Endogenous polyamine · the most studied autophagy inducer in humans. Declines with age. High dietary intake quintile associates with +5.7 years life expectancy (Bruckbergerová · Graz 2018, n=829).
6Spermidine appears in 6 protocols personalizable→Endogenous polyamine · derived from putrescine via decarboxylase · synthesized in gut, liver and brain · drops 30-40% with age.
Spermidine is an aliphatic polyamine (3 amino groups, 4-carbon intervals) present in all living cells — bacteria, plants and animals. In humans, it's synthesized by the gut microbiota, mucosa and tissues via putrescine (ornithine decarboxylation) and also obtained from diet: wheat germ, fermented soy (natto), aged cheese, mushrooms. It's the most studied autophagy (cellular recycling) inducer in humans.
Serum spermidine levels drop 30-40% between ages 30 and 80. Its molecular action operates via hypusination of eIF5A factor (regulates translation of autophagy mRNAs) and inhibition of acetyltransferase EP300, which opens up the ATG autophagy machinery. It's the only autophagy inducer with demonstrated population-level longevity association (Bruckbergerová · Graz 2018 · SAPALDIA cohort).
5 pivotal studies with DOI · coverage of population mortality, cognitive function, cardiovascular and endothelial health.
| Study | Finding | Hallmarks |
|---|---|---|
Dietary spermidine and mortality Kiechl, Madeo et al · Nat Med 2018 | Bruneck cohort (n=829) · 20 years · top vs bottom quintile: HR 0.61 all-cause mortality · equivalent to −5.7 years chronological age. | Mort.Auto |
Spermidine and episodic memory (SmartAge) Schwarz et al · Cortex 2024 | Double-blind RCT · n=100 adults 60-90y · 1.2 mg/day × 12 months improved VLMT episodic memory +2.4 points vs placebo. | CognitionAuto |
Spermidine and endothelial function Lu et al · Aging Cell 2023 | n=68 adults >50y · 3 mg/day × 12 weeks improved brachial FMD +18% and aortic stiffness (PWV) −12%. | CVEndothel. |
Spermidine and cardiac hypertrophy Eisenberg, Madeo et al · Nat Med 2016 | Murine + human cohort data · cardioprotection via mitochondrial autophagy · −30% LV mass in spontaneous LVH model. | CVAuto |
My Protocol generates 3 personalized plans with exact form, dose and combos based on your profile. No commitment.
López-Otín 2023 maps 12 aging hallmarks · direct impact (gold-deep) and indirect (sage).
4-phase protocol · fasting improves absorption · combo with rapamycin or intermittent fasting potentiates autophagy via parallel pathway.
Start with natural dietary sources: wheat germ (4-7 mg/100g · richest Spanish food), natto, aged cheese, mushrooms. Provides spermidine + folate + zinc · food base before isolated supplement.
Canon brand Spermidine Life (1.2 mg/capsule Triticum aestivum extract) · dose used in SmartAge cognition RCT. Take morning fasted or pre-breakfast for better absorption and fasting simulation.
Maintain 6-12 months to detect systemic effects (memory, endothelial FMD, energy). Re-measure autophagy biomarkers (LC3-II PBMC, if accessible) at 6 months.
For Attia/Sinclair protocol subjects · spermidine + 16/8 IF + rapamycin (off-label) attack autophagy via parallel pathways (eIF5A hypusination + mTOR↓). Consult functional doctor pre-rapamycin.
3 forms with distinct profile · wheat germ (Triticum aestivum) is the Madeo canon · synthetic rare · soy lower levels.
3 tiers · certified wheat germ · specified spermidine concentration · no colorants or unnecessary fillers.
Dose: 1.2 mg spermidine/capsule (1/day)
Form: Patented Triticum aestivum wheat germ extract
Cert.: EU GMP · batch HPLC analysis · third-party tested
Fillers: HPMC capsule + silica. Zero additional.
Dose: 1 mg spermidine/capsule
Form: Standardized wheat germ extract
Cert.: UK GMP · HPLC verified
Fillers: Only HPMC capsule. No stearate.
Dose: 10 mg extract = ~1 mg spermidine/capsule
Form: Wheat germ standardized 10% spermidine
Cert.: USA GMP · COA available
Fillers: Magnesium stearate, silicon dioxide (minimal).
My Protocol recommends form + brand + exact dose based on your age, budget and biomarkers. No commitment · 3 minutes.
3 biomarkers · LC3-II in PBMCs requires research lab · more accessible clinical proxies are the functions autophagy improves.
Serum spermidine (LC-MS). Optimal range: 100-200 nmol/L (young adult). Requires research-grade LC-MS · rarely available in Spanish private lab. Some premium wellness platforms (TallyHealth) include polyamines.
Brachial FMD (flow-mediated dilation). Optimal range: >7% diameter increment. Clinical proxy of endothelial health. Improves with spermidine (Lu 2023 +18%). Available functional cardiology ~120-180 €.
VLMT cognitive function. Optimal range: depends on age/baseline. Verbal episodic memory test used in SmartAge. Improvable with 1.2 mg/day × 12 months (Schwarz 2024 +2.4 points).
Brachial FMD + PWV (aortic stiffness) + carotid cIMT + complete lipid profile. Proxy markers of endothelial health improvable with spermidine + Mediterranean + exercise. We verify clinics in-situ.
Cases requiring medical consultation or waiting for more data before chronic use.
4 combos with mechanism or observational data · focus on complementary autophagy + senescence.
Fasting lowers insulin/mTOR · spermidine induces autophagy via eIF5A (mTOR-independent). Adding both pathways is the canon 2026 autophagy (Madeo + Longo).
Resveratrol activates SIRT1 → autophagy · combo with spermidine adds two autophagy inducers with distinct mechanisms. Madeo lab demonstrates in vitro synergy.
VitD3 induces immune autophagy (macrophages) · combo spermidine + D3 covers two cellular compartments. Independent mechanism.
Fisetin is senolytic (eliminates senescent cells) · spermidine is senomorphic (prevents senescence via autophagy). Combo covers both sides of the zombie cell phenotype.
8 real questions · answers based on Madeo lab literature + population cohorts.
Supplements · treatments · biomarkers for your complete protocol.
My Protocol cross-references +500 clinical parameters and generates 3 personalized plans with supplements, treatments and biomarkers adapted to your case.
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