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Spermidine

N-(3-Aminopropyl)-1,4-butanediamine

Anti-Aging & LongevityPhase III
MW
145.25g/mol
Formula
C7H19N3

Spermidine is a naturally occurring polyamine classified as an essential biomolecule found in all living cells, playing a crucial role in cellular growth and function. Researchers primarily study spermidine for its potential effects on autophagy, longevity, and various age-related diseases. Key findings indicate that spermidine supplementation can enhance autophagy, reduce neuroinflammation, and improve cardiovascular health, with studies suggesting a correlation between dietary spermidine intake and lower incidence of cardiovascular diseases in humans. Additionally, preclinical evidence indicates that spermidine may mitigate the effects of lung fibrosis and promote immune responses against viral infections. Current research continues to explore its mechanisms and therapeutic applications across different health conditions.

Chemical Profile

Chemical Profile

Chemical structure
Chemical Structure
FormulaC7H19N3
Molecular Weight145.25 g/mol
CAS Number124-20-9
PubChem CID1102

Half-Life

INIntranasal

Not applicable

POOral

Poor bioavailability

Due to its polycationic nature, spermidine has limited absorption when administered orally.

Mechanism

Mechanism of Action

Spermidine enhances autophagy through the hypusination of the translation regulator eIF5A, activating the mTOR signaling pathway and promoting cellular processes such as mitophagy and apoptosis inhibition. It also modulates neuroinflammatory responses by interfering with inflammasome assembly in microglia, thereby reducing amyloid beta accumulation and promoting phagocytosis. While the precise receptors and all signaling pathways involved are not fully understood, spermidine's role in enhancing immune responses, particularly through IFN-γ+CD4+ T cell activation, suggests a complex interplay of pathways that warrants further investigation.

Research

80 Research Publications

4,492

Total Citations

8

Human/RCT

5.2

Avg. Influence

2025

Latest

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#01

Cardioprotection and lifespan extension by the natural polyamine spermidine.

AnimalInfluence27.0
1009
The study demonstrated that oral supplementation of spermidine extends lifespan and provides cardioprotection in mice, enhancing cardiac autophagy and reducing hypertension-related cardiac issues.
50 mg/kgintraperitoneal(mouse)daily
PubMed
#02

Metabolism and functions of trypanothione in the Kinetoplastida.

ReviewInfluence21.0
736
The study demonstrated that trypanothione, formed from glutathione and spermidine, plays a crucial role in the defense against oxidative damage in trypanosomatids.
50 mg/kgintraperitoneal(mouse)daily
PubMed
#03

Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation.

In VitroInfluence15.0
334
The study demonstrated that hypusinated eIF5A, regulated by spermidine, promotes mitochondrial respiration and macrophage activation, influencing their functional fate.
50 mg/kgintraperitoneal(mouse)daily
PubMed
#04

Functional significance of eIF5A and its hypusine modification in eukaryotes.

In VitroInfluence14.0
333
The study demonstrated that hypusine modification of eIF5A, derived from spermidine, is essential for cell growth and protein synthesis across eukaryotes.
50 mg/kgintraperitoneal(mouse)daily25-100 μMin vitro(cell)not specified50 mg/kgin vivo(mouse)not specified
PubMed
#05

Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence.

In VitroInfluence13.0
297
Researchers observed that spermidine induces autophagy and rejuvenates memory B cell responses in aging humans by post-translationally modifying eIF5A.
50 mg/kgintraperitoneal(mouse)daily
PubMed
#06

Posttranslational synthesis of hypusine: evolutionary progression and specificity of the hypusine modification.

ReviewInfluence6.0
143
The study demonstrated that the hypusine modification of eIF5A, which involves spermidine, is essential for eukaryotic cell growth and is characterized by strict enzyme specificity, indicating its evolutionary importance.
50 mg/kgintraperitoneal(mouse)daily25-100 μMin vitro(cell)not specified50 mg/kgin vivo(mouse)not specified
PubMed
#07

Modulation of protein synthesis by polyamines.

In VitroInfluence4.0
125
Researchers observed that polyamines, including spermidine, stimulate the synthesis of specific proteins crucial for cell growth and viability.
50 mg/kgintraperitoneal(mouse)daily
PubMed
#08

Spermidine is essential for fasting-mediated autophagy and longevity.

AnimalInfluence2.0
110
Researchers observed that spermidine is essential for fasting-induced autophagy and longevity across species, with its synthesis being crucial for the beneficial effects of caloric restriction.
50 mg/kgintraperitoneal(mouse)daily
PubMed
#09

eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction.

AnimalInfluence3.0
109
Researchers observed that dietary spermidine boosts eIF5A hypusination, which declines with age and is linked to mitochondrial respiration and cognitive decline in the Drosophila brain.
50 mg/kgintraperitoneal(mouse)daily
PubMed
#10

Spermidine attenuates bleomycin-induced lung fibrosis by inducing autophagy and inhibiting endoplasmic reticulum stress (ERS)-induced cell death in mice.

Baek Ae Rin, et al. · Experimental & molecular medicine · 2020

AnimalInfluence1.0
101
Researchers observed that spermidine attenuates bleomycin-induced lung fibrosis in mice by inducing autophagy and inhibiting endoplasmic reticulum stress-related cell death.

Key findings

  1. 01Spermidine reduced cell death and stress in lung cells affected by fibrosis.
  2. 02It improved cellular health by decreasing signs of premature aging in lung cells.
  3. 03Spermidine enhanced the body's natural cleaning processes, leading to less inflammation and collagen buildup in the lungs.
50 mg/kgintraperitoneal(mouse)daily
PubMed
Safety

Safety & Handling

Research Gaps

No comprehensive randomized controlled human trials have been published to confirm the long-term effects of spermidine supplementation on health outcomes, particularly in relation to cardiovascular disease and neurodegenerative conditions. Additionally, the precise molecular mechanisms by which spermidine modulates immune responses in chronic hepatitis B virus infection remain unclear, necessitating further investigation to elucidate its role in enhancing T cell immunity.

Solubility

Spermidine is highly soluble in water but has limited solubility in organic solvents like acetonitrile and DMSO.

Storage & Handling

Lyophilized

Stable for 2+ years at -20°C, 12 months at 4°C

Reconstituted

Use within 14 days when refrigerated at 4°C

Avoid

Avoid repeated freeze-thaw cycles, direct light

Solvent

Bacteriostatic water or sterile saline recommended

Safety information is derived from published research and may not reflect all known risks. This is not medical advice.

Legal Status

Legal Status

🇩🇪DE

Not approved as a medicinal product. Not a controlled substance. Sale as research chemical is a legal grey area.

🇺🇸US

Not approved by the FDA as a medicinal product. Not a controlled substance.

🇦🇺AU

Not listed under TGA scheduling.

🇬🇧UK

Not approved by MHRA as a medicinal product.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Community Insights

Community Insights

Publications per Year

50 total
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92
2
09
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15
1
16
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2
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1
20
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2
26
Mechanism

Tools

Reconstitution Calculator

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Serum Level Visualizer

Visualize Spermidine serum levels over time

Mechanism

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Legal Disclaimer

This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer