What is Spermidine
Spermidine is a naturally occurring polyamine compound that declines with age and functions primarily as an autophagy inducer with potential anti-aging properties. 1
Chemical Classification and Natural Sources
- Spermidine is a biogenic polyamine, a small positively charged molecule that is ubiquitously found within organisms and cells 2
- It is naturally present in aged cheese, wheat germs, nuts, soybeans, and fermented products 3
- The compound is available to humans through three routes: dietary intake, intracellular biosynthesis, and microbial production in the gut 3
Primary Mechanism of Action
- Spermidine induces macroautophagy through inhibition of histone acetylases such as EP300 1
- This autophagy enhancement is critical because autophagy becomes dysfunctional with aging and contributes to immunosenescence 1, 4
- The compound works at least in part through TORC1 inhibition and enhancement of autophagy, with blockage of autophagy removing most positive effects of spermidine 1
Age-Related Changes and Clinical Significance
- Tissue levels of spermidine decline with age in model organisms and humans, though they remain unusually high in healthy nonagenarians and centenarians 1, 4
- Spermidine administration increases lifespan and healthspan in multicellular model organisms including yeast, nematodes, flies, and mice 1
- Recent epidemiological data show that increased dietary intake of spermidine diminishes overall mortality associated with cardiovascular diseases and cancer 5
Molecular Functions Beyond Autophagy
- Spermidine enhances EIF5A hypusination, which promotes translation elongation and regulates TFEB synthesis 1
- The compound preserves mitochondrial and cognitive function during aging through this hypusination pathway 3
- It plays a crucial role in various cellular homeostasis and growth processes 6
Important Pharmacokinetic Considerations
- A critical caveat: High-dose oral spermidine supplementation (15 mg/d) does not increase spermidine levels in blood plasma or saliva 6
- Instead, dietary spermidine is presystemically converted into spermine, which then enters systemic circulation 6
- This suggests that the clinical effects of spermidine supplementation may be at least partially attributable to its metabolite, spermine 6
- Supplements with doses below 15 mg/d are unlikely to exert any short-term effects 6
Safety Profile
- Spermidine has not been shown to interact with common medications such as PDE5 inhibitors 4
- Unlike vaginal spermicides (nonoxynol-9), spermidine supplements have no contraindications related to HIV risk 4
- The compound is considered a natural part of the human diet with a well-established safety profile across multiple species 2