Spermidine, a compound found in foods like aged cheese, mushrooms, and whole grains, has been linked to remarkable health benefits, including promoting cellular renewal and potentially extending lifespan. This blog post dives deep into how spermidine works at the cellular level to enhance autophagy, the body’s way of cleaning out damaged cells, to prevent aging and disease. Discover practical tips for increasing your spermidine intake naturally and the science behind its health-promoting properties.
What is Spermidine
Spermidine, a natural polyamine, has been associated with a range of potential health benefits. It is known to stimulate cytoprotective macroautophagy/autophagy, which is implicated in cellular homeostasis and growth.
Spermidine is a naturally occurring polyamine that is synthesized from putrescine and serves as a precursor of spermine. It is also found in a variety of foods and is produced endogenously in most cells and by the intestinal microbiome.
It is involved in various cellular functions, including stabilizing DNA and RNA, modulating autophagy, and forming eIF5A. Additionally, spermidine has been shown to have antioxidant properties, protecting cells from oxidative damage.
Spermidine has been shown to have potential health benefits, such as extending lifespan and health span across species, and has been associated with reduced overall mortality related to cardiovascular diseases and cancer in humans. Furthermore, spermidine has been associated with anti-inflammatory and anti-aging effects, and it has been implicated in the modulation of mitochondrial function and cognitive function.
Spermidine’s role in autophagy is particularly notable, as it has been identified as a novel autophagy inducer and has been hypothesized to be involved in longevity and cytoprotection against various noxious agents.
Additionally, spermidine has been implicated in immune cell regulation and anticancer responses, with recent studies highlighting its effectiveness in enhancing antitumor responses in aged animals.
The decline of endogenous spermidine levels with aging has been suggested to correlate with age-related deterioration, and epidemiological data indicate that increased dietary intake of spermidine may reduce overall mortality, particularly from cardiovascular diseases and cancer.
Potential Benefits of Spermidine
In the context of cognitive function, spermidine has been shown to pass the blood-brain barrier, enhance cerebral mitochondrial function, and improve spatial learning and memory in aged mice.
These effects are thought to be mediated through mechanisms such as eEF5/EIF5A hypusination and the maintenance of mitochondrial and autophagic function.
Spermidine also exhibits cardioprotective and neuroprotective effects and has been shown to stimulate anticancer immunosurveillance in rodent models.
Its anti-inflammatory properties and ability to preserve mitochondrial function are also noteworthy. Furthermore, spermidine has been reported to improve the angiogenic capacity of senescent endothelial cells and enhance ischemia-induced neovascularization in aged mice, suggesting therapeutic potential against ischemic diseases.
In addition to these benefits, spermidine has been implicated in the modulation of the gut microbiome, potentially offering therapeutic potential for inflammatory bowel disease treatment by promoting anti-inflammatory macrophages and preserving epithelial barrier integrity.
While the precise mechanisms through which spermidine exerts its effects are still being elucidated, the literature suggests that its role in autophagy induction, mitochondrial function, and anti-inflammatory processes are central to its health-promoting properties.
It is important to note that while these findings are promising, further research is needed to fully understand the clinical implications and optimal dosages for spermidine supplementation in humans.
Mechanism of action of Spermidine
The mechanism of action of spermidine in the body involves several pathways. Spermidine is synthesized from putrescine and serves as a precursor of spermine, playing a role in various biological processes, including protein and nucleic acid synthesis, protection from oxidative damage, and regulation of cell proliferation, differentiation, and apoptosis.
It is essential for viability and acts as the precursor of hypusine, a post-translational modification of eIF5A, which is necessary for the translation of mRNAs encoding proteins with polyproline tracts.
Spermidine’s anti-ageing effects are primarily mediated through the induction of autophagy, a cellular process that degrades and recycles cellular components.
It has been shown to act via the MAPK pathway and can influence other mechanisms such as inflammation reduction, lipid metabolism, and regulation of cell growth, proliferation, and death.[2] Spermidine also has cardioprotective and neuroprotective effects, stimulates anticancer immunosurveillance, and preserves mitochondrial function.
Additionally, it has been implicated in the modulation of histone acetyltransferase and histone deacetylase activity, which can affect the expression of genes involved in processes like inflammation and matrix remodeling.
In the context of cancer, spermidine interferes with the tumour cell cycle, inhibits tumour cell proliferation, and suppresses tumour growth. It regulates key oncologic pathways and autophagy, and spermidine/spermine N-1-acetyltransferase (SSAT) plays a critical role in polyamine homeostasis and serves as a diagnostic marker in human cancers.
In terms of inflammation, spermidine has been shown to inhibit the production of pro-inflammatory cytokines and may attenuate osteoarthritis progression by inhibiting the TNF-α-induced NF-κB pathway via the deubiquitination of RIP1.
While these mechanisms have been elucidated in preclinical studies, the translation of spermidine’s effects to clinical practice requires further investigation, and dosage information is not provided within the context of the current medical literature.
Natural sources of Spermidine
- Wheat Germ: One of the richest sources of spermidine, often used as a supplement or a dietary addition.
- Aged cheese: This is especially true of types like blue cheese, which are higher in spermidine content.
- Mushrooms: Various types of mushrooms are good sources, with shiitake mushrooms being particularly notable.
- Natto: A traditional Japanese food made from fermented soybeans, known for its high spermidine content.
- Whole Grains: Such as wheat, rice, and corn, which contain moderate amounts of spermidine.
- Legumes: Beans, peas, and lentils are good plant-based sources of spermidine.
- Green Peas: Particularly high in spermidine compared to other vegetables.
- Broccoli: Along with other cruciferous vegetables, it offers a decent amount of spermidine.
- Pears: Fruits are generally lower in spermidine than some other foods, but pears are among the better fruit sources.
- Potatoes: An everyday dietary staple that provides spermidine.
- Chicken Liver: Among animal products, chicken liver is a notable source.
Who might benefit from Spermidine?
Based on the medical literature, specific conditions or populations that might particularly benefit from spermidine supplementation include older adults with subjective cognitive decline, as spermidine has shown preliminary evidence of memory improvement in this group.
Additionally, spermidine may have cardioprotective effects, which could benefit individuals at risk for cardiovascular diseases.
It has also been suggested that spermidine could enhance antitumor immune responses, which may be of interest in the context of ageing and cancer.
Furthermore, spermidine has potential therapeutic applications in ocular diseases such as glaucoma, optic nerve injury, and age-related macular degeneration.
In the context of metabolic disorders, spermidine has been shown to ameliorate nonalcoholic steatohepatitis and improve gut barrier integrity and function in diet-induced obese mice.
However, the optimal dosages for human use in these conditions are not well established in the literature provided, and further research is needed to validate these potential benefits and determine appropriate dosages for therapeutic use.
Negative effects of Spermidine
The medical literature indicates that while spermidine has been associated with various health benefits, there are potential negative effects or contraindications associated with high levels of spermidine in the body.
Supraphysiological doses of spermidine have been shown to induce oxidative stress and apoptosis in mouse ovarian granulosa cells, suggesting that excessive levels can be detrimental to ovarian function.
Additionally, elevated spermidine plasma levels have been associated with markers of advanced brain ageing and may serve as an early biomarker for Alzheimer’s disease and vascular brain pathology. However, it is important to note that the concentrations found to be toxic in vitro are above those typically found in food, and a 90-day oral toxicity study in rats with spermidine trihydrochloride did not report adverse effects up to the highest dose tested.
Furthermore, a study on dietary polyamine intake did not find a significant association with all-cause or cause-specific mortality, although there was a suggestive positive association between spermidine intake and cancer mortality in women.
These findings suggest that while spermidine supplementation is generally safe and well-tolerated at certain doses, caution may be warranted with high levels, and further research is needed to understand the implications of excessive spermidine intake fully.
Resources
Spermidine: A Physiological Autophagy Inducer Acting as an Anti-Aging Vitamin in Humans?
Madeo F, Bauer MA, Carmona-Gutierrez D, Kroemer G.
Autophagy. 2019;15(1):165-168. doi:10.1080/15548627.2018.1530929.
Hofer SJ, Liang Y, Zimmermann A, et al.
Autophagy. 2021;17(8):2037-2039.
Dietary Spermidine Improves Cognitive Function.
Schroeder S, Hofer SJ, Zimmermann A, et al.
Cell Reports. 2021;35(2):108985.
Spermidine in Health and Disease.
Madeo F, Eisenberg T, Pietrocola F, Kroemer G.
Science (New York, N.Y.). 2018;359(6374)
Ueno D, Ikeda K, Yamazaki E, et al.
Scientific Reports. 2023;13(1):8338.
Niechcial A, Schwarzfischer M, Wawrzyniak M, et al.
Journal of Crohn’s & Colitis. 2023;17(9):1489-1503.
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