Rapamycin for Health & Longevity

Created on 10/23/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5.5 – Audit

Rapamycin is a prescription medication used to prevent kidney transplant rejection; some adults take it once weekly, outside its approved uses, hoping to slow aging. It extended lifespan in laboratory animals, but small human studies show mixed signals and none has shown longer or healthier human lives. Mouth sores, modest rises in blood fats and blood sugar, and more minor side effects are documented; the long-term payoff is unknown. (Full Review)

Protocol

Weekly commercial sirolimus
6 mg once weekly
Most common dose among surveyed weekly users; range 1–20 mg
Weekly compounded rapamycin
5 or 10 mg weekly
Compounded capsules delivered about 31% of the blood level per milligram; doses not interchangeable
Time of day
Morning, fixed weekday
No study compares timing; common practice, taken consistently with or without food
Time to effect
Body composition
24 and 48 weeks
Signals only; no outcome benefit has a defined onset
Vaccine response
After 6 weeks
Seen with everolimus, a rapamycin derivative
Lifespan
Not observable in an individual
No human lifespan data exist

Benefits

Contraindications
  • Hypersensitivity to sirolimus
  • Pregnancy, breastfeeding, or women of reproductive potential without highly effective contraception during use and for 12 weeks after the last dose
  • Liver or lung transplant recipients (boxed warning)
  • Children under 13 years
  • Anemia (hemoglobin below 9.0 g/dL), leukopenia (white cells below 3,500/mm³), neutropenia (neutrophils below 2,000/mm³) or thrombocytopenia (platelets below 125,000/mm³)
  • Chronic infections requiring ongoing treatment (e.g., human immunodeficiency virus)
  • Immune deficiency
  • Major surgery within 12 months or chronic open wounds
  • Untreated dyslipidemia (e.g., total cholesterol above 350 mg/dL or triglycerides above 880 mg/dL)
  • Poorly controlled (HbA1c above 7%) or insulin-dependent diabetes
  • Glomerular filtration rate below 30
  • Impaired liver function
  • Severe hepatic impairment (Child-Pugh C) unless the dose is reduced and levels monitored
Key Interactions
  • Strong CYP3A4/P-gp inhibitors (ketoconazole, clarithromycin, erythromycin): Avoid; raise sirolimus exposure
  • Other label-listed CYP3A4/P-gp inhibitors (diltiazem, verapamil, fluconazole): Monitor; raise sirolimus exposure
  • Strong CYP3A4/P-gp inducers (rifampin, rifabutin): Avoid; cut sirolimus exposure
  • Other label-listed CYP3A4/P-gp inducers (carbamazepine, phenytoin): Caution; can lower sirolimus levels
  • Calcineurin inhibitors (cyclosporine, tacrolimus): Caution; cyclosporine raises sirolimus levels (sirolimus taken 4 hours after it)
  • ACE inhibitors (such as lisinopril, ramipril): Caution; co-use increases angioedema
  • Statins and fibrates (such as atorvastatin, fenofibrate): Monitor for muscle symptoms
  • Live vaccines (measles-mumps-rubella, yellow fever, varicella): Avoid during treatment
  • Cimetidine and clotrimazole: Monitor; raise sirolimus concentrations
  • Cannabidiol (CBD): Monitor; can raise sirolimus levels
  • St. John's wort: Caution; can lower sirolimus levels
  • Grapefruit juice: Avoid per label; raises sirolimus exposure
  • Resveratrol: Monitor
  • Supplements with additive mTOR-suppressing or CYP3A4-inhibiting effects (berberine, goldenseal): Caution (theoretical)
  • High-fat meals: Monitor; raise sirolimus exposure
  • Surgery and dental procedures: Caution; impaired wound healing
  • Resistance and endurance training: Monitor; trended toward smaller functional gains

Risk & Side Effects

  • High: [risks_high]
  • Medium: Mouth ulcers; raised blood lipids; raised blood glucose; gastrointestinal, joint and muscle pain, and other minor adverse events; blood cell count changes; skin rash and acne
  • Low: Fluid accumulation and impaired wound healing; infections; increased mortality in kidney transplant recipients; reduced testosterone and fertility; proteinuria; venous thromboembolism; veno-occlusive disease and thrombotic microangiopathy after stem-cell transplantation; lymphoma and other cancers; interstitial pneumonitis; liver injury; hypersensitivity and angioedema; posterior reversible encephalopathy syndrome; blunted exercise gains; raised blood pressure
  • Speculative: Embryo-fetal harm; rise in brain-injury biomarkers; gut dysbiosis

Monitoring

Marker Target Why
Sirolimus whole-blood level (48 hours post-dose) No established target; track own level after each dose or product change Confirms exposure
LDL cholesterol No established target; track change from own pre-treatment baseline A rise prompts diet, drug or dose change
Total cholesterol Not specified in the ER Paired with LDL; may rise
Triglycerides No established target; track change from own pre-treatment baseline A rise prompts diet, drug or dose change
HbA1c No established target; track change from own pre-treatment baseline Safety check; may rise
Fasting glucose 65–99 mg/dL Rising values prompt dose review
Hemoglobin and platelets (complete blood count) Hemoglobin 13.2–17.1 g/dL (men), 11.7–15.5 g/dL (women); platelets 140–400 ×10⁹/L Falls prompt pause or dose reduction
Mean red-cell volume Not specified in the ER Red cells may shrink
White blood cell count 3.8–10.8 ×10⁹/L Low counts raise infection risk
BUN and creatinine BUN 7–25 mg/dL; creatinine 0.6–1.3 mg/dL Kidney function
Urine protein-to-creatinine ratio Below 0.2 g/g Proteinuria prompts dose review
Liver enzymes (ALT, AST) ALT about 7–55 U/L, AST about 8–48 U/L (lab-specific) Liver impairment raises drug exposure
Total testosterone (men) 264–916 ng/dL Decline may prompt dose review

Cadence: Baseline before the first dose; 2 and 4 weeks after starting, then 24 and 48 weeks; every 3–6 months once values are stable (common practice). Sirolimus level rechecked after any change of dose, product or interacting drug.

Qualitative Assessment

  • Frequency and severity of mouth ulcers
  • Frequency and duration of infections, and recovery time from minor illness
  • Healing speed of minor cuts and dental work
  • Energy, exercise performance and recovery from training
  • Gastrointestinal comfort (nausea, diarrhea)
  • Menstrual regularity in women; libido and morning erections in men
  • Self-rated general health and bodily pain