Spermidine vs PE-22-28
Side-by-side comparison of key properties, dosing, and research.
Anti-Aging & LongevityCognitive Enhancement
SpermidineCognitive Enhancement
PE-22-28- Summary
- Spermidine is a naturally occurring polyamine found in all living cells, with exceptionally high concentrations in wheat germ, aged cheese, and human sperm. It is the most studied autophagy-inducing dietary compound, shown to extend lifespan across multiple species and reduce cardiovascular and cognitive aging.
- PE-22-28 is a synthetic analog of spadin derived from sortilin, designed to block TREK-1 potassium channels with rapid-onset antidepressant and neurogenic effects. It shows fast-acting depression relief (within 24 hours) and promotes hippocampal neurogenesis.
- Half-Life
- ~30–60 minutes, but gut bacteria produce it continuously; supplementation raises tissue levels over weeks
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- Admin Route
- Oral
- SubQ, Intranasal
- Research
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- Typical Dose
- 1–5 mg
- 200–400 mcg
- Frequency
- Once daily
- Once daily
- Key Benefits
- Induces autophagy — cellular self-cleaning
- Extends lifespan in yeast, flies, worms, and mice
- Reduces cardiovascular aging and arterial stiffness
- Reduces all-cause mortality (human epidemiological data)
- Neuroprotective: reduces amyloid and tau pathology
- Promotes hair growth (anagen phase activation)
- Reduces age-related immune decline
- Improves memory in aging models
- Rapid-onset antidepressant effects (within 24 hours)
- Promotes hippocampal neurogenesis
- Improves cognitive performance and memory
- Reduces anxiety and depressive behavior
- Novel mechanism — does not act on serotonin/dopamine/GABA receptors directly
- May help treatment-resistant depression
- Neuroprotective effects
- Side Effects
- Generally very well tolerated
- Rare: mild GI discomfort at high doses
- May temporarily reduce some gut bacteria species
- Rare: headache at initiation
- Generally well tolerated in animal models
- Limited human data available
- Possible mild headache or transient mood changes at initiation
- Injection site reactions (SC)
- Stacks With
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