Of all the longevity compounds I’ve personally run on myself, rapamycin is the one I respect the most and the one I’d warn the most people to stay away from. That’s not a contradiction. It’s the honest read on a drug that has the strongest evidence in any organism we’ve ever tested for actually extending lifespan, and the most complicated risk profile for anyone using it off-label.
I’ve been pulsing rapamycin for almost two years now. I’ve got bloodwork. I’ve got body composition data. I’ve got subjective notes. I’m going to walk you through what I learned, what I’d do differently, and what my current protocol looks like.
What rapamycin actually is
Rapamycin (sirolimus) is an FDA-approved immunosuppressant originally used to prevent organ rejection after transplant. It was discovered in a soil sample on Easter Island — Rapa Nui — in 1972, hence the name. It works by inhibiting mTOR, the mechanistic target of rapamycin, a protein kinase that acts as a master switch between growth mode and repair mode in nearly every cell in your body.
When mTOR is high, your cells are building, growing, dividing. When mTOR is low, your cells are recycling damaged components through autophagy, repairing DNA, and conserving energy. Modern life keeps mTOR pegged high — too much protein, too many calories, not enough fasting. Rapamycin is the most powerful pharmacological tool we have for transiently turning that signal down.
The longevity evidence
This is the part that turned me from skeptic to user. Rapamycin has extended median and maximum lifespan in every species it has ever been tested in. Yeast. Worms. Flies. Mice. Marmosets. The mouse data is the most striking — Interventions Testing Program (ITP) studies at the National Institute on Aging have shown 10–25% lifespan extension in mice, even when dosing started at the equivalent of mid-life in human terms.
There is no human lifespan data yet, because humans live too long for the trial. But the biomarker data, the dog longevity trial (TRIAD), the immune-rejuvenation work, and the targeted indications (Roy Walford’s protégés, the AgelessRx prescriber network, the Blagosklonny model) all point in the same direction. This isn’t a supplement. It’s a real drug with a real mechanism that does what it claims to do.
My protocol — 6 mg weekly, pulsed
Daily rapamycin is what transplant patients take, and it’s also what produces the worst side effects — mouth ulcers, immune suppression, metabolic dysregulation, insulin resistance. The longevity community figured out years ago that weekly pulsing largely sidesteps those issues while preserving the autophagy and senolytic benefits.
Here’s the exact protocol I’m currently running, after a year of titrating up from a starting dose of 3 mg.
Dose: 6 mg sirolimus, taken once weekly on Sunday morning. Empty stomach, water only, no food for 2 hours before or 2 hours after. Rapamycin absorption is highly variable and concomitant food, especially fat, can multiply blood levels unpredictably.
Co-ingestion: 200 mg of grapefruit-derived bioflavonoids, or a small glass of grapefruit juice. This boosts bioavailability about 3.5x through CYP3A4 inhibition, which lets me use a lower nominal dose for the same biological effect. I lean on the bioflavonoids for predictability — grapefruit juice variability is real.
Off-cycle every 12 weeks: one week off, full week. The purpose is to let mTORC2 fully re-establish if it was getting partially inhibited. Long-term low-dose weekly rapa eventually starts touching mTORC2 in some users, and mTORC2 inhibition is what drives the metabolic side effects.
Training days around dose day: heavy resistance training Saturday, rest day Sunday, light cardio Monday. Because rapamycin transiently blunts muscle protein synthesis, I keep the heavy hypertrophy work in the 5-day window after the dose has cleared.
What my bloodwork looks like
The most important markers to watch on rapamycin are fasting glucose, fasting insulin, lipid panel (especially triglycerides), and white blood cell count. I run a quarterly panel.
Pre-rapamycin baseline (2 years ago): Fasting glucose 92, fasting insulin 6.2, HOMA-IR 1.4, total cholesterol 178, triglycerides 88, HDL 58, LDL 102, WBC 6.8.
Six months into 6 mg weekly: Fasting glucose 96, fasting insulin 5.8, HOMA-IR 1.4, total cholesterol 195, triglycerides 124, HDL 54, LDL 116, WBC 6.2.
Current (18 months in): Fasting glucose 94, fasting insulin 5.4, HOMA-IR 1.3, total cholesterol 188, triglycerides 109, HDL 56, LDL 110, WBC 6.5.
Translation: my metabolic markers held steady, my lipids took a brief hit and came back, my immune cell count is unchanged. This is roughly what the rapamycin longevity literature predicts for a healthy, lean, active user on a weekly pulse. It is not what you see in transplant patients on daily dosing.
The subjective stuff
Bloodwork is one thing. Feel is another. Here’s what I noticed.
Within the first month: Slightly more vivid dreams the night of the dose. Modest reduction in joint inflammation — I have a chronically grumpy left shoulder from years of bench pressing and the achiness dropped noticeably. No mouth ulcers, no GI symptoms.
By month three: Body composition started shifting slightly toward leaner without any change in training or diet. I assume this is autophagy doing its job clearing damaged cells. My visceral fat measurement on DEXA dropped meaningfully.
By month six: Subjective recovery from training felt better. Bouncing back from a heavy leg day went from 72 hours to 48 hours. I’m 41, and I can tell the difference between recovery in my late twenties and recovery now. This felt like a meaningful step back toward the earlier baseline.
