Spermidine and Polyamines
tags: [compound, spermidine, autophagy, polyamine]
Spermidine and Polyamines
The mTOR-independent autophagy inducer. Produced by gut bacteria. Present in highest concentrations in natto and wheat germ. The mechanism — eIF5A hypusination — operates even when insulin resistance has disrupted mTOR.
What Polyamines Are
Polyamines (putrescine, spermidine, spermine) are small positively charged molecules produced by all living cells from ornithine and methionine. They stabilize nucleic acids, regulate gene expression, and modulate cell growth.
Spermidine's Autophagy Mechanism
The eIF5A hypusination pathway:
Spermidine → deoxyhypusine synthase → hypusination of eIF5A Lys⁵⁰
↓
Active hypusinated eIF5A
↓
Selective translation of autophagy gene mRNAs (ATG3, ATG7, ATG12)
↓
Autophagy induction
This is entirely independent of:
- mTOR (which is often dysregulated in metabolic disease and insulin resistance)
- AMPK (berberine/metformin pathway)
- Energy status
Clinical implication: In cells where insulin resistance has disrupted normal mTOR regulation, spermidine-induced autophagy continues to function. This makes it complementary to fasting-induced autophagy (mTOR-dependent) rather than redundant with it.
The Olfactory Signal Problem
Putrescine and cadaverine — the two simpler polyamines produced by amino acid decarboxylation during protein decomposition — produce the characteristic smell of rotting flesh and are evolved avoidance signals.
This is the same chemistry producing the dysbiosis smell. Gram-negative bacteria in a dysbiotic gut produce putrescine (from lysine) and cadaverine (from ornithine) through the same decarboxylase enzymes active in decomposing protein. The olfactory avoidance system evolved for external detection is warning about a process happening internally in dysbiotic gut ecology.
Spermidine (the beneficial polyamine) at physiological concentrations does not have the same olfactory properties — it's less volatile and at lower concentrations than the putrescine/cadaverine that produces avoidance response.
Food Sources
| Source | Spermidine content | Notes |
|---|---|---|
| Natto | ~25–30mg/100g | Highest combined with fermentation enhancement |
| Wheat germ | ~24.3mg/100g (~243mg/kg) | Added to formulation specifically |
| Mushrooms | ~8–20mg/100g | Variable by species |
| Aged cheese | ~8–13mg/100g | Histamine concern for MCAS |
| Whole soybeans | ~10–15mg/100g | |
| Peas | ~6–8mg/100g |
Natto is the overall highest-value single food for spermidine delivery. Also provides MK-7 (vitamin K2) for efferocytosis Gas6/Protein S activation. Recommend: 2 tablespoons daily as a protocol foundation.
Dosing for Therapeutic Autophagy
Studied effective doses for autophagy induction in humans: 1–3mg spermidine daily
From natto (2 tbsp = ~30g): ~7.5–9mg spermidine — above therapeutic range From wheat germ in formulation (1g per serving): ~0.24mg — additive From fermentation (spermidine produced by Lactobacillus): variable but meaningful
The combination of natto + wheat germ in formulation + fermentation-derived spermidine reliably exceeds the 1mg threshold.
Connections
- [[Phase 3 - Epigenetic Reprogramming]] — primary use
- [[Phase 5 - Adipose Remodeling]] — adipose lipophagy
- [[Gut Microbiome Ecology]] — putrescine/cadaverine as dysbiosis markers
- [[Evolutionary Sensory Framework]] — olfactory detection of decomposition polyamines
- [[Botanical Pack]] — wheat germ in formulation