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Rapamycin (sirolimus)
An FDA-approved mTOR-inhibitor immunosuppressant (sirolimus, Rapamune) taken off-label for longevity. It is the most robustly lifespan-extending compound in animal studies across species, but human longevity benefit is unproven — the human data are short-term immune/biomarker trials, and it carries real immunosuppression risks. A prescription drug, not a supplement.
Prescription medication — not a dietary supplement
Rapamycin is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Most Rapamycin studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 1999–2026 with a typical study size of 218 participants.
Based on 306 studies · 25 meta-analyses · 255 RCTs · 242 total participants
Confidence
High confidenceBy outcome
Rapamycin is the most reproducible lifespan extender in animal models (including late-life dosing in the NIA ITP) and has positive short-term human immune-function trials, but no human study shows it extends lifespan or healthspan, and continuous dosing carries real immunosuppression risks — so the longevity use remains promising-but-unproven and off-label.
307 rigorous studies
257 randomized trials · 29 meta-analyses · 21 systematic reviews
Our evidence rating for Rapamycin is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
174 trials ongoing or recruiting · 580 completed on ClinicalTrials.gov
244 of the completed trials have posted results
Registered trials show research momentum for Rapamycin, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Aug 2026
Rapamycin (sirolimus) is a macrolide produced by Streptomyces hygroscopicus, FDA-approved as an immunosuppressant to prevent transplant rejection and in drug-eluting stents.
It is the best-validated pharmacological lifespan extender in geroscience: inhibiting the mechanistic target of rapamycin (mTOR, specifically mTORC1) it mimics aspects of caloric restriction, enhancing autophagy and dampening anabolic/growth signaling.
In the NIA Interventions Testing Program, rapamycin extended median and maximal lifespan in genetically heterogeneous mice even when started late in life — a result reproduced across yeast, worms, flies and mice, making mTOR inhibition the most reproducible aging intervention known.
The honest gap is human longevity evidence: there are NO trials showing rapamycin extends human lifespan or healthspan.
What exists are short-term randomized trials of mTOR inhibitors (rapamycin and the analog everolimus) showing improved vaccine response and immune function in older adults, plus small safety/biomarker studies (e.g. the PEARL-type trials) suggesting intermittent low doses are tolerated.
Continuous immunosuppressive dosing carries real risks — immunosuppression/infection, stomatitis (mouth ulcers), hyperlipidemia, glucose intolerance, and impaired wound healing — which is why the longevity community uses intermittent (e.g. weekly) low doses, a regimen that is itself unproven.
Rapamycin is a prescription drug used off-label for longevity; it is not a dietary supplement, and self-dosing without monitoring is risky. The score reflects exceptional preclinical evidence and promising human immune data against an absence of human longevity outcomes and genuine immunosuppression risk.
Rapamycin binds FKBP12 and allosterically inhibits mTORC1, the central growth-signaling hub. Reducing mTOR signaling mimics aspects of caloric restriction.
Lower mTOR signaling de-represses autophagy, clearing damaged proteins and organelles — a proposed driver of the longevity effect.
Dampened protein synthesis and cell growth shift cells toward maintenance — beneficial for aging but the basis of immunosuppression and wound-healing effects.
How Rapamycin works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Avoid — mTOR inhibition is contraindicated in pregnancy.
Monitor glucose and lipids; mTOR inhibition can worsen both, especially continuous dosing.
Hold around procedures — impaired wound healing and immunosuppression.
Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit) sharply raise levels; inducers (rifampin) lower them. Dose must account for this.
Immunosuppression can blunt vaccine response and makes live vaccines inadvisable during continuous dosing.
Additive immunosuppression and infection risk.
Tip: Dose-related; often improves with intermittent dosing.
Tip: Monitor lipids; more pronounced with continuous dosing.
Tip: Monitor for infection; hold during acute illness or before surgery.
Tip: Pause around surgery/procedures.
Rapamycin has an evidence score of 4.5/10 — emerging evidence based on 23 indexed studies, including 1 meta-analysis. An FDA-approved mTOR-inhibitor immunosuppressant (sirolimus, Rapamune) taken off-label for longevity. It is the most robustly lifespan-extending compound in animal studies across species, but human longevity benefit is unproven — the human data are short-term immune/biomarker trials, and it carries real immunosuppression risks. A prescription drug, not a supplement. Representative study: PMID 27519886.
The commonly studied dose of Rapamycin is No validated longevity dose. Off-label protocols use intermittent low doses (e.g. ~5–6 mg once weekly) under physician supervision — this is unproven and not an approved regimen. Approved transplant dosing is daily and immunosuppressive.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
Timing is flexible for Rapamycin — consistent daily use matters more than the time of day. Absorption varies with food; consistency matters more than timing.
Rapamycin should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are mouth ulcers (stomatitis), hyperlipidemia, infection (immunosuppression). Use caution if any of these apply to you: Active infection; Pregnancy / breastfeeding; Significant immunosuppression or upcoming surgery (wound healing).
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Berberine
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Likely helpsPlant sterol that reduces BPH urinary symptoms in clinical trials and blocks intestinal cholesterol absorption.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 306 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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