Comparison
Rapamycin vs Spermidine
Side-by-side of Rapamycin and Spermidine. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Rapamycin
Rapamycin for longevity: sirolimus, an mTOR inhibitor with ITP mouse lifespan data. Off-label geroprotective dosing remains investigational.
Spermidine
Spermidine supplement benefits cover autophagy induction, longevity signals, and cognition. Wheat germ extract data, doses, and human trials reviewed.
Effects at a glance
Rapamycin
- •Inhibits mTORC1 signaling by binding FKBP12, reducing protein synthesis and relieving autophagy suppression
- •ITP mouse program reproduced lifespan extension of ~10 to 25% across multiple genetic backgrounds and sexes
- •Mannick trials showed improved influenza vaccine response in elderly adults using analogs of rapamycin
- •PEARL human trial reported acceptable safety at 5 to 10 mg weekly with some functional and lean-mass signals
- •Common dose-limiting adverse effects include stomatitis, acne-like rash, and mildly elevated lipid markers
- •CYP3A4 substrate: grapefruit, ketoconazole, and clarithromycin substantially raise rapamycin exposure
Spermidine
- •Endogenous polyamine that induces autophagy via EP300 acetyltransferase inhibition and TFEB activation
- •Concentrated in wheat germ, soybeans, aged cheese, and mushrooms; ~10 to 15 mg/day in Mediterranean diets
- •Eisenberg 2016 reported dietary spermidine extended mouse lifespan and improved cardiac function
- •Wirth 2018 pilot (n=28) reported cognitive signal at 0.9 mg/day in older adults at risk for dementia
- •Larger Wirth 2019 follow-up (n=85) did not replicate the memory benefit at 12 months
- •Generally regarded as safe at supplemental doses; food-source position is reassuring
Side-by-side
| Attribute | Rapamycin | Spermidine |
|---|---|---|
| Category | pharmaceutical | supplement |
| Also known as | Sirolimus, Rapamune | spermidine trihydrochloride, wheat-germ-extract spermidine |
| Half-life (hr) ↗ | 62 | 6 |
| Typical dose (mg) ↗ | 6 | 1.2 |
| Dosing frequency | weekly (longevity protocols); daily for transplant indication | daily, typically morning with food |
| Routes | oral | oral |
| Onset (hr) | 1 | 2 |
| Peak (hr) | 2 | 4 |
| Molecular weight | 914.17 | 145.25 |
| Molecular formula | C51H79NO13 | C7H19N3 |
| Mechanism | Binds FKBP12, and the resulting complex inhibits mTORC1, reducing protein synthesis and autophagy suppression downstream of nutrient and growth-factor signaling. | Induces macroautophagy via inhibition of EP300 histone acetyltransferase and activation of TFEB-mediated lysosomal biogenesis. Substrate for hypusination of eIF5A, required for translation of mitochondrial respiration proteins. |
| Legal status | Prescription only (off-label for longevity) | OTC dietary supplement (wheat-germ extract has GRAS status in US) |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance) | OTC supplement (not scheduled) |
| Pregnancy | Not recommended | Insufficient data; not routinely recommended at supplemental doses |
| CAS | 53123-88-9 | 124-20-9 |
| PubChem CID | 5284616 | 1102 |
| Wikidata | Q410174 | Q411089 |
Safety profile
Rapamycin
Common side effects
- mouth ulcers (stomatitis)
- acne-like rash
- GI upset
- altered lipid panel
- delayed wound healing
Contraindications
- active infection
- severe hepatic impairment
- planned surgery (delayed wound healing)
- pregnancy
- live vaccines within dosing window
Interactions
- strong CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit): substantially raises rapamycin levels, toxicity risk(major)
- strong CYP3A4 inducers (rifampin, St John's wort): lowers rapamycin levels, reduced effect(major)
- ACE inhibitors: increased risk of angioedema(moderate)
- live vaccines: reduced vaccine efficacy due to immunosuppression(major)
Spermidine
Common side effects
- mild GI upset (rare)
- headache (rare)
Contraindications
- wheat-germ allergy or celiac disease (for wheat-germ-extract products)
- active cancer (theoretical)
- pregnancy and lactation (insufficient data)
Interactions
- DFMO (difluoromethylornithine): competing polyamine metabolism; do not combine without oncology guidance(moderate)
Which Should You Take?
Spermidine comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-A outcome catalogued. Rapamycin is the right call when one of the conditionals below applies.
- → If your priority is immune support, pick Rapamycin.
- → If your priority is focus or working memory, pick Spermidine.
- → If your priority is healthspan extension, pick Spermidine.
Edge case: If you want to avoid prescription-only, Spermidine is the more accessible choice.
Default choice: Spermidine. Lower friction to source, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for Rapamycin only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Rapamycin and Spermidine?
Rapamycin and Spermidine differ in category (pharmaceutical vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Rapamycin or Spermidine?
Rapamycin half-life is 62 hours; Spermidine half-life is 6 hours.
Can you stack Rapamycin with Spermidine?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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