the stacks that waste your money
- What compounds the risk, so a side effect arrives sooner than any one of them suggests
- Coach Cam's read on running it alongside the rest of your protocol
Everything above is free and stays free. Skool is where it becomes a plan — Rapamycin in an order, with the rest of what you're running.
Unlock in Skool — $10/mo →Bloodwork to run alongside Rapamycin
Baseline first, then again at 8–12 weeks.
| Marker | What it’s watching for |
|---|---|
| Lipid Panel (Cholesterol, HDL, LDL, Triglycerides) | Raises triglycerides and LDL in a large share of users. Expect it |
| HbA1c (Hemoglobin A1c) | Impairs glucose tolerance — the trade-off nobody mentions |
| Complete Blood Count (CBC) with Differential | Immunosuppressant. Watch white cells and platelets |
| Comprehensive Metabolic Panel (CMP) | Liver, kidney and electrolytes |
| Sirolimus (Rapamycin), Whole Blood | Rapamycin IS sirolimus — trough levels are how it's actually dosed |
The Longevity Baseline panel covers these in one order — 13 markers, $219.10 with the discount applied.
Check results you already have → · All 103 markers A–Z
Rapamycin — frequently asked questions
What is Rapamycin?
Rapamycin (Sirolimus) is a longevity & bioregulators research compound. mTOR inhibitor — intermittent inhibition of mTORC1 upregulates autophagy and mimics caloric restriction; the most-studied longevity small molecule.
Is the full Rapamycin protocol on this page?
The reported research dose is on this page, along with how Rapamycin works and the evidence behind it. The protocol — how to work up to it, frequency, cycle length, time off, what not to stack it with and Coach Cam's notes — is inside Skool.
What is the half-life of Rapamycin?
Rapamycin has an approximate half-life of ~60 hrs, which is part of what determines how often it's dosed.
What's the evidence behind Rapamycin?
Current evidence level: FDA-approved (transplant); longevity off-label. Rapamycin is offered for research purposes only and is not an approved medicine.
Rapamycin inside a finished plan
One arm of 1 Protocol Blueprint, free to read in full.
What Rapamycin is used for
Rapamycin appears under 1 goal in the goal router.
Related Longevity & Bioregulators compounds
Where this goes next
Rapamycin is the nutrient-sensing arm of this plan. The page above is the free breakdown of one compound; the plan it belongs to — the dosing, the order to correct things in, the week-by-week schedule and what to retest — is a lesson inside Skool.