By month twelve: Honestly, the subjective gains plateaued. Whatever rapamycin was going to do for me, it did in the first six months. That’s worth knowing. People come into this expecting a perpetual improvement curve, and that’s not what longevity drugs do. They reset, then maintain.
Side effects and risks I take seriously
I don’t want to soft-pedal this. Rapamycin is a serious drug and the off-label longevity community has had a few close calls.
Wound healing. Rapamycin slows wound healing because that process is mTOR-dependent. If you’re getting surgery, having dental work, or — most importantly — getting injured in training, you need to be off the drug for at least 2 weeks before and 2 weeks after. I stopped a 4 mg/week course for 6 weeks around a minor surgery in 2024 with my doctor’s blessing.
Immune function. Even at weekly pulse doses, there is some immune dampening for 24–48 hours post-dose. If you’re going into a high-risk infection environment — flying internationally, visiting hospitals, traveling to a place where you don’t have local antibody coverage — push the dose back a week. I do not dose rapamycin in the week before international travel.
Lipid changes. Most users see a 10–20% bump in LDL and triglycerides in the first 3 months that often resolves on its own. If it doesn’t, you have to ask whether the cardiovascular risk of a chronic LDL increase outweighs the longevity benefit. There is no clean answer to this question yet.
Glucose dysregulation. Rare on weekly pulse dosing, common on daily. Watch fasting insulin every 3 months. If it starts climbing, drop the dose.
Mouth ulcers (aphthous stomatitis). The most common dose-limiting side effect on daily dosing. I’ve had two in 18 months on weekly. They go away in 5 days. Lysine 1 g per day during outbreaks shortens the duration.
Drug interactions. Rapamycin is metabolized by CYP3A4. Anything that inhibits or induces CYP3A4 — most statins, certain antibiotics, antifungals, some antidepressants — will alter your effective dose dramatically. Tell every doctor you see that you’re on sirolimus.
Who absolutely should not run rapamycin
If you’re under 35, this isn’t your fight yet. Your endogenous autophagy still works. Fast occasionally, exercise hard, get your sleep right. Rapamycin is for people who are pushing through the second half of life and want to compress the morbidity window.
If you’re trying to build serious muscle, rapamycin is going to fight you. mTOR is the muscle growth signal. Blocking it once a week is fine. Blocking it more frequently than that means you’re going to leave gains on the table. Choose your goal — hypertrophy or longevity — and dose accordingly.
If you have diabetes, prediabetes, uncontrolled lipids, or active cancer — talk to a real specialist, not me. The metabolic profile of rapamycin is hostile in these populations.
If you’re trying to get pregnant or you might be pregnant, rapamycin is contraindicated. mTOR inhibition during gestation is bad. Same for the partner — fertility implications for men on rapamycin haven’t been fully characterized.
Stacking — what I run alongside rapamycin
Rapamycin isn’t a solo act in my longevity protocol. Here’s the full picture:
Metformin 500 mg twice daily. Modest insulin-sensitizing benefit, possibly synergistic with rapa for autophagy. There is some controversy about whether metformin blunts exercise adaptations, so I cycle off metformin during heavy hypertrophy blocks.
NAD+ precursors. 500 mg of NMN sublingual most mornings. Whether NMN actually raises tissue NAD+ in humans is still debated, but the price has come down and the downside is minimal.
Acarbose 50 mg before high-carb meals. Another ITP-positive compound. Blunts postprandial glucose spikes, increases short-chain fatty acid production in the gut.
Senolytic pulse: dasatinib + quercetin, 2 days per month. This is the most experimental part of my stack. I run it because the senescent cell clearance literature is compelling and the risk profile of a 2-day pulse is acceptable. I do not recommend this for general use.
Fasting. A 36-hour fast once per quarter, and a daily 16:8 schedule. Fasting raises endogenous autophagy and is essentially free.
Training. Heavy resistance training 4x/week, zone 2 cardio 3x/week, sprint intervals once a week. None of this protocol replaces the training. Training is the foundation.
How to source it
Rapamycin is available in the U.S. through compounding pharmacies with a prescription. AgelessRx and Healthspan are two telehealth services that prescribe rapamycin specifically for longevity indications. The cost runs around $100–$150 per month for a 6 mg/week dose. International sourcing is country-specific — in Thailand, where I’m based, the drug is available with a Thai prescription at standard pharmacy pricing.
Whatever you do, do not buy rapamycin from a sketchy peptide site. This isn’t a peptide that gets shipped lyophilized. Pharmaceutical-grade sirolimus from a regulated pharmacy is the only acceptable source. The downside risk of contaminated product on a drug this potent is too high.
The honest verdict
Rapamycin is the single most evidence-based longevity drug currently accessible. It is also the one that demands the most respect, the most bloodwork discipline, and the most willingness to abort if your numbers go sideways. I plan to keep running it through my forties and reassess at 50 based on the data we have at that point.
If you are healthy, lean, training hard, and over 40 — this is a tool worth investigating with a knowledgeable prescriber. If you are under 35 and looking for an edge — go fix your sleep, your training, your protein intake, and your stress, and check back in a decade. If you are someone who reaches for novel compounds the moment they hit the longevity podcast circuit without doing the bloodwork — please, for your own sake, get the bloodwork before you take the pill.
Longevity isn’t a single compound. It’s a discipline. Rapamycin is one of the most powerful tools in that discipline. Use it like a tool, not a shortcut